Reduced thrombin formation and excessive fibrinolysis are associated with bleeding complications in patients with dengue fever: a case–control study comparing dengue fever patients with and without bleeding manifestations

PubMed Central

2013-01-01

Background Dengue cases have been classified according to disease severity into dengue fever (DF) and dengue hemorrhagic fever (DHF). Although DF is considered a non-severe manifestation of dengue, it has been recently demonstrated that DF represents a heterogeneous group of patients with varied clinical complications and grades of severity. Particularly, bleeding complications, commonly associated to DHF, can be detected in half of the patients with DF. Although a frequent complication, the causes of bleedings in DF have not been fully addressed. Thus, the aim of this study was to perform a comprehensive evaluation of possible pathophysiological mechanisms that could contribute to the bleeding tendency observed in patients with DF. Methods This is a case–control study that enrolled adults with DF without bleeding and adults with DF and bleeding complications during the defervescence period. Healthy controls were also included. Peripheral blood counts, inflammatory, fibrinolysis and endothelial cell activation markers, and thrombin generation were evaluated in patients and controls. Results We included 33 adults with DF without complications, 26 adults with DF and bleeding and 67 healthy controls. Bleeding episodes were mild in 15 (57.6%) and moderate in 11 (42.4%) patients, 8 (30.7%) patients had bleedings in multiple sites. Patients with DF and bleedings had lower platelet counts than DF without bleeding (median = 19,500 vs. 203,500/mm3, P < 0,0001). Levels of TNF-α, thrombomodulin and VWF were significantly increased in the two dengue groups than in healthy controls, but similar between patients with and without bleedings. Plasma levels of tPA and D-dimer were significantly increased in patients with bleedings (median tPA levels were 4.5, 5.2, 11.7 ng/ml, P < 0.0001 and median D-dimer levels were 515.5, 1028 and 1927 ng/ml, P < 0.0001). The thrombin generation test showed that patients with bleeding complications had reduced thrombin formation (total thrombin generated were 3753.4 in controls, 3367.5 in non-bleeding and 2274.5nM in bleeding patients, P < 0.002). Conclusions DF can manifest with spontaneous bleedings, which are associated with specific coagulation and fibrinolysis profiles that are not significantly present in DF without this complication. Particularly, thrombocytopenia, excessive fibrinolysis and reduced thrombin formation may contribute to the bleeding manifestations in DF. PMID:23890510

Reduced thrombin formation and excessive fibrinolysis are associated with bleeding complications in patients with dengue fever: a case-control study comparing dengue fever patients with and without bleeding manifestations.

PubMed

Orsi, Fernanda A; Angerami, Rodrigo N; Mazetto, Bruna M; Quaino, Susan K P; Santiago-Bassora, Fernanda; Castro, Vagner; de Paula, Erich V; Annichino-Bizzacchi, Joyce M

2013-07-28

Dengue cases have been classified according to disease severity into dengue fever (DF) and dengue hemorrhagic fever (DHF). Although DF is considered a non-severe manifestation of dengue, it has been recently demonstrated that DF represents a heterogeneous group of patients with varied clinical complications and grades of severity. Particularly, bleeding complications, commonly associated to DHF, can be detected in half of the patients with DF. Although a frequent complication, the causes of bleedings in DF have not been fully addressed. Thus, the aim of this study was to perform a comprehensive evaluation of possible pathophysiological mechanisms that could contribute to the bleeding tendency observed in patients with DF. This is a case-control study that enrolled adults with DF without bleeding and adults with DF and bleeding complications during the defervescence period. Healthy controls were also included. Peripheral blood counts, inflammatory, fibrinolysis and endothelial cell activation markers, and thrombin generation were evaluated in patients and controls. We included 33 adults with DF without complications, 26 adults with DF and bleeding and 67 healthy controls. Bleeding episodes were mild in 15 (57.6%) and moderate in 11 (42.4%) patients, 8 (30.7%) patients had bleedings in multiple sites. Patients with DF and bleedings had lower platelet counts than DF without bleeding (median = 19,500 vs. 203,500/mm3, P < 0,0001). Levels of TNF-α, thrombomodulin and VWF were significantly increased in the two dengue groups than in healthy controls, but similar between patients with and without bleedings. Plasma levels of tPA and D-dimer were significantly increased in patients with bleedings (median tPA levels were 4.5, 5.2, 11.7 ng/ml, P < 0.0001 and median D-dimer levels were 515.5, 1028 and 1927 ng/ml, P < 0.0001). The thrombin generation test showed that patients with bleeding complications had reduced thrombin formation (total thrombin generated were 3753.4 in controls, 3367.5 in non-bleeding and 2274.5nM in bleeding patients, P < 0.002). DF can manifest with spontaneous bleedings, which are associated with specific coagulation and fibrinolysis profiles that are not significantly present in DF without this complication. Particularly, thrombocytopenia, excessive fibrinolysis and reduced thrombin formation may contribute to the bleeding manifestations in DF.

Platelet von Willebrand factor in Hermansky-Pudlak syndrome.

PubMed

McKeown, L P; Hansmann, K E; Wilson, O; Gahl, W; Gralnick, H R; Rosenfeld, K E; Rosenfeld, S J; Horne, M K; Rick, M E

1998-10-01

The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone. Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P-0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients.

Treatability of U.S. wood species with pigment emulsified creosote

Treesearch

Douglas M. Crawford; Rodney C. De Groot; John B. Watkins; Harry Greaves; Karl J. Schmalzl; T. L. Syers

2000-01-01

Since the 1920s creosote has been used extensively in the United States for treatment of construction timbers, poles, and posts. However, creosote has the tendency to exude or bbleedc from some treated commodities, producing a tar-like covered surface. In the United States, creosote-treated products exhibiting cleaner dried surfaces and a reduced tendency to bleed have...

Alcohol Abuse Increases Rebleeding Risk and Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding.

PubMed

Kärkkäinen, Jussi M; Miilunpohja, Sami; Rantanen, Tuomo; Koskela, Jenni M; Jyrkkä, Johanna; Hartikainen, Juha; Paajanen, Hannu

2015-12-01

No current data are available on rebleeding and mortality risk in patients who use alcohol excessively and are admitted for non-variceal upper gastrointestinal bleeding (NVUGIB). This information could help in planning interventions and follow-up protocols for these patients. This study provides contemporary data on the long-term outcome after first-time NVUGIB in alcohol abusers (AAs) compared to non-abusers (NAs). Consecutive patients hospitalized for their first acute gastrointestinal bleeding from 2009 through 2011 were retrospectively recorded and categorized as AA or NA. Risk factors for one-year mortality and rebleeding were identified, and patients were further monitored for long-term mortality until 2015. Alcohol abuse was identified in 19.7% of patients with NVUGIB (n = 518). The one-year rebleeding rate was 16.7% in AAs versus 9.1% in NAs (P = 0.027). Alcohol abuse was associated with a twofold increase in rebleeding risk (P = 0.025); the risk especially increased 6 months after the initial bleeding. The study groups did not differ significantly in 30-day (6.0%) or one-year mortality rates (20.5%). However, there was a tendency for higher overall mortality in AAs than NAs after adjustment of comorbidities. AAs with NVUGIB are at high risk of rebleeding, and mortality is increased in AA patients. A close follow-up strategy and long-term proton pump inhibitor therapy are recommended for AA patients with peptic ulcer or esophagitis.

[Colonic angiodysplasia in a chronic renal failure patient].

PubMed

Tudor, S; Dima, B; Herlea, V; Chiriac-Babei, Gh; Vasilescu, C

2006-01-01

An important cause of intestinal bleeding in patients with chronic renal failure is angiodysplasia. In retrospective reports up to 19-32% of patients had bleeding from angiodysplastic lesions. These are usually multiple, have a high tendency of rebleeding (25-47%) and are often located in the stomach and duodenum, but can affect the colon and the jejunum as well. Bleeding from angiodysplastic lesions is usually low grade and stops spontaneously in more than 90% of patients, but some times may be life threatening necessitate therapeutic interventions to achieve hemostasis. We report a case of an 18-year old female with renal failure on CAPD who presented a massive lower gastrointestinal bleeding and imposed emergency surgery.

Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US.

PubMed

Altomare, Ivy; Cetin, Karynsa; Wetten, Sally; Wasser, Jeffrey S

2016-01-01

Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. The goal of ITP therapy is to treat or prevent bleeding. Actual rates of bleeding are unknown. Clinical trial data may not reflect real-world bleeding rates because of the inclusion of highly refractory patients and more frequent use of rescue therapy. We used administrative medical claims data in the US to examine the occurrence of bleeding-related episodes (BREs) - a composite end point including bleeding and/or rescue therapy use - in adults diagnosed with primary ITP (2008-2012). BRE rates were calculated overall and by ITP phase and splenectomy status. Patients were followed from ITP diagnosis until death, disenrollment from the health plan, or June 30, 2013, whichever came first. We identified 6,651 adults diagnosed with primary ITP over the study period (median age: 53 years; 59% female). During 13,064 patient-years of follow-up, 3,768 patients (57%) experienced ≥1 BRE (1.08 BREs per patient-year; 95% confidence interval: 1.06-1.10). The majority (58%) of BREs consisted of rescue therapy use only. Common bleeding types were gastrointestinal hemorrhage, hematuria, ecchymosis, and epistaxis. Intracranial hemorrhage was reported in 74 patients (1%). Just over 7% of patients underwent splenectomy. Newly diagnosed and splenectomized patients had elevated BRE rates. We provide current real-world estimates of BRE rates in adults with primary ITP. The majority of ITP patients experienced ≥1 BRE, and over half were defined by rescue therapy use alone. This demonstrates the importance of examining both bleeding and rescue therapy use to fully assess disease burden.

Symptomatic Intracerebral Hemorrhage Secondary to Ventriculoperitoneal Shunt in Adults without Bleeding Tendency.

PubMed

Hou, Kun; Suo, Shihuan; Gao, Xianfeng; Zhu, Xiaobo; Zhang, Yang; Li, Guichen

2017-10-01

Ventriculoperitoneal shunt (VPS) is a common procedure in daily neurosurgical practice. According to some reports, the rate of intracerebral hemorrhage secondary to VPS in patients with no bleeding tendency can be 43.1%; however, symptomatic intracerebral hemorrhage (SICH) secondary to VPS is rare with only sporadic cases reported in adults. To further elucidate the characteristics, mechanism, management, and prognosis of SICH secondary to VPS, we performed a retrospective study in our institution and a systematic review of the literature. A retrospective review of the medical records of patients admitted for VPS was performed. We also performed a systematic PubMed search of published studies. Of 5 patients identified at our institution, 3 experienced a favorable recovery. Including our case series, there were 16 (8 female) patients. The time interval from the termination of VPS procedure to SICH was 4 hours to 15 days. All but 1 patient experienced intracerebral hemorrhage adjacent to cannulation. Of 11 patients in whom a Glasgow Outcome Scale score could be obtained, the score was 5 in 4 patients, 4 in 1 patient, 3 in 1 patient, and 1 in 5 patients. SICH is a rare complication after VPS in adults without bleeding tendency. The mechanism is obscure, management is challenging, and prognosis is dismal. Future prospective study is anticipated. Copyright © 2017 Elsevier Inc. All rights reserved.

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Molecular characterization of FXI deficiency.

PubMed

Berber, Ergul

2011-02-01

Factor XI (FXI) deficiency is a rare autosomal bleeding disease associated with genetic defects in the FXI gene. It is a heterogeneous disorder with variable tendency in bleeding and variable causative FXI gene mutations. It is characterized as a cross-reacting material-negative (CRM-) FXI deficiency due to decreased FXI levels or cross-reacting material-positive (CRM+) FXI deficiency due to impaired FXI function. Increasing number of mutations has been reported in FXI mutation database, and most of the mutations are affecting serine protease (SP) domain of the protein. Functional characterization for the mutations helps to better understand the molecular basis of FXI deficiency. Prevalence of the disease is higher in certain populations such as Ashkenazi Jews. The purpose of this review is to give an overview of the molecular basis of congenital FXI deficiency.

Disseminated intravascular coagulation: pathophysiology and principles of management.

PubMed

Marwaha, R K; Mitra, S; Marwaha, N

1998-03-01

DIC is a thrombohemorrhagic syndrome which occurs in association with well-defined clinical disorders such as septicemia, acute leukemia, snake envenomation, hypoxic states, etc. These disease conditions trigger the coagulation cascade in vivo resulting in formation of microthrombi, activation of fibrinolysis and a bleeding tendency. The important and most frequently observed laboratory abberrations include reduced platelet counts, low levels of fibrinogen, factors V and XIII with increased FDP's. Therapy primarily consists of recognizing the cause of DIC, removing the triggering process and administering anticoagulant therapy in specific situations. Component replacement is required if patients continue to bleed inspite of instituting the above mentioned measures. Rarely, drugs which inhibit fibrinolysis may be indicated. Early recognition and prompt institution of appropriate remedial measures coupled with adequate laboratory monitoring help in reducing morbidity and mortality due to DIC.

A rare case of bleeding disorder: Glanzmann's thrombasthenia.

PubMed

Swathi, Jami; Gowrishankar, A; Jayakumar, S A; Jain, Karun

2017-01-01

Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. To highlight this rare but potentially life-threating disorder, GT. We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.

A Rare Case of Bleeding Disorder: Glanzmann's Thrombasthenia

PubMed Central

Swathi, Jami; Gowrishankar, A.; Jayakumar, S. A.; Jain, Karun

2017-01-01

Background: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. Objective: To highlight this rare but potentially life-threating disorder, GT. Case Report: We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. Conclusion: GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder. PMID:29063905

[Point-of-care Coagulation Testing in Neurosurgery].

PubMed

Adam, Elisabeth Hannah; Füllenbach, Christoph; Lindau, Simone; Konczalla, Jürgen

2018-06-01

Disorders of the coagulation system can seriously impact the clinical course and outcome of neurosurgical patients. Due to the anatomical location of the central nervous system within the closed skull, bleeding complications can lead to devastating consequences such as an increase in intracranial pressure or enlargement of intracranial hematoma. Point-of-care (POC) devices for the testing of haemostatic parameters have been implemented in various fields of medicine. Major advantages of these devices are that results are available quickly and that analysis can be performed at the bedside, directly affecting patient management. POC devices allow identification of increased bleeding tendencies and therefore may enable an assessment of hemorrhagic risks in neurosurgical patients. Although data regarding the use of POC testing in neurosurgical patients are limited, they suggest that coagulation testing and hemostatic therapy using POC devices might have beneficial effects in this patient population. This article provides an overview of the application of point-of-care coagulation testing in clinical practice in neurosurgical patients. Georg Thieme Verlag KG Stuttgart · New York.

Prevalence and impact of obesity in people with haemophilia: Review of literature and expert discussion around implementing weight management guidelines.

PubMed

Kahan, S; Cuker, A; Kushner, R F; Maahs, J; Recht, M; Wadden, T; Willis, T; Majumdar, S; Ungar, D; Cooper, D

2017-11-01

Obesity affects more than 35% of Americans, increasing the risk of more than 200 comorbid conditions, impaired quality of life and premature mortality. This review aimed to summarize literature published over the past 15 years regarding the prevalence and impact of obesity in people with haemophilia (PWH) and to discuss implementing general guidelines for weight management in the context of the haemophilia comprehensive care team. Although few studies have assessed the effects of obesity on haemophilia-specific outcomes, existing evidence indicates an important impact of weight status on lower extremity joint range of motion and functional disability, with potentially important effects on overall quality of life. Data regarding bleeding tendency in PWH with coexisting obesity are largely inconclusive; however, some individuals may experience reduced joint bleeds following moderate weight loss. Additionally, conventional weight-based dosing of factor replacement therapy leads to increased treatment costs for PWH with obesity or overweight, suggesting pharmacoeconomic benefits of weight loss. Evidence-based recommendations for weight loss include behavioural strategies to reduce caloric intake and increase physical activity, pharmacotherapy and surgical therapy in appropriate patients. Unique considerations in PWH include bleed-related risks with physical activity; thus, healthcare professionals should advise patients on types and intensities of, and approaches to, physical activity, how to adjust treatment to accommodate exercise and how to manage potential activity-related bleeding. Increasing awareness of these issues may improve identification of PWH with coexisting obesity and referral to appropriate specialists, with potentially wide-ranging benefits in overall health and well-being. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Homozygous factor V Leiden mutation in type IV Ehlers-Danlos patient

PubMed Central

Refaat, Marwan; Hotait, Mostafa; Winston, Brion

2014-01-01

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. Several hemostatic abnormalities have been described in EDS patients that increase the bleeding tendencies of these patients. This case report illustrates a patient with an unusual presentation of a patient with type IV EDS, platelet δ-storage pool disease and factor V Leiden mutation. Young woman having previous bilateral deep vein thrombosis and pulmonary emboli coexisting with ruptured splenic aneurysm and multiple other aneurysms now presented with myocardial infarction. Presence of factor V Leiden mutation raises the possibility that the infarct was due to acute coronary thrombosis, although coronary artery aneurysm and dissection with myocardial infarction is known to occur in vascular type EDS. This is the first report in the medical literature of factor V Leiden mutation in an EDS patient which made the management of our patient challenging with propensity to both bleeding and clotting. PMID:24653990

[Waist-hip ratio and perioperative bleeding in patients who underwent radical prostatectomy].

PubMed

León-Ramírez, Víctor; Santiago-López, Janaí; Reyes-Rivera, Juan Gabriel; Miguel-Soto, Edgar

2016-01-01

Radical prostatectomy is associated with perioperative bleeding and multiple transfusions. Abdominal obesity is a perioperative risk factor. We suggest that the adipocytes have a protective effect in oncological patients undergoing radical prostatectomy. The aim was to evaluate the effect of waist-hip ratio (WHR) on the amount of bleeding and perioperative transfusion requirements in oncological patients undergoing radical prostatectomy. We performed a cohort study in 156 patients. We had two groups: the control group (WHR<0.95) and the problem group (WHR≥0.95). Blood loss and fractions transfused during surgery and in the postoperative period were recorded. In the analysis of variables, for descriptive statistics we used measures of central tendency and dispersion. Inferential statistics was obtained by chi square, Student's t test, Mann-Whitney U and ANOVA. A p<0.05 was significant. We found significant differences in weight, body mass index, waist, WHR, perioperative bleeding, fractions transfused, permanence of the catheter, and hospital days. Patients who underwent radical prostatectomy with a WHR≥0.95 had a magnitude of perioperative bleeding and transfusion requirements with a WHR<0.95.

Similar bleeding phenotype in young children with haemophilia A or B: a cohort study.

PubMed

Clausen, N; Petrini, P; Claeyssens-Donadel, S; Gouw, S C; Liesner, R

2014-11-01

The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL(-1) respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A. © 2014 John Wiley & Sons Ltd.

F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study.

PubMed

Quintavalle, Gabriele; Riccardi, Federica; Rivolta, Gianna Franca; Martorana, Davide; Di Perna, Caterina; Percesepe, Antonio; Tagliaferri, Annarita

2017-08-01

Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C<50 %. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:C<0.10 %. Epistaxis (11 %) and menorrhagia (32 % of females in fertile age) were the most frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in the F7 international databases. Most mutations (62 %) were missense, large deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi 2 =43.709, p<0,001). The polymorphisms distribution was significantly different among the three F7 genotypic groups (Chi 2 =72.289, p<0,001). The presence of truncating mutations was associated with lowest FVII:C levels (Chi 2 =21.351, p=0.002). This study confirms the clinical and molecular variability of the disease and the type of symptoms. It shows a good correlation between the type of F7 mutation and/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.

Balancing between bleeding and thromboembolism after percutaneous coronary intervention in patients with atrial fibrillation. Could triple anticoagulant therapy be a solution?

PubMed

Dąbrowska, Magdalena; Ochała, Andrzej; Cybulski, Wiesław; Tendera, Michał

2013-01-01

Atrial fibrillation (AF) has nowadays become a common disease as it comes along with medical procedures propagation in the ageing population with coexistent diseases. Hence a need for use of combined anticoagulant and antithrombotic therapy has arisen. According to the 2010 ESC guidelines on myocardial revascularization, short-term triple antithrombotic therapy after percutaneous coronary intervention (PCI) should be given if compelling indications exist. To assess bleeding and thromboembolic events depending on the antithrombotic regimen in short- and long-term follow-up in patients with AF after PCI with stent implantation. A 12-month prospective, non-randomized registry was conducted in the 3(rd) Department of Cardiology in the Upper Silesian Medical Center in Katowice from October 2008 to April 2011. One hundred and four patients in two groups - on triple therapy (TT; aspirin + clopidogrel + vitamin K antagonists (VKA; warfarin or acenocoumarol) n = 44) and on dual therapy (DT; aspirin + clopidogrel; n = 60) - were assessed 30 days and 12 months after angioplasty. All bleeding events occurred more often in the triple anticoagulated group in 30 days (TT 20.5% vs. DT 6.7%; p = 0.03) and after 12 months (TT 38.9% vs. DT 17.2%, p = 0.09). The difference in major bleeding events was not significant after 30 days (TT 9.1% vs. DT 3.3%; p = NS) or 12 months (TT 11.1% vs. DT 6.9%; p = NS). Thromboembolic events after 30 days (DT 5.0% vs. TT 2.3%) and 12 months (TT 11.1% vs. DT 3.4%) were comparable. The percentage of deaths after 30 days (DT 1.7% vs. TT 0.0%, p = NS) increased after 12 months (DT 13.8% vs. TT 0.0%, p = 0.09). Significantly higher risk of bleeding on TT becomes blurred by a tendency to increased mortality in patients on DT.

Clinical study of heparin-free hemodialysis with the inside of hollow fibers in dialyzer coated by human albumins.

PubMed

Wu, Xixin; Chen, Huaji

2002-12-01

To investigate the therapeutics of heparin-free hemodialysis (HD) with the inside of hollow fibers in a dialyzer coated with human albumins (HFHd-A1). Clinical contrast study between HFHd-A1 and heparin-free HD with hollow fibers in dialyzer by normal saline flush (HFHd-NS) was performed by adopting the cross-over design method. The dialysis effect, the effect on life signs, blood platelet functions, change of dialyzer fiber-bundle volume, appearance image, and image of scanning electron microscopy of the inside of hollow fibers in dialyzer after dialysis and the biocompatibility of dialyzer of two HD methods were compared. HFHd-A1 could overcome all shortcomings of HFHd-NS and had more merits and increased expenses for HFHd-A1 were not high. HFHd-A1 was an effective and feasible method which could salvage patients with bleeding diseases or bleeding tendency and who need HD. Copyright 2002 S. Karger AG, Basel

Comparison of postoperative coagulation profiles and outcome for sugammadex versus pyridostigmine in 992 living donors after living-donor hepatectomy

PubMed Central

Moon, Young-Jin; Kim, Sung-Hoon; Kim, Jae-Won; Lee, Yoon-Kyung; Jun, In-Gu; Hwang, Gyu-Sam

2018-01-01

Abstract Donor safety is the major concern in living donor liver transplantation, although hepatic resection may be associated with postoperative coagulopathy. Recently, the use of sugammadex has been gradually increased, but sugammadex is known to prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the postoperative coagulation profiles and outcomes of sugammadex versus pyridostigmine group in donors receiving living donor hepatectomy. Consecutive donor hepatectomy performed between September 2013 and August 2016 was retrospectively analyzed. For reversal of rocuronium-induced neuromuscular blockade, donors received sugammadex 4 mg/kg or pyridostigmine 0.25 mg/kg. The primary end-points were laboratory findings (PT, aPTT, hemoglobin, platelet count) and clinically evaluated postoperative bleeding (relaparotomy for bleeding, cumulative volume collected in drains). Secondary outcomes were anesthesia time, postoperative hospital day. Of 992 donors, 383 treated with sugammadex and 609 treated with pyridostigmine for the reversal of neuromuscular blockade. There were no significant differences between both groups for drop in hemoglobin and platelet, prolongation in PT, aPTT, and the amount of 24-h drain volume. Bleeding events within 24 h were reported in 2 (0.3%) for pyridostigmine group and 0 (0%) for sugammadex group (P = .262). Anesthesia time was significantly longer in pyridostigmine group than that in sugammadex group (438.8 ± 71.4 vs. 421.3 ± 62.3, P < .001). Postoperative hospital stay was significantly longer in pyridostigmine group than that in sugammadex group (P = .002). Sugammadex 4 mg/kg was not associated with increased bleeding tendency, but associated with reduced anesthesia time and hospital stay. Therefore, sugammadex may be safely used and will decrease morbidity in donor undergoing living-donor hepatectomy. PMID:29538210

Comparison of postoperative coagulation profiles and outcome for sugammadex versus pyridostigmine in 992 living donors after living-donor hepatectomy.

PubMed

Moon, Young-Jin; Kim, Sung-Hoon; Kim, Jae-Won; Lee, Yoon-Kyung; Jun, In-Gu; Hwang, Gyu-Sam

2018-03-01

Donor safety is the major concern in living donor liver transplantation, although hepatic resection may be associated with postoperative coagulopathy. Recently, the use of sugammadex has been gradually increased, but sugammadex is known to prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the postoperative coagulation profiles and outcomes of sugammadex versus pyridostigmine group in donors receiving living donor hepatectomy.Consecutive donor hepatectomy performed between September 2013 and August 2016 was retrospectively analyzed. For reversal of rocuronium-induced neuromuscular blockade, donors received sugammadex 4 mg/kg or pyridostigmine 0.25 mg/kg. The primary end-points were laboratory findings (PT, aPTT, hemoglobin, platelet count) and clinically evaluated postoperative bleeding (relaparotomy for bleeding, cumulative volume collected in drains). Secondary outcomes were anesthesia time, postoperative hospital day.Of 992 donors, 383 treated with sugammadex and 609 treated with pyridostigmine for the reversal of neuromuscular blockade. There were no significant differences between both groups for drop in hemoglobin and platelet, prolongation in PT, aPTT, and the amount of 24-h drain volume. Bleeding events within 24 h were reported in 2 (0.3%) for pyridostigmine group and 0 (0%) for sugammadex group (P = .262). Anesthesia time was significantly longer in pyridostigmine group than that in sugammadex group (438.8 ± 71.4 vs. 421.3 ± 62.3, P < .001). Postoperative hospital stay was significantly longer in pyridostigmine group than that in sugammadex group (P = .002).Sugammadex 4 mg/kg was not associated with increased bleeding tendency, but associated with reduced anesthesia time and hospital stay. Therefore, sugammadex may be safely used and will decrease morbidity in donor undergoing living-donor hepatectomy.

Management of internal hemorrhoids by Kshara karma: An educational case report.

PubMed

Mahapatra, Anita; Srinivasan, A; Sujithra, R; Bhat, Ramesh P

2012-07-01

A 66-year-old male patient came to the anorectal clinic, Outpatient department, AVT Institute for Advanced Research, Coimbatore, Tamil Nadu, with complaints of prolapsing pile mass during defecation and bleeding while passing stool. The case was diagnosed as "Raktarsha" - 11 & 7 'o' clock position II degree internal hemorrhoids, deeply situated, projecting one and caused by pitta and rakta; with bleeding tendency. Kshara karma (application of caustic alkaline paste) intervention was done in this case to internal hemorrhoids under local anesthesia. The pile mass and per rectal bleeding resolved in 8 days and the patient was relieved from all symptoms within 21 days. No complications were reported after the procedure. The patient was followed up regularly from 2004 onward till date and proctoscopic examination did not reveal any evidence of recurrence of the hemorrhoids.

Management of internal hemorrhoids by Kshara karma: An educational case report

PubMed Central

Mahapatra, Anita; Srinivasan, A.; Sujithra, R.; Bhat, Ramesh P.

2012-01-01

A 66-year-old male patient came to the anorectal clinic, Outpatient department, AVT Institute for Advanced Research, Coimbatore, Tamil Nadu, with complaints of prolapsing pile mass during defecation and bleeding while passing stool. The case was diagnosed as “Raktarsha” - 11 & 7 ‘o’ clock position II degree internal hemorrhoids, deeply situated, projecting one and caused by pitta and rakta; with bleeding tendency. Kshara karma (application of caustic alkaline paste) intervention was done in this case to internal hemorrhoids under local anesthesia. The pile mass and per rectal bleeding resolved in 8 days and the patient was relieved from all symptoms within 21 days. No complications were reported after the procedure. The patient was followed up regularly from 2004 onward till date and proctoscopic examination did not reveal any evidence of recurrence of the hemorrhoids. PMID:23125506

Preoperative Detailed Coagulation Tests Are Required in Patients With Noonan Syndrome.

PubMed

Morice, Anne; Harroche, Annie; Cairet, Pascale; Khonsari, Roman H

2017-12-29

Patients with Noonan syndrome often require surgery at young ages. They are at high risk of perioperative bleeding from coagulation defects that might not have been detected by routine screening. These risks are rarely described in the oral and maxillofacial surgery (OMS) literature. The aim of this study was to evaluate the perioperative bleeding risks associated with Noonan syndrome and to propose preoperative guidelines. This report describes a retrospective case series of patients with Noonan syndrome who underwent OMS procedures during a continuous observational period (2013 through 2016) in the authors' center. Clinical data, blood screening test results, and perioperative bleeding were analyzed. Five patients (age, 4 to 20 yr) with Noonan syndrome who underwent OMS procedures were included in this study. One patient presented a spontaneous bleeding tendency (epistaxis requiring cauterization). Blood screening showed clotting defects in 3 patients. One patient presented abnormal perioperative bleeding owing to a mild defect in factor XI. Patients with Noonan syndrome must be referred to a hematologist for specific preoperative investigations and for adapted perioperative management. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Acquired Dysfibrinogenemia Caused by Autoantibody Inhibiting Fibrin Polymerization in a Patient with MELAS Syndrome and Bleeding Tendency.

PubMed

Lee, Nuri; Kim, Ji-Eun; Yoo, Hyun Ju; Gu, JaYoon; Kim, Hyori; Chung, Junho; Koh, Youngil; Kim, Hyun Kyung

2016-12-01

We present a case of acquired dysfibrinogenemia caused by an autoantibody that inhibited fibrin polymerization in a patient previously diagnosed with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes). The patient showed prolonged PT, aPTT, and thrombin time. There was no factor deficiency but fibrinogen antigen and activity were decreased. ELISA for detection of fibrinogen antibodies were performed and IgG purified from the patient's plasma bound to fibrinogen more strongly than did control IgG, indicating the presence of a fibrinogen-specific antibody. Thrombin-mediated fibrin polymerization was severely impaired in the patient, although thrombin-induced fibrinopeptide A release was normal. Scanning electron microscopy was used to investigate the structure of fibrin clots and revealed many pores on the surface of patient's fibrin clots. Since MELAS is often associated with autoimmune disorders, a work-up for the presence of anti-fibrinogen antibody is necessary when bleeding tendency occurs in MELAS patients along with prolonged thrombin time. © 2016 by the Association of Clinical Scientists, Inc.

Surgery of a cyanotic heart defect in an 11-year-old boy with thrombocytopenic thrombocytopathy and severe anemia due to a GATA-1 defect: hemostatic therapy.

PubMed

Hoefer, J; Streif, W; Kilo, J; Grimm, M; Berger, G; Velik-Salchner, C

2012-10-01

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved. © Georg Thieme Verlag KG Stuttgart · New York.

Physiotherapy home exercise program for haemophiliacs.

PubMed

Pierstorff, K; Seuser, A; Weinspach, S; Laws, H-J

2011-05-01

Regular physiotherapy can improve the stability and flexibility of joints and decrease the bleeding risk in patients with haemophilia. To reduce the appointments for the patients and to make exercising a part of daily live, an individualized home exercise program (HEP) was designed. Retrospectively the number of bleedings during the HEP was compared to number of bleedings before. 8 patients aged between 4 and 16 years with haemophilia A were evaluated. At start and after 13 month patients had a motion analysis via topographic ultrasound. According to the results and clinical findings an individualized HEP was created. Standardised scores for clinical evaluation and the patient based evaluation of exercises were designed. At every appointment exercises were individually adjusted. Patients exercised in median 1.7 times a week. No training related bleeds occurred. 7 of 8 patients showed reduced joint and/or muscle bleeds (p<0.02). Clinical scores raised slightly in every patient. However the second motion analysis of squat and gait showed a worsening in 7 of 8 patients (p>0.05). A HEP can help to advance in physical fitness and coordination and may reduce bleeding tendency, but needs to be accomplished regularly. Patients are interested but the motivation to exercise at home is low. Disorders measured by motion analysis seem not to be sufficiently influenced by our surrogate training program. © Georg Thieme Verlag KG Stuttgart · New York.

Analysis of risk factor and clinical characteristics of angiodysplasia presenting as upper gastrointestinal bleeding.

PubMed

Kim, Dae Bum; Chung, Woo Chul; Lee, Seok Jong; Sung, Hea Jung; Woo, Seokyung; Kim, Hyo Suk; Jeong, Yeon Oh; Lee, Hyewon; Kim, Yeon-Ji

2016-07-01

Angiodysplasia is important in the differential diagnosis of upper gastrointestinal bleeding (UGIB), but the clinical features and outcomes associated with UGIB from angiodysplasia have not been characterized. We aimed to analyze the clinical characteristics and outcomes of angiodysplasia presented as UGIB. Between January 2004 and December 2013, a consecutive series of patients admitted with UGIB were retrospectively analyzed. Thirty-five patients with bleeding from angiodysplasia were enrolled. We compared them with an asymptomatic control group (incidental finding of angiodysplasia in health screening, n = 58) and bleeding control group (simultaneous finding of angiodysplasia and peptic ulcer bleeding, n = 28). When patients with UGIB from angiodysplasia were compared with the asymptomatic control group, more frequent rates of nonantral location and large sized lesion (≥ 1 cm) were evident in multivariate analysis. When these patients were compared with the bleeding control group, they were older (mean age: 67.94 ± 9.16 years vs.55.07 ± 13.29 years, p = 0.03) and received less transfusions (p = 0.03). They also had more frequent rate of recurrence (40.0% vs. 20.7%, p = 0.02). Non-antral location and large lesions (≥ 1 cm) could be risk factors of UGIB of angiodysplasia. UGIB due to angiodysplasia was more common in older patients. Transfusion requirement would be less and a tendency of clinical recurrence might be apparent.

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

PubMed

Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

2017-04-03

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Immunosuppressive agents are associated with peptic ulcer bleeding.

PubMed

Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

2017-05-01

Peptic ulcer bleeding can be fatal. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppressive agents are administered for long-term usage. The present study assessed the association between peptic ulcer bleeding and administration of NSAIDs, corticosteroids and immunosuppressive agents. Furthermore, the efficacy of lowering the risk of peptic ulcer bleeding with proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was evaluated. Medical records were retrospectively analyzed for patients subjected to an upper gastrointestinal (GI) endoscopy performed at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) from October 2014 to September 2015. During this period, a total of 1,023 patients underwent an upper GI endoscopy. A total of 1,023 patients, including 431 males (age, 68.1±12.9 years) and 592 females (age, 66.4±12.3 years), who had been administered NSAIDs, corticosteroids, immunosuppressive agents, PPIs and H2RAs, were respectively enrolled. Endoscopic findings of the patients were reviewed and their data were statistically analyzed. Logistic regression analysis was used to determine the odds ratio of peptic ulcer bleeding for each medication; immunosuppressive agents had an odds ratio of 5.83, which was larger than that for NSAIDs (4.77). The Wald test was applied to confirm the correlation between immunosuppressive agents and peptic ulcer bleeding. Furthermore, χ 2 tests were applied to the correlation between peptic ulcer bleeding and administration of PPIs or H2RAs. Immunosuppressive agents had the largest χ 2 , and the P-value was 0.03. Administration of PPIs was significantly correlated with non-peptic ulcer bleeding (P=0.02); furthermore, a tendency toward non-peptic ulcer bleeding with administration of H2RA was indicated, but it was not statistically significant (P=0.12). In conclusion, immunosuppressive agents were correlated with peptic ulcer bleeding and PPIs were effective at lowering the risk of peptic ulcer bleeding.

Immunosuppressive agents are associated with peptic ulcer bleeding

PubMed Central

Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

2017-01-01

Peptic ulcer bleeding can be fatal. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppressive agents are administered for long-term usage. The present study assessed the association between peptic ulcer bleeding and administration of NSAIDs, corticosteroids and immunosuppressive agents. Furthermore, the efficacy of lowering the risk of peptic ulcer bleeding with proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was evaluated. Medical records were retrospectively analyzed for patients subjected to an upper gastrointestinal (GI) endoscopy performed at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) from October 2014 to September 2015. During this period, a total of 1,023 patients underwent an upper GI endoscopy. A total of 1,023 patients, including 431 males (age, 68.1±12.9 years) and 592 females (age, 66.4±12.3 years), who had been administered NSAIDs, corticosteroids, immunosuppressive agents, PPIs and H2RAs, were respectively enrolled. Endoscopic findings of the patients were reviewed and their data were statistically analyzed. Logistic regression analysis was used to determine the odds ratio of peptic ulcer bleeding for each medication; immunosuppressive agents had an odds ratio of 5.83, which was larger than that for NSAIDs (4.77). The Wald test was applied to confirm the correlation between immunosuppressive agents and peptic ulcer bleeding. Furthermore, χ2 tests were applied to the correlation between peptic ulcer bleeding and administration of PPIs or H2RAs. Immunosuppressive agents had the largest χ2, and the P-value was 0.03. Administration of PPIs was significantly correlated with non-peptic ulcer bleeding (P=0.02); furthermore, a tendency toward non-peptic ulcer bleeding with administration of H2RA was indicated, but it was not statistically significant (P=0.12). In conclusion, immunosuppressive agents were correlated with peptic ulcer bleeding and PPIs were effective at lowering the risk of peptic ulcer bleeding. PMID:28565788

THROMBIN GENERATION AND BLEEDING IN HEMOPHILIA A

PubMed Central

Brummel-Ziedins, Kathleen E.; Whelihan, Matthew F.; Gissel, Matthew; Mann, Kenneth G.; Rivard, Georges E.

2012-01-01

Introduction Hemophilia A displays phenotypic heterogeneity with respect to clinical severity. Aim To determine if tissue factor (TF)-initiated thrombin generation profiles in whole blood in the presence of corn trypsin inhibitor (CTI) are predictive of bleeding risk in hemophilia A. Methods We studied factor(F) VIII deficient individuals (11 mild, 4 moderate and 12 severe) with a well-characterized five-year bleeding history that included hemarthrosis, soft tissue hematoma and annual FVIII concentrate usage. This clinical information was used to generate a bleeding score. The bleeding scores (range 0–32) were separated into three groups (bleeding score groupings: 0, 0 and ≤9.6, >9.6), with the higher bleeding tendency having a higher score. Whole blood collected by phlebotomy and contact pathway suppressed by 100μg/mL CTI was stimulated to react by the addition of 5pM TF. Reactions were quenched at 20min by inhibitors. Thrombin generation, determined by ELISA for thrombin – antithrombin was evaluated in terms of clot time (CT), maximum level (MaxL) and maximum rate (MaxR) and compared to the bleeding score. Results Data are shown as the mean±SD. MaxL was significantly different (p<0.001) between the groups: 504±114nM, 315±117nM, and 194±91nM; with higher thrombin concentrations in the groups with lower bleeding scores. MaxR was higher in the groups with a lower bleeding score; 97±51nM/min, 86±60nM/min and 39±16nM/min (p=0.09). No significant difference was detected in CT among the groups, 5.6±1.3min, 4.7±0.7min, 5.6±1.3min. Conclusions Our empirical study in CTI-inhibited whole blood shows that the MaxL of thrombin generation appears to correlate with the bleeding phenotype of hemophilia A. PMID:19563500

An Inherited Platelet Function Defect in Basset Hounds

PubMed Central

Johnstone, I. B.; Lotz, F.

1979-01-01

An inherited platelet function defect occurring in a family of basset hounds has been described. The trait is transmitted as an autosomal characteristic and appears to be expressed clinically only in the homozygous state. The characteristics of this platelet defect include: 1) marked bleeding tendencies and prolonged skin bleeding times in either male or female dogs. 2) normal blood coagulation mechanism. 3) adequate numbers of circulating platelets which appear morphologically normal by light microscopy. 4) normal whole blood clot retraction. 5) deficient in vivo platelet consumption and in vitro platelet retention in glass bead columns. 6) defective ADP-induced platelet aggregation in homozygotes, apparently normal ADP response in heterozygotes, and defective collagen-induced platelet aggregation in both. PMID:509382

Using Socio-Dramatic Play to Support a Beginning Writer: "Daniel, the Doctor and the Bleeding Ball"

ERIC Educational Resources Information Center

Boyle, Bill; Charles, Marie

2010-01-01

This article reports on a case study of a young child (aged five) at a very early stage of his journey as a writer, evidencing "pre-alphabetic tendencies", who has not yet internalised the construction of his name. Analysis of a "baseline" piece of Daniel's writing demonstrates his awareness that the production of random…

[Comparison on Endoscopic Hemoclip and Hemoclip Combination Therapy in Non-variceal Upper Gastrointestinal Bleeding Patients Based on Clinical Practice Data: Is There Difference between Prospective Cohort Study and Randomized Study?].

PubMed

Lee, Su Hyun; Jung, Jin Tae; Lee, Dong Wook; Ha, Chang Yoon; Park, Kyung Sik; Lee, Si Hyung; Yang, Chang Heon; Park, Youn Sun; Jeon, Seong Woo

2015-08-01

Endoscopic hemoclip application is an effective and safe method of endoscopic hemostasis. We conducted a multicenter retrospective study on hemoclip and hemoclip combination therapy based on prospective cohort database in terms of hemostatic efficacy not in clinical trial but in real clinical practice. Data on endoscopic hemostasis for non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively collected from February 2011 to December 2013. Among 1,584 patients with NVUGIB, 186 patients treated with hemoclip were enrolled in this study. Subjects were divided into three groups: Group 1 (n = 62), hemoclipping only; group 2 (n = 88), hemoclipping plus epinephrine injection; and group 3 (n = 36), hemocliping and epinephrine injection plus other endoscopic hemostatic modalities. Primary outcomes included rebleeding, other therapeutic management, hospitalization period, fasting period and mortality. Secondary outcomes were bleeding associated mortality and overall mortality. Active bleeding and peptic ulcer bleeding were more common in group 3 than in group 1 and in group 2 (p <œ 0.001). However, primary outcomes (rebleeding, other management, morbidity, hospitalization period, fasting period and mortality) and secondary outcomes (bleeding associated mortality and total mortality) were not different among groups. Combination therapy of epinephrine injection and other modalities with hemoclips did not show advantage over hemoclipping alone in this prospective cohort study. However, there is a tendency to perform combination therapy in active bleeding which resulted in equivalent hemostatic success rate, and this reflects the role of combination therapy in clinical practice.

Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families.

PubMed

Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

2018-01-01

Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients' families. Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients' F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson's correlation coefficient and the nonparametric Mann-Whitney test. Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity.

Long-term efficacy of a 0.07% cetylpyridinium chloride mouth rinse in relation to plaque and gingivitis: a 6-month randomized, vehicle-controlled clinical trial.

PubMed

Van Leeuwen, M P C; Rosema, N A M; Versteeg, P A; Slot, D E; Van Winkelhoff, A J; Van der Weijden, G A

2015-05-01

To evaluate the effectiveness of 0.07% cetylpyridinium chloride (CPC) mouth rinse for reduction of gingival inflammation and inhibition of plaque compared to a vehicle control (VC) mouth rinse over a 6-month period. Participants (n = 62) used their randomly assigned product as adjunct to toothbrushing. Bleeding, plaque and staining scores were assessed at baseline, 3 and 6 months. Plaque and saliva samples were taken at each assessment monitoring possible shifts in the composition of the microbiota. A significant difference (P = 0.002) in favour of the CPC mouth rinse, with respect to plaque scores, was found. Bleeding scores at 6 months were not significantly different (P = 0.089). However, when correcting for baseline values, a tendency towards a significant difference in bleeding scores at end trail was observed in favour of the CPC mouth rinse (P = 0.061). Regarding staining at 3 and 6 months, a small but significant difference (8.6% and 10.4%, respectively) (P < 0.0001) was observed with lower scores for the VC group. There was a significant reduction in total anaerobic count in the CPC group at 6 months (P < 0.05). The ratio of aerobes/anaerobes was markedly increased at 3 months, especially in the CPC group. No further differences were observed between groups at 6 months. The use of 0.07% CPC mouth rinse was significantly more effective in reducing plaque scores than the vehicle control. Bleeding scores were not different at 6 months. The test product was well accepted and did not cause any serious clinical side effects or negatively affected the microbiota. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Retrospective Review of Platelet Transfusion Practices during 2013 Dengue Epidemic of Delhi, India.

PubMed

Chaurasia, Rahul; Zaman, Shamsuz; Chatterjee, Kabita; Das, Bankim

2015-07-01

Dengue infection is a major public health problem. During explosive outbreaks, there is sudden surge in demands of platelet products. The present study was carried out in order to review platelet transfusion practices during the epidemic of dengue. We retrospectively reviewed the clinical details including the platelet counts and haemorrhagic tendencies of dengue patients as well as the transfusion requirements of diagnosed dengue cases admitted at our centre. A total of 1,750 random donor platelet and 114 single donor platelet units were transfused to 531 patients. 23.2% platelet transfusions were found to be inappropriate Mean dosage of platelets transfused was 2 × 10(11) platelets per patient. A total of 347 (65.3%) patients had bleeding diathesis at the time of presentation. Skin and the oropharynx were the most common bleeding sites. Major bleeding was seen in 119 (34.3%) patients, whereas 228 (65.7%) patients had minor bleeding episodes. The study emphasises the need for minimising unnecessary transfusions and for using this scarce resource judiciously, which can be achieved by strict adherence to evidence-based transfusion guidelines and regular review of the on-going transfusion practices.

[No clinical evidence for an enhanced bleeding tendency due to perioperative treatment with bromelain].

PubMed

Johann, K; Eschmann, K; Meiser, P

2011-06-01

Systemic enzyme therapy with bromelain resembles a sensible alternative to nonsteroidal antiinflammatory drugs for the treatment of sports injuries, with particular consideration of therapeutic benefits and possible risks. Beyond aftertreatment of sports injuries, bromelain is used postoperatively as well. Besides the desired effects remission of oedema and pain relief, however, the postoperative use of bromelain raises uncertainty in some patients and physicians since an enhanced bleeding tendency in case of concomitant therapy with anticoagulants was described as a possible interaction. Therefore, the goal of this study was to investigate the clinical relevance of this interaction. In two non-interventional studies, altogether 260 patients were peri- or postoperatively (cruciate ligament- or coxarthrosis surgery) treated with bromelain (n = 129, 1000 - 3000 F. I. P. units/day) or diclofenac (n = 131; 150 mg/day) under concomitant thrombosis prophylaxis with low molecular weight heparin. Parameters tested were prothrombin time, thrombin time, activated partial thromboplastin time, fibrinogen and tolerability of the medication. Only marginal changes and a low variability of coagulation parameters were observed in both treatment groups (bromelain vs. diclofenac) in both studies. Elevated laboratory parameters were observed in both treatment groups for thrombin time which is very likely attributable to the therapy with low molecular weight heparin, due to the substantially parallel course of this parameter in both treatment groups. Therapy with bromelain was superior to the treatment with diclofenac concerning the number and the severity of undesirable effects, as was expected. The presented studies therefore support the previous clinical evidence that a perioperative treatment with bromelain is well tolerated and does not lead to an increased risk of haemorrhage when used concomitantly with low molecular weight heparin. © Georg Thieme Verlag KG Stuttgart · New York.

[The use of superselective embolization of the maxillary artery in treatment of bleedings in the Rendu-Osler-Weber syndrome].

PubMed

Kantor, Ireneusz; Winiarski, Michał; Jurkiewicz, Dariusz; Osiecki, Mirosław; Brzozowski, Krzysztof

2005-01-01

Rendu-Osler-Weber syndrome is a rare genetically determined disorder that affects blood vessels throughout the body and results in a tendency for bleeding. Authors describe the case of superselective embolization of the left maxillary artery with polyvinyl alcohol particles in a patient with the Rendu-Osler-Weber syndrome hospitalized and treated in the Department of Otolaryngology and the Department of Radiology of the Military Institute in Warszawa, Poland due to persistent, severe and difficult to manage nasal bleeding. After the procedure had been performed patient condition improved and frequency and severity of nasal bleeding significantly diminished. Authors conclude that superselective embolization of the maxillary artery in a patient with Rendu-Osler-Weber syndrome is safe and effective and can be a valuable alternative to the maxillary artery or the carotis externa artery ligation. Authors also describe other methods of nasal bleeding management: laser photocoagulation, argon plasma coagulation, nasal dermoplasty and pharmacological treatment. Authors indicate that treating patients with Rendu-Osler-Weber syndrome is a diagnostic and therapeutic challenge for a physician and surgeon that require special approach to a patient due to difficult to manage symptoms. Patients with Rendu-Osler-Weber syndrome should be treated in a hospital setting due to access to diagnostic imaging techniques that can be helpful in revealing possible life threatening conditions.

Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice

PubMed Central

Gu, Ruo-lan; Liu, Liang; Xie, Liang-zhi; Gai, Wen-lin; Cao, Si-shuo; Meng, Zhi-yun; Gan, Hui; Wu, Zhuo-na; Li, Jian; Zheng, Ying; Zhu, Xiao-xia; Dou, Gui-fang

2016-01-01

Aim: SCT800 is a new third-generation recombinant FVIII agent that is undergoing promising preclinical study. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles of SCT800 in hemophilia A mice. Methods: After hemophilia A mice were intravenously injected with single dose of SCT800 (80, 180, and 280 IU/kg) or the commercially available product Xyntha (280 IU/kg), pharmacokinetics profiles were evaluated based on measuring plasma FVIII: C. For pharmacodynamics study, dose-response curves of SCT800 and Xyntha (1–200 IU/kg) were constructed using a tail bleeding model monitoring both bleeding time and blood loss. Results: Pharmacokinetics profile analysis showed a dose independency of SCT800 ranging from 80 to 280 IU/kg and comparable pharmacokinetic profiles between SCT800 and Xyntha at the doses tested. Pharmacodynamics study revealed comparable ED50 values of SCT800 and Xyntha in the tail bleeding model: 14.78 and 15.81 IU/kg for bleeding time, respectively; 13.50 and 13.58 IU/kg for blood loss, respectively. Moreover, at the doses tested, the accompanying dose-related safety evaluation in the tail bleeding model showed lower hypercoagulable tendency and wider dosage range potential for SCT800 than Xyntha. Conclusion: In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties. PMID:26806305

Neurosurgical management in children with bleeding diathesis: auditing neurological outcome.

PubMed

Zakaria, Zaitun; Kaliaperumal, Chandrasekaran; Crimmins, Darach; Caird, John

2018-01-01

OBJECTIVE The aim of this study was to assess the outcome of neurosurgical treatment in children with bleeding diathesis and also to evaluate the current management plan applied in the authors' service. METHODS The authors retrospectively analyzed all cases in which neurosurgical procedures were performed in pediatric patients presenting with intracranial hematoma due to an underlying bleeding tendency over a 5-year period at their institution. They evaluated the patients' neurological symptoms from the initial referral, hematological abnormalities, surgical treatment, neurological outcome, and scores on the Pediatric Glasgow Outcome Scale-Extended (GOS-E Peds) obtained 1 year after the last operation. RESULTS Five patients with a bleeding diathesis who underwent surgery for intracranial hematoma were identified; the diagnosis was hemophilia A in 3 cases, idiopathic thrombocytopenic purpura in 1 case, and severe aplastic anemia in 1 case. Intracerebral hematoma (ICH) (n = 4) and acute subdural hematoma (n = 1) were confirmed on radiological investigations. In 2 of the 4 patients with ICH, the diagnosis of bleeding diathesis was made for the first time on presentation. Four patients (all male) were younger than 2 years; the patient with severe aplastic anemia and spontaneous ICH was 15 years old and female. The duration of symptoms varied from 24 hours to 5 days. Neurological examination at 1 year's follow-up showed complete recovery (GOS-E Peds score of 1) in 3 cases and mild weakness (GOS-E Peds score of 2) in 2 cases. CONCLUSIONS Neurosurgical management of patients with bleeding diathesis should be carried out in a tertiary-care setting with multidisciplinary team management, including members with expertise in neuroimaging and hematology, in addition to neurosurgery. Early diagnosis and prompt treatment of a bleeding diathesis is crucial for full neurological recovery.

Ibudilast, a phosphodiesterase inhibitor, in combination with low-dose aspirin potently inhibits guinea pig carotid artery thrombosis without extending bleeding time and causing gastric mucosal injury.

PubMed

Matsuzawa, S; Hoshina, K; Sueyoshi, S; Miyata, Y; Manita, S; Ooie, T; Yasue, T; Sasahara, T

2012-12-01

A combination of low-dose aspirin (ASA) and a phosphodiesterase inhibitor has been clinically tried for the secondary prevention of atherothrombotic diseases. The in vivo antithrombotic property of ibudilast (CAS 50847-11-5), a phosphodiesterase 4 (PDE4) inhibitor, was evaluated in a photochemically-induced guinea pig carotid artery thrombosis model in combination with low-dose ASA. The time required to decrease the carotid artery blood flow to the reading "zero" was defined as the time to occlusion (TTO) of the artery through thrombogenesis. Each independent use of ASA (300 mg/kg, p.o.) and ibudilast (3 and 10 mg/kg, p.o.) significantly prolonged the TTO, and ASA (300 mg/kg) significantly increased bleeding time (BT) and gastric mucosal injury. A selective PDE4 inhibitor rolipram (1 and 5 mg/kg, p.o.) tended to prolong the TTO without extending BT. ASA (100 mg/kg) plus ibudilast (3 mg/kg) and ASA (100 mg/kg) plus rolipram (5 mg/kg) markedly prolonged the TTO compared with each agent alone. Interestingly, ASA (100 mg/kg) plus ibudilast (3 mg/kg) caused a longer TTO than ASA (300 mg/kg) alone, without significant extension of BT and gastric mucosal injury as observed in ASA (300 mg/kg). These results indicate that the combination of low-dose ASA and ibudilast has a more potent antithrombotic effect than ASA alone without increasing bleeding tendency and gastric mucosal injury. The potent in vivo antithrombotic effect of this combination may be brought about by an action that is associated with PDE4 inhibition of ibudilast. © Georg Thieme Verlag KG Stuttgart · New York.

Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review.

PubMed

Franchini, Massimo; Lippi, Giuseppe; Targher, Giovanni

2011-08-01

A kaleidoscope of coagulation disorders have been reported in patients with thyroid dysfunctions. Globally, these disorders involve both primary and secondary hemostasis and range from subclinical laboratory abnormalities to, more rarely, life-threatening hemorrhages or thrombotic events. While overt hypothyroidism appears to be associated with a bleeding tendency, hyperthyroidism emerged to have an increased risk of thrombotic events. In particular, a number of case reports have documented acute venous thrombosis complications in patients with overt hyperthyroidism, especially at cerebral sites. Nevertheless, further observational and intervention studies might be needed to provide a more definitive information on the clinical relevance of this association, along with the potential implication for prevention and treatment of coagulation-fibrinolytic abnormalities in patients with thyroid dysfunction.

EVALUATION OF CLINICAL PERIODONTAL CONDITIONS IN SMOKERS AND NON-SMOKERS

PubMed Central

Luzzi, Lucinara Ignez Tavares; Greghi, Sebastião Luiz Aguiar; Passanezi, Euloir; Sant'ana, Adriana Campos Passanezi; Lauris, José Roberto Pereira; Cestari, Tânia Mary

2007-01-01

Given that tobacco smoking habit is a risk factor for periodontal diseases, the aim of this study was to compare clinical periodontal aspects between smokers and non-smokers. The clinical status were assessed in 55 patients, 29 smokers and 26 non-smokers, aged 30 to 50 years, with mean age of 40. The clinical parameters used were: probing depth (PD), plaque index (PI), gingival index (GI), clinical attachment level (CAL), gingival recession (GR) and gingival bleeding index (GBI) for arches (upper and lower) and teeth (anterior and posterior). Tooth loss was also evaluated in both groups. Multiple regression analysis showed: tendency of greater probing depth and clinical attachment level means for smokers; greater amount of plaque in smokers in all regions; greater gingival index means for non-smokers with clinical significance (p<0.05) in all regions. Although, without statistical significance, the analysis showed greater gingival bleeding index means almost always for non-smokers; similar gingival recession means in both groups and tendency of upper tooth loss in smokers and lower tooth loss in non-smokers. The findings of this study showed that clinical periodontal parameters may be different in smokers when compared to non-smokers and that masking of some periodontal signs can be a result of nicotine's vasoconstrictor effect. PMID:19089190

Development and implementation of a novel immune thrombocytopenia bleeding score for dogs.

PubMed

Makielski, Kelly M; Brooks, Marjory B; Wang, Chong; Cullen, Jonah N; O'Connor, Annette M; LeVine, Dana N

2018-04-21

A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials. To develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation. Client-owned dogs (n = 61) with platelet counts <50,000/μL; 34 classified as primary ITP, 17 as secondary ITP, and 10 as non-ITP. A novel bleeding assessment tool, DOGiBAT, comprising bleeding grades from 0 (none) to 2 (severe) at 9 anatomic sites, was developed. Clinicians and technicians completed a training course and quiz before scoring thrombocytopenic patients. The training course was assessed by randomizing student volunteers to take the quiz with or without prior training. A logistic regression model assessed the association between training and quiz performance. The correlation of DOGiBAT score with platelet count and outcome measures was assessed in the thrombocytopenic dogs. Clinicians and technicians consistently applied the DOGiBAT, correctly scoring all quiz cases. The odds of trained students answering correctly were higher than those of untrained students (P < .0001). In clinical cases, DOGiBAT score and platelet count were inversely correlated (r s  = -0.527, P < .0001), and DOGiBAT directly correlated with transfusion requirements (r s  = 0.512, P < .0001) and hospitalization duration (r s  = 0.35, P = .006). The DOGiBAT and assessment quiz are simple tools to standardize evaluation of bleeding severity. With further validation, the DOGiBAT may provide a clinically relevant metric to characterize ITP severity and monitor response in treatment trials. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Successful early romiplostim use in a case of severe immune thrombocytopenia with critical carotid arterial injury.

PubMed

Watanabe, Reiko; Tabayashi, Takayuki; Tomikawa, Tatsuki; Sagawa, Morihiko; Anan-Nemoto, Tomoe; Kimura, Yuta; Takahashi, Yasuyuki; Tokuhira, Michihide; Otaki, Satoshi; Oi, Hidenori; Sawano, Makoto; Sugiyama, Satoshi; Kizaki, Masahiro

2017-01-01

Thrombopoietin receptor (TPO-R) agonists have been shown to be effective in refractory chronic immune thrombocytopenia (ITP); however, their efficacy in patients under critical care is not known. We report the case of a female patient with a newly diagnosed ITP who experienced severe bleeding from an external wound. The patient was administered the standard treatments for ITP, which are high-dose intravenous immunoglobulin (IVIg) and corticosteroids. However, following failure of these treatments, we administered romiplostim on day 6 after the onset of ITP. On day 6 after the initiation of romiplostim, there was improvement in platelet count and bleeding tendency. We were subsequently able to perform a splenectomy successfully. The efficacy of TPO-R agonists in ITP has been reported in several situations, including before surgery in an ITP patient; however, the use of TPO-R for arterial bleeding with shock has not been reported. To our knowledge, the present article is a rare case report of the use of a TPO-R agonist in a patient with critical artery injury. Our data suggest that the early use of romiplostim is effective in emergency cases of newly diagnosed ITP with life-threatening bleeding, which is refractory to standard treatment.

[Research of bleeding volume and method in blood-letting acupuncture therapy based on data mining].

PubMed

Liu, Xin; Jia, Chun-Sheng; Wang, Jian-Ling; Du, Yu-Zhu; Zhang, Xiao-Xu; Shi, Jing; Li, Xiao-Feng; Sun, Yan-Hui; Zhang, Shen; Zhang, Xuan-Ping; Gang, Wei-Juan

2014-03-01

Through computer-based technology and data mining method, with treatment in cases of bloodletting acupuncture therapy in collected literature as sample data, the association rule in data mining was applied. According to self-built database platform, the data was input, arranged and summarized, and eventually required data was acquired to perform the data mining of bleeding volume and method in blood-letting acupuncture therapy, which summarized its application rules and clinical values to provide better guide for clinical practice. There were 9 kinds of blood-letting tools in the literature, in which the frequency of three-edge needle was the highest, accounting for 84.4% (1239/1468). The bleeding volume was classified into six levels, in which less volume (less than 0.1 mL) had the highest frequency (401 times). According to the results of the data mining, blood-letting acupuncture therapy was widely applied in clinical practice of acupuncture, in which use of three-edge needle and less volume (less than 0.1 mL) of blood were the most common, however, there was no central tendency in general.

TC-325 versus the conventional combined technique for endoscopic treatment of peptic ulcers with high-risk bleeding stigmata: A randomized pilot study.

PubMed

Kwek, Boon Eu Andrew; Ang, Tiing Leong; Ong, Peng Lan Jeannie; Tan, Yi Lyn Jessica; Ang, Shih Wen Daphne; Law, Ngai Moh; Thurairajah, Prem Harichander; Fock, Kwong Ming

2017-06-01

Preliminary studies on a new topical hemostatic agent, TC-325, have shown its safety and effectiveness in treating active upper gastrointestinal (GI) bleeding. However, to date there have been no randomized trials comparing TC-325 with the conventional combined technique (CCT). Our pilot study aimed to compare the efficacy and safety of TC-325 with those of CCT in treating peptic ulcers with active bleeding or high-risk stigmata. This was a comparative randomized study of patients with upper GI bleeding who had Forrest class I, IIA or IIB ulcers. Altogether 20 patients with a mean age of 70 years (range 23-87 years) were recruited, including 16 men, with a mean hemoglobin of 97 g/L. Initial hemostasis was successful in 19 (95.0%) patients, including 90.0% (9/10) in the TC-325 group and 100% (10/10) in the CCT group. TC-325 monotherapy failed to stop bleeding in a patient with Forrest IB posterior duodenal wall ulcer. Rebleeding was seen in 33.3% (3/9) of the patients in the TC-325 group and 10.0% (1/10) in the CCT group. One patient required angio-embolization therapy while three had successful conventional endotherapy. Two patients from the TC-325 group had serious adverse events that were not procedure- or therapy-related. In patients with Forrest IIA or IIB ulcers, five received TC-325 monotherapy; none had rebleeding. Our pilot study showed that TC-325 has a tendency towards a higher rebleeding rate than CCT, when treating actively bleeding ulcers. Larger trials are necessary for definitive results. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families

PubMed Central

Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

2018-01-01

Background Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients’ families. Material and methods Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients’ F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson’s correlation coefficient and the nonparametric Mann-Whitney test. Results Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Discussion Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity. PMID:27723456

Subdural hemorrhage: A unique case involving secondary vitamin K deficiency bleeding due to biliary atresia.

PubMed

Miyao, Masashi; Abiru, Hitoshi; Ozeki, Munetaka; Kotani, Hirokazu; Tsuruyama, Tatsuaki; Kobayashi, Naho; Omae, Tadaki; Osamura, Toshio; Tamaki, Keiji

2012-09-10

Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Association between physical activity and risk of bleeding in children with hemophilia.

PubMed

Broderick, Carolyn R; Herbert, Robert D; Latimer, Jane; Barnes, Chris; Curtin, Julie A; Mathieu, Erin; Monagle, Paul; Brown, Simon A

2012-10-10

Vigorous physical activity is thought to increase risk of bleeds in children with hemophilia, but the magnitude of the risk is unknown. To quantify the transient increase in risk of bleeds associated with physical activity in children with hemophilia. A case-crossover study nested within a prospective cohort study was conducted at 3 pediatric hemophilia centers in Australia between July 2008 and October 2010. A total of 104 children and adolescent boys aged 4 through 18 years with moderate or severe hemophilia A or B were monitored for bleeds for up to 1 year. Following each bleed, the child or parent was interviewed to ascertain exposures to physical activity preceding the bleed. Physical activity was categorized according to expected frequency and severity of collisions. The risk of bleeds associated with physical activity was estimated by contrasting exposure to physical activity in the 8 hours before the bleed with exposures in two 8-hour control windows, controlling for levels of clotting factor in the blood. Association of physical activity and factor level with risk of bleeding. The participants were observed for 4839 person-weeks during which time 436 bleeds occurred. Of these, 336 bleeds occurred more than 2 weeks after the preceding bleed and were used in the primary analysis of risk. Compared with inactivity and category 1 activities (eg, swimming), category 2 activities (eg, basketball) were associated with a transient increase in the risk of bleeding (30.6% of bleed windows vs 24.8% of first control windows; odds ratio, 2.7; 95% CI, 1.7-4.8, P < .001). Category 3 activities (eg, wrestling) were associated with a greater transient increase in risk (7.0% of bleed windows vs 3.4% of first control windows; odds ratio, 3.7; 95% CI, 2.3-7.3, P < .001). To illustrate absolute risk increase, for a child who bleeds 5 times annually and is exposed on average to category 2 activities twice weekly and to category 3 activities once weekly, exposure to these activities was associated with only 1 of the 5 annual bleeds. For every 1% increase in clotting factor level, bleeding incidence was lower by 2% (95% CI, 1%-3%; P = .004). In children and adolescents with hemophilia, vigorous physical activity was transiently associated with a moderate relative increase in risk of bleeding. Because the increased relative risk is transient, the absolute increase in risk of bleeds associated with physical activity is likely to be small.

Risk of Vascular Thrombotic Events Following Discontinuation of Antithrombotics After Peptic Ulcer Bleeding.

PubMed

Kim, Seung Young; Hyun, Jong Jin; Suh, Sang Jun; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Park, Jong Jae; Chun, Hoon Jai; Lee, Sang Woo

2016-04-01

To evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. Peptic ulcer bleeding associated with antithrombotics has increased due to the increase in the proportion of elderly population. Little is known about the long-term effects of discontinuing antithrombotics after peptic ulcer bleeding. The aim of this study was to evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. We reviewed the medical records of patients with ulcer bleeding who were taking antiplatelet agents or anticoagulants at the time of ulcer bleeding. Cox-regression model was used to adjust for potential confounders, and analyzed association between discontinuation of antithrombotic drugs after ulcer bleeding and thrombotic events such as ischemic heart disease or stroke. Of the 544 patients with ulcer bleeding, 72 patients who were taking antithrombotics and followed up for >2 months were analyzed. Forty patients discontinued antithrombotics after ulcer bleeding (discontinuation group) and 32 patients continued antithrombotics with or without transient interruption (continuation group). Thrombotic events developed more often in discontinuation group than in the continuation group [7/32 (21.9%) vs. 1/40 (2.5%), P=0.019]. Hazard ratio for thrombotic event when antithrombotics were continuously discontinued was 10.9 (95% confidence interval, 1.3-89.7). There were no significant differences in recurrent bleeding events between the 2 groups. Discontinuation of antithrombotics after peptic ulcer bleeding increases the risk of cardiovascular events. Therefore, caution should be taken when discontinuing antithrombotics after ulcer bleeding.

Patterns of in-hospital mortality and bleeding complications following PCI for very elderly patients: insights from the Dartmouth Dynamic Registry.

PubMed

Li, Shawn X; Chaudry, Hannah I; Lee, Jiyong; Curran, Theodore B; Kumar, Vishesh; Wong, Kendrew K; Andrus, Bruce W; DeVries, James T

2018-02-01

Very elderly patients (age ≥ 85 years) are a rapidly increasing segment of the population. As a group, they experience high rates of in-hospital mortality and bleeding complications following percutaneous coronary intervention (PCI). However, the relationship between bleeding and mortality in the very elderly is unknown. Retrospective review was performed on 17,378 consecutive PCI procedures from 2000 to 2015 at Dartmouth-Hitchcock Medical Center. Incidence of bleeding during the index PCI admission (bleeding requiring transfusion, access site hematoma > 5 cm, pseudoaneurysm, and retroperitoneal bleed) and in-hospital mortality were reported for four age groups (< 65 years, 65-74 years, 75-84 years, and ≥ 85 years). The mortality of patients who suffered bleeding complications and those who did not was calculated and multivariate analysis was performed for in-hospital mortality. Lastly, known predictors of bleeding were compared between patients age < 85 years and age ≥ 85 years. Of 17,378 patients studied, 1019 (5.9%) experienced bleeding and 369 (2.1%) died in-hospital following PCI. Incidence of bleeding and in-hospital mortality increased monotonically with increasing age (mortality: 0.94%, 2.27%, 4.24% and 4.58%; bleeding: 3.96%, 6.62%, 10.68% and 13.99% for ages < 65, 65-74, 75-84 and ≥ 85 years, respectively). On multivariate analysis, bleeding was associated with increased mortality for all age groups except patients age ≥ 85 years [odds ratio (95% CI): age < 65 years, 3.65 (1.99-6.74); age 65-74 years, 2.83 (1.62-4.94); age 75-84 years, 3.86 (2.56-5.82), age ≥ 85 years: 1.39 (0.49-3.95)]. Bleeding and mortality following PCI increase with increasing age. For the very elderly, despite high rates of bleeding, bleeding is no longer predictive of in-hospital mortality following PCI.

[Factor V congenital deficiency: about a case].

PubMed

Boujrad, Saloua; El Hasbaoui, Brahim; Echahdi, Hanae; Malih, Mohamed; Agadr, Aomar

2017-01-01

Factor V congenital deficiency is a rare coagulation disorder initially described by Owren in 1947 and known as para hemophilia. It is transmitted through autosomal-recessive inheritance and homozygous cases are usually symptomatic. Factor V is an essential cofactor in the conversion of prothrombin to thrombin by activated factor X. In the absence of factor V, thrombin generation is slowed down and fibrin formation is delayed. This results in a bleeding tendency. We report a case of factor V congenital deficiency in an infant with recurrent epistaxis.

The hemostatic efficacy of chitosan-pads in hemodialysis patients with significant bleeding tendency.

PubMed

Misgav, Mudi; Lubetszki, Ahron; Brutman-Barazani, Tami; Martinowitz, Uri; Kenet, Gili

2017-05-15

Patients on chronic hemodialysis often have acquired coagulopathy that can aggravate bleeding from puncture site after needle extraction. Chitosan-based pads have been reported to accelerate hemostasis even in the presence of coagulopathy. The aim of this study was to evaluate the hemostatic efficacy of the chitosan pads compared to gauze pads, applied for local hemostasis. A crossover study in a cohort of patients on hemodialysis with extended time to hemostasis after needle extraction. At the end of each dialysis, either gauze or chitosan pad was applied on both access points (arterial and venous). The type of pad was changed in the next dialysis all together 5 times in each patient (10 applications per patient for every pad). A total of 288 applications, 144 for each type of pad, were performed in 15 patients. The average time to hemostasis for the entire group was significantly shorter with the chitosan pads compared to the regular gauze pads ("arterial" point 3 vs. 18.5 min, p<0.001 "venous" access 2.8 vs. 13.2 min, p<0.001, respectively). Chitosan pads significantly reduce time to hemostasis and should be considered for the treatment of accessible bleeds in patients with coagulopathy.

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

PubMed Central

Punyadee, Nuntaya; Mairiang, Dumrong; Thiemmeca, Somchai; Komoltri, Chulaluk; Pan-ngum, Wirichada; Chomanee, Nusara; Charngkaew, Komgrid; Tangthawornchaikul, Nattaya; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida

2014-01-01

ABSTRACT Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1–anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. IMPORTANCE Dengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care. PMID:25410854

Microparticles provide a novel biomarker to predict severe clinical outcomes of dengue virus infection.

PubMed

Punyadee, Nuntaya; Mairiang, Dumrong; Thiemmeca, Somchai; Komoltri, Chulaluk; Pan-Ngum, Wirichada; Chomanee, Nusara; Charngkaew, Komgrid; Tangthawornchaikul, Nattaya; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida; Avirutnan, Panisadee

2015-02-01

Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1-anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. Dengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency.

PubMed

Borhany, M; Boijout, H; Pellequer, J-L; Shamsi, T; Moulis, G; Aguilar-Martinez, P; Schved, J-F; Giansily-Blaizot, M

2013-11-01

Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series. © 2013 John Wiley & Sons Ltd.

Risk Factors for Post-TAVI Bleeding According to the VARC-2 Bleeding Definition and Effect of the Bleeding on Short-Term Mortality: A Meta-analysis.

PubMed

Wang, Jiayang; Yu, Wenyuan; Jin, Qi; Li, Yaqiong; Liu, Nan; Hou, Xiaotong; Yu, Yang

2017-04-01

In this study we investigated the effect of post-transcatheter aortic valve implantation (TAVI) bleeding (per Valve Academic Research Consortium-2 [VARC-2] bleeding criteria) on 30-day postoperative mortality and examined the correlation between pre- or intraoperative variables and bleeding. Multiple electronic literature databases were searched using predefined criteria, with bleeding defined per Valve Academic Research Consortium-2 criteria. A total of 10 eligible articles with 3602 patients were included in the meta-analysis. The meta-analysis revealed that post-TAVI bleeding was associated with a 323% increase in 30-day postoperative mortality (odds risk [OR]; 4.23, 95% confidence interval [CI], 2.80-6.40; P < 0.0001) without significant study heterogeneity or publication bias. In subgroup analysis we found that patients with major bleeding/life-threatening bleeding showed a 410% increase in mortality compared with patients without bleeding (OR, 5.10; 95% CI, 3.17-8.19; P < 0.0001). Transapical access was associated with an 83% increase in the incidence of bleeding compared with transfemoral access (OR, 1.83; 95% CI, 1.43-2.33; P < 0.0001). Multiple logistic regression analysis revealed that atrial fibrillation (AF) was independently correlated with TAVI-associated bleeding (OR, 2.63; 95% CI, 1.33-5.21; P = 0.005). Meta-regression showed that potential modifiers like the Society of Thoracic Surgeons (STS) score, mortality, the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), aortic valve area, mean pressure gradient, left ventricular ejection fraction, preoperative hemoglobin and platelet levels, and study design had no significant effects on the results of the meta-analysis. Post-TAVI bleeding, in particular, major bleeding/life-threatening bleeding, increased 30-day postoperative mortality. Transapical access was a significant bleeding risk factor. Preexisting AF independently correlated with TAVI-associated bleeding, likely because of AF-related anticoagulation. Recognition of the importance and determinants of post-TAVI bleeding should lead to strategies to improve outcomes. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

A novel F11 mutation in a Korean pediatric patient with recurrent epistaxis.

PubMed

Kim, Juwon; Kim, Yoonjung; Shin, Seam; Lyu, Chuhl Joo; Choi, Jong Rak; Lee, Kyung-A

2013-06-01

Congenital FXI deficiency (hemophilia C) is a rare bleeding disorder that has been documented mostly in Ashkenazi Jews. Unlike other hemophilias, bleeding tendency varies considerably among individuals, and FXI deficiency rarely manifests as spontaneous bleeding. FXI deficiency is caused primarily by mutations in the F11 gene. Herein, we report a case of a 10-year-old boy with recurrent nose bleeding due to FXI deficiency who was confirmed to have a novel mutation in F11. A molecular analysis of DNA extracted from peripheral blood collected from the patient [FXI clotting activity (FXI:C): 11%] revealed compound heterozygous mutations, Q226X and L424F, in F11, consistent with the severe disease phenotype of the patient. Pedigree analysis showed that the patient received L424F from his father (FXI:C = 49%) and Q226X from the mother (FXI:C = 48%). The sister (FXI:C = 47%) of the patient only had L424F, presumably inherited from her father. Multiple sequence alignment demonstrated that L424 is highly conserved across mammals, indicating that it is important for the function of FXI. In-silico analysis indicated that replacement of L424 by phenylalanine had a detrimental influence on FXI, consistent with the severe phenotype of the patient. Compilation of FXI deficiency cases in east Asian populations would be of great value because different populations appear to have different F11 mutation spectra.

Obstetric bleeding among women with inherited bleeding disorders: a retrospective study.

PubMed

Hawke, L; Grabell, J; Sim, W; Thibeault, L; Muir, E; Hopman, W; Smith, G; James, P

2016-11-01

Women with inherited bleeding disorders are at increased risk for bleeding complications during pregnancy and the postpartum period, particularly postpartum haemorrhage (PPH). This retrospective study evaluates pregnancy management through the Inherited Bleeding Disorders Clinic of Southeastern Ontario, the clinical factors associated with pregnancy-related abnormal bleeding and assesses tranexamic acid use in the postpartum treatment of bleeding disorder patients. A chart review of 62 pregnancies, from 33 women, evaluated patient characteristics (age, haemostatic factor levels) and delivery conditions (mode of delivery, postpartum treatment) in relation to abnormal postpartum bleeding. This cohort revealed increased risk of immediate PPH with increased age at delivery (mean age: 30.1 years with PPH, 26.5 years without PPH, P < 0.013), and birth by vaginal delivery (P < 0.042). Low von Willebrand factor (VWF) antigen or factor VIII (FVIII) in the third trimester was not associated with an increased risk of PPH; however, low VWF:RCo was associated with increased immediate PPH despite treatment with continuous factor infusion (P < 0.042). Women treated with tranexamic acid postpartum had less severe bleeding in the 6-week postpartum (P < 0.049) with no thrombotic complications. This study contributes to the growing body of work aimed at optimizing management of bleeding disorder patients through pregnancy and the postpartum period, showing patients are at a higher risk of PPH as they age. Risk factors such as low third trimester VWF:RCo have been identified. Treatment with tranexamic acid in the postpartum period is associated with a reduced incidence of abnormal postpartum bleeding. © 2016 John Wiley & Sons Ltd.

Gastrointestinal bleeding in patients with renal failure under hemodialysis treatment: a single-center experience.

PubMed

Can, Özgür; Koç, Gözde; Ocak, Sema Berk; Akbay, Nursel; Ahishali, Emel; Canbakan, Mustafa; Şahin, Gülizar Manga; Apaydin, Süheyla

2017-05-01

Gastrointestinal bleeding remains the leading cause of morbidity and mortality for patients who need hemodialysis treatment. Our aim was to evaluate patients who needed hemodialysis and presented with bleeding during their hospital stay (uremic bleeding patients). Factors that increased the risk of bleeding and death were evaluated. Additionally, uremic bleeding patients were compared to non-uremic bleeding patients regarding gastrointestinal findings. Fifty-one uremic bleeding patients were compared to two control groups which included uremic (hemodialysis dependent and non-bleeding) and non-uremic (no renal insufficiency and bleeding) patients. NSAIDs and anti-ulcer drug usage were more common in uremic bleeding and in uremic non-bleeding groups, respectively. Dialysis vintage was longer in uremic bleeding group. Comparison of uremic bleeding and non-bleeding uremic patients regarding the usage of ACEI or ARB drugs yielded non-significant results. Acute kidney injury, lower plasma albumin level and high CRP level were significantly increased the risk of mortality in uremic bleeding patients. Hospital stay more than 1 week was the only strong factor for mortality when multivariate analysis was performed. Gastroduodenal and duodenal ulcers were significantly detected in uremic bleeding and non-uremic bleeding patients; respectively. Hemodialysis patients presenting with gastrointestinal bleeding should be evaluated regarding use of prescriptions and efforts should be done in order to shorten their hospital stay and decrease their mortality. Effect of ACEI or ARB drugs should also be evaluated in future studies.

Increased bleeding risk during percutaneous coronary interventions by arterial hypertension.

PubMed

Ndrepepa, Gjin; Groha, Philipp; Lahmann, Anna L; Lohaus, Raphaela; Cassese, Salvatore; Schulz-Schüpke, Stefanie; Kufner, Sebastian; Mayer, Katharina; Bernlochner, Isabell; Byrne, Robert A; Fusaro, Massimiliano; Laugwitz, Karl-Ludwig; Schunkert, Heribert; Kastrati, Adnan

2016-08-01

We aimed to assess the association between arterial hypertension and bleeding in patients undergoing percutaneous coronary intervention (PCI). The impact of arterial hypertension on bleeding risk of patients with coronary artery disease undergoing PCI is unknown. This study included 14,180 patients who underwent PCI. Bleeding was defined using the Bleeding Academic Research Consortium (BARC) criteria. Arterial hypertension was defined as treatment with antihypertensive drugs or a systolic blood pressure >140 mm Hg and/or diastolic blood pressure value >90 mm Hg documented on at least 2 occasions. The primary outcome was bleeding rate within 30 days of PCI. Overall, 11,066 patients (78.0%) had arterial hypertension. Bleeding events occurred in 1,232 patients with arterial hypertension and 278 patients without arterial hypertension (11.1% vs 8.9%; odds ratio [OR] = 1.28, 95% confidence interval [CI] 1.11-1.46, P < 0.001). Access-site bleeding occurred in 730 patients with arterial hypertension and 175 patients without arterial hypertension (6.6% vs 5.6%: OR = 1.19 [1.01-1.41], P = 0.049). Non-access-site bleeding occurred in 502 patients with and 103 patients without arterial hypertension (4.5% vs 3.3%; OR = 1.39 [1.12-1.72], P = 0.003). After adjustment, arterial hypertension was significantly associated with any bleeding (adjusted OR = 1.41 [1.19-1.67], P < 0.001), access-site bleeding (adjusted OR = 1.36 [1.10-1.68], P = 0.005) and non-access-site bleeding (adjusted OR = 1.42 [1.09-1.83], P = 0.008). A history of arterial hypertension increased the risk of non-access-site bleeding (P = 0.002), whereas systolic blood pressure at the time of PCI increased the risk of access site bleeding (P = 0.018). Arterial hypertension is associated with increased risk of bleeding during PCI procedures. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

[The significance of endocrine factors and microorganisms in the development of gingivitis in pregnant women].

PubMed

Abraham-Inpijn, L; Polsacheva, O V; Raber-Durlacher, J E

1996-01-01

40-100% of pregnant women suffer from the co-called pregnancy gingivitis. The cause of pregnancy gingivitis is possible multicausal: increased plasma female sex-hormones, alteration in dental plague and perhaps Prevotella intermedia in the subgingival plague, together with alteration of immunoresponse. Increasing levels of progesterone in the gingiva as well as estrogens due to specific receptors affect vascular permeability and exudation, provoke stasis of microcirculation, increase prostaglandine E2 formation in human gingiva. Decreased gingival keratinization and capability of cell regeneration may affect the epithelial barrier. This can perhaps explain the direct dependence between progesterone and estrogens increasing and the intensification of gingivitis clinical manifestation. The experimental gingivitis model of women during pregnancy and post-partum showed identical amounts of dental plague, but clinical manifestations were more intense during pregnancy and they had a relation with increasing P. Intermedia, no statistical significance was shown in the proportion of P. gingivalis. Increasing steroid hormones can substitute for the naphtoquinone requirement of P. intermedia. Optimal oral hygiene performed during pregnancy reduced gingival swelling, redness and bleeding tendency to levels which can be considered as physiologic for the pregnant state.

[Predictive value of ultrasonography in portal hypertension].

PubMed

Moreno, E; Torres, P; Trejo, C; Barra Ostoni, V; Ortega, C; Römer, H

1991-01-01

Portal hypertension is a common pathology in childhood and one of its most common causes is cavernomatosis of the portal vein. This obstruction causes hemodynamic changes which lead to splenomegaly and collateral circulation. Esophageal varices are one of the most important sequelae, which endanger the patient's life because of a bleeding tendency. Ecosonography helps to detect the thickening of the lesser omentum vis a vis the aortic diameter, caused by the collateral circulation. We studied 15 children presenting with portal hypertension resulting from portal vein cavernomatosis; we performed an upper GI endoscopy and abdominal ecosonography. The endoscopy revealed grade II esophageal varices in 20% of cases, the remaining 80% had grade III and grade IV. Ecosonography revealed an increased lesser omentum/aorta ratio in children with portal hypertension, compared to controls (p < 0.001). Our results suggest that the lesser omentum/aorta ratio has diagnostic value in pediatric portal hypertension.

Noonan syndrome.

PubMed

Bhambhani, Vikas; Muenke, Maximilian

2014-01-01

Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome-specific growth charts and treatment guidelines are available.

Congenital Type III von Willebrand's disease unmasked by hypothyroidism in a Shetland sheepdog.

PubMed

Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

2015-09-01

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand's disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog's sudden bleeding tendency as has been seen with hypothyroidism in humans.

Congenital Type III von Willebrand’s disease unmasked by hypothyroidism in a Shetland sheepdog

PubMed Central

Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

2015-01-01

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand’s disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog’s sudden bleeding tendency as has been seen with hypothyroidism in humans. PMID:26347307

Determinants of re-operation for bleeding in head and neck cancer surgery.

PubMed

Haapio, E; Kinnunen, I; Airaksinen, J K E; Irjala, H; Kiviniemi, T

2018-04-01

Post-operative bleeding in the head and neck area is potentially fatal. This 'real world' study sought to assess factors that increase the risk of re-operation for post-operative bleeding in head and neck cancer surgery. A total of 456 patients underwent surgery for head and neck cancer (591 operations). The primary endpoint was re-operation for bleeding. The rate of re-operation for bleeding was 5 per cent of all operations. Re-operation for bleeding was an independent risk factor for 30-day mortality (odds ratio = 5.27, p = 0.014). Risk factors for re-operation because of bleeding included excessive (more than 4000 ml) fluid administration (over 24 hours) (p < 0.001), heavy alcohol consumption (p = 0.014), pre-operative oncological treatment (p = 0.017), advanced disease stage (p = 0.020) and higher tumour (T) classification (p = 0.034). Operations with more excessive bleeding (700 ml or more) were associated with an increased risk (p = 0.001) of re-operation for post-operative bleeding. Moreover, the risk of re-operation was significantly higher in patients undergoing microvascular surgery compared to those who had no oncological treatment pre-operatively (18 vs 6 per cent, p = 0.001). The 30-day mortality risk increased over 5-fold in patients undergoing re-operation for bleeding.

Histopathological Findings of Endometrial Samples and its Correlation Between the Premenopausal and Postmenopausal Women in Abnormal Uterine Bleeding.

PubMed

Sharma, S; Makaju, R; Shrestha, S; Shrestha, A

2014-01-01

Abnormal uterine bleeding is considered as one of the most common problems among women. The therapy is incomplete without knowing the underlying pathology. To determine the types and frequency of endometrial pathologies in patients presenting with abnormal uterine bleeding at Dhulikhel Hospital Kathmandu university Hospital. This is retrospective study total 100 cases were included over a period of one year of Abnormal Uterine bleeding. Out of 100 cases of Abnormal uterine bleeding, 61% were due to non-organic cause with a commonest histopathological findings proliferative endometrium. 27% cases were due to organic cause with pregnancy related condition as most common finding. 12% were reported as inadequate. The rate of postmenopausal bleeding declined with increasing age in the postmenopausal period and endometritis was the predominant finding. There is an age specific association of Abnormal uterine bleeding with increased incidence in perimenopausal age group. Postmenopausal bleeding declined with increasing with endometritis the most common finding. Dilation and curettage is helpful to exclude other organic pathology. It is useful for diagnosis and to know pathological incidence of organic lesions in cases of Abnormal uterine bleeding prior to surgery.

Oral surgery in patients under antithrombotic therapy: perioperative bleeding as a significant risk factor for postoperative hemorrhage.

PubMed

Rocha, Amanda L; Souza, Alessandra F; Martins, Maria A P; Fraga, Marina G; Travassos, Denise V; Oliveira, Ana C B; Ribeiro, Daniel D; Silva, Tarcília A

2018-01-01

: To investigate perioperative and postoperative bleeding, complications in patients under therapy with anticoagulant or antiplatelet drugs submitted to oral surgery. To evaluate the risk of bleeding and safety for dental surgery, a retrospective chart review was performed. Medical and dental records of patients taking oral antithrombotic drugs undergoing dental surgery between 2010 and 2015 were reviewed. Results were statistically analyzed using Fisher's exact test, t test or the χ test. One hundred and seventy-nine patients underwent 293 surgical procedures. A total of eight cases of perioperative and 12 episodes of postoperative bleeding were documented. The complications were generally managed with local measures and did not require hospitalization. We found significant association of postoperative hemorrhage with increased perioperative bleeding (P = 0.043) and combination of anticoagulant and antiplatelet therapy (P < 0.001). The chance of postoperative hemorrhage for procedures with increased perioperative bleeding is 8.8 times bigger than procedures without perioperative bleeding. Dental surgery in patients under antithrombotic therapy might be carried out without altering the regimen because of low risk of perioperative and postoperative bleeding. However, patients with increased perioperative bleeding should be closely followed up because of postoperative complications risk.

THE STATE OF HEALTH OF PEOPLE SUBJECTED TO THE ACTION OF IONIZING RADIATION UNDER INDUSTRIAL-LABORATORY CONDITIONS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morozov, A.L.; Drogichina, E.A.; Kazakevich, M.A.

1957-01-01

A group of 60 people exposed to gamma radiation in the course of radiographic work, and a group of 170 people working with various radiation sources were subjected to clinical tests. An additional group of 40 people who showed symptoms of radiation sickness were subjected to more careful examination. The great majority of the subjects worked with radioactivity from 1 to 5 years, but about 20% were in contact with ionizing radiation for less than one year. Functional disturbances of the nervous system characterized by headaches, insomnia, increased tendency to fatigue, and weakness occurred three times more frequently with peoplemore » who worked from 2 to 5 years with radiation as compared with people who worked with radiation less than one year. A decrease in sensitivity to vibration was noted in people with signs of radiation sickness. An increased threshold of olfactory sensitivity to thymol (in 77% of the patients) and rosemary was observed in a group of 107 people. This insensitivity to smell was particularly pronounced in the second group of people who were in direct contact with radioactive materials. The arterial blood pressure was low (100 mm or lower) in 40% of the subjects, an indication of an increase in vascular permeability. There was a tendency for the total albumins to increase, but the increase of globulin was especially marked in that the normal ratio of albumin to globulin of l.3 to l.82 was lowered to 0.94 to 1.2. The leukocyte and thrombocyte count was quite variable. A tendency to a slight lymnphocytosis occurred more often. A neutrophilic shift to the left was frequently observed. In a significant number of cases there was a tendency to a moderate decrease in thrombocyte production. The most characteristic change in the blood was a heightened reticulocytosis observable in 40% of the subjects. There was a clear tendency to a prolonged bleeding time in almost one-half the patients, while other symptoms of hemorrhage such as a lower thrombocyte count were absent. The frequency of occurrence of cataracts in a group of 130 people could be correlated with the time of exposure to radiation. The relative frequency of cataracts was 7% for those under 40 years of age and 14% for those above 40 years of age for less than 5 years service. It was 25% for those under 40 years of age and 50% for those above 40 years of age for 6 to 10 years of service. It was 66% for those ahove 40 years of age with greater than 10 years of service. The possibility of some unknown process initiated by ionizing radiation that results in dystrophy changes in the eye cannot be excluded at this time. (TTT)« less

Role of the growth arrest-specific gene 6 (gas6) product in thrombus stabilization.

PubMed

Saller, François; Burnier, Laurent; Schapira, Marc; Angelillo-Scherrer, Anne

2006-01-01

Growth arrest-specific gene 6 (gas6) product enhances the formation of stable platelet macroaggregates in response to various agonists. To determine whether Gas6 amplifies the response to known platelet agonists through one or more of its receptor tyrosine kinases of the Tyro3 family, mice deficient in any one of the Gas6 receptors (Gas6-Rs: Tyro3, Axl, or Mer) were submitted to thrombosis challenge and their platelet function. The loss of any one of the Gas6-Rs protects mice against thromboembolism induced by collagen-epinephrine and stasis-induced thrombosis. Importantly, these mice do not suffer spontaneous bleeding and have a normal bleeding time but a tendency to repetitively re-bleed after transient hemostasis. Re-bleeding in mice lacking any one of the Gas6-Rs is not due to thrombocytopenia or coagulopathy but to a platelet dysfunction characterized by a lack of the second wave of platelet aggregation and an impaired clot retraction, at least in part by reducing outside-in alpha(IIb)beta(3) signaling and platelet granule secretion. The early release of Gas6 by agonists perpetuates platelet activation through its three receptors, reinforcing outside-in alpha(IIb)beta(3) signaling by activation of PI3K and Akt signaling and stimulation of tyrosine phosphorylation of the beta(3) integrin. Furthermore, "trapping" Gas6 prevents pathological thrombosis, which indicates that blocking this novel cross-talk between the Gas6-Rs and alpha(IIb)beta(3) integrin may constitute a novel target for antithrombotic therapy.

Coagulation is more affected by quick than slow bleeding in patients with massive blood loss.

PubMed

Zhao, Juan; Yang, Dejuan; Zheng, Dongyou

2017-03-01

Profuse blood loss affects blood coagulation to various degrees. However, whether bleeding speed affects coagulation remains uncertain. This study aimed to evaluate the effect of bleeding speed on coagulation function. A total of 141 patients in the Department of Thoracic Surgery of our hospital were evaluated between January 2007 and February 2014. There are two groups of patients, those who received decortication for chronic encapsulated empyema were called the slow-bleeding group, and those who received thoracoscopic upper lobectomy were called the fast bleeding group; each group was further subdivided into three: group A, 1000 ml ≤ bleeding amount < 1500 ml; group B, 1500 ml ≤ bleeding amount < 1700 ml; group C, 1700 ml ≤ bleeding amount < 2000 ml. Then, coagulation function was assessed in all patients before and during surgery and at 1, 2, and 24 h after surgery, measuring prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, blood pressure, hematocrit, hemoglobin, and platelets. Bleeding duration was overtly longer in the slow-bleeding group than that in quick bleeding individuals (2.3 ± 0.25 h vs. 0.41 ± 0.13 h, P < 0.001). Fibrinogen, hematocrit, hemoglobin, and platelets strikingly decreased, whereas prothrombin time and APTT values significantly increased with bleeding amounts in both quick and slow-bleeding groups. Interestingly, compared with slow-bleeding patients, coagulation indices at each time point and bleeding amounts had significant differences in the quick bleeding group.Increased consumption of coagulation factors in quick bleeding may have greater impact on coagulation function.

COMPLICATIONS OF ORAL AND MAXILLOFACIAL SURGERY UNDER GENERAL ANESTHESIA IN TUBE-FED CHILDREN: A RETROSPECTIVE ANALYSIS.

PubMed

Nguyen, Trang D; Freilich, Marshall M; Macpherson, Bruce A

2016-06-01

To assess morbidity and mortality associated with oral and maxillofacial surgery procedures requiring general anesthesia among children with aspiration tendency requiring enteral feeding. A retrospective chart review was conducted of children surgically treated under general anesthesia by the oral and maxillofacial surgery service at the Hospital for Sick Children in Toronto, Canada. Medical and dental records over a 9-year period (January 1, 2000 to January 1, 2010) were reviewed. Data were collected on demographics, primary illness, coexisting medical conditions, procedures performed, medications administered, type of airway management used, duration of general anesthesia, American Society of Anesthesiologists' physical status classification and adverse events. During the period reviewed, 28 children underwent 35 oral and maxillofacial surgery procedures under general anesthesia. The mean patient age was 12 years (range 4-17 years). No deaths occurred. Of the 35 surgeries, 10 (29%) were associated with at least 1adverse event. Adverse events included 1incident of respiratory distress, 2incidents of fever, 5incidents of bleeding, 1incident of seizure and 4incidents of oxygen saturation below 90% for more than 30s. Children with a history of aspiration tendency that necessitates enteral feeding, who undergo oral and maxillofacial surgery under general anesthesia, are at increased risk of morbidity. Before initiating treatment, the surgeon and parents or guardians of such children should carefully consider these risks compared with the anticipated benefit of surgery.

Implications of bleeding in acute coronary syndrome and percutaneous coronary intervention

PubMed Central

Pham, Phuong-Anh; Pham, Phuong-Thu; Pham, Phuong-Chi; Miller, Jeffrey M; Pham, Phuong-Mai; Pham, Son V

2011-01-01

The advent of potent antiplatelet and antithrombotic agents over the past decade has resulted in significant improvement in reducing ischemic events in acute coronary syndrome (ACS). However, the use of antiplatelet and antithrombotic combination therapy, often in the settings of percutaneous coronary intervention (PCI), has led to an increase in the risk of bleeding. In patients with non-ST elevation myocardial infarction treated with antithrombotic agents, bleeding has been reported to occur in 0.4%–10% of patients, whereas in patients undergoing PCI, periprocedural bleeding occurs in 2.2%–14% of cases. Until recently, bleeding was considered an intrinsic risk of antithrombotic therapy, and efforts to reduce bleeding have received little attention. There have been increasing data demonstrating that bleeding is associated with adverse outcomes, including myocardial infarction, stroke, and death. Therefore, it is imperative to optimize patient outcomes by adopting pharmacological and nonpharmacological strategies to minimize bleeding while maximizing treatment efficacy. In this paper, we present a review of the bleeding classifications used in large-scale clinical trials in patients with ACS and those undergoing PCI treated with antiplatelets and antithrombotic agents, adverse outcomes, particularly mortality associated with bleeding complications, and suggested predictive risk factors. Potential mechanisms of the association between bleeding and mortality and strategies to reduce bleeding complications are also discussed. PMID:21915172

First trimester vaginal bleeding and adverse pregnancy outcomes among Chinese women: from a large cohort study in China.

PubMed

Sun, Lu; Tao, Fangbiao; Hao, Jiahu; Su, Puyu; Liu, Fang; Xu, Rong

2012-08-01

To examine the effect of first trimester vaginal bleeding on adverse pregnancy outcomes including preterm delivery, low birth weight and small for gestational age. This is a prospective population-based cohort study. A questionnaire survey was conducted on 4342 singleton pregnancies by trained doctors. Binary logistic regression was used to estimate risk ratios (RRs) and 95% confidence intervals (95% CI). Vaginal bleeding occurred among 1050 pregnant women, the incidence of vaginal bleeding was 24.2%, 37.4% of whom didn't see a doctor, 62.6% of whom saw a doctor for vaginal bleeding. Binary logistic regression demonstrated that bleeding with seeing a doctor was significantly associated with preterm birth (RR 1.84, 95% CI 1.25-2.69) and bleeding without seeing a doctor was related to increased of low birth weight (RR 2.52, 95% CI 1.34-4.75) and was 1.97-fold increased of small for gestational age (RR 1.97, 95% CI 1.19-3.25). These results suggest that first trimester vaginal bleeding is an increased risk of low birth weight, preterm delivery and small for gestational age. Find ways to reduce the risk of vaginal bleeding and lower vaginal bleeding rate may be helpful to reduce the incidence of preterm birth, low birth weight and small for gestational age.

Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

PubMed

Bondon-Guitton, Emmanuelle; Mourgues, Thibaut; Rousseau, Vanessa; Cousty, Sarah; Cottin, Judith; Drablier, Guillaume; Micallef, Joëlle; Montastruc, Jean-Louis

2017-09-01

Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spontaneous Bleeding Associated with Ginkgo biloba

PubMed Central

Bent, Stephen; Goldberg, Harley; Padula, Amy; Avins, Andrew L

2005-01-01

BACKGROUND Ginkgo biloba (ginkgo) is a herbal remedy used by over 2% of the adult population in the United States. Several review articles have suggested that ginkgo may increase the risk of bleeding. OBJECTIVE To report a case of bleeding associated with using ginkgo, to systematically review the literature for similar case reports, and to evaluate whether using ginkgo is causally related to bleeding. DATA SOURCES We searched MEDLINE, EMBASE, IBIDS, and the Cochrane Collaboration Database from 1966 to October 2004 with no language restrictions. REVIEW METHODS Published case reports of bleeding events in persons using ginkgo were selected. Two reviewers independently abstracted a standard set of information to assess whether ginkgo caused the bleeding event. RESULTS Fifteen published case reports described a temporal association between using ginkgo and a bleeding event. Most cases involved serious medical conditions, including 8 episodes of intracranial bleeding. However, 13 of the case reports identified other risk factors for bleeding. Only 6 reports clearly described that ginkgo was stopped and that bleeding did not recur. Bleeding times, measured in 3 reports, were elevated when patients were taking ginkgo. CONCLUSION A structured assessment of published case reports suggests a possible causal association between using ginkgo and bleeding events. Given the widespread use of this herb and the serious nature of the reported events, further studies are needed. Patients using ginkgo, particularly those with known bleeding risks, should be counseled about a possible increase in bleeding risk. PMID:16050865

Thrombin-stimulated platelet aggregation is inhibited by kallikrein in a time- and concentration-dependent manner.

PubMed

Veloso, D

2003-01-01

Many in vitro studies have shown that activation of prekallikrein (PK) to kallikrein (KAL) in normal plasma triggers rapid activation of the coagulation cascade. In agreement, the coagulation activation is impaired in PK-deficient plasma. Paradoxically, PK-deficient patients show a tendency to thrombosis. To investigate the discrepancy between the in vitro and in vivo findings, we analyzed the effect of KAL on the rate of platelet aggregation. For this research, physiologic concentrations of washed human platelets were incubated for 5 and/or 10 min with approximately 2.2 to 88 nM human plasma KAL (< 1/100 to approximately 1/3 of PK concentrations in plasma) prior to the addition of high concentrations of alpha-thrombin (54 nM) or fibrinogen plus ADP. KAL concentrations were arbitrarily selected on the assumption that concentrations of free KAL (the enzymatically active species) were minute in normal plasma and higher when KAL production was enhanced, and/or inhibitors were depleted. Full platelet aggregation was that seen in the absence of KAL or PK. Inhibition of platelet aggregation stimulated by thrombin was markedly increased with increased KAL concentrations and incubation times. The degree of inhibition by KAL was smaller when ADP was the agonist. The data suggest that KAL may play a role in the modulation of platelet aggregation in vivo under normal conditions as well as when prolonged, high concentrations of KAL occur in blood. The data may also help to explain the intriguing observation that PK-deficient patients show a tendency to thrombotic episodes and myocardial infarction whereas in vitro assays predict bleeding.

Suicidal ingestion of potassium permanganate crystals: a rare encounter.

PubMed

Karthik, Ravikanti; Veerendranath, Hari Prasad Kanakapura; Wali, Siddraj; Mohan, Murali N T; Kumar, Praveen A C; Trimurty, Gaganam

2014-01-01

Potassium permanganate poisoning is not common. Although Symptoms of potassium permanganate ingestion are gastrointestinal and Complications due to ingestion of potassium permanganate include cardiovascular depression, hepatic and renal damage, upper airway obstruction, bleeding tendency and methemoglobinemia. Gastric damage due to potassium permanganate has rarely been reported previously. We are reporting a 34-year old female patient who presented to our Emergency Department after suicidal ingestion of potassium permanganate crystals. After treatment, the patient was discharged home on the 8(th) day after admission. So we conclude that Emergency endoscopy has a significant role in diagnosis and management of potassium permanganate ingestion.

The perioperative management of patients with polycythaemia.

PubMed Central

Cundy, J.

1980-01-01

The types of polycythaemia are reviewed and evidence presented indicating the need for reduction of the packed cell volume in polycythaemic patients before operation. Such patients must also be offered a full regimen of perioperative antithrombosis therapy, the only possible exception being in cases of primary polycythaemia with a bleeding tendency. Either heparin or dextran should be given intravenously and pulsating boots or elastic stockings placed on the patient's legs. An indication is given of the evidence pointing towards mild anaemia, by British standards, being the optimum state for circulatory efficiency and ways of producing this in the polycythaemic patient are described. PMID:7436307

Effects of bleed air extraction on thrust levels on the F404-GE-400 turbofan engine

NASA Technical Reports Server (NTRS)

Yuhas, Andrew J.; Ray, Ronald J.

1992-01-01

A ground test was performed to determine the effects of compressor bleed flow extraction on the performance of F404-GE-400 afterburning turbofan engines. The two engines were installed in the F/A-18 High Alpha Research Vehicle at the NASA Dryden Flight Research Facility. A specialized bleed ducting system was installed onto the aircraft to control and measure engine bleed airflow while the aircraft was tied down to a thrust measuring stand. The test was conducted on each engine and at various power settings. The bleed air extraction levels analyzed included flow rates above the manufacturer's maximum specification limit. The measured relationship between thrust and bleed flow extraction was shown to be essentially linear at all power settings with an increase in bleed flow causing a corresponding decrease in thrust. A comparison with the F404-GE-400 steady-state engine simulation showed the estimation to be within +/- 1 percent of measured thrust losses for large increases in bleed flow rate.

To Bleed or Not to Bleed: That is the Question. The Side Effects of Apixaban.

PubMed

Ciccone, Marco Matteo; Zito, Annapaola; Devito, Fiorella; Maiello, Maria; Palmiero, Pasquale

2018-01-01

Apixaban is a new oral anticoagulant (NOACs: Novel Oral Anticoagulant), like dabigatran, rivaroxaban, and edoxaban. All of them are prescribed to patients with non valvular atrial fibrillation or venous thromboembolism, to replace warfarin, because of the lower probability of bleeding, however they can cause bleeding by themselves. Bleeding is an adverse event in patients taking anticoagulants. It is associated with a significant increase of morbidity and risk of death. However, these drugs should be used only for the time when anticoagulation is strictly required, especially when used for preventing deep vein thrombosis. Prolonged use increases the risk of bleeding. In the ARISTOTLE Trial Apixaban, compared with warfarin, was associated with a lower rate of intracranial hemorrhages and less adverse consequences following extracranial hemorrhage. Many physicians still have limited experience with new oral anticoagulants and about bleeding risk managment. We reviewed the available literature on extracranial and intracranial bleeding concerning apixaban. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

PubMed

Laursen, S B; Leontiadis, G I; Stanley, A J; Hallas, J; Schaffalitzky de Muckadell, O B

2017-08-01

Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding. © 2017 John Wiley & Sons Ltd.

The HAT Score-A Simple Risk Stratification Score for Coagulopathic Bleeding During Adult Extracorporeal Membrane Oxygenation.

PubMed

Lonergan, Terence; Herr, Daniel; Kon, Zachary; Menaker, Jay; Rector, Raymond; Tanaka, Kenichi; Mazzeffi, Michael

2017-06-01

The study objective was to create an adult extracorporeal membrane oxygenation (ECMO) coagulopathic bleeding risk score. Secondary analysis was performed on an existing retrospective cohort. Pre-ECMO variables were tested for association with coagulopathic bleeding, and those with the strongest association were included in a multivariable model. Using this model, a risk stratification score was created. The score's utility was validated by comparing bleeding and transfusion rates between score levels. Bleeding also was examined after stratifying by nadir platelet count and overanticoagulation. Predictive power of the score was compared against the risk score for major bleeding during anti-coagulation for atrial fibrillation (HAS-BLED). Tertiary care academic medical center. The study comprised patients who received venoarterial or venovenous ECMO over a 3-year period, excluding those with an identified source of surgical bleeding during exploration. None. Fifty-three (47.3%) of 112 patients experienced coagulopathic bleeding. A 3-variable score-hypertension, age greater than 65, and ECMO type (HAT)-had fair predictive value (area under the receiver operating characteristic curve [AUC] = 0.66) and was superior to HAS-BLED (AUC = 0.64). As the HAT score increased from 0 to 3, bleeding rates also increased as follows: 30.8%, 48.7%, 63.0%, and 71.4%, respectively. Platelet and fresh frozen plasma transfusion tended to increase with the HAT score, but red blood cell transfusion did not. Nadir platelet count less than 50×10 3 /µL and overanticoagulation during ECMO increased the AUC for the model to 0.73, suggesting additive risk. The HAT score may allow for bleeding risk stratification in adult ECMO patients. Future studies in larger cohorts are necessary to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative effects of the anti-platelet drugs, clopidogrel, ticlopidine, and cilostazol on aspirin-induced gastric bleeding and damage in rats.

PubMed

Takeuchi, Koji; Takayama, Shinichi; Izuhara, Chitose

2014-08-21

The present study compared the effects of frequently used anti-platelet drugs, such as clopidogrel, ticlopidine, and cilostazol, on the gastric bleeding and ulcerogenic responses induced by intraluminal perfusion with 25 mM aspirin acidified with 25 mM HCl (acidified ASA) in rats. The stomach was perfused with acidified ASA at a rate of 0.4 ml/min for 60 min under urethane anesthesia, and gastric bleeding was measured as the concentration of hemoglobin in the luminal perfusate, which was collected every 15 min. Clopidogrel (10-100mg/kg), ticlopidine (10-300 mg/kg), or cilostazol (3-30 mg/kg) was given p.o. 24h or 90 min before the perfusion of acidified ASA, respectively. Perfusion of the stomach with acidified ASA alone led to slight bleeding and lesions in the stomach. The pretreatment with clopidogrel, even though it did not cause bleeding or damage by itself, dose-dependently increased the gastric bleeding and ulcerogenic responses induced by acidified ASA. Ticlopidine also aggravated the severity of damage by increasing gastric bleeding, and the effects of ticlopidine at 300 mg/kg were equivalent to those of clopidogrel at 100mg/kg. In contrast, cilostazol dose-dependently decreased gastric bleeding and damage in response to acidified ASA. These results demonstrated that clopidogrel and ticlopidine, P2Y12 receptor inhibitors, increased gastric bleeding and ulcerogenic responses to acidified ASA, to the same extent, while cilostazol, a phosphodiesterase III inhibitor, suppressed these responses. Therefore, cilostazol may be safely used in dual anti-platelet therapy combined with ASA, without increasing the risk of gastric bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel approach to assess the spontaneous gastrointestinal bleeding risk of antithrombotic agents using Apc(min/+) mice.

PubMed

Wei, Huijun; Shang, Jin; Keohane, CarolAnn; Wang, Min; Li, Qiu; Ni, Weihua; O'Neill, Kim; Chintala, Madhu

2014-06-01

Assessment of the bleeding risk of antithrombotic agents is usually performed in healthy animals with some form of vascular injury to peripheral organs to induce bleeding. However, bleeding observed in patients with currently marketed antithrombotic drugs is typically spontaneous in nature such as intracranial haemorrhage (ICH) and gastrointestinal (GI) bleeding, which happens most frequently on top of preexisting pathologies such as GI ulcerations and polyps. Apc(min/+) mice are reported to develop multiple adenomas through the entire intestinal tract and display progressive anaemia.In this study, we evaluated the potential utility of Apc(min/+) mice as a model for assessing spontaneous GI bleeding with antithrombotic agents. Apc(min/+) mice exhibited progressive blood loss starting at the age of nine weeks. Despite the increase in bleeding, Apc(min/+) mice were in a hypercoagulable state and displayed an age-dependent increase in thrombin generation and circulating fibrinogen as well as a significant decrease in clotting times. We evaluated the effect of warfarin, dabigatran etexilate, apixaban and clopidogrel in this model by administering them in diet or in the drinking water to mice for 1-4 weeks. All of these marketed drugs significantly increased GI bleeding in Apc(min/+) mice, but not in wild-type mice. Although different exposure profiles of these antithrombotic agents make it challenging to compare the bleeding risk of compounds, our results indicate that the Apc(min/+) mouse may be a sensitive preclinical model for assessing the spontaneous GI bleeding risk of novel antithrombotic agents.

The effect of cod liver oil in two populations with low and high intake of dietary fish.

PubMed

Simonsen, T; Nordøy, A; Sjunneskog, C; Lyngmo, V

1988-01-01

Two subgroups of healthy males from an inland and a coastal community in Norway with a traditionally low and high consumption of dietary fish were given a dietary supplement of 20 ml cod liver oil rich in n-3 polyunsaturated fatty acids for 3 weeks. Cod liver oil induced an increase in serum high density lipoprotein (HDL) cholesterol in men from the inland. Both groups showed a prolonged primary bleeding time, whereas platelet aggregation and thromboxane A2 production induced by collagen were mainly unaffected. Platelet phospholipid fatty acids showed similar changes in both groups with a decrease in n-6 and an increase in n-3 polyunsaturated fatty acids. No changes were observed in total cholesterol or platelet phospholipid content. This study shows that dietary supplement with cod liver oil induces changes in serum lipids and platelets that may reduce the tendency to thrombosis both in subjects with a low and in those with a high intake of dietary fish. The effects were more pronounced in the subjects with a traditionally low fish consumption.

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases.

PubMed

Hapsari Putri, Indri; Tunjungputri, Rahajeng N; De Groot, Philip G; van der Ven, Andre J; de Mast, Quirijn

2018-06-18

Thrombocytopenia is a well-known manifestation of acute tropical infectious diseases. The role of platelets in infections has received much attention recently because of their emerging activities in modulation of inflammatory responses, host defense, and vascular integrity. However, while many studies have addressed thrombocytopenia in tropical infections, abnormalities in platelet function have been largely overlooked. This is an important research gap, as platelet dysfunction may contribute to the bleeding tendency that characterizes some tropical infections. The development of novel platelet function assays that can be used in thrombocytopenic conditions (e.g., flow cytometry assays) has contributed to important new insights in recent years. In this review, the importance of platelets in tropical infections is discussed with special emphasis on the underlying mechanisms and consequences of thrombocytopenia and platelet dysfunction in these infections. Special attention is paid to malaria, a disease characterized by microvascular obstruction in which bleeding is rare, and to infections in which bleeding is common, such as dengue, other viral hemorrhagic fevers, and the bacterial infection leptospirosis. Given the importance of platelet function abnormalities in these infections, the development of affordable assays for monitoring of platelet function in low-resource countries, as well as pharmacologic interventions to prevent or reverse platelet function abnormalities, might improve clinical care and the prognosis of these infections. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Should helical tomotherapy replace brachytherapy for cervical cancer? Case report.

PubMed

Hsieh, Chen-Hsi; Wei, Ming-Chow; Hsu, Yao-Peng; Chong, Ngot-Swan; Chen, Yu-Jen; Hsiao, Sheng-Mou; Hsieh, Yen-Ping; Wang, Li-Ying; Shueng, Pei-Wei

2010-11-23

Stereotactic body radiation therapy (SBRT) administered via a helical tomotherapy (HT) system is an effective modality for treating lung cancer and metastatic liver tumors. Whether SBRT delivered via HT is a feasible alternative to brachytherapy in treatment of locally advanced cervical cancer in patients with unusual anatomic configurations of the uterus has never been studied. A 46-year-old woman presented with an 8-month history of abnormal vaginal bleeding. Biopsy revealed squamous cell carcinoma of the cervix. Magnetic resonance imaging (MRI) showed a cervical tumor with direct invasion of the right parametrium, bilateral hydronephrosis, and multiple uterine myomas. International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer was diagnosed. Concurrent chemoradiation therapy (CCRT) followed by SBRT delivered via HT was administered instead of brachytherapy because of the presence of multiple uterine myomas with bleeding tendency. Total abdominal hysterectomy was performed after 6 weeks of treatment because of the presence of multiple uterine myomas. Neither pelvic MRI nor results of histopathologic examination at X-month follow-up showed evidence of tumor recurrence. Only grade 1 nausea and vomiting during treatment were noted. Lower gastrointestinal bleeding was noted at 14-month follow-up. No fistula formation and no evidence of haematological, gastrointestinal or genitourinary toxicities were noted on the most recent follow-up. CCRT followed by SBRT appears to be an effective and safe modality for treatment of cervical cancer. Larger-scale studies are warranted.

[Incidence of peptic ulcer at the Instituto Nacional de la Nutrición "Salvador Zubirán": study of localization, associated factors and temporal trends].

PubMed

Bobadilla, J; Vargas-Vorácková, F; Gómez, A; Jesús Villalobos, J

1996-01-01

To know the frequency, trends and associated factors of peptic ulcer disease in our Institute. Peptic ulcer is an important disease; about 5-10% of the population can expect to develop this disease during lifetime. We reviewed 1,123 patients with peptic ulcer in five years. Sex, age, habits (tobacco and alcohol consumption), non-steroidal anti-inflammatory drugs use, ulcer location and complications were analyzed. To evaluate temporal trends, our results were compared with previous studies made in our Institute. The male-female ratio was 1:1, with a mean age of 52.2 years. Forty percent of the patients had duodenal ulcer, 42% had gastric ulcer, and 19% had esophageal, anastomotic or multiple ulcers. The most common complication was bleeding, which occurred more frequently in gastric (37%) than duodenal ulcer (24%) (P < 0.005). Gastric ulcer occurred in older patients when compared to duodenal ulcer (P < 0.02). Non-steroidal anti-inflammatory drugs consumption was more frequent in patients with gastric (14%) than duodenal ulcer (10%) (P < 0.04). The frequency of tobacco and alcohol consumption was higher in multiple ulcers. A tendency toward a decreased frequency of duodenal ulcer and increased frequency of gastric ulcer was observed in our Institute during the last 30 years. In the same period, bleeding has been the leading complication, suggesting a higher referral of complicated peptic ulcer.

Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial.

PubMed

Cornel, Jan H; Lopes, Renato D; James, Stefan; Stevens, Susanna R; Neely, Megan L; Liaw, Danny; Miller, Julie; Mohan, Puneet; Amerena, John; Raev, Dimitar; Huo, Yong; Urina-Triana, Miguel; Gallegos Cazorla, Alex; Vinereanu, Dragos; Fridrich, Viliam; Harrington, Robert A; Wallentin, Lars; Alexander, John H

2015-04-01

Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF. Copyright © 2015 Elsevier Inc. All rights reserved.

Post-Discharge Bleeding after Percutaneous Coronary Intervention and Subsequent Mortality and Myocardial Infarction: Insights from the HMO Research Network-Stent Registry

PubMed Central

Valle, Javier A.; Shetterly, Susan; Maddox, Thomas M.; Ho, P. Michael; Bradley, Steven M.; Sandhu, Amneet; Magid, David; Tsai, Thomas T.

2016-01-01

Background Bleeding following hospital discharge from percutaneous coronary intervention (PCI) is associated with increased risk of subsequent myocardial infarction (MI) and death, however the timing of adverse events following these bleeding events is poorly understood. Defining this relationship may help clinicians identify critical periods when patients are at highest risk. Methods and Results All patients undergoing PCI from 2004–2007 who survived to hospital discharge without a bleeding event were identified from the HMO Research Network-Stent Registry. Post-discharge rates and timing of bleeding-related hospitalizations, MI and death were defined. We then assessed the association between post-discharge bleeding-related hospitalizations with death and MI using Cox proportional hazards models. Among 8,137 post-PCI patients surviving to hospital discharge without in-hospital bleeding, 391 (4.8%) suffered bleeding-related hospitalization after discharge, with the highest incidence of bleeding-related hospitalizations occurring within 30 days of discharge (n=79, 20.2%). Post-discharge bleeding-related hospitalization after PCI was associated with subsequent death or MI (hazard ratio [HR] 3.09; 95% confidence interval [CI] 2.41–3.96), with the highest risk for death or MI occurring in the first 60 days after bleeding-related hospitalization (HR 7.16, CI 3.93–13.05). Conclusions Approximately 1 in 20 post-PCI patients are readmitted for bleeding, with the highest incidence occurring within 30 days of discharge. Patients suffering post-discharge bleeding are at increased risk for subsequent death or MI, with the highest risk occurring within the first 60 days following a bleeding-related hospitalization. These findings suggest a critical period after bleeding events when patients are most vulnerable for further adverse events. PMID:27301394

Throat-bypass bleed systems for increasing the stable airflow range of a Mach 2.50 axisymmetric inlet with 40-percent internal contraction

NASA Technical Reports Server (NTRS)

Sanders, B. W.; Mitchell, G. A.

1973-01-01

The results of an experimental investigation to increase the stable airflow range of a super sonic mixed-compression inlet are presented. Various throat-bypass bleeds were located on the inlet cowl. The bleed types were distributed porous normal holes, a forward slanted slot, or distributed educated slots. Large inlet stability margins were obtained with the inlet throat bleed systems if a constant pressure was maintained in the throat-bypass bleed plenum. Stability limits were determined for steady-state and limited transient internal air flow changes. Limited unstart angle-of-attack data are presented.

Validation of the Valve Academic Research Consortium Bleeding Definition in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

PubMed

Stortecky, Stefan; Stefanini, Giulio G; Pilgrim, Thomas; Heg, Dik; Praz, Fabien; Luterbacher, Fabienne; Piccolo, Raffaele; Khattab, Ahmed A; Räber, Lorenz; Langhammer, Bettina; Huber, Christoph; Meier, Bernhard; Jüni, Peter; Wenaweser, Peter; Windecker, Stephan

2015-09-25

The Valve Academic Research Consortium (VARC) has proposed a standardized definition of bleeding in patients undergoing transcatheter aortic valve interventions (TAVI). The VARC bleeding definition has not been validated or compared to other established bleeding definitions so far. Thus, we aimed to investigate the impact of bleeding and compare the predictivity of VARC bleeding events with established bleeding definitions. Between August 2007 and April 2012, 489 consecutive patients with severe aortic stenosis were included into the Bern-TAVI-Registry. Every bleeding complication was adjudicated according to the definitions of VARC, BARC, TIMI, and GUSTO. Periprocedural blood loss was added to the definition of VARC, providing a modified VARC definition. A total of 152 bleeding events were observed during the index hospitalization. Bleeding severity according to VARC was associated with a gradual increase in mortality, which was comparable to the BARC, TIMI, GUSTO, and the modified VARC classifications. The predictive precision of a multivariable model for mortality at 30 days was significantly improved by adding the most serious bleeding of VARC (area under the curve [AUC], 0.773; 95% confidence interval [CI], 0.706 to 0.839), BARC (AUC, 0.776; 95% CI, 0.694 to 0.857), TIMI (AUC, 0.768; 95% CI, 0.692 to 0.844), and GUSTO (AUC, 0.791; 95% CI, 0.714 to 0.869), with the modified VARC definition resulting in the best predictivity (AUC, 0.814; 95% CI, 0.759 to 0.870). The VARC bleeding definition offers a severity stratification that is associated with a gradual increase in mortality and prognostic information comparable to established bleeding definitions. Adding the information of periprocedural blood loss to VARC may increase the sensitivity and the predictive power of this classification. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia.

PubMed

Spindler, Markus; van Eeuwijk, Judith M M; Schurr, Yvonne; Nurden, Paquita; Nieswandt, Bernhard; Stegner, David; Reinhold, Annegret; Bender, Markus

2018-06-27

Bone marrow megakaryocytes (MKs) produce platelets by extending proplatelets into sinusoidal blood vessels. Defects in thrombopoiesis can lead to thrombocytopenia associated with increased bleeding tendency. Recently, the platelet disorder congenital autosomal recessive small-platelet thrombocytopenia (CARST) was described which is caused by mutations in the ADAP (Adhesion and degranulation promoting adaptor protein; synonym: FYB, SLAP130/120) gene, and characterized by microthrombocytopenia and bleeding symptoms. In this study we used constitutive ADAP-deficient mice (Adap -/- ) as a model to investigate mechanisms underlying the microthrombocytopenia in CARST. We show that Adap -/- mice display several characteristics of human CARST, with moderate thrombocytopenia and smaller-sized platelets. Adap -/- platelets had a shorter life span than control platelets, and macrophage depletion, but not splenectomy, increased platelet counts in mutant mice to control levels. Whole sternum 3D confocal imaging and intravital two-photon microscopy revealed altered morphology of ADAP-deficient MKs with signs of fragmentation and ectopic release of (pro)platelet-like particles into the bone marrow compartment. In addition, cultured bone marrow-derived MKs lacking ADAP showed reduced spreading on extracellular matrix proteins as well as activation of β1 integrins, impaired podosome formation, and displayed defective polarization of the demarcation membrane system in vitro. MK-/platelet-specific ADAP deficient mice (PF4-cre) also produced less and smaller-sized platelets and released platelets ectopically. These data demonstrate that the abnormal platelet production in the mutant mice is a MK-intrinsic defect. Taken together, these results point to a so far unidentified role of ADAP in the process of MK polarization and platelet biogenesis. Copyright © 2018 American Society of Hematology.

National and international registries of rare bleeding disorders.

PubMed

Peyvandi, Flora; Spreafico, Marta

2008-09-01

Rare bleeding disorders (RBDs) are autosomal recessive disorders, representing 3-5% of all the inherited deficiencies of coagulation factors. Their frequency in the general population ranges from 1:500,000 to 1:2 millions. In countries with a high rate of consanguineous marriages RBDs occur more frequently, representing a significant clinical and social problem. Patients affected by RBDs have a wide spectrum of clinical symptoms that vary from a mild or moderate bleeding tendency to potentially serious or life-threatening haemorrhages. Current treatment is based on both replacement therapy and non-transfusional treatment. However, despite the existence of several concentrates, there is no Factor V concentrate available for the treatment of Factor V deficiency, yet. In 2004, to improve the understanding of RBDs prevalence, diagnosis and treatments, the Rare Bleeding Disorders database (RBDD, www.rbdd.org) was developed. The RBDD project allowed the collection of epidemiological information on 3,230 patients from 66 Centres scattered all over the world. Epidemiological data can also be derived from the annual survey of the World Federation of Hemophilia (www.wfh.org) and from other existing national registries. However, these data are not homogenous and global surveys provide a non-real picture of the distribution of RBDs, as about 50% of data refers to European patients. Hence, we focused on Europe and, thanks to a European project (EN-RBD), we set up a network of 10 Treatment Centres to develop a homogeneous communication tool for inserting, managing and viewing information on RBD patients (www.rbdd.eu). This on-line database resulted to be a powerful tool to improve the quality of data collection. Preliminary results showed that a homogeneous and harmonized data collection using a unique model will help to have more accurate data for statistical analysis.

Is endoscopic papillary large balloon dilation safe for treating large CBD stones?

PubMed

Shim, Chan Sup; Kim, Ji Wan; Lee, Tae Yoon; Cheon, Young Koog

2016-01-01

In recent years, endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) has been shown to be an effective technique for the removal of large or difficult common bile duct (CBD) stones, as an alternative to EST. Reviewing the literature published since 2003, it is understood that EPLBD has fewer associated overall complications than EST. Bleeding occurred less frequently with EPLBD than with EST. There was no significant difference in postendoscopic retrograde cholangiopancreatography pancreatitis or perforation. Recent accumulated results of EPLBD with or even without EST suggest that it is a safe and effective procedure for the removal of large or difficult bile duct stones without any additional risk of severe adverse events, when performed under appropriate guidelines. Since use of a larger balloon can tear the sphincter as well as the bile duct, possibly resulting in bleeding and perforation, a balloon size that is equal to or smaller in diameter than the diameter of the native distal bile duct is recommended. The maximum transverse diameter of the stone and the balloon-stone diameter ratio have a tendency to affect the success or failure of complete removal of stones by large balloon dilation to prevent adverse effects such as perforation and bleeding. One should take into account the size of the native bile duct, the size and burden of stones, the presence of stricture of distal bile duct, and the presence of the papilla in or adjacent to a diverticulum. Even though the results of EPLBD indicate that it is a relatively safe procedure in patients with common duct stones with a dilated CBD, the recommended guidelines should be followed strictly for the prevention of major adverse events such as bleeding and perforation.

Predictors for identification of stigmata of recent hemorrhage on colonic diverticula in lower gastrointestinal bleeding.

PubMed

Niikura, Ryota; Nagata, Naoyoshi; Aoki, Tomonori; Shimbo, Takuro; Tanaka, Shohei; Sekine, Katsunori; Kishida, Yoshihiro; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Yanase, Mikio; Akiyama, Junichi; Mizokami, Masashi; Uemura, Naomi

2015-03-01

The aim of this study was to identify predictors for the identification of stigmata of recent hemorrhage (SRH) on colonic diverticula. Several factors influence the identification of SRH in the diagnosis of colonic diverticular bleeding. A total of 396 patients hospitalized for lower gastrointestinal bleeding were analyzed. Comorbidities, medications, timing of colonoscopy [<24 h (h); urgent, 24 to 48 h, >48 h], preparation, expert colonoscopist, use of a cap, use of a water-jet scope, total colonoscopy, and procedure time (over 60 min) were assessed. A multivariable logistic regression model was used to estimate odds ratio (OR) and 95% confidence interval (CI). Two hundred fifteen patients were diagnosed with colonic diverticular bleeding and 37 (17%) were identified with SRH. Urgent colonoscopy (OR, 8.4; 95% CI, 2.3-30; P<0.01), expert colonoscopist (OR, 3.0; 95% CI, 1.2-7.3; P=0.02), use of a cap (OR, 3.4; 95% CI, 1.4-8.0; P=0.01), and use of water-jet scope (OR, 5.8; 95% CI, 2.3-15; P<0.01) were found to be independent predictive factors for SRH. The accuracy of these factors in combination was 0.90 (95% CI, 0.85-0.96) as measured by area under the receiver operating characteristic curve (ROC-AUC). SRH identification rate was higher in the urgent (22%) than in the 24 to 48 hours (2.9%, P<0.01) and >48 hours groups (1.0%, P<0.01), showing a tendency to decrease with time (P<0.01 for trend). Factors of urgent colonoscopy, expert colonoscopist, use of a cap, and use of water-jet scope are useful for identifying SRH diverticula.

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study

PubMed Central

Hogg, Kerstin; Bahl, Bharat; Latrous, Meriem; Scaffidi Argentina, Sarina; Thompson, Jesse; Chatha, Aasil Ayyaz; Castellucci, Lana; Stiell, Ian G.

2015-01-01

Background: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. Methods: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. Results: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12%, respectively. Interpretation: We observed increasing time trends in intracranial bleeding, both associated with and not associated with oral anticoagulants, over the study period. Although aggregate provincial data showed increased prescribing of oral anticoagulants, other more likely explanations for our findings include an aging population or increasing frailty. PMID:26770966

Prognostic Significance of Bleeding Location and Severity Among Patients With Acute Coronary Syndromes

PubMed Central

Vavalle, John P.; Clare, Robert; Chiswell, Karen; Rao, Sunil V.; Petersen, John L.; Kleiman, Neal S.; Mahaffey, Kenneth W.; Wang, Tracy Y.

2013-01-01

Objectives This study sought to determine if there is an association between bleed location and clinical outcomes in acute coronary syndromes (ACS) patients. Background The prognostic significance of bleeding location among ACS patients undergoing cardiac catheterization is not well known. Methods We analyzed in-hospital bleeding events among 9,978 patients randomized in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) study. Bleeding events were categorized by location as access site, systemic, surgical, or superficial, and severity was graded using the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definition. We assessed the association of each bleeding location and severity with 6-month risk of death or myocardial infarction using a multicovariate-adjusted Cox proportional hazard model. Results A total of 4,900 bleeding events were identified among 3,694 ACS patients with in-hospital bleeding. Among 4,679 GUSTO mild/moderate bleeding events, only surgical and systemic bleeds were associated with an increased risk of 6-month death or myocardial infarction (adjusted hazard ratio [HR]: 2.52 [95% confidence interval (CI): 2.16 to 2.94, and 1.40 [95% CI: 1.16 to 1.69], respectively). Mild/moderate superficial and access-site bleeds were not associated with downstream risk (adjusted HR: 1.17 [95% CI: 0.97 to 1.40], and 0.96 [95% CI: 0.82 to 1.12], respectively). Among 221 GUSTO severe bleeds, surgical bleeds were associated with the highest risk (HR: 5.27 [95% CI: 3.80 to 7.29]), followed by systemic (HR: 4.48 [95% CI: 2.98 to 6.72]), and finally access-site bleeds (HR: 3.57 [95% CI: 2.35 to 5.40]). Conclusions Among ACS patients who develop in-hospital bleeding, systemic and surgical bleeding are associated with the highest risks of adverse outcomes regardless of bleeding severity. Although the most frequent among bleeds, GUSTO mild/moderate access-site bleeding is not associated with increased risk. These data underscore the importance of strategies to minimize overall bleeding risk beyond vascular access site management. PMID:23866183

Major bleeding after percutaneous coronary intervention and risk of subsequent mortality: a systematic review and meta-analysis

PubMed Central

Kwok, Chun Shing; Rao, Sunil V; Myint, Phyo K; Keavney, Bernard; Nolan, James; Ludman, Peter F; de Belder, Mark A; Loke, Yoon K; Mamas, Mamas A

2014-01-01

Objectives To examine the relationship between periprocedural bleeding complications and major adverse cardiovascular events (MACEs) and mortality outcomes following percutaneous coronary intervention (PCI) and study differences in the prognostic impact of different bleeding definitions. Methods We conducted a systematic review and meta-analysis of PCI studies that evaluated periprocedural bleeding complications and their impact on MACEs and mortality outcomes. A systematic search of MEDLINE and EMBASE was conducted to identify relevant studies. Data from relevant studies were extracted and random effects meta-analysis was used to estimate the risk of adverse outcomes with periprocedural bleeding. Statistical heterogeneity was assessed by considering the I2 statistic. Results 42 relevant studies were identified including 533 333 patients. Meta-analysis demonstrated that periprocedural major bleeding complications was independently associated with increased risk of mortality (OR 3.31 (2.86 to 3.82), I2=80%) and MACEs (OR 3.89 (3.26 to 4.64), I2=42%). A differential impact of major bleeding as defined by different bleeding definitions on mortality outcomes was observed, in which the REPLACE-2 (OR 6.69, 95% CI 2.26 to 19.81), STEEPLE (OR 6.59, 95% CI 3.89 to 11.16) and BARC (OR 5.40, 95% CI 1.74 to 16.74) had the worst prognostic impacts while HORIZONS-AMI (OR 1.51, 95% CI 1.11 to 2.05) had the least impact on mortality outcomes. Conclusions Major bleeding after PCI is independently associated with a threefold increase in mortality and MACEs outcomes. Different contemporary bleeding definitions have differential impacts on mortality outcomes, with 1.5–6.7-fold increases in mortality observed depending on the definition of major bleeding used. PMID:25332786

Recurrent Bleeding After Perimesencephalic Hemorrhage.

PubMed

Kauw, Frans; Velthuis, Birgitta K; Kizilates, Ufuk; van der Schaaf, Irene C; Rinkel, Gabriel J E; Vergouwen, Mervyn D I

2017-12-01

Perimesencephalic hemorrhage (PMH) is a type of subarachnoid hemorrhage with excellent long-term outcomes. Only 1 well-documented case of in-hospital rebleeding after PMH is described in the literature, which occurred after initiating antithrombotic treatment because of myocardial ischemia. We describe a patient with PMH without antithrombotic treatment who had 2 episodes of recurrent bleeding on the day of ictus. To validate the radiologic findings, we conducted a case-control study. Six neuroradiologists and 2 neuroradiology fellows performed a blinded assessment of serial unenhanced head computed tomography (CT) scans of 8 patients with a perimesencephalic bleeding pattern (1 index patient, 6 patients with PMH, 1 patient with perimesencephalic bleeding pattern and basilar artery aneurysm) to investigate a potential increase in amount of subarachnoid blood. A 56-year-old woman with a perimesencephalic bleeding pattern and negative CT angiography had 2 episodes after the onset headache with a sudden increase of the headache. Blinded assessment of serial head CT scans of 8 patients with a perimesencephalic bleeding pattern identified the patient who was clinically suspected to have 2 episodes of recurrent bleeding to have an increased amount of subarachnoid blood on 2 subsequent CT scans. Recurrent bleeding after PMH may also occur in patients not treated with antithrombotics. Even after early rebleeding, the prognosis of PMH is excellent. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of Bleeding Events Requiring Hospitalization in Patients With Atrial Fibrillation Receiving Dabigatran, Warfarin, or Antiplatelet Therapy.

PubMed

Riley, Tanya R; Gauthier-Lewis, Mary L; Sanchez, Chelsea K; Riley, Treavor T

2017-04-01

To determine the incidence and severity of bleeding events requiring hospitalization among patients with atrial fibrillation (AF) receiving anticoagulants (dabigatran or warfarin) or antiplatelet agents (eg, aspirin and clopidogrel). This was a single-center, retrospective cohort study involving 1494 patients with AF hospitalized from November 1, 2010, to November 1, 2011, with prior warfarin, dabigatran, or antiplatelet therapy. Overall bleeding events in the dabigatran group compared to the warfarin group were 24% and 12%, respectively ( P = .004). Of these events, individually, there were no significant differences in major (56% vs 58%, P = .88), life-threatening (25% vs 36%, P = .38), or minor bleeding (44% vs 42%, P = .06). Gastrointestinal (GI) bleeding occurred more in the dabigatran group compared to the warfarin group ( P = .02). Intracranial bleeding occurred in 15% of patients in the warfarin group and did not occur at all in the dabigatran group. Warfarin patients had significantly more overall bleeding events compared to antiplatelet therapy ( P < .001), with an increasing trend seen in major bleeding ( P = .06). GI bleeding, however, favored the warfarin group over the antiplatelet group (48% vs 73%, P = .04). Anticoagulation with dabigatran was associated with an overall increased occurrence of bleeding requiring hospital admission compared to warfarin. GI bleeding was more prevalent with dabigatran and antiplatelets than with warfarin. There were more intracranial hemorrhages seen in the warfarin group.

Use of non-steroidal anti-inflammatory drugs and proton pump inhibitors in correlation with incidence, recurrence and death of peptic ulcer bleeding: an ecological study

PubMed Central

Lu, Yunxia; Sverdén, Emma; Ljung, Rickard; Söderlund, Claes; Lagergren, Jesper

2013-01-01

Background Non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are regarded as two types of drugs that respectively increase and decrease the risk of peptic ulcer bleeding. However, their relation to occurrence, recurrence and death of bleeding in the population level is not clear. Study objective To clarify recent calendar-time correlations between sales of NSAIDs and PPIs and the occurrence of peptic ulcer bleeding, re-bleeding and death. Design Ecological study. Results The time trend of peptic ulcer bleeding did not correlate with PPI sales but did correlate with NSAIDs in mem (Rmale=0.6571, Pmale=0.05). Sales of PPIs (inverse) and NSAIDs correlated with re-bleeding in women (Rmale=−0.8754, Pmale=0.002 and Rfemale=0.7161, Pfemale=0.03, respectively), but not in men. An inverse correlation between PPI sales and 30-day death after bleeding was found (Rmale=−0.9392, Pmale=0.0002 and Rfemale=−0.8561, Pfemale=0.003), and NSAID sales were found to correlate with increased death after bleeding ((Rmale=0.7278, Pmale=0.03, Rfemale=0.7858, Pfemale=0.01). Conclusions The sales of NSAIDs and PPIs correlate with recurrence of peptic ulcer bleeding in women and death after peptic ulcer bleeding in both genders in the population level. PMID:23293249

Bleeding risks associated with inheritance of the Quebec platelet disorder.

PubMed

McKay, Heather; Derome, Francine; Haq, M Anwar; Whittaker, Susan; Arnold, Emmy; Adam, Frédéric; Heddle, Nancy M; Rivard, Georges E; Hayward, Catherine P M

2004-07-01

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with increased urokinase-type plasminogen activator in platelets and alpha-granule protein degradation. To determine bleeding risks and common manifestations of QPD, a history questionnaire was developed and administered to 127 relatives in a family with QPD. Data entry was done blinded to affected and unaffected status, determined by assays for platelet urokinase-type plasminogen activator (u-PA) and fibrinogen degradation. Odds ratios (ORs), with 95% confidence intervals (CIs), were determined for items queried. Summative bleeding scores for each individual were calculated using items with OR more than 1. Mean ages (34 years; range, 1-89 years) were similar for affected (n = 23) and unaffected (n = 104) family members. Affected individuals had higher mean bleeding scores (P <.0001) and a much higher likelihood (OR > 20) of having bleeding that led to lifestyle changes, bruises that spread lower or as large or larger than an orange or both, joint bleeds, bleeding longer than 24 hours after dental extractions or deep cuts, and received or been recommended other treatments (fibrinolytic inhibitors) for bleeding. Individuals with QPD and exposure(s) to hemostatic challenges had experienced excessive bleeding only when fibrinolytic inhibitors had not been used. These data illustrate that QPD is associated with increased risks of bleeding that can be modified by fibrinolytic inhibitors.

Bleed-through correction for rendering and correlation analysis in multi-colour localization microscopy

PubMed Central

Kim, Dahan; Curthoys, Nikki M.; Parent, Matthew T.; Hess, Samuel T.

2015-01-01

Multi-colour localization microscopy has enabled sub-diffraction studies of colocalization between multiple biological species and quantification of their correlation at length scales previously inaccessible with conventional fluorescence microscopy. However, bleed-through, or misidentification of probe species, creates false colocalization and artificially increases certain types of correlation between two imaged species, affecting the reliability of information provided by colocalization and quantified correlation. Despite the potential risk of these artefacts of bleed-through, neither the effect of bleed-through on correlation nor methods of its correction in correlation analyses has been systematically studied at typical rates of bleed-through reported to affect multi-colour imaging. Here, we present a reliable method of bleed-through correction applicable to image rendering and correlation analysis of multi-colour localization microscopy. Application of our bleed-through correction shows our method accurately corrects the artificial increase in both types of correlations studied (Pearson coefficient and pair correlation), at all rates of bleed-through tested, in all types of correlations examined. In particular, anti-correlation could not be quantified without our bleed-through correction, even at rates of bleed-through as low as 2%. Demonstrated with dichroic-based multi-colour FPALM here, our presented method of bleed-through correction can be applied to all types of localization microscopy (PALM, STORM, dSTORM, GSDIM, etc.), including both simultaneous and sequential multi-colour modalities, provided the rate of bleed-through can be reliably determined. PMID:26185614

Bleed-through correction for rendering and correlation analysis in multi-colour localization microscopy.

PubMed

Kim, Dahan; Curthoys, Nikki M; Parent, Matthew T; Hess, Samuel T

2013-09-01

Multi-colour localization microscopy has enabled sub-diffraction studies of colocalization between multiple biological species and quantification of their correlation at length scales previously inaccessible with conventional fluorescence microscopy. However, bleed-through, or misidentification of probe species, creates false colocalization and artificially increases certain types of correlation between two imaged species, affecting the reliability of information provided by colocalization and quantified correlation. Despite the potential risk of these artefacts of bleed-through, neither the effect of bleed-through on correlation nor methods of its correction in correlation analyses has been systematically studied at typical rates of bleed-through reported to affect multi-colour imaging. Here, we present a reliable method of bleed-through correction applicable to image rendering and correlation analysis of multi-colour localization microscopy. Application of our bleed-through correction shows our method accurately corrects the artificial increase in both types of correlations studied (Pearson coefficient and pair correlation), at all rates of bleed-through tested, in all types of correlations examined. In particular, anti-correlation could not be quantified without our bleed-through correction, even at rates of bleed-through as low as 2%. Demonstrated with dichroic-based multi-colour FPALM here, our presented method of bleed-through correction can be applied to all types of localization microscopy (PALM, STORM, dSTORM, GSDIM, etc.), including both simultaneous and sequential multi-colour modalities, provided the rate of bleed-through can be reliably determined.

The use of prophylactic gastroprotective therapy in patients with nonsteroidal anti-inflammatory drug- and aspirin-associated ulcer bleeding: a cross-sectional study.

PubMed

Ho, C W; Tse, Y K; Wu, B; Mulder, C J J; Chan, F K L

2013-04-01

Poor adherence to gastroprotective agents (GPAs) is common among users of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (ASA). There are little data on the utilization of GPAs among NSAID and ASA users complicated by ulcer bleeding. To study the utilization of GPA among NSAID and ASA ulcers before the onset of ulcer bleeding. We conducted a cross-sectional study to determine the exposure to NSAIDs, ASA, and GPAs within 4 weeks before endoscopically confirmed ulcer bleeding. Sensitivity analysis was performed to study how improving adherence to GPA use would reduce the risk of ulcer bleeding in high-risk users. Between 2000 and 2009, 1093 and 2277 patients had NSAID- and ASA-associated ulcer bleeding respectively. The incidence of NSAID-associated ulcer bleeding declined by 40%, whereas that of ASA-associated ulcer bleeding increased by 46%. Thirty-nine per cent of NSAID users and 75% of ASA users belonged to high ulcer risk category. Although GPA prescription rate has increased over time, only 41.6% and 30.6% of high-risk NSAID and ASA users received GPAs before ulcer bleeding respectively. Sensitivity analysis showed that if GPAs could reduce bleeding risk by 50%, improving adherence would prevent up to 35% of ulcer bleeding in high-risk users. A substantial proportion of high-risk NSAID and ASA users had not received prophylaxis with gastroprotective agents before ulcer bleeding. These bleeding episodes may be preventable with better adherence to gastroprotective agent use. © 2013 Blackwell Publishing Ltd.

Incidence of Gastrointestinal Bleeding After Percutaneous Coronary Intervention: A Single Center Experience.

PubMed

Aziz, Fahad

2014-02-01

Gastrointestinal (GI) bleeding is a hemorrhagic complication after percutaneous coronary intervention in patients with acute myocardial infarction. The purpose of the study is to determine predictors of GI bleeding and impact of GI bleeding on the patients undergoing percutaneous coronary intervention. GI bleeding occurred in 6 (7.1%) of 84 patients with STEMI/NSETMI (ST-segment elevated myocardial infarction/Non ST-segment elevated myocardial infarction) undergoing primary percutaneous coronary intervention. Univariate analysis demonstrates that patients with GI bleeding had a significantly higher previous GI bleeding (16.66% vs. 8.6%, P < 0.001). Higher Killip classification at presentation was associated with higher incidence of GI bleeding (61% vs. 18%, P < 0.01). The use of proton pump inhibitors did not reduce the risk of GI bleeding. The GI bleeding in these patients was associated with higher mortality and morbidity in the post percutaneous coronary intervention period. Although, GI bleeding in patients with MI significantly increases mortality and morbidity, previous GI bleeding and higher Killip class are associated with higher incidence of GI bleeding. High-risk patients for GI bleeding can be identified at presentation.

Incidence and Prognostic Implications of Late Bleeding After Myocardial Infarction or Unstable Angina According to Treatment Strategy.

PubMed

Brinkert, Miriam; Southern, Danielle A; James, Matthew T; Knudtson, Merrill L; Anderson, Todd J; Charbonneau, François

2017-08-01

Bleeding complications accompanying coronary revascularization are associated with increased mortality; however, few data are available on subsequent bleeding risk. We used administrative data to assess the incidence of late bleeding events in patients with acute coronary syndrome (ACS) according to treatment allocation. The cohort and bleeding events were identified through the Canadian Institute for Health Information discharge abstract database. Crude and adjusted odds ratios (ORs) were calculated for index and postindex admission bleeding up to 1 year after discharge. Of 31,941 patients hospitalized with ACS, 7681 (32.4%) patients were treated with medication alone, 3728 (15.2%) underwent angiography without intervention, and 13,075 (53.4%) underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The overall incidence of readmission with bleeding based on administrative codes was low (3.8% for medically treated patients, 2.8% for patients who underwent angiography alone, 2.6% for patients who underwent CABG, and 1.8% for patients who underwent PCI; P < 0.0001). Bleeding codes were mainly gastrointestinal bleeding (52%), but 7.8% were intracranial episodes of bleeding. Patients who received PCI had significantly lower odds of late bleeding compared with medically treated patients (OR, 0.76; 95% CI, 0.62-0.94). Late bleeding during the first year after ACS was associated with mortality (OR, 4.96; 95% CI, 2.47-9.93). Patients who underwent revascularization procedures had a relatively low risk for late bleeding events after a hospitalization for ACS. Late bleeding events were associated with an increased risk of death. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Variceal bleeding and portal hypertension: new lights on old horizon.

PubMed

Bhasin, D K; Siyad, I

2004-02-01

New clinical, endoscopic, and imaging modalities for diagnosing varices and predicting bleeding are being investigated. Transnasal endoscopy and ultrathin battery-powered esophagoscopes are being used to improve patient comfort and compliance. Patients who respond to portal pressure-reducing drugs not only have a reduced risk of bleeding, but also a reduced risk of developing other complications, with improved survival. Nitrates have been shown to have no definite role in primary prophylaxis against variceal bleeding. The hemodynamic response to treatment has an independent prognostic value for the risk of variceal bleeding. Newer drugs have been investigated for reducing the hepatic venous pressure gradient, but with little success. Survival after bleeding has increased due to improved patient care and technological advances. Combined radiographic and endoscopic management of gastric varices is evolving and appears to be promising. Nonvariceal bleeding from portal hypertensive gastropathy is increasingly being recognized as a potential cause of bleeding in patients with portal hypertension, and pharmacotherapy with octreotide appears to be promising for the treatment of this condition. Variceal band ligation in children has been found to be as safe and effective as in adults.

Overview of the coagulation system.

PubMed

Palta, Sanjeev; Saroa, Richa; Palta, Anshu

2014-09-01

Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms 'coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same.

Overview of the coagulation system

PubMed Central

Palta, Sanjeev; Saroa, Richa; Palta, Anshu

2014-01-01

Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms ‘coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same. PMID:25535411

Advances in Gene Therapy for Hemophilia.

PubMed

Nathwani, Amit C; Davidoff, Andrew M; Tuddenham, Edward G D

2017-11-01

Gene therapy provides hope for a cure for patients with hemophilia by establishing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene copy to replace the hemophilic patient's own defective gene. Hemophilia may be considered a "low-hanging fruit" for gene therapy because a small increment in blood factor levels (≥2% of normal) significantly improves the bleeding tendency from severe to moderate, eliminating most spontaneous bleeds. After decades of research, the first trial to provide clear evidence of efficiency after gene transfer in patients with hemophilia B using adeno-associated virus vectors was reported by the authors' group in 2011. This has been followed by unprecedented activity in this area, with the commencement of seven new early-phase trials involving >55 patients with hemophilia A or hemophilia B. These studies have, in large part, generated promising clinical data that lay a strong foundation for gene therapy to move forward rapidly to market authorization. This review discusses the data from the authors' studies and emerging results from other gene therapy trials in both hemophilia A and B.

President's Address

PubMed Central

Kidd, Frank

1928-01-01

Twenty-four cases of purpura of the urinary tract are discussed and analysed. Purpura of the kidney may be a cause of painless hæmaturia. In some cases nephrectomy may be necessary to check the bleeding. Purpura of the bladder is a cause of painful hæmaturia. In such cases the diagnosis can be made with the cytoscope. A number of the cases appear to be caused by a streptococcal infection of throat, teeth or bowel. The exhibition of horse serum by the mouth usually has an immediate effect in checking the bleeding tendency Splenectomy should be considered in severe chronic recurrent cases. Purpura is a symptom and not a disease. It can attack the kidney or bladder in any type of case. The attacks may be simple, recurrent or fulminating. In many cases no cause can be discovered, in others it is associated with acute rheumatism. In a number of cases a proximate cause can be discovered, in the nature of a bacterial infection, a chemical poison, a thrombocytopenia, splenomegaly, or the deprivation of some vitamin. ImagesFig. 1Fig. 2Fig. 3 PMID:19986473

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies.

PubMed

Danesh, B J; Saniabadi, A R; Russell, R I; Lowe, G D

1987-12-01

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

Platelet Function Analyzed by Light Transmission Aggregometry.

PubMed

Hvas, Anne-Mette; Favaloro, Emmanuel J

2017-01-01

Analysis of platelet function is widely used for diagnostic work-up in patients with increased bleeding tendency. During the last decades, platelet function testing has also been introduced for evaluation of antiplatelet therapy, but this is still recommended for research purposes only. Platelet function can also be assessed for hyper-aggregability, but this is less often evaluated. Light transmission aggregometry (LTA) was introduced in the early 1960s and has since been considered the gold standard. This optical detection system is based on changes in turbidity measured as a change in light transmission, which is proportional to the extent of platelet aggregation induced by addition of an agonist. LTA is a flexible method, as different agonists can be used in varying concentrations, but performance of the test requires large blood volumes and experienced laboratory technicians as well as specialized personal to interpret results. In the present chapter, a protocol for LTA is described including all steps from pre-analytical preparation to interpretation of results.

Variation of Shrinkage Strain within the Depth of Concrete Beams.

PubMed

Jeong, Jong-Hyun; Park, Yeong-Seong; Lee, Yong-Hak

2015-11-16

The variation of shrinkage strain within beam depth was examined through four series of time-dependent laboratory experiments on unreinforced concrete beam specimens. Two types of beam specimens, horizontally cast and vertically cast, were tested; shrinkage variation was observed in the horizontally cast specimens. This indicated that the shrinkage variation within the beam depth was due to water bleeding and tamping during the placement of the fresh concrete. Shrinkage strains were measured within the beam depth by two types of strain gages, surface-attached and embedded. The shrinkage strain distribution within the beam depth showed a consistent tendency for the two types of gages. The test beams were cut into four sections after completion of the test, and the cutting planes were divided into four equal sub-areas to measure the aggregate concentration for each sub-area of the cutting plane. The aggregate concentration increased towards the bottom of the beam. The shrinkage strain distribution was estimated by Hobbs' equation, which accounts for the change of aggregate volume concentration.

Variation of Shrinkage Strain within the Depth of Concrete Beams

PubMed Central

Jeong, Jong-Hyun; Park, Yeong-Seong; Lee, Yong-Hak

2015-01-01

The variation of shrinkage strain within beam depth was examined through four series of time-dependent laboratory experiments on unreinforced concrete beam specimens. Two types of beam specimens, horizontally cast and vertically cast, were tested; shrinkage variation was observed in the horizontally cast specimens. This indicated that the shrinkage variation within the beam depth was due to water bleeding and tamping during the placement of the fresh concrete. Shrinkage strains were measured within the beam depth by two types of strain gages, surface-attached and embedded. The shrinkage strain distribution within the beam depth showed a consistent tendency for the two types of gages. The test beams were cut into four sections after completion of the test, and the cutting planes were divided into four equal sub-areas to measure the aggregate concentration for each sub-area of the cutting plane. The aggregate concentration increased towards the bottom of the beam. The shrinkage strain distribution was estimated by Hobbs’ equation, which accounts for the change of aggregate volume concentration. PMID:28793677

[Gastrointestinal bleeding in the elderly].

PubMed

Glaser, J

2014-08-01

Peptic ulcer disease is a common cause of gastrointestinal bleeding, independent of the patient's age. With advancing age, an increase of lower gastrointestinal bleeding (diverticula, angiodysplasia) has been observed. The administration of non-steroidal anti-inflammatory drugs and aspirin is an important risk factor for upper and lower gastrointestinal bleeding, thus in patients aged 65 years and more a concomitant therapy with proton pump inhibitors is recommended in order to prevent ulcer bleeding. Even in very old individuals endoscopy should be used for the diagnosis of gastrointestinal bleeding, providing the opportunity for definite endoscopic bleeding therapy. In elderly patients with comorbidities and recurrent bleeding after endoscopic therapy or continuous blood loss, surgery or transarterial embolisation should be considered in good time. Georg Thieme Verlag KG Stuttgart · New York.

Prognostic value of intraventricular bleeding in spontaneous intraparenchymal cerebral hemorrhage of small volume: a prospective cohort study.

PubMed

Fortes Lima, Telmo Tiburcio; Prandini, Mirto Nelso; Gallo, Pasquale; Cavalheiro, Sérgio

2012-04-01

The literature is controversial on whether intraventricular bleeding has a negative impact on the prognosis of spontaneous intracerebral hemorrhage. Nevertheless, an association between intraventricular bleeding and spontaneous intracerebral hemorrhage volumes has been consistently reported. To evaluate the prognostic value of intraventricular bleeding in deep intraparenchymal hypertensive spontaneous hemorrhage with a bleeding volume <30 cm(3). Of the 320 patients initially evaluated, 33 met the inclusion criteria and were enrolled in this prospective study. The volume of intraparenchymal hemorrhage was calculated by brain computed tomography (CT) image analysis, and the volume of intraventricular bleeding was calculated by the LeRoux scale. Clinical data, including neurological complications, were collected daily during hospitalization. Neurological outcome was evaluated 30 days after the event by using the Glasgow outcome scale. Patients were assigned to 1 of 3 groups according to intraventricular bleeding: Control, no intraventricular bleeding; LR 1, intraventricular bleeding with LeRoux scale scores of 1 to 8; or LR 2, intraventricular bleeding with LeRoux scale scores >8. There were no significant differences among groups concerning age, mean blood pressure, and time from onset to brain CT scan. Patients with greater intraventricular bleeding presented lower initial Glasgow coma scale scores, increased ventricular index and width of temporal horns, increased number of clinical and neurological complications, and longer hospitalization. Furthermore, their relative risk for unfavorable clinical outcome was 1.9 (95% confidence interval 1.25-2.49). Intraventricular bleeding with a LeRoux scale score >8 appears to have a negative effect on deep spontaneous intraparenchymal cerebral hemorrhage of small volume.

Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists.

PubMed

van Rein, Nienke; Lijfering, Willem M; Bos, Mettine H A; Herruer, Martien H; Vermaas, Helga W; van der Meer, Felix J M; Reitsma, Pieter H

2016-01-01

Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

Chronic liver disease and 90-day mortality in 21,359 patients following peptic ulcer bleeding--a Nationwide Cohort Study.

PubMed

Holland-Bill, L; Christiansen, C F; Gammelager, H; Mortensen, R N; Pedersen, L; Sørensen, H T

2015-03-01

Bleeding is a serious and frequent complication of peptic ulcer disease. Hepatic dysfunction can cause coagulopathy and increases the risk of peptic ulcer bleeding. However, whether chronic liver disease increases mortality after peptic ulcer bleeding remains unclear. To examine the prognostic impact of chronic liver disease on mortality after peptic ulcer bleeding. We used population-based medical registries to conduct a cohort study of all Danish residents hospitalised with incident peptic ulcer bleeding from 2004 through 2011. We identified patients diagnosed with liver cirrhosis or non-cirrhotic chronic liver disease before their admission for peptic ulcer bleeding. We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan-Meier method (1 - survival function) and used a Cox regression model to estimate mortality rate ratios (MRRs), controlling for potential confounders. We identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these, 653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3% and 20.7%, respectively, compared to 18.3% among patients without chronic liver disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95% CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non-cirrhotic chronic liver disease. Patients with chronic liver disease, particularly liver cirrhosis, are at increased risk of death within 90 days after hospitalisation for peptic ulcer bleeding compared to patients without chronic liver disease. © 2015 John Wiley & Sons Ltd.

Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis.

PubMed

Martin, Karlyn

2017-10-01

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are characterized by both thrombotic and bleeding complications. The purpose of this review is to describe the risk factors associated with bleeding and thrombosis in MPN, as well as to review prevention strategies and management of these complications. Well-described risk factors for thrombotic complications include older age and history of prior thrombosis, along with traditional cardiovascular and venous thromboembolic risk factors. More recently, JAK2 V617F mutation has been found to carry an increased risk of thrombotic complications, whereas CALR has a lower risk than JAK2 mutation. Factors associated with an increased risk of bleeding in MPN include a prior history of bleeding, acquired von Willebrand syndrome, and primary myelofibrosis. Recent findings suggest that thrombocytosis carries a higher risk of bleeding than thrombosis in MPN, and aspirin may exacerbate this risk of bleeding, particularly in CALR-mutated ET. Much of the management of MPN focuses on predicting risk of bleeding and thrombosis and initiating prophylaxis to prevent complications in those at high risk of thrombosis. Emerging evidence suggests that sub-populations may have bleeding risk that outweighs thrombotic risk, particularly in setting of antiplatelet therapy. Future work is needed to better characterize this balance. At present, a thorough assessment of the risks of bleeding and thrombosis should be undertaken for each patient, and herein, we review risk factors for and management of these complications.

Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin.

PubMed

Davidson, Bruce L; Verheijen, Sara; Lensing, Anthonie W A; Gebel, Martin; Brighton, Timothy A; Lyons, Roger M; Rehm, Jeffrey; Prins, Martin H

2014-06-01

Combined anticoagulant and aspirin therapy is associated with increased bleeding risk in patients with atrial fibrillation, but the bleeding risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs) is poorly documented. To estimate the bleeding risk of combined anticoagulant (rivaroxaban or enoxaparin-vitamin K antagonist [VKA]) and NSAID or aspirin therapy in patients with venous thromboembolism. Prospective analysis of observational data from the EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and clinics in 8246 patients enrolled from 2007 to 2009. Bleeding event rates during exposure to NSAID and aspirin therapy were compared to time without exposure. Days of NSAID or aspirin use and nonuse, clinically relevant bleeding event and major bleeding event rates by patient-years, and hazard ratios. During NSAID-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 37.5 per 100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID-anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years, compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51-3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]). Major bleeding in aspirin-anticoagulant-treated patients occurred with an event rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA anticoagulation regimens. Among patients with venous thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or aspirin is associated with an increased risk of clinically relevant and major bleeding.

Perioperative bleeding and blood transfusion are major risk factors for venous thromboembolism following bariatric surgery.

PubMed

Nielsen, Alexander W; Helm, Melissa C; Kindel, Tammy; Higgins, Rana; Lak, Kathleen; Helmen, Zachary M; Gould, Jon C

2018-05-01

Morbidly obese patients are at increased risk for venous thromboembolism (VTE) after bariatric surgery. Perioperative chemoprophylaxis is used routinely with bariatric surgery to decrease the risk of VTE. When bleeding occurs, routine chemoprophylaxis is often withheld due to concerns about inciting another bleeding event. We sought to evaluate the relationship between perioperative bleeding and postoperative VTE in bariatric surgery. The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) dataset between 2012 and 2014 was queried to identify patients who underwent bariatric surgery. Gastric bypass (n = 28,145), sleeve gastrectomy (n = 30,080), bariatric revision (n = 324), and biliopancreatic diversion procedures (n = 492) were included. Univariate and multivariate regressions were used to determine perioperative factors predictive of postoperative VTE within 30 days in patients who experience a bleeding complication necessitating transfusion. The rate of bleeding necessitating transfusion was 1.3%. Bleeding was significantly more likely to occur in gastric bypass compared to sleeve gastrectomy (1.6 vs. 1.0%) (p < 0.0001). For all surgeries, increased age, length of stay, operative time, and comorbidities including hypertension, dyspnea with moderate exertion, partially dependent functional status, bleeding disorder, transfusion prior to surgery, ASA class III/IV, and metabolic syndrome increased the perioperative bleeding risk (p < 0.05). Multivariate analysis revealed that the rate of VTE was significantly higher after blood transfusion [Odds Ratio (OR) = 4.7; 95% CI 2.9-7.9; p < 0.0001). Predictive risk factors for VTE after transfusion included previous bleeding disorder, ASA class III or IV, and COPD (p < 0.05). Bariatric surgery patients who receive postoperative blood transfusion are at a significantly increased risk for VTE. The etiology of VTE in those who are transfused is likely multifactorial and possibly related to withholding chemoprophylaxis and the potential of a hypercoagulable state induced by the transfusion. In those who bleed, consideration should be given to reinitiating chemoprophylaxis when safe, extending treatment after discharge, and screening ultrasound.

Improving care and treatment options for women and girls with bleeding disorders.

PubMed

Kulkarni, Roshni

2015-12-01

Women and girls may experience increased bleeding symptoms as carriers of haemophilia. They can also be affected by other hereditary bleeding diatheses such as von Willebrand disease, platelet dysfunction defects or deficiencies of coagulation factors (F) such as FI, FII, FV, FVII, FX, FXI and FXIII. In addition to general bleeding symptoms, such disorders pose unique problems for women due to their impact on reproductive health. Women and adolescent girls with undiagnosed bleeding disorders frequently experience heavy menstrual bleeding (HMB; menorrhagia), leading to impairment of daily activities. Other gynaecological and obstetric manifestations, for example miscarriage, bleeding during pregnancy and postpartum haemorrhage (PPH), can occur. Treatment for HMB should consider patient wishes relating to preservation of fertility, and management options include hormonal measures, desmopressin, antifibrinolytics, platelet concentrate transfusions and clotting factor therapy. During pregnancy, monitoring clotting factor levels informs the need for prophylactic therapy; subsequent haemostatic cover can minimise PPH. Under-recognition of bleeding disorders in females may lead to inappropriate, or lack of, treatment. This may be avoided by increased disease awareness, prompt and accurate diagnosis, and a multidisciplinary approach to patient care. This review considers the range of hereditary bleeding disorders that may affect women and adolescent girls, and their evaluation and management. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Suicidal Ingestion of Potassium Permanganate Crystals: A Rare Encounter

PubMed Central

Karthik, Ravikanti; Veerendranath, Hari Prasad Kanakapura; Wali, Siddraj; Mohan, Murali N T; Kumar, Praveen A. C.; Trimurty, Gaganam

2014-01-01

Potassium permanganate poisoning is not common. Although Symptoms of potassium permanganate ingestion are gastrointestinal and Complications due to ingestion of potassium permanganate include cardiovascular depression, hepatic and renal damage, upper airway obstruction, bleeding tendency and methemoglobinemia. Gastric damage due to potassium permanganate has rarely been reported previously. We are reporting a 34-year old female patient who presented to our Emergency Department after suicidal ingestion of potassium permanganate crystals. After treatment, the patient was discharged home on the 8th day after admission. So we conclude that Emergency endoscopy has a significant role in diagnosis and management of potassium permanganate ingestion. PMID:25948978

Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis.

PubMed

Anglin, Rebecca; Yuan, Yuhong; Moayyedi, Paul; Tse, Frances; Armstrong, David; Leontiadis, Grigorios I

2014-06-01

There is emerging concern that selective serotonin reuptake inhibitors (SSRIs) may be associated with an increased risk of upper gastrointestinal (GI) bleeding, and that this risk may be further increased by concurrent use of nonsteroidal anti-inflammatory (NSAID) medications. Previous reviews of a relatively small number of studies have reported a substantial risk of upper GI bleeding with SSRIs; however, more recent studies have produced variable results. The objective of this study was to obtain a more precise estimate of the risk of upper GI bleeding with SSRIs, with or without concurrent NSAID use. MEDLINE, EMBASE, PsycINFO, the Cochrane central register of controlled trials (through April 2013), and US and European conference proceedings were searched. Controlled trials, cohort, case-control, and cross-sectional studies that reported the incidence of upper GI bleeding in adults on SSRIs with or without concurrent NSAID use, compared with placebo or no treatment were included. Data were extracted independently by two authors. Dichotomous data were pooled to obtain odds ratio (OR) of the risk of upper GI bleeding with SSRIs +/- NSAID, with a 95% confidence interval (CI). The main outcome and measure of the study was the risk of upper GI bleeding with SSRIs compared with placebo or no treatment. Fifteen case-control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper GI bleeding with SSRI medications in the case-control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50). The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881. The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42). SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.

Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy. A case-control study nested in a large insurance- and population-based German cohort.

PubMed

Abbas, Sascha; Ihle, Peter; Harder, Sebastian; Schubert, Ingrid

2014-05-05

There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenprocoumon users ≥ 18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20-2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84-2.38 and OR 1.34, 95% CI 1.03-1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62-3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08-4.84) and fluorquinolones (OR 3.13, 95% CI 2.74-3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01-8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics - particularly quinolones and cotrimoxazole - should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.

Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants.

PubMed

Lanas, Ángel; Carrera-Lasfuentes, Patricia; Arguedas, Yolanda; García, Santiago; Bujanda, Luis; Calvet, Xavier; Ponce, Julio; Perez-Aísa, Ángeles; Castro, Manuel; Muñoz, Maria; Sostres, Carlos; García-Rodríguez, Luis A

2015-05-01

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is associated with increased risk of upper gastrointestinal bleeding. There is little evidence on the risk of lower gastrointestinal bleeding with NSAIDs, antiplatelet agents (APAs), or anticoagulants. We aimed to quantify the relative risk (RR) of upper and lower gastrointestinal bleeding associated with use of NSAIDs, APAs, or anticoagulants. We performed a case-control study that used data collected from consecutive patients hospitalized for gastrointestinal bleeding (563 upper, mean age, 63.6 ± 16.7 years and 415 lower, mean age, 70.8 ± 13.8 years), confirmed by endoscopy or other diagnostic procedures. Unhospitalized patients were used as controls (n = 1008) and matched for age, hospital, and month of admission. Drug use was considered current when taken within 7 days or less before hospitalization. RRs and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis. Use of anticoagulants, low-dose aspirin, and other drugs (non-aspirin-APA, 82.3% thienopiridines) was associated with upper and lower gastrointestinal bleeding; the risk was 2-fold higher for anticoagulants (RR, 4.2; 95% CI, 2.9-6.2) than for low-dose aspirin (RR, 2.1; 95% CI, 1.4-3.3) or other non-aspirin-APA drugs (RR, 2.0; 95% CI, 1.6-2.6). NSAID use was also associated with increased risk of gastrointestinal bleeding and greater for upper (RR, 2.6; 95% CI, 2.0-3.5) than lower gastrointestinal bleeding (RR, 1.4; 95% CI, 1.0-1.9). Use of proton pump inhibitors was associated with reduced risk of upper, but not lower, gastrointestinal bleeding. Anticoagulants, low-dose aspirin, NSAIDs, and other non-aspirin-APA drugs are associated with increased risk of upper and lower gastrointestinal bleeding. Use of anticoagulants appears to be the strongest risk factor for gastrointestinal bleeding. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke.

PubMed

Stone, David H; Nolan, Brian W; Schanzer, Andres; Goodney, Philip P; Cambria, Robert A; Likosky, Donald S; Walsh, Daniel B; Cronenwett, Jack L

2010-03-01

Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry. We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis. Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death. Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke, or death, in this large, contemporary registry. In light of significant complications referable to bleeding, liberal use of protamine during CEA appears warranted.

Central nervous system bleeding in pediatric patients with factor XIII deficiency: a study on 23 new cases.

PubMed

Naderi, Majid; Alizadeh, Shaban; Kazemi, Ahmad; Tabibian, Shadi; Zaker, Farhad; Bamedi, Taregh; Kashani Khatib, Zahra; Dorgalaleh, Akbar

2015-03-01

Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder, which has the highest incidence in Sistan and Baluchistan Province in Iran, compared to its overall incidence around the world. This disorder has different clinical manifestations ranging from mild bleeding tendency to lethal bleeding episodes including central nervous system (CNS) hemorrhage. The aim of this study was to evaluate the demographic data, pattern of CNS bleeding, and the role of plasminogen activator inhibitor-1 (PAI-1) (PAI-1) 4G/5G and thrombin activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphisms in intracranial and extracranial hemorrhages in 23 new cases of FXIII-deficient subjects. This case-control study was conducted on 23 FXIII-deficient patients with CNS bleeding episodes and 23 patients as the control group with FXIII deficiency but without any history of CNS bleeding. Initially, to confirm the molecular defect, both groups were evaluated for the most frequently reported mutation of FXIII (Trp187Arg mutation) in a previous study in Sistan and Baluchistan Province. Then, demographic data, clinical manifestations, and pattern of CNS bleeding were determined. Eventually, the patients were assessed for PAI-14G/5G and TAFI Thr325Ile polymorphisms. The results of this study revealed that all the subjects (including the case and control groups) were homozygous for Trp187Arg mutation. Nineteen patients (82.6%) had intracranial hemorrhage (ICH) and four patients (17.4%) had extracranial hemorrhage (ECH). Intraparenchymal hemorrhage was the most common form of ICH (89.5%), and epidural hemorrhage was observed in two patients (10.5%). Anatomic regions in patients with intraparenchymal hemorrhage were temporal in six (35.3%), occipital in four (23.5%), diffused intraparenchymal in four (23.5%), temporal-occipital in two (11.8%), and subdural with temporal in one (5.9%) patient. We found that in the case group, 14 patients (60.8%) were homozygous for TAFI Thr325Ile polymorphism and 8 cases (34.7%) were heterozygous. In the control group, 4 (17.4%) and 13 (56.5%) patients were homozygous and heterozygous, respectively (P < 0.001 vs. P < 0.01).We also found that an equal number of patients (two individuals) in the case and control groups (8.7% in each group) were heterozygous for PAI-14G/5G polymorphism. It seems that PAI-14G/5G polymorphism does not have any effect on occurrence of ICH and ECH in patients with FXIII deficiency, while TAFI Thr325Ile is a strong genetic risk factor (odds ratio:14.9, 95% confidence interval: 7.4-31.1).

Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

PubMed

Held, Claes; Hylek, Elaine M; Alexander, John H; Hanna, Michael; Lopes, Renato D; Wojdyla, Daniel M; Thomas, Laine; Al-Khalidi, Hussein; Alings, Marco; Xavier, Dennis; Ansell, Jack; Goto, Shinya; Ruzyllo, Witold; Rosenqvist, Mårten; Verheugt, Freek W A; Zhu, Jun; Granger, Christopher B; Wallentin, Lars

2015-05-21

In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Variation of renal function over time is associated with major bleeding in patients treated with direct oral anticoagulants for atrial fibrillation.

PubMed

Becattini, C; Giustozzi, M; Ranalli, M G; Bogliari, G; Cianella, F; Verso, M; Agnelli, G; Vedovati, M C

2018-05-01

Essential In patients on treatment with direct anticoagulants (DOACs) variation of renal function is common. The effect of variations of renal function over time on major bleeding is not well defined. Variation of renal function over time is an independent predictor of major bleeding. Identifying conditions associated with variation of renal function may increase safety of DOACs. Background Chronic kidney disease is a risk factor for major bleeding in patients with atrial fibrillation (AF) treated with warfarin. Objective To assess the effect of variations in renal function over time on the risk of major bleeding during treatment with direct oral anticoagulants (DOACs) in patients with non-valvular AF. Methods Consecutive AF patients were prospectively followed after they had received the first DOAC prescription. Estimated glomerular filtration rate (eGFR) was periodically assessed, and the incidence of major bleeding was recorded. A joint survival model was used to estimate the association between variation in eGFR and the risk of major bleeding. Results During a mean follow-up of 575 days, 44 major bleeds occurred in 449 patients (6.1% per patient-year). eGFR over time was inversely and independently associated with the risk of major bleeding; every 1 mL min -1 absolute decrease in eGFR was associated with a 2% increase in the risk of major bleeding (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.04). A similar effect of the variation in eGFR over time was observed on the risk of clinically relevant non-major bleeding (HR 1.02, 95% CI 1.01-1.03). Deterioration of renal function leading to a change in eGFR staging was associated with an increase in the risk of major bleeding (HR 2.43, 95% CI 1.33-4.45). Conclusions Variation in renal function over time is associated with the risk of major bleeding in AF patients treated with DOACs in real life. Identification of intervening clinical conditions associated with variation in renal function is essential to reduce the risk of major bleeding and to make DOAC treatment more safe. © 2018 International Society on Thrombosis and Haemostasis.

Eye movement abnormalities in hermansky-pudlak syndrome.

PubMed

Gradstein, Libe; FitzGibbon, Edmond J; Tsilou, Ekaterini T; Rubin, Benjamin I; Huizing, Marjan; Gahl, William A

2005-08-01

Hermansky-Pudlak Syndrome (HPS) is a type of oculocutaneous albinism associated with a bleeding diathesis and pulmonary fibrosis. Although it is known that patients with HPS exhibit nystagmus, the nature of these abnormal eye movements has not been studied. Twenty-seven patients with HPS, diagnosed by platelet morphology and genetic analysis, underwent a systemic evaluation and complete eye examination. Twenty-five had eye movement recordings using magnetic search coil, infrared, or video oculography. All patients had iris transillumination, foveal hypoplasia, and variable hypopigmentation in skin and eyes. All had bleeding tendencies, and 2 reported excessive bleeding during strabismus surgery. Nine patients had pulmonary fibrosis. Visual acuities ranged from 20/20- to 20/320. Twenty patients had strabismus despite 6 having strabismus surgery previously. Ocular oscillations consistent with congenital nystagmus (CN) were clinically evident in 24 of 27 patients, and half showed periodic alternating nystagmus. In 3 patients without CN, eye movement recordings revealed minimal end-gaze nystagmus, square-wave jerks, drift during fixation and saccades, and low-gain pursuit. These patients had melanin in the posterior pole and better visual acuities than the others (P = 0.002). Most patients with HPS have CN, and many have periodic alternating nystagmus. Some have subtle eye movement abnormalities without clinically evident nystagmus, which can obscure the diagnosis, especially if hypopigmentation is mild. Absence of clinical nystagmus in a child with HPS suggests good vision. Patients with albinism, especially before surgery, should be evaluated for HPS to prevent life-threatening complications.

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

2018-01-01

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists

PubMed Central

van Rein, Nienke; Lijfering, Willem M.; Bos, Mettine H. A.; Herruer, Martien H.; Vermaas, Helga W.; van der Meer, Felix J. M.; Reitsma, Pieter H.

2016-01-01

Background Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. Objectives To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. Methods A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. Results Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66–2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. Conclusion BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment. PMID:27935941

Incidence and correlates of major bleeding after percutaneous coronary intervention across different clinical presentations.

PubMed

Loh, Joshua P; Pendyala, Lakshmana K; Torguson, Rebecca; Chen, Fang; Satler, Lowell F; Pichard, Augusto A; Waksman, Ron

2014-09-01

Bleeding after percutaneous coronary intervention (PCI) is identified as a strong predictor for adverse events, including mortality. This study aims to compare the incidence and correlates of post-PCI bleeding across different clinical presentations. The study included 23,943 consecutive PCI patients categorized according to their clinical presentation: stable angina pectoris (n = 6,741), unstable angina pectoris (UAP) (n = 5,215), non-ST-segment elevation myocardial infarction (NSTEMI) (n = 8,418), ST-segment elevation myocardial infarction (STEMI) (n = 2,721), and cardiogenic shock (CGS) (n = 848). Severity of clinical presentation was associated with a greater use of preprocedural anticoagulation, glycoprotein IIb/IIIa inhibitors, and intraaortic balloon pump (IABP). TIMI-defined major bleeding increased with increasing severity of clinical presentation: stable angina pectoris, 0.7%; UAP, 1.0%; NSTEMI, 1.6%; STEMI, 4.6%; and CGS, 13.5% (P < .001). On multivariable analysis, CGS (odds ratio [OR], 4.67; 95% CI [2.62-8.34]), STEMI (OR, 3.39; 95% CI [2.07-5.55]), and NSTEMI (OR, 2.00; 95% CI [1.29-3.10]) remained correlated with major bleeding even after adjusting for baseline and procedural differences, whereas UAP did not. The multivariable model also identified the use of IABP, female gender, congestive heart failure, no prior PCI, increased baseline hematocrit, and increased procedure time as correlates for major bleeding. In patients undergoing PCI, the worsening severity of clinical presentation corresponds to an increase in incidence of post-PCI major bleeding. The increased risk with CGS, STEMI, and NSTEMI persisted despite adjusting for more aggressive pharmacotherapy and use of IABP. Careful attention to antithrombotic pharmacotherapy is warranted in this high-risk population. Copyright © 2014 Mosby, Inc. All rights reserved.

Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol 20 mcg based on 2 years of clinical trial data in Canada.

PubMed

Reid, Robert L; Fortier, Michel P; Smith, Lynne; Mirkin, Sebastian; Grubb, Gary S; Constantine, Ginger D

2010-12-01

The study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg. Healthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events. Seventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively. Continuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting. Copyright © 2010 Elsevier Inc. All rights reserved.

Predictors of in-hospital mortality in a cohort of elderly Egyptian patients with acute upper gastrointestinal bleeding.

PubMed

Elsebaey, Mohamed A; Elashry, Heba; Elbedewy, Tamer A; Elhadidy, Ahmed A; Esheba, Noha E; Ezat, Sherif; Negm, Manal Saad; Abo-Amer, Yousry Esam-Eldin; Abgeegy, Mohamed El; Elsergany, Heba Fadl; Mansour, Loai; Abd-Elsalam, Sherief

2018-04-01

Acute upper gastrointestinal bleeding (UGIB) affects large number of elderly with high rates of morbidity and mortality. Early identification and management of the factors predicting in-hospital mortality might decrease mortality. This study was conducted to identify the causes of acute UGIB and the predictors of in-hospital mortality in elderly Egyptian patients.286 elderly patients with acute UGIB were divided into: bleeding variceal group (161 patients) and bleeding nonvariceal group (125 patients). Patients' monitoring was done during hospitalization to identify the risk factors that might predict in-hospital mortality in elderly.Variceal bleeding was the most common cause of acute UGIB in elderly Egyptian patients. In-hospital mortality rate was 8.74%. Increasing age, hemodynamic instability at presentation, co-morbidities (especially liver cirrhosis associated with other co-morbidity) and failure to control bleeding were the predictors of in-hospital mortality.Increasing age, hemodynamic instability at presentation, co-morbidities (especially liver cirrhosis associated with other co-morbidity) and failure to control bleeding should be considered when triaging those patients for immediate resuscitation, close observation, and early treatment.

Acoustic testing of a 1.5 pressure ratio low tip speed fan with casing tip bleed (QEP Fan B scale model)

NASA Technical Reports Server (NTRS)

Kazin, S. B.; Minzner, W. R.; Paas, J. E.

1971-01-01

A scale model of the bypass flow region of a 1.5 pressure ratio, single stage, low tip speed fan was tested with a rotor tip casing bleed slot to determine its effects on noise generation. The bleed slot was located 1/2 inch (1.3 cm) upstream of the rotor leading edge and was configured to be a continuous opening around the circumference. The bleed manifold system was operated over a range of bleed rates corresponding to as much as 6% of the fan flow at approach thrust and 4.25% of the fan flow at takeoff thrust. Acoustic results indicate that a bleed rate of 4% of the fan flow reduces the fan maximum approach 200 foot (61.0 m) sideline PNL 0.5 PNdB and the corresponding takeoff thrust noise 1.1 PNdB below the level with zero bleed. However, comparison of the standard casing (no bleed slot) and the slotted bleed casing with zero bleed shows that the bleed slot itself caused a noise increase.

Risk Factors for Vascular Occlusive Events and Death Due to Bleeding in Trauma Patients; an Analysis of the CRASH-2 Cohort

PubMed Central

Pealing, Louise; Perel, Pablo; Prieto-Merino, David; Roberts, Ian

2012-01-01

Background Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding. Methods and Findings We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001). Conclusions Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients. PMID:23251374

Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults

PubMed Central

Baillargeon, Jacques; Holmes, Holly M.; Lin, Yu-li; Raji, Mukaila A.; Sharma, Gulshan; Kuo, Yong-Fang

2011-01-01

Background Antibiotic medications are associated with an increased risk of bleeding among patients receiving warfarin. The recent availability of data from the Medicare Part D prescription drug program provides an opportunity to assess the association of antibiotic medications and the risk of bleeding in a national population of older adults receiving warfarin. Methods We conducted a case-control study nested within a cohort of 38,762 patients aged 65 years and older who were continuous warfarin users, using enrollment and claims data for a 5% national sample of Medicare beneficiaries with Part D benefits. Cases were defined as persons hospitalized for a primary diagnosis of bleeding and were matched with three control subjects on age, race, gender, and indication for warfarin. Logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk of bleeding associated with prior exposure to antibiotic medications. Results Exposure to any antibiotic agent within the 15 days of the event/index date was associated with an increased risk of bleeding (aOR 2.01; 95% CI, 1.62-2.50). All six specific antibiotic drug classes examined [azole antifungals (aOR, 4.57; 95% CI, 1.90-11.03), macrolides (aOR, 1.86; 95% CI, 1.08-3.21), quinolones (aOR, 1.69; 95% CI, 1.09-2.62), cotrimoxazole (aOR, 2.70; 95% CI, 1.46-5.05), penicillins (aOR, 1.92; 95% CI, 1.21-2.07) and cephalosporins (aOR, 2.45; 95% CI, 1.52-3.95) were associated with an increased risk of bleeding. Conclusion Among older continuous warfarin users, exposure to antibiotic agents—particularly azole antifungals—was associated with an increased risk of bleeding. PMID:22269622

Thromboelastographic tracings in retired racing greyhounds and in non-greyhound dogs.

PubMed

Vilar, P; Couto, C G; Westendorf, N; Iazbik, C; Charske, J; Marín, L

2008-01-01

Bleeding disorders in patients with normal coagulation test results are frequently reported in Greyhounds. The purpose of this study was to compare Greyhounds to non-Greyhounds by thromboelastography (TEG). TEG parameters in Greyhounds are different from those in non-Greyhounds. Forty-three healthy dogs (28 Greyhounds and 15 non-Greyhounds) based on the results of physical examination, CBC, activated partial thromboplastin time, prothrombin time, fibrinogen, and platelet count. Recalcified citrated native TEGs were performed in both groups; data were compared using Student's, Mann-Whitney, and Pearson's statistical tests. In Greyhounds, mean +/- SD were as follows: R-time 4.3 +/- 1.7 minutes, K-time 3.8 +/- 1.4 minutes, angle (alpha) 50.0 +/- 8.0 degrees , maximum amplitude (MA) 47.6 +/- 5.6 mm, clot strength (G) 4,647 +/- 1,097 dyn/cm2, and percent lysis at 60 minutes (LY60) 2.8 +/- 5.0%. In the non-Greyhounds they were R-time 3.7 +/- 1.6 minutes, K-time 2.5 +/- 0.9 minutes, angle 59.8 +/- 7.0 degrees , MA 53.1 +/- 5.6 mm, G 5,811 +/- 1,256 dyn/cm2, and LY60 3.1 +/- 2.5%. All parameters were significantly different between the groups, except for R-time and LY60. In Greyhounds, clotting kinetics are slower and clot strength are weaker than in non-Greyhounds, supporting the increased tendency to bleed observed after minor trauma or surgical procedures in the breed. The findings may also be attributed to blood viscosity or to the concentration of citrate in the sample (ie, Greyhounds have higher hematocrit and less plasma per unit volume).

The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis.

PubMed

Chai-Adisaksopha, Chatree; Crowther, Mark; Isayama, Tetsuya; Lim, Wendy

2014-10-09

Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed and found to be at least noninferior to VKAs with regard to efficacy, but the risk of bleeding with TSOACs remains controversial. We performed a systematic review and meta-analysis of phase-3 randomized controlled trials (RCTs) to assess the bleeding side effects of TSOACs compared with VKAs in patients with venous thromboembolism or atrial fibrillation. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials; conference abstracts; and www.clinicaltrials.gov with no language restriction. Two reviewers independently performed study selection, data extraction, and study quality assessment. Twelve RCTs involving 102 607 patients were retrieved. TSOACs significantly reduced the risk of overall major bleeding (relative risk [RR] 0.72, P < .01), fatal bleeding (RR 0.53, P < .01), intracranial bleeding (RR 0.43, P < .01), clinically relevant nonmajor bleeding (RR 0.78, P < .01), and total bleeding (RR 0.76, P < .01). There was no significant difference in major gastrointestinal bleeding between TSOACs and VKAs (RR 0.94, P = .62). When compared with VKAs, TSOACs are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant nonmajor bleeding, and total bleeding. Additionally, TSOACs do not increase the risk of gastrointestinal bleeding. © 2014 by The American Society of Hematology.

Side Effects: Bleeding and Bruising

Cancer.gov

Cancer treatments, such as chemotherapy and targeted therapy, can increase patients’ risk of bleeding and bruising, also called thrombocytopenia. Learn about steps to take if you are at increased risk of a low platelet count.

Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.

PubMed

Laporte, Silvy; Chapelle, Céline; Caillet, Pascal; Beyens, Marie-Noëlle; Bellet, Florelle; Delavenne, Xavier; Mismetti, Patrick; Bertoletti, Laurent

2017-04-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association between emergency admission for peptic ulcer bleeding and air pollution: a case-crossover analysis in Hong Kong's elderly population.

PubMed

Tian, Linwei; Qiu, Hong; Sun, Shengzhi; Tsang, Hilda; Chan, King-Pan; Leung, Wai K

2017-05-01

Air pollution increases intestinal permeability, alters the gut microbiome, and promotes inflammation, which might contribute towards gastrointestinal bleeding. In the present study, we aim to examine whether short-term elevations in air pollution are associated with increased numbers of emergency hospital admissions for peptic ulcer bleeding in Hong Kong. Daily air pollution (particulate matter with aerodynamic diameter less than 2·5 μm [PM 2·5 ], nitric oxide [NO 2 ], sulpher dioxide [SO 2 ], and ozone [O 3 ]) data during 2005-10 were collected from the Environmental Protection Department and emergency admission data for peptic ulcer bleeding in elderly people (aged 65 years or older) from the Hospital Authority of Hong Kong. A time stratified case-crossover analysis with conditional logistic regression was used to estimate the excess risk of peptic ulcer bleeding associated with each air pollutant, in single-pollutant and multi-pollutant models. Cardiorespiratory diseases were used as positive controls. 8566 emergency admissions for peptic ulcer bleeding were recorded among Hong Kong's elderly population during 2005-10; the daily number of admissions ranged from 0 to 13. An IQR increment of 5-day moving average (lag 04 ) of NO 2 concentration (25·8 μg/m 3 ) was associated with a 7·6% (95% CI 2·2-13·2) increase in emergency admissions for peptic ulcer bleeding. Multi-pollutant models confirmed the robustness of the risk estimates for NO 2 . Other pollutants (PM 2·5 , SO 2 , and O 3 ) were not associated with peptic ulcer bleeding admissions. Short-term elevation in ambient NO 2 might trigger peptic ulcer bleeding events and increase the risk of emergency admissions for peptic ulcer bleeding in Hong Kong's elderly population. These findings strengthen the hypothesis that air pollution affects not just cardiopulmonary diseases, but also certain diseases of the digestive system. None. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation.

PubMed

Hilkens, Nina A; Algra, Ale; Greving, Jacoba P

2017-11-01

Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR 2 HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin. During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category. Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance. © 2017 American Heart Association, Inc.

Predictors of perioperative major bleeding in patients who interrupt warfarin for an elective surgery or procedure: Analysis of the BRIDGE trial.

PubMed

Clark, Nathan P; Douketis, James D; Hasselblad, Vic; Schulman, Sam; Kindzelski, Andrei L; Ortel, Thomas L

2018-01-01

The use of low-molecular weight heparin bridge therapy during warfarin interruption for elective surgery/procedures increases bleeding. Other predictors of bleeding in this setting are not well described. BRIDGE was a randomized, double-blind, placebo-controlled trial of bridge therapy with dalteparin 100 IU/kg twice daily in patients with atrial fibrillation requiring warfarin interruption. Bleeding outcomes were documented from the time of warfarin interruption until up to 37 days postprocedure. Multiple logistic regression and time-dependent hazard models were used to identify major bleeding predictors. We analyzed 1,813 patients of whom 895 received bridging and 918 received placebo. Median patient age was 72.6 years, and 73.3% were male. Forty-one major bleeding events occurred at a median time of 7.0 days (interquartile range, 4.0-18.0 days) postprocedure. Bridge therapy was a baseline predictor of major bleeding (odds ratio [OR]=2.4, 95% CI: 1.2-4.8), as were a history of renal disease (OR=2.9, 95% CI: 1.4-6.0), and high-bleeding risk procedures (vs low-bleeding risk procedures) (OR=2.9, 95% CI: 1.4-5.9). Perioperative aspirin use (OR=3.6, 95% CI: 1.1-11.9) and postprocedure international normalized ratio >3.0 (OR=2.1, 95% CI: 1.5-3.1) were time-dependent predictors of major bleeding. Major bleeding was most common in the first 10 days compared with 11-37 days postprocedure (OR=3.5, 95% CI: 1.8-6.9). In addition to bridge therapy, perioperative aspirin use, postprocedure international normalized ratio >3.0, a history of renal failure, and having a high-bleeding risk procedure increase the risk of major bleeding around the time of an elective surgery/procedure requiring warfarin interruption. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Dietary Supplements in Postsurgical Bleeding: An Update for the Practitioner.

PubMed

Grisa, Alessandro; Florio, Salvatore; Bellia, Elisabetta; Cho, Sang-Choon; Froum, Stuart J

In the United States, dietary supplement use in adults aged 20 and older has increased significantly in the last 2 decades. Intraoperative and postoperative bleeding has been among the complications linked with usage, which is particularly problematic if patients do not disclose use to the dental practitioner. The aim of this article is to present a case report of a patient who had been taking dietary supplements for only 1 month and developed severe bleeding after receiving second-stage implant abutment insertion surgery. The article also presents a review of several supplements that can increase the risk for bleeding complications.

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force.

PubMed

Whitlock, Evelyn P; Burda, Brittany U; Williams, Selvi B; Guirguis-Blake, Janelle M; Evans, Corinne V

2016-06-21

The balance between potential aspirin-related risks and benefits is critical in primary prevention. To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) primary prevention. PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews. Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults. One investigator abstracted data, another checked for accuracy, and 2 assessed study quality. In CVD primary prevention studies, very-low-dose aspirin use (≤100 mg daily or every other day) increased major gastrointestinal (GI) bleeding risk by 58% (odds ratio [OR], 1.58 [95% CI, 1.29 to 1.95]) and hemorrhagic stroke risk by 27% (OR, 1.27 [CI, 0.96 to 1.68]). Projected excess bleeding events with aspirin depend on baseline assumptions. Estimated excess major bleeding events were 1.39 (CI, 0.70 to 2.28) for GI bleeding and 0.32 (CI, -0.05 to 0.82) for hemorrhagic stroke per 1000 person-years of aspirin exposure using baseline bleeding rates from a community-based observational sample. Such events could be greater among older persons, men, and those with CVD risk factors that also increase bleeding risk. Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined. Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient. Agency for Healthcare Research and Quality.

Estimating unknown parameters in haemophilia using expert judgement elicitation.

PubMed

Fischer, K; Lewandowski, D; Janssen, M P

2013-09-01

The increasing attention to healthcare costs and treatment efficiency has led to an increasing demand for quantitative data concerning patient and treatment characteristics in haemophilia. However, most of these data are difficult to obtain. The aim of this study was to use expert judgement elicitation (EJE) to estimate currently unavailable key parameters for treatment models in severe haemophilia A. Using a formal expert elicitation procedure, 19 international experts provided information on (i) natural bleeding frequency according to age and onset of bleeding, (ii) treatment of bleeds, (iii) time needed to control bleeding after starting secondary prophylaxis, (iv) dose requirements for secondary prophylaxis according to onset of bleeding, and (v) life-expectancy. For each parameter experts provided their quantitative estimates (median, P10, P90), which were combined using a graphical method. In addition, information was obtained concerning key decision parameters of haemophilia treatment. There was most agreement between experts regarding bleeding frequencies for patients treated on demand with an average onset of joint bleeding (1.7 years): median 12 joint bleeds per year (95% confidence interval 0.9-36) for patients ≤ 18, and 11 (0.8-61) for adult patients. Less agreement was observed concerning estimated effective dose for secondary prophylaxis in adults: median 2000 IU every other day The majority (63%) of experts expected that a single minor joint bleed could cause irreversible damage, and would accept up to three minor joint bleeds or one trauma related joint bleed annually on prophylaxis. Expert judgement elicitation allowed structured capturing of quantitative expert estimates. It generated novel data to be used in computer modelling, clinical care, and trial design. © 2013 John Wiley & Sons Ltd.

Standardizing a simpler, more sensitive and accurate tail bleeding assay in mice

PubMed Central

Liu, Yang; Jennings, Nicole L; Dart, Anthony M; Du, Xiao-Jun

2012-01-01

AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay. METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 °C, continuously monitoring bleeding patterns and measuring bleeding volume from changes in the body weight. Sensitivity and extent of variation of bleeding time and bleeding volume were compared in mice treated with the P2Y receptor inhibitor prasugrel at various doses or in mice deficient of FcRγ, a signaling protein of the glycoprotein VI receptor. RESULTS: We described details of the bleeding assay with the aim of standardizing this commonly used assay. The bleeding assay detailed here was simple to operate and permitted continuous monitoring of bleeding pattern and detection of re-bleeding. We also reported a simple and accurate way of quantifying bleeding volume from changes in the body weight, which correlated well with chemical assay of hemoglobin levels (r2 = 0.990, P < 0.0001). We determined by tail bleeding assay the dose-effect relation of the anti-platelet drug prasugrel from 0.015 to 5 mg/kg. Our results showed that the correlation of bleeding time and volume was unsatisfactory and that compared with the bleeding time, bleeding volume was more sensitive in detecting a partial inhibition of platelet’s haemostatic activity (P < 0.01). Similarly, in mice with genetic disruption of FcRγ as a signaling molecule of P-selectin glycoprotein ligand-1 leading to platelet dysfunction, both increased bleeding volume and repeated bleeding pattern defined the phenotype of the knockout mice better than that of a prolonged bleeding time. CONCLUSION: Determination of bleeding pattern and bleeding volume, in addition to bleeding time, improved the sensitivity and accuracy of this assay, particularly when platelet function is partially inhibited. PMID:24520531

Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants.

PubMed

Weitz, Jeffrey I; Pollack, Charles V

2015-11-25

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

[Severe lower gastrointestinal bleeding due to GIST tumor. Radiological embolization and surgery].

PubMed

Navas, Diana; Ríos, Antonio; Febrero, Beatriz; Rodríguez, José Manuel; Lloret, Francisco; Parrilla, Pascual

2014-01-01

Gastrointestinal stromal tumors (GIST) were identified only recently. These tumors usually have no symptoms, although they are localized, operable and curable. Although rare, if they are not diagnosed and treated early, they become very aggressive. The most common manifestation is gastrointestinal bleeding from mucosal erosion. Their presentation as severe lower gastrointestinal bleeding is exceptional. We report a patient with severe lower gastrointestinal bleeding stabilized by interventional radiology that subsequently required surgery for definitive care. Therapeutic use of radiological embolization is increasingly widespread in bleeding at various levels, achieving hemodynamic stabilization of patients. However, it must be kept in mind that, in cases of unknown etiology of lower gastrointestinal bleeding, possible causes must be investigated.

Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding.

PubMed

Douketis, James D; Arneklev, Karin; Goldhaber, Samuel Z; Spandorfer, John; Halperin, Frank; Horrow, Jay

2006-04-24

Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring. We undertook a pooled analysis of 7329 patients with nonvalvular atrial fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target international normalized ratio, 2.0-3.0). We determined annual risk of bleeding (any, major), case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment. Annual incidence of any bleeding was 31.75% with ximelagatran and 38.82% with warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0-23.1; P<.001). Annual incidence of major bleeding was 2.01% with ximelagatran and 2.68% with warfarin (relative risk reduction, 25.1%; 95% CI, 3.2-42.1; P = .03). Case-fatality rate of bleeding was comparable in ximelagatran- and warfarin-treated patients (8.16% vs 8.09%; P = .98). Cumulative incidence of major bleeding was higher with warfarin than ximelagatran after 24 months of treatment (4.7% vs 3.7%; P = .04). Anatomic sites of bleeding were comparable with both treatments. Risk factors for bleeding with ximelagatran were as follows (hazard ratios and 95% CIs in parentheses): diabetes mellitus (1.81; 1.19-2.77; P = .006), previous stroke or transient ischemic attack (1.78; 1.16-2.73; P = .008), age 75 years or greater (1.70; 1.33-2.18; P<.001), and aspirin use (1.68; 1.08-2.59; P = .02). Risk factors for bleeding in warfarin-treated patients were previous liver disease (4.88; 1.55-15.39; P = .007); aspirin use (2.41; 1.69-3.43; P<.001); and age 75 years or greater (1.26; 1.03-1.52; P = .02). Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation. Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.

Proton pump inhibitors are associated with lower gastrointestinal tract bleeding in low-dose aspirin users with ischaemic heart disease.

PubMed

Miyake, Kazumasa; Akimoto, Teppei; Hanada, Yuriko; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Ueki, Nobue; Kusunoki, Masafumi; Kawagoe, Tetsuro; Futagami, Seiji; Takahashi, Yasuhiro; Takano, Hitoshi; Sakamoto, Choitsu

2015-09-01

Impact of acid suppressants on lower gastrointestinal bleeding remains unclear in low-dose aspirin users; we aimed to investigate this relationship. Retrospective cohort study of low-dose aspirin users who underwent coronary angiography for ischaemic heart disease in our institution between October 2005 and December 2006; patients were evaluated for upper or lower gastrointestinal bleedings within 3 years post-angiography. 538 patients were enrolled (males, 74.4%; mean age 67.4±10.6 years). Risk for upper gastrointestinal bleeding decreased with concomitant use of statins (HR, 0.37; 95% CI, 0.15-0.89), calcium channel blockers (HR, 0.29; 95% CI, 0.10-0.85), and histamine-2 receptor antagonists (HR, 0.26; 95% CI, 0.08-0.89). Concomitant use of proton pump inhibitors tended to decrease risk of upper gastrointestinal bleeding (HR, 0.27; 95% CI, 0.06-1.18). Risk for lower gastrointestinal bleeding increased with both concomitant use of warfarin (HR, 15.68; 95% CI, 4.43-55.53) and proton pump inhibitors (HR, 6.55; 95% CI, 2.01-21.32), but not with histamine-2 receptor antagonists. Hyperuricemia lowered risk for lower gastrointestinal bleeding (HR, 0.12; 95% CI, 0.02-0.88). In low-dose aspirin users, concomitant use of proton pump inhibitors increased lower gastrointestinal bleeding risk, independent from effects on upper gastrointestinal bleeding. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

[TREATMENT DILEMMAS IN BEHÇET'S SYNDROME].

PubMed

Zeller, Lior; Ling, Edoard; Abu-Shakra, Mahmoud

2016-02-01

Behçet's disease is an inflammatory systemic disorder, characterized by a relapsing and remitting course, it manifests with oral and genital ulcerations, skin lesions, uveitis, vasculitis, central nervous system and gastrointestinal involvement. The main histopathological finding is widespread vasculitis of the arteries and veins. Therapy is variable and depends largely on the severity of the disease and organ involvement. There is common practice to treat with anticoagulation in patients suffering from vessel thrombosis, but there are no control trials to support this tendency. Anticoagulation treatment can cause major bleeding events in patients suffering from aneurysms. In this case report we describe a treatment dilemma in a patient suffering from deep vein thrombosis and pulmonary aneurysms.

Cosmic rays as a novel hypothetic explanation for the ancient mentioned effects of sleeping under the night sky

PubMed Central

Amini-Behbahani, Farshad

2018-01-01

Traditional medicine scientists believed that sleeping under the stars and moonlight is not healthy because it brings about nose bleeds and respiratory problems. In Avicenna’s view, the spirit and its tendency to the light are introduced as main etiology, which cannot explain star light as a proper etiology. In modern knowledge, it seems cosmic rays that reach our planet’s atmosphere by electron cascade, play a key role. Internal organs’ electrical charge distribution disturbance caused by these electrons can lead to irregular spasms in the muscular walls of arteries and other organs. These interactions may finally lead to circulation (epistaxis and hypertension) and respiratory (catarrh) problems. PMID:29629052

The effect of desmopressin on platelet aggregation defect in systemic amyloidosis: a preliminary report.

PubMed

Demiroğlu, H; Barişta, I; Gürsoy, M; Oymak, O; Dündar, S

1996-05-01

Systemic amyloidosis may often be complicated with haemorrhagic tendency. The causes of this manifestation are factor deficiencies, hyperfibrinolysis and vasculopathy. In order to investigate the role of platelets, if any, we performed platelet aggregation tests with different aggregants in 10 patients with systemic amyloidosis due to familial Mediterranean fever and 10 healthy controls. Platelet aggregation was defective with different aggregants (ADP, epinephrine, collagen) in patients compared with controls. Platelet aggregation tests repeated after desmopressin (DDAVP) administration were normalized. These findings may suggest a role of a platelet aggregation defect in haemorrhagic diathesis complicating systemic amyloidosis. DDAVP may benefit patients with this disease in case of bleeding and before surgical interventions.

Cosmic rays as a novel hypothetic explanation for the ancient mentioned effects of sleeping under the night sky.

PubMed

Amini-Behbahani, Farshad; Ghafarzadeh, Jafar

2018-02-01

Traditional medicine scientists believed that sleeping under the stars and moonlight is not healthy because it brings about nose bleeds and respiratory problems. In Avicenna's view, the spirit and its tendency to the light are introduced as main etiology, which cannot explain star light as a proper etiology. In modern knowledge, it seems cosmic rays that reach our planet's atmosphere by electron cascade, play a key role. Internal organs' electrical charge distribution disturbance caused by these electrons can lead to irregular spasms in the muscular walls of arteries and other organs. These interactions may finally lead to circulation (epistaxis and hypertension) and respiratory (catarrh) problems.

Prevalence of Drug Combinations Increasing Bleeding Risk Among Warfarin Users With and Without Alzheimer's Disease.

PubMed

Taipale, Heidi; Vuorikari, Hanna; Tanskanen, Antti; Koponen, Marjaana; Tiihonen, Jari; Kettunen, Raimo; Hartikainen, Sirpa

2015-11-01

The aim of this study was to analyse the prevalence and predictors of drug combinations increasing bleeding risk among warfarin users with and without Alzheimer's disease (AD). This retrospective observational study utilised data from the Finnish MEDALZ-2005 cohort. The MEDALZ-2005 study included all community-dwelling persons with a clinically verified diagnosis of AD at the end of 2005, and one comparison person without AD for each case. Data on drug use was collected from the Prescription Register. We included persons who were warfarin users during the study period 2006-2009. Drug combinations increasing bleeding risk with warfarin included selective serotonin reuptake inhibitors (SSRIs), non-steroidal anti-inflammatory agents (NSAIDs), other antithrombotic drugs and tramadol. Factors associated with combination use were investigated with logistic regression. During the follow-up, 3385 persons with AD and 4830 persons without AD used warfarin. Drug combinations increasing bleeding risk were more common in warfarin users with AD than without AD [35.9 and 30.5%, respectively (p < 0.0001)]. The most common combination was SSRIs and warfarin, which was more common among persons with AD (23.8%) than among persons without AD (10.9%). NSAIDs and warfarin combination was more common among persons without AD. Combination use was associated with AD, female gender, younger age, diabetes mellitus, rheumatoid arthritis and asthma/chronic obstructive pulmonary disease (COPD). Use of drug combinations increasing bleeding risk was more common among warfarin users with AD. Special attention should be paid to minimise the duration of concomitant use and to find safer alternatives without increased bleeding risk.

Bleeding outcome during a dengue outbreak in 2005 in the East-coast region of Peninsular Malaysia: a prospective study.

PubMed

Fariz-Safhan, M N; Tee, H P; Abu Dzarr, G A; Sapari, S; Lee, Y Y

2014-06-01

During a dengue outbreak in 2005 in the East-coast region of Peninsular Malaysia, one of the worst hit areas in the country at that time, we undertook a prospective study. We aimed to describe the bleeding outcome and changes in the liver and hematologic profiles that were associated with major bleeding outcome during the outbreak. All suspected cases of dengue admitted into the only referral hospital in the region during the outbreak were screened for WHO 2002 criteria and serology. Liver function, hematologic profile and severity of bleeding outcome were carefully documented. The association between symptoms, liver and hematologic impairments with the type of dengue infection (classical vs. hemorrhagic) and bleeding outcome (major vs. non-major) was tested. Dengue fever was confirmed in 183 cases (12.5/100,000 population) and 144 cases were analysed. 59.7% were dengue hemorrhagic fever, 3.5% were dengue shock syndrome and there were 3 in-hospital deaths. Major bleeding outcome (gastrointestinal bleeding, intracranial bleeding or haemoptysis) was present in 14.6%. Elevated AST, ALT and bilirubin were associated with increasing severity of bleeding outcome (all P < 0.05). Platelet count and albumin level were inversely associated with increasing severity of bleeding outcome (both P < 0.001). With multivariable analysis, dengue hemorrhagic fever was more likely in the presence of abdominal pain (OR 1.1, 95% CI 0.02- 1.6) and elevated AST (OR 1.0, 95% CI 1.0-1.1) but the presence of pleural effusion (OR 5.8, 95% CI: 1.1-29.9) and elevated AST (OR 1.008, 95% CI: 1.005-1.01) predicted a severe bleeding outcome. As a conclusion, the common presence of a severe hemorrhagic form of dengue fever may explain the rising death toll in recent outbreaks and the worst impairment in liver and hematologic profiles was seen in major bleeding outcome.

Mortality caused by intracranial bleeding in non-severe hemophilia A patients.

PubMed

Loomans, J I; Eckhardt, C L; Reitter-Pfoertner, S E; Holmström, M; van Gorkom, B Laros; Leebeek, F W G; Santoro, C; Haya, S; Meijer, K; Nijziel, M R; van der Bom, J G; Fijnvandraat, K

2017-06-01

Essentials Data on bleeding-related causes of death in non-severe hemophilia A (HA) patients are scarce. Such data may provide new insights into areas of care that can be improved. Non-severe HA patients have an increased risk of dying from intracranial bleeding. This demonstrates the need for specialized care for non-severe HA patients. Background Non-severe hemophilia (factor VIII concentration [FVIII:C] of 2-40 IU dL -1 ) is characterized by a milder bleeding phenotype than severe hemophilia A. However, some patients with non-severe hemophilia A suffer from severe bleeding complications that may result in death. Data on bleeding-related causes of death, such as fatal intracranial bleeding, in non-severe patients are scarce. Such data may provide new insights into areas of care that can be improved. Aims To describe mortality rates, risk factors and comorbidities associated with fatal intracranial bleeding in non-severe hemophilia A patients. Methods We analyzed data from the INSIGHT study, an international cohort study of all non-severe hemophilia A patients treated with FVIII concentrates during the observation period between 1980 and 2010 in 34 participating centers across Europe and Australia. Clinical data and vital status were collected from 2709 patients. We report the standardized mortality rate for patients who suffered from fatal intracranial bleeding, using a general European male population as a control population. Results Twelve per cent of the 148 deceased patients in our cohort of 2709 patients died from intracranial bleeding. The mortality rate between 1996 and 2010 for all ages was 3.5-fold higher than that in the general population (95% confidence interval [CI] 2.0-5.8). Patients who died from intracranial bleeding mostly presented with mild hemophilia without clear comorbidities. Conclusion Non-severe hemophilia A patients have an increased risk of dying from intracranial bleeding in comparison with the general population. This demonstrates the need for specialized care for non-severe hemophilia A patients. © 2017 International Society on Thrombosis and Haemostasis.

Clopidogrel bisulfate (Plavix) does not increase bleeding complications in patients undergoing rubber band ligation for symptomatic hemorrhoids.

PubMed

Hite, Nathan; Klinger, Aaron L; Miller, Peter; Beck, David E; Whitlow, Charles B; Hicks, Terry C; Green, Heather M; Margolin, David A

2018-09-01

The incidence of postprocedural bleeding in patients undergoing rubber band ligation (RBL) for symptomatic internal hemorrhoids while taking clopidogrel bisulfate is unknown. To determine the postprocedural bleeding risk of RBL for patients taking clopidogrel compared with age- and sex-matched controls. This is a retrospective case-controlled cohort study analyzing data from 2005 to 2013 conducted at a single tertiary care academic center. The study included a total of 80 rubber bands placed on 41 patients taking clopidogrel bisulfate and 72 bands placed on 41 control patients not taking clopidogrel matched for age and sex. The 30-d rates of significant and insignificant bleeding events after RBL were recorded. A bleeding event was considered significant if the patient required admission to the hospital, transfusion of blood products, or additional procedures to stop the bleeding. Insignificant bleeding was defined as passage of blood or clots per rectum with spontaneous cessation and no need for additional intervention. There was no significant difference in the number of bleeding events per band placed in the clopidogrel group when compared with the control group (3.75% versus 2.78%, P = 0.7387). The rate of significant (2.5% versus 1.39%, P = 0.6244) and insignificant bleeding events (1.25% versus 1.39%, P = 0.9399) was also similar between the two groups. Two significant bleeding events occurred in the clopidogrel group requiring intervention: cauterization in one patient and colonoscopy and transfusion in the other. The risk of a bleeding complication after RBL for hemorrhoids does not appear to be increased in patients taking clopidogrel. Our results support the practice of continuing clopidogrel bisulfate in the periprocedural period as the associated risk of thrombosis is greater than the risk of bleeding. Copyright © 2018 Elsevier Inc. All rights reserved.

Factors Associated With Major Bleeding Events

PubMed Central

Goodman, Shaun G.; Wojdyla, Daniel M.; Piccini, Jonathan P.; White, Harvey D.; Paolini, John F.; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Patel, Manesh R.; Sherwood, Matthew W.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Breithardt, Gunter; Fox, Keith A. A.; Califf, Robert M.

2014-01-01

Objectives This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). Background The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. Methods The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. Results The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Conclusions Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767) PMID:24315894

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk

PubMed Central

Dolwani, Sunil; Graziano, J. Michael; Lanas, Angel; Longley, Marcus; Phillips, Ceri J.; Roberts, Stephen E.; Soon, Swee S.; Steward, Will

2016-01-01

Background Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. Methods In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. Results Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of ‘major’ incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). Conclusions The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer. PMID:27846246

The use of recombinant factor VIIa in a patient with Noonan syndrome and life-threatening bleeding.

PubMed

Tofil, Nancy M; Winkler, Margaret K; Watts, Raymond G; Noonan, Jacqueline

2005-05-01

To present a case report of a patient with Noonan syndrome who developed life-threatening gastrointestinal bleeding shortly after cardiac surgery that was successfully treated with recombinant factor VIIa. Case report. Pediatric intensive care unit of a children's hospital. Ten-month-old with Noonan syndrome and massive gastrointestinal bleeding resulting in severe hypovolemic shock. Recombinant factor VIIa was used in this patient's severe bleeding associated with Noonan syndrome after no other supportive measures were successful. Recombinant Factor VIIa significantly decreased the patient's bleeding and allowed his hypovolemic shock to improve. Ultimately, the patient made a complete recovery. Noonan syndrome has a constellation of both cardiac and noncardiac malformations including an increased risk of bleeding, and recombinant factor VIIa is an important agent in the treatment of significant bleeding.

Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.

PubMed

Kander, Elizabeth M; Raza, Sania; Zhou, Zheng; Gao, Juehua; Zakarija, Anaadriana; McMahon, Brandon J; Stein, Brady L

2015-11-01

The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.

Risk Factors Associated with Mortality and Increased Drug Costs in Nonvariceal Upper Gastrointestinal Bleeding.

PubMed

Lu, Mingliang; Sun, Gang; Zhang, Xiu-li; Zhang, Xiao-mei; Liu, Qing-sen; Huang, Qi-yang; Lau, James W Y; Yang, Yun-sheng

2015-06-01

To determine risk factors associated with mortality and increased drug costs in patients with nonvariceal upper gastrointestinal bleeding. We retrospectively analyzed data from patients hospitalized with nonvariceal upper gastrointestinal bleeding between January 2001-December 2011. Demographic and clinical characteristics and drug costs were documented. Univariate analysis determined possible risk factors for mortality. Statistically significant variables were analyzed using a logistic regression model. Multiple linear regression analyzed factors influencing drug costs. p < 0.05 was considered statistically significant. The study included data from 627 patients. Risk factors associated with increased mortality were age > 60, systolic blood pressure<100 mmHg, lack of endoscopic examination, comorbidities, blood transfusion, and rebleeding. Drug costs were higher in patients with rebleeding, blood transfusion, and prolonged hospital stay. In this patient cohort, re-bleeding rate is 11.20% and mortality is 5.74%. The mortality risk in patients with comorbidities was higher than in patients without comorbidities, and was higher in patients requiring blood transfusion than in patients not requiring transfusion. Rebleeding was associ-ated with mortality. Rebleeding, blood transfusion, and prolonged hospital stay were associated with increased drug costs, whereas bleeding from lesions in the esophagus and duodenum was associated with lower drug costs.

Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.

PubMed

van Rein, N; Biedermann, J S; van der Meer, F J M; Cannegieter, S C; Wiersma, N; Vermaas, H W; Reitsma, P H; Kruip, M J H A; Lijfering, W M

2017-07-01

Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily. Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased major bleeding risk as compared with once-daily dosing, as also suggested in a meta-analysis of controlled clinical trials. © 2017 International Society on Thrombosis and Haemostasis.

Automated registration of tail bleeding in rats.

PubMed

Johansen, Peter B; Henriksen, Lars; Andresen, Per R; Lauritzen, Brian; Jensen, Kåre L; Juhl, Trine N; Tranholm, Mikael

2008-05-01

An automated system for registration of tail bleeding in rats using a camera and a user-designed PC-based software program has been developed. The live and processed images are displayed on the screen and are exported together with a text file for later statistical processing of the data allowing calculation of e.g. number of bleeding episodes, bleeding times and bleeding areas. Proof-of-principle was achieved when the camera captured the blood stream after infusion of rat whole blood into saline. Suitability was assessed by recording of bleeding profiles in heparin-treated rats, demonstrating that the system was able to capture on/off bleedings and that the data transfer and analysis were conducted successfully. Then, bleeding profiles were visually recorded by two independent observers simultaneously with the automated recordings after tail transection in untreated rats. Linear relationships were found in the number of bleedings, demonstrating, however, a statistically significant difference in the recording of bleeding episodes between observers. Also, the bleeding time was longer for visual compared to automated recording. No correlation was found between blood loss and bleeding time in untreated rats, but in heparinized rats a correlation was suggested. Finally, the blood loss correlated with the automated recording of bleeding area. In conclusion, the automated system has proven suitable for replacing visual recordings of tail bleedings in rats. Inter-observer differences can be eliminated, monotonous repetitive work avoided, and a higher through-put of animals in less time achieved. The automated system will lead to an increased understanding of the nature of bleeding following tail transection in different rodent models.

Health-related quality of life in children with newly diagnosed immune thrombocytopenia

PubMed Central

Heitink-Pollé, Katja M.J.; Haverman, Lotte; Annink, Kim V.; Schep, Sarah J.; de Haas, Masja; Bruin, Marrie C.A.

2014-01-01

Despite its generally transient and benign course, childhood immune thrombocytopenia has a large impact on health-related quality of life. Recently published guidelines state that quality of life should be taken into account while making decisions on management in childhood immune thrombocytopenia. We, therefore, assessed health-related quality of life in children with newly diagnosed immune thrombocytopenia in a prospective multicenter study. One hundred and seven children aged 6 months-16 years (mean age 5.57 years) were included. We used Pediatric Quality of Life Inventory™ and Kids’ ITP Tools questionnaires at diagnosis and during standardized follow-up. Scores on the Pediatric Quality of Life Inventory™ Core Scales were compared with those of healthy children. Relationships between health-related quality of life scores and treatment modality, bleeding tendency and course of the disease were examined. Kids’ ITP Tools proxy reports and parent self-reports showed significant higher health-related quality of life scores in children who recovered than in children with persistent immune thrombocytopenia (at 3 months: Kids’ ITP Tools parent self-report score 80.85 for recovered patients (n=69) versus 58.98 for patients with persistent disease (n=21), P<0.001). No significant differences in health-related quality of life were found between children with mild or moderate bleeding or between children who received intravenous immunoglobulin or children who were carefully observed. In conclusion, health-related quality of life of children with newly diagnosed immune thrombocytopenia is not influenced by treatment modality or bleeding severity, but only by clinical course of the disease. (Dutch Trial Register identifier: NTR TC1563) PMID:24951468

Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors.

PubMed

Venerito, M; Schneider, C; Costanzo, R; Breja, R; Röhl, F-W; Malfertheiner, P

2018-06-01

Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non-aspirin antiplatelet agents. H. pylori-positive patients on combined antiplatelet therapy carry the highest risk for peptic ulcer bleeding. © 2018 John Wiley & Sons Ltd.

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

PubMed

Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

2016-08-01

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

A Multicenter Analysis of Factors Associated With Apixaban-Related Bleeding in Hospitalized Patients With End-Stage Renal Disease on Hemodialysis.

PubMed

Steuber, Taylor D; Shiltz, Dane L; Cairns, Alex C; Ding, Qian; Binger, Katie J; Courtney, Julia R

2017-11-01

In 2014, the United States Food and Drug Administration approved a labeling change for apixaban to include recommendations for patients with severe renal impairment and patients with end-stage renal disease (ESRD) on hemodialysis (HD), though these recommendations are largely based on pharmacokinetic and pharmacodynamic data. Identify variables associated with bleeding events in hospitalized patients with ESRD on HD receiving apixaban. This retrospective, multicenter cohort study evaluated hospitalized patients with ESRD on HD receiving apixaban from January 1, 2013, through March 31, 2016. Correlational analysis and logistic regression were completed to identify factors associated with bleeding. A total of 114 adults were included in the analysis. The median length of stay (LOS) was 6.2 (interquartile range = 3.8-11.9) days and bleeding events occurred in a total of 17 patients (15%). A weak correlation was identified for higher cumulative apixaban exposure, increased number of HD sessions while receiving apixaban, and increased hospital LOS ( P < 0.05; correlation coefficient < 0.40). When controlling for confounders, logistic regression revealed that composite bleeding events were independently increased by continuation of outpatient apixaban (odds ratio = 13.07; 95% CI = 1.54-110.54; P = 0.018), increased total daily dose of apixaban (odds ratio = 1.72; 95% CI = 1.20 to 2.48; P = 0.003), and total HD sessions while receiving apixaban (odds ratio = 2.04; 95% CI = 1.06-3.92; P = 0.033). The association between these factors and increased bleeding should prompt concern for long-term anticoagulation with apixaban in patients with ESRD receiving chronic HD.

Prevention of bleeding after islet transplantation: lessons learned from a multivariate analysis of 132 cases at a single institution.

PubMed

Villiger, P; Ryan, E A; Owen, R; O'Kelly, K; Oberholzer, J; Al Saif, F; Kin, T; Wang, H; Larsen, I; Blitz, S L; Menon, V; Senior, P; Bigam, D L; Paty, B; Kneteman, N M; Lakey, J R T; Shapiro, A M James

2005-12-01

Islet transplantation is being offered increasingly for selected patients with unstable type 1 diabetes. Percutaneous transhepatic portal access avoids a need for surgery, but is associated with potential risk of bleeding. Between 1999 and 2005, we performed 132 percutaneous transhepatic islet transplants in 67 patients. We encountered bleeding in 18/132 cases (13.6%). In univariate analysis, the risk of bleeding in the absence of effective track ablation was associated with an increasing number of procedures (2nd and 3rd procedures with an odds ratio (OR) of 9.5 and 20.9, respectively), platelets count <150,000 (OR 4.4), elevated portal pressure (OR 1.1 per mm Hg rise), heparin dose > or =45 U/kg (OR 9.8) and pre-transplant aspirin (81 mg per day) (OR 2.6, p = 0.05). A multivariate analysis further confirmed the cumulative transplant procedure number (p < 0.001) and heparin dose > or =45 U/kg (p = 0.02) as independent risk factors for bleeding. Effective mechanical sealing of the intrahepatic portal catheter tract with thrombostatic coils and tissue fibrin glue completely prevented bleeding in all subsequent procedures (n = 26, p = 0.02). We conclude that bleeding after percutaneous islet implantation is an avoidable complication provided the intraparenchymal liver tract is sealed effectively.

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

PubMed Central

Iwamoto, Junichi; Saito, Yoshifumi; Honda, Akira; Matsuzaki, Yasushi

2013-01-01

Low-dose aspirin (LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society. On the other hand, a very low dose of aspirin (10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage. The incidence of LDA-induced gastrointestinal mucosal injury and bleeding has increased. It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug (NSAID)-induced lesions. The pathogenesis related to inhibition of cyclooxygenase (COX)-1 includes reduced mucosal flow, reduced mucus and bicarbonate secretion, and impaired platelet aggregation. The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence. The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation. The factors associated with an increased risk of upper gastrointestinal (GI) complications in subjects taking LDA are aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs, and Helicobacter pylori (H. pylori) infection. Moreover, no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea, acid regurgitation, heartburn, and bloating. It has been shown that the ratios of ulcers located in the body, fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA. Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers. In contrast to NSAID-induced gastrointestinal ulcers, a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers. The eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates, as stopping aspirin therapy is associated with higher mortality rates. It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding, and every effort should be exercised to prevent the bleeding complications. PMID:23555156

Temporal trend of in-hospital major bleeding among patients with non ST-elevation acute coronary syndromes.

PubMed

Elbarouni, Basem; Elmanfud, Omran; Yan, Raymond T; Fox, Keith A A; Kornder, Jan M; Rose, Barry; Spencer, Frederick A; Welsh, Robert C; Wong, Graham C; Goodman, Shaun G; Yan, Andrew T

2010-09-01

Although randomized controlled trials support the use of intensive medical and invasive therapies for non-ST segment elevation acute coronary syndromes (NSTE-ACS), major bleeding is a serious treatment complication. We sought to determine the temporal trend of in-hospital major bleeding among patients with NSTE-ACS, in relation to the evolving management pattern. We identified 14 111 NSTE-ACS patients enrolled in 4 successive, prospective, multicenter registries (ACS I, 1999-2001; ACS II, 2002-2003; GRACE, 2004-2007; and CANRACE, 2008) in Canada between 1999 and 2008. We collected data on patient characteristics, use of cardiac medications and procedures on standardized case report forms. In all registries, major bleeding was defined a priori as life threatening or fatal bleeding, bleeding requiring transfusion of ≥2 U of packed red cells, or resulting in an absolute decrease in hemoglobin of >30g/L. A total of 14 111 patients had a final diagnosis of NSTE-ACS and were included in this study (3294 in the ACS-I registry, 1956 in the ACS-II registry, 7543 in GRACE, and 1318 in CANRACE). Over time, there was a substantial increase in the use of dual anti-platelet (aspirin and thienopyridine) therapy (P for trend <.001), and in rates of in-hospital cardiac catheterization and percutaneous coronary intervention (both Ps for trend <.001). Overall, major bleeding was relatively infrequent (1.7%). There was no significant increase in the unadjusted rates of major bleeding over time (P for trend = .19). In multivariable analysis adjusting for GRACE risk score and intensive treatment, enrolment period was not an independent predictor of bleeding (P for trend = .98). There was no interaction between the enrolment period and the use of intensive medical and invasive management. Despite more widespread use of dual anti-platelet therapies and invasive cardiac procedures in the management of NSTE-ACS, the rate of major bleeding remains relatively low and has not increased significantly over time. Our findings suggest that physicians selectively target treatment for their patients, and these evidence-based therapies can be safely administered to ACS patients in clinical practice. 2010 Mosby, Inc. All rights reserved.

Bleeding risk in patients with atrial fibrillation: the AMADEUS study.

PubMed

Lane, Deirdre A; Kamphuisen, Pieter W; Minini, Pascal; Büller, Harry R; Lip, Gregory Y H

2011-07-01

This study aimed to assess the impact of combination antithrombotic therapy on stroke and bleeding risk compared with anticoagulation therapy only in patients with atrial fibrillation (AF). Post hoc analysis of 4,576 patients with AF (mean ± SD age, 70.1 ± 9.1 years; men, 66.5%) enrolled in the Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation (AMADEUS) trial were randomized to receive either subcutaneous idraparinux (2.5 mg weekly) (n = 2,283) or dose-adjusted vitamin K antagonists (VKAs) (international normalized ratio, 2.0-3.0) (n = 2,293). Of these patients, 848 (18.5%) received antiplatelet therapy (aspirin, clopidogrel, ticlopidine, etc) in addition to anticoagulation treatment (combination antithrombotic therapy). A total of 572 (15.3% per year) clinically relevant bleeding and 103 (2.6% per year) major bleeding events occurred. Patients receiving combination antithrombotic therapy had a 2.3- to 2.5-fold increased risk of clinically relevant bleeding events and major bleeding events, respectively, compared with those receiving anticoagulation therapy only. Multivariate analyses (hazard ratio, 95% CI) revealed that the risk of clinically relevant bleeding was significantly increased by age 65 to 74 years (1.44, 1.14-1.82) and ≥ 75 years (1.59, 1.24-2.04, P = .001) and by combination antithrombotic therapy (2.47, 2.07-2.96, P < .0001). The same held true for major bleeding events, with analogous figures for age 65 to 74 years (2.26, 1.08-4.71) and ≥ 75 years (4.19, 1.98-8.87, P = .0004) and for combination antithrombotic therapy (2.23, 1.49-3.34, P < .0001). Combination antithrombotic therapy was not associated with a decrease in ischemic stroke risk compared with anticoagulation therapy only (11 [1.4% per year] vs 22 [0.7% per year]; adjusted hazard ratio, 2.01; 95% CI, 0.94-4.30; P = .07). Combination antithrombotic therapy increases the risk of clinically relevant bleeding and major bleeding in patients with AF and does not appear to reduce the risk of stroke.

Bleeding complications after myocardial infarction in a real world population - An observational retrospective study with a sex perspective.

PubMed

Holm, Anna; Lawesson, Sofia Sederholm; Zolfagharian, Shima; Swahn, Eva; Ekstedt, Mattias; Alfredsson, Joakim

2018-05-18

The aim of the current study was to assess bleeding events, including severity, localisation and prognostic impact, in a real world population of men and women with myocardial infarction (MI). In total 850 consecutive patients were included during 2010 and followed for one year. Bleeding complications were identified by searching of each patients' medical records and characterised according to the TIMI criteria. For this analysis, only the first event was calculated. The total incidence of bleeding events was 24.4% (81 women and 126 men, p = ns). The incidence of all in-hospital bleeding events was 13.2%, with no sex difference. Women had significantly more minor non-surgery related bleeding events than men (5% vs 2.2%, p = 0.02). During follow-up, 13.5% had a bleeding, with more non-surgery related bleeding events among women, 14.7% vs 9.7% (p = 0.03). The most common bleeding localisation was the gastrointestinal tract, more in women than men (12.1% vs 7.6%, p = 0.03). Women had also more access site bleeding complications (4% vs 1.7%, p = 0.04), while men had more surgery related bleeding complications (6.4% vs 0.9%, p ≤0.001). Increased mortality was found only in men with non-surgery related bleeding events (p = 0.008). Almost one in four patients experienced a bleeding complication through 12 months follow-up after a myocardial infarction. Women experienced more non-surgery related minor/minimal bleeding complications than men, predominantly GI bleeding events and access site bleeding events, with no apparent impact on outcome. In contrast men with non-surgery related bleeding complications had higher mortality. Improved bleeding prevention strategies are warranted for both men and women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predictors of bleeding and user satisfaction during consecutive use of the levonorgestrel-releasing intrauterine system.

PubMed

Heikinheimo, O; Inki, P; Kunz, M; Gemzell-Danielsson, K

2010-06-01

Consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS) is increasing. However, little is known about factors that predict the bleeding during consecutive use. The objective of this study was to analyse the possible factors which may predict the bleeding pattern during the first year of use of a second LNG-IUS. Fertile-aged women (n = 204) who had used their first LNG-IUS for over 4 years and who opted for a second LNG-IUS were recruited. Bleeding data were reported using 90-day reference periods (RPs) starting from the last 90 days of the first LNG-IUS use (baseline), until the end of the first year of the second LNG-IUS (RPs 1-4). Demographic factors such as age, parity, body mass index, indication of LNG-IUS use or smoking could not be identified as predictors for bleeding and spotting (B/S). Mean (+/-SD) number of B/S days was 8.9 (+/-9.1) at baseline. This increased slightly during RP1 and fell to 6.4 (+/-8.1) during RP4. Compared with the mean, women with uterine fibroids or a bleeding pattern of >9 days of spotting or any bleeding at RP1 had more B/S days during RP1-4. Although the number of B/S days decreased progressively from RP1 to RP4 in the group with a bleeding pattern of >9 days of spotting or any bleeding at baseline, such a phenomenon was not observed for women with fibroids. The difference for the change in B/S days between women with and without fibroids was statistically significant at RP3 and RP4. A high degree (91.7%) of satisfaction with the bleeding pattern was observed, with amenorrhoeic women being most satisfied. Uterine B/S is reduced during consecutive use of the LNG-IUS. Women with uterine fibroids or any bleeding at baseline continued to have more B/S than other women.

Retrospective evaluation of acute liver failure in dogs (1995-2012): 49 cases.

PubMed

Lester, Carrie; Cooper, Johanna; Peters, Rachel M; Webster, Cynthia R L

2016-07-01

To characterize the clinical presentation and outcome of dogs with acute liver failure (ALF). Retrospective case series from January 1995 to December 2012. University teaching hospital. Forty-nine dogs were diagnosed with ALF defined as the acute onset of clinical signs accompanied by serum hyperbilirubinemia and coagulopathy (prothrombin time >1.5 times the upper limit of the reference interval) with or without signs of hepatic encephalopathy. Medical records were retrospectively analyzed for clinical presentation, history, physical examination findings, clinicopathologic data, diagnostic imaging findings, hepatic histopathology, treatment, and outcome. Presenting signs included anorexia (28/49, 57%), vomiting (25/49, 51%), neurologic abnormalities (17/49, 35%), and polydipsia/polyuria (10/49, 20%). Neurologic impairment compatible with hepatic encephalopathy occurred at some point during hospitalization in 28/49 (57%) of dogs. Common clinicopathologic abnormalities on presentation other than hyperbilirubinemia and increased serum liver enzyme activity included thrombocytopenia (25/49, 51%), hypoalbuminemia (23/49, 46%), leukocytosis (17/49, 34%), anemia (14/49, 29%), hypokalemia (13/49, 27%), and hypoglycemia (10/49, 20%). The causes of ALF included neoplasia (13/49, 27%), presumptive leptosporosis (4/49, 8%), and ischemia (1/49, 2%). The remaining cases were idiopathic although 15 of these dogs had exposure to possible hepatotoxins. Common lesions in the 35/49 (71%) dogs that had hepatic histopathology were necrosis (19/39, 48%), lipidosis (16/39, 41%), vacuolar change (7/49, 14%), and inflammation (4/49, 8%). Complications included ascites (20/49, 41%), bleeding tendencies (14/49, 29%), pancreatitis (12/49, 24%), and acute tubular necrosis (11/49, 22%). Seven (14%) dogs survived to discharge. Survivors had higher alanine aminotransferase activity, and were more likely to maintain normal albumin concentrations and not develop clinical bleeding or ascites during hospitalization. Canine ALF is associated with multiple etiologies and a high mortality rate. Strategies to increase survival are urgently required. © Veterinary Emergency and Critical Care Society 2016.

[Gastrointestinal bleeding--concepts of surgical therapy in the upper gastrointestinal tract].

PubMed

Knoefel, W T; Rehders, A

2006-02-01

Bleeding of the upper gastrointestinal tract is the main symptom of a variety of possible conditions and still results in considerable mortality. Endoscopy is the first diagnostic modality, enabling rapid therapeutic intervention. In case of intractable or relapsing bleeding, surgery is often inevitable. However, emergency operations result in significantly higher mortality rates. Therefore the option of early elective surgical intervention should be considered for patients at increased risk of relapsing bleeding. If bleeding is symptomatic due to a complex underlying condition such as hemosuccus pancreaticus or hemobilia, angiography is now recognized as the definitive investigation. Angiographic hemostasis can be achieved in most cases. Due to the underlying condition, surgical management still remains the mainstay in treating these patients. This paper reviews surgical strategy in handling upper gastrointestinal bleeding.

The effects of compressor seventh-stage bleed air extraction on performance of the F100-PW-220 afterburning turbofan engine

NASA Technical Reports Server (NTRS)

Evans, Alison B.

1991-01-01

A study was conducted to determine the effects of seventh-stage compressor bleed on the performance of the F100 afterburning turbofan engine. The effects of bleed on thrust, specific fuel consumption, fan turbine inlet temperature, bleed total pressure, and bleed total temperature were obtained from the engine manufacturer's status deck computer simulation. These effects were determined for power settings of intermediate, partial afterburning, and maximum afterburning for Mach numbers between 0.6 and 2.2 and for altitudes of 30,000, 40,000, and 50,000 ft. It was found that thrust loss and specific fuel consumption increase were approximately linear functions of bleed flow and, based on a percent-thrust change basis, were approximately independent of power setting.

Therapeutic options to manage bleeding in a dentist’s office

PubMed

Rostetter, Claudio; Finkenstädt, Tim; Rücker, Martin; Lübbers, Heinz-Theo

2018-06-18

This manuscript provides an overview of therapeutic options for the problem of bleeding in a dentist’s office. Bleeding after tooth extraction is a very common finding in dental medicine and persistent blood in the mouth is obviously uncomfortable and sometimes terrifying for the patient. Most bleedings can be stopped simply with compression, in some cases a homeostatic therapy is necessary. For local compression, a swab with tranexamic acid is useful. If local compression is not sufficient, sutures are often an option. A very effective therapy would also be Tabotamp®, a local hemostypticum which is placed onto the bleeding and should increase the thrombocytic aggregation. In the worst case Floseal®, a human Thrombin, can be placed locally. It stops the bleeding very fast and sufficiently.

Calculated effects of turbine rotor-blade cooling-air flow, altitude, and compressor bleed point on performance of a turbojet engine

NASA Technical Reports Server (NTRS)

Arne, Vernon L; Nachtigall, Alfred J

1951-01-01

Effects of air-cooling turbine rotor blades on performance of a turbojet engine were calculated for a range of altitudes from sea level to 40,000 feet and a range of coolant flows up to 3 percent of compressor air flow, for two conditions of coolant bleed from the compressor. Bleeding at required coolant pressure resulted in a sea-level thrust reduction approximately twice the percentage coolant flow and in an increase in specific fuel consumption approximately equal to percentage coolant flow. For any fixed value of coolant flow ratio the percentage thrust reduction and percentage increase in specific fuel consumption decreased with altitude. Bleeding coolant at the compressor discharge resulted in an additional 1 percent loss in performance at sea level and in smaller increase in loss of performance at higher altitudes.

Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies.

PubMed

Nishikawa, Masakatsu; Isshiki, Takaaki; Kimura, Takeshi; Ogawa, Hisao; Yokoi, Hiroyoshi; Miyazaki, Shunichi; Ikeda, Yasuo; Nakamura, Masato; Tanaka, Yuko; Saito, Shigeru

2017-04-01

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.Trial registration numbers: JapicCTI-101339 and JapicCTI-111550.

Bleeding-related admissions in patients with atrial fibrillation receiving antithrombotic therapy: results from the Tasmanian Atrial Fibrillation (TAF) study.

PubMed

Admassie, Endalkachew; Chalmers, Leanne; Bereznicki, Luke R

2017-12-01

Limited data are available from the Australian setting regarding bleeding in patients with atrial fibrillation (AF) receiving antithrombotic therapy. We aimed to investigate the incidence of hospital admissions due to bleeding and factors associated with bleeding in patients with AF who received antithrombotic therapy. A retrospective cohort study was conducted involving all patients with AF admitted to the Royal Hobart Hospital, Tasmania, Australia, between January 2011 and July 2015. Bleeding rates were calculated per 100 patient-years (PY) of follow-up, and multivariable modelling was used to identify predictors of bleeding. Of 2202 patients receiving antithrombotic therapy, 113 presented to the hospital with a major or minor bleeding event. These patients were older, had higher stroke and bleeding risk scores and were more often treated with warfarin and multiple antithrombotic therapies than patients who did not experience bleeding. The combined incidence of major and minor bleeding was significantly higher in warfarin- versus direct-acting oral anticoagulants (DOAC)- and antiplatelet-treated patients (4.1 vs 3.0 vs 1.2 per 100 PY, respectively; p = 0.002). Similarly, the rate of major bleeding was higher in patients who received warfarin than in the DOAC and antiplatelet cohorts (2.4 vs 0.4 vs 0.6 per 100 PY, respectively; p = 0.001). In multivariate analysis, increasing age, prior bleeding, warfarin and multiple antithrombotic therapies were independently associated with bleeding. The overall rate of bleeding in this cohort was low relative to similar observational studies. The rate of major bleeding was higher in patients prescribed warfarin compared to DOACs, with a similar rate of major bleeding for DOACs and antiplatelet agents. Our findings suggest potential to strategies to reduce bleeding include using DOACs in preference to warfarin, and avoiding multiple antithrombotic therapies in patients with AF.

Observational study of haemostatic dysfunction and bleeding in neonates with hypoxic-ischaemic encephalopathy.

PubMed

Pakvasa, Mitali A; Winkler, Anne M; Hamrick, Shannon E; Josephson, Cassandra D; Patel, Ravi M

2017-02-09

Evaluate the relationship between initial haemostatic parameters and the frequency and severity of bleeding in neonates with hypoxic-ischaemic encephalopathy (HIE). Retrospective observational cohort study. 2 academically affiliated level III neonatal intensive care units in Atlanta, Georgia. 98 neonates with moderate-to-severe HIE who underwent haemostatic testing within 12 hours of birth and were born from 1 January 2008 to 31 December 2013. Initial haemostatic dysfunction was defined as one or more of the following: prothrombin time (PT) ≥18 s, platelet count <100×10 3 /μL or fibrinogen <150 mg/dL. Bleeding assessed using the Neonatal Bleeding Assessment Tool and graded according to the WHO bleeding scale. The robust Poisson regression was used to evaluate the independent association between components of initial haemostatic dysfunction and bleeding. Among the 98 neonates evaluated, the prevalence of initial haemostatic dysfunction was 69% (95% CI 59% to 78%). 27 neonates (28%; 95% CI 19% to 38%) had abnormal bleeding events and 56 (57%) received at least 1 blood product transfusion. 3 neonates died from bleeding complications. The most common products transfused were fresh-frozen plasma (71%), followed by packed red blood cells (24%) and platelets (21%). In multivariable analysis, fibrinogen <150 mg/dL (adjusted relative risk 2.41, 95% CI 1.09 to 5.36) and platelet count <100×10 3 /μL (adjusted relative risk 2.59, 95% CI 1.30 to 5.16), but not initial PT, were associated with an increased risk of bleeding. The most severe bleeding occurred in neonates with a fibrinogen <150 mg/dL. Among neonates with moderate-to-severe HIE, haemostatic dysfunction is prevalent and associated with an increased risk of bleeding and high transfusion burden. Further studies are needed to determine the appropriate transfusion approaches in this population to prevent bleeding. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).

PubMed

Goodman, Shaun G; Wojdyla, Daniel M; Piccini, Jonathan P; White, Harvey D; Paolini, John F; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Patel, Manesh R; Sherwood, Matthew W; Becker, Richard C; Halperin, Jonathan L; Hacke, Werner; Singer, Daniel E; Hankey, Graeme J; Breithardt, Gunter; Fox, Keith A A; Califf, Robert M

2014-03-11

This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present With Pulmonary Complications and Iliac Arterial Dissection.

PubMed

Gu, Guangchao; Yang, Hang; Cui, Lijia; Fu, Yuanyuan; Li, Fangda; Zhou, Zhou; Zheng, Yuehong

2018-02-01

Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder due to its high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. We present a young male patient with vEDS who developed severe pulmonary complications and severe rupture of the iliac artery at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed based on clinical manifestations and confirmed by the identification of COL3A1 gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity, conservative treatment was taken for him. To our knowledge, this is the first report of vEDS case in which the patient developed both pulmonary complications and dissection of large arteries. Our report emphasizes the importance of considering vEDS when an adolescent develops unexplained pulmonary cysts with fragility of lung tissues. Genetic counseling and close monitoring should be performed for earlier diagnosis and prevention of severe complications of large arteries. The typical presentations of vEDS were also discussed by means of a review of case reports on vEDS with pulmonary complications.

[Glanzmann's thrombasthenia: first case descriptions in sub-Saharan Africa].

PubMed

Dokekias, A Elira; Galiba, F O Atipo; Koko, I

2008-08-01

Constitutive hemorrhagic diseases that affect primary haemostasis are reportedly rare in sub-Saharan Africa. This study arrived to report within a Congolese family five cases of Glanzmann's thromboasthenia. 5 cases of the congenital form of Glanzmann's thromboasthenia were depicted in a Congolese family. The disease was first discovered with a young student who was transferred in France, who had shown a tendency to develop hemorrhages since childhood. This tendency was enhanced following abdominal surgery to treat peritonitis. Like the other 3 cases, she had a prolonged bleeding time, albeit with normal von Willebrand factor plasma values. A 7 year old girl died following appendectomy from post-surgery hemorrhages. In this young patient, platelet aggregation could be induced only by ristocetine, all other conventional agonists failed. Flow cytometric analysis showed the total absence of GPIIbIIIa. The hemorrhages in the girls could be managed by cyclic administration of oestrogens and iron supplementation. Serologic analysis showed this patient to be positive for hepatitis C virus antibodies. This first description of Glanzmann's thrombo-asthenia in Blacks in sub-Saharan Africa shows the necessity of establish inter-hospital cooperation for the improvement of the management of constitutive hemorrhagic diseases in the Hematology wards.

Incidence of endometrial spotting or bleeding during continuous-combined estrogen-progestin therapy in postmenopausal women with and without hypertension.

PubMed

Sriprasert, Intira; Beydoun, Hind; Barnabei, Vanessa; Nassir, Rami; LaCroix, Andrea Z; Archer, David F

2015-10-01

Endometrial spotting or bleeding is a common adverse effect among women taking continuous-combined estrogen-progestin therapy. The renin-angiotensin-aldosterone system plays a major role in hypertension and is present in the endometrium. We hypothesized that postmenopausal women with hypertension would have a higher incidence of bleeding compared with postmenopausal women without hypertension. A multivariate mixed-effects logistic model estimated the odds ratios for the relationship of hypertension status or use of antihypertensive drugs with endometrial bleeding using the Women's Health Initiative database. The incidence of spotting or bleeding in the first 12 months of estrogen-progestin use was 42% in women aged 50 to 79 years. Women with hypertension were more likely to experience bleeding than women without hypertension (odds ratio, 1.07; 95% CI, 1.02-1.13). Overall antihypertensive medication use increased bleeding with an odds ratio of 1.24, whereas angiotensin II receptor antagonists had a reduced odds ratio (0.53). Postmenopausal women with hypertension are more likely to bleed than postmenopausal women without hypertension when taking continuous estrogen-progestin, with less bleeding in women using angiotensin II receptor antagonists. This finding is novel and supports our hypothesis that the endometrial renin-angiotensin-aldosterone system may contribute to endometrial bleeding.

Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

PubMed Central

Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

2011-01-01

Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

Effects of hyaluronic acid on bleeding following third molar extraction.

PubMed

Gocmen, Gokhan; Aktop, Sertac; Tüzüner, Burcin; Goker, Bahar; Yarat, Aysen

2017-01-01

To explore the effects of hyaluronic acid (HA) on bleeding and associated outcomes after third molar extraction. Forty patients who had undergone molar extraction were randomly divided into two groups; 0.8% (w/v) HA was applied to the HA group (n=20) whereas a control group (n=20) was not treated. Salivary and gingival tissue factor (TF) levels, bleeding time, maximum interincisal opening (MIO), pain scored on a visual analog scale (VAS), and the swelling extent were compared between the two groups. HA did not significantly affect gingival TF levels. Salivary TF levels increased significantly 1 week after HA application but not in the control group. Neither the VAS pain level nor MIO differed significantly between the two groups. The swelling extent on day 3 and the bleeding time were greater in the HA group than in the control group. Local injection of HA at 0.8% prolonged the bleeding time, and increased hemorrhage and swelling in the early postoperative period after third molar extractions.

Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR.

PubMed

Sandén, Per; Renlund, Henrik; Svensson, Peter J; Själander, Anders

2017-01-05

High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well-managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70 %, 2.91 (CI 95 % 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95 % 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.

Effect of posterior crown margin placement on gingival health.

PubMed

Reitemeier, Bernd; Hänsel, Kristina; Walter, Michael H; Kastner, Christian; Toutenburg, Helge

2002-02-01

The clinical impact of posterior crown margin placement on gingival health has not been thoroughly quantified. This study evaluated the effect of posterior crown margin placement with multivariate analysis. Ten general dentists reviewed 240 patients with 480 metal-ceramic crowns in a prospective clinical trial. The alloy was randomly selected from 2 high gold, 1 low gold, and 1 palladium alloy. Variables were the alloy used, oral hygiene index score before treatment, location of crown margins at baseline, and plaque index and sulcus bleeding index scores recorded for restored and control teeth after 1 year. The effect of crown margin placement on sulcular bleeding and plaque accumulation was analyzed with regression models (P<.05). The probability of plaque at 1 year increased with increasing oral hygiene index score before treatment. The lingual surfaces demonstrated the highest probability of plaque. The risk of bleeding at intrasulcular posterior crown margins was approximately twice that at supragingival margins. Poor oral hygiene before treatment and plaque also were associated with sulcular bleeding. Facial sites exhibited a lower probability of sulcular bleeding than lingual surfaces. Type of alloy did not influence sulcular bleeding. In this study, placement of crown margins was one of several parameters that affected gingival health.

Design of a very-low-bleed Mach 2.5 mixed-compression inlet with 45 percent internal contraction

NASA Technical Reports Server (NTRS)

Wasserbauer, J. F.; Shaw, R. J.; Neumann, H. E.

1975-01-01

A full-scale, mixed-compression inlet was designed for operation with the TF30-P-3 turbofan engine and tested at Mach numbers of 2.5 and 2.0. The two-cone axisymmetric inlet had minimum internal contraction consistent with high total pressure recovery and low cowl drag. At Mach 2.5, inlet recovery was 0.906 with only 0.021 centerbody bleed mass-flow ratio and no cowl bleed. Increased centerbody bleed gave a maximum inlet unstart angle of attack of 6.85 deg. At Mach 2.0, inlet recovery was 0.94 with only 0.014 centerbody bleed mass-flow ratio and no cowl bleed. Inlet performance and angle-of-attack tolerance is presented for operation at Mach numbers of 2.5 and 2.0.

Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids.

PubMed

Misra, Ankita; Anil Kumar, K S; Jain, Manish; Bajaj, Kirti; Shandilya, Shyamali; Srivastava, Smriti; Shukla, Pankaj; Barthwal, Manoj K; Dikshit, Madhu; Dikshit, Dinesh K

2016-03-03

N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular, the compound 4j offered significant protection against collagen epinephrine induced pulmonary thromboembolism as well as ferric chloride induced arterial thrombosis, without affecting bleeding tendency in mice. Therefore, the present study suggests that the compound 4j displays a remarkable antithrombotic efficacy much better than aspirin and clopidogrel. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Excessive bleeding predictors after cardiac surgery in adults: integrative review.

PubMed

Lopes, Camila Takao; Dos Santos, Talita Raquel; Brunori, Evelise Helena Fadini Reis; Moorhead, Sue A; Lopes, Juliana de Lima; Barros, Alba Lucia Bottura Leite de

2015-11-01

To integrate literature data on the predictors of excessive bleeding after cardiac surgery in adults. Perioperative nursing care requires awareness of the risk factors for excessive bleeding after cardiac surgery to assure vigilance prioritising and early correction of those that are modifiable. Integrative literature review. Articles were searched in seven databases. Seventeen studies investigating predictive factors for excessive bleeding after open-heart surgery from 2004-2014 were included. Predictors of excessive bleeding after cardiac surgery were: Patient-related: male gender, higher preoperative haemoglobin levels, lower body mass index, diabetes mellitus, impaired left ventricular function, lower amount of prebypass thrombin generation, lower preoperative platelet counts, decreased preoperative platelet aggregation, preoperative platelet inhibition level >20%, preoperative thrombocytopenia and lower preoperative fibrinogen concentration. Procedure-related: the operating surgeon, coronary artery bypass surgery with three or more bypasses, use of the internal mammary artery, duration of surgery, increased cross-clamp time, increased cardiopulmonary bypass time, lower intraoperative core body temperature and bypass-induced haemostatic disorders. Postoperative: fibrinogen levels and metabolic acidosis. Patient-related, procedure-related and postoperative predictors of excessive bleeding after cardiac surgery were identified. The predictors summarised in this review can be used for risk stratification of excessive bleeding after cardiac surgery. Assessment, documentation and case reporting can be guided by awareness of these factors, so that postoperative vigilance can be prioritised. Timely identification and correction of the modifiable factors can be facilitated. © 2015 John Wiley & Sons Ltd.

Head Injury and Aging: The Importance of Bleeding Injuries

PubMed Central

Mallory, Ann

The current study analyzed 1993–2007 data from NASS/CDS (National Automotive Sampling System / Crashworthiness Data System) to explore the types of serious head injuries sustained by adult motor vehicle crash occupants and how the types of head injuries sustained shifted with age. The purpose was to determine which head injuries are most important for older occupants by identifying specific injuries that become more likely for aging occupants and taking into consideration previous reports on the potential outcome of those injuries for an older population. Results confirmed previous reports that older head injury victims in motor vehicle collisions were more likely to sustain bleeding injuries than younger head injury victims. The current study showed that, in particular, the rate of extra-axial bleeding injury (which includes epidural, subdural, and subarachnoid bleeding) increased with age. The increase in extra-axial bleeding injury rate was especially prominent in relatively low Delta-V crashes. Among the extra-axial bleeding injuries that had increased odds of injury for older occupants, subdural hematoma and subarachnoid hemorrhage were notable, with increased odds of injury for occupants age 50 to 69 as well as for occupants age 70 and older. The importance of subdural hematoma for aging occupants is emphasized by previous studies showing its high mortality rate, while the impact of subarachnoid hemorrhage is linked in previous studies to its aggravating effect on other injuries. The results highlight a need to further explore the injury mechanisms of subdural hematoma and subarachnoid hemorrhage in older occupants in order to define age-adjusted injury tolerance and develop countermeasures. PMID:21050591

Warfarin Use in Hemodialysis Patients With Atrial Fibrillation: A Systematic Review of Stroke and Bleeding Outcomes

PubMed Central

Tsai, Chieh; Marcus, Laura Quinn; Patel, Priya; Battistella, Marisa

2017-01-01

Background: Given the lack of clear indications for the use of warfarin in the treatment of atrial fibrillation (AF) in patients on hemodialysis and the potential risks that accompany warfarin use in these patients, we systematically reviewed stroke and bleeding outcomes in hemodialysis patients treated with warfarin for AF. Objective: To systematically review the stroke and bleeding outcomes associated with warfarin use in the hemodialysis population to treat AF. Design: Systematic review. Setting: All adult hemodialysis patients. Patients: Patients on hemodialysis receiving warfarin for the management of AF. Measurements: Any type of stroke and/or bleeding outcomes. Methods: MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) via OVID (1946 to January 11, 2017), and EMBASE via OVID (1974 to January 11, 2017) were searched for relevant literature. Inclusion criteria were randomized controlled trials, observational studies, and case series in English that examined stroke and bleeding outcomes in adult population of patients (over 18 years old) who are on hemodialysis and taking warfarin for AF. Studies with less than 10 subjects, case reports, review articles, and editorials were excluded. Quality of selected articles was assessed using Newcastle-Ottawa Scale (NOS). Results: Of the 2340 titles and abstracts screened, 7 met the inclusion criteria. Two studies showed an association between warfarin use and an increased risk of stroke (Hazard Ratio: 1.93-3.36) but no association with an increased risk of bleed (HR: 0.85-1.04), while 4 studies showed no association between warfarin and stroke outcomes (HR: 0.12-1.17) but identified an association between warfarin and increased bleeding outcome (HR: 1.41-3.96). And 1 study reported neither beneficial nor harmful effects associated with warfarin use. Limitations: The major limitation to this review is that the 7 included studies were observational cohort studies, and thus the outcome measures were not specified and predetermined in a research protocol. Conclusion: Our systematic review demonstrated that for patients with AF who are on hemodialysis, warfarin was not associated with reduced outcomes of stroke but was rather associated with increased bleeding events. PMID:29093823

Triple anticoagulation therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention – real life assessment

PubMed Central

Kabłak-Ziembicka, Anna; Bryniarski, Krzysztof; Wrotniak, Leszek; Ostrowska-Kaim, Elżbieta; Żmudka, Krzysztof; Przewłocki, Tadeusz

2016-01-01

Introduction Triple anticoagulation therapy (TT), comprising dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC), is essential in atrial fibrillation (AF) patients after percutaneous coronary intervention (PCI), but it increases the bleeding risk. Aim To assess TT models, in- and out-hospital bleeding and thromboembolic complications, and TT alterations. Material and methods During 12 months, consecutive AF post-PCI patients were scheduled for TT. Alterations in TT and thromboembolic events (death, myocardial infarction, ischemic stroke, in-stent thrombosis, peripheral embolization) were recorded. Major, non-major and minor bleeding episodes were assessed. Results One hundred and thirty-six out of 3171 patients, aged 73.0 ±8.4 years (90 male), were included. Intra-hospitally, thrombotic events occurred in 9 (6.6%), while bleeding events occurred in 71 (52.2%) patients. Access-site hematoma and blood transfusions during in-hospital stay predisposed physicians to heparin administration as part of TT on discharge (p = 0.018 and p = 0.033 respectively). Eventually, DAPT plus warfarin or plus novel oral anticoagulant (NOAC) or plus low molecular weight heparin was prescribed in 72 (52.9%), 53 (39%), and 11 (8.1%) patients, respectively. HAS-BLED and CHA2DS2-VASc scores were similar between subgroups (p = 0.63 and p = 0.64 respectively). During 10.2 ±4.2 months of follow-up, 11 (8.1%) deaths, and 9 (6.6%) non-fatal thromboembolic events occurred. Bleeding events occurred in 45 (34.6%) patients, including 14 (10.3%) major. TT was the only factor associated with increased risk of major bleeding (18.6% vs. 4.2%, p = 0.008). Early termination of any TT component, which concerned 59 (45.4%) patients, did not increase the risk of thromboembolic events (p = 0.89). Conclusions Our study indicates that TT is associated with high mortality and bleeding rates in a relatively short period of time. Discontinuation of any TT drug did not increase the thromboembolic event rate, while it was associated with reduced risk of major bleeding. PMID:27980543

Comparing the effect of mefenamic Acid and vitex agnus on intrauterine device induced bleeding.

PubMed

Yavarikia, Parisa; Shahnazi, Mahnaz; Hadavand Mirzaie, Samira; Javadzadeh, Yousef; Lutfi, Razieh

2013-09-01

Increased bleeding is the most common cause of intrauterine device (IUD) removal. The use of alternative therapies to treat bleeding has increased due to the complications of medications. But most alternative therapies are not accepted by women. Therefore, conducting studies to find the right treatment with fewer complications and being acceptable is necessary. This study aimed to compare the effect of mefenamic acid and vitex agnus castus on IUD induced bleeding. This was a double blinded randomized controlled clinical trial. It was conducted on 84 women with random allocation in to two groups of 42 treated with mefenamic acid and vitex agnus capsules taking three times a day during menstruation for four months. Data were collected by demographic questionnaire and Higham 5 stage chart (1 month before the treatment and 4 months during the treatment)., Paired t-test, independent t-test, chi-square test, analysis of variance (ANOVA) with repeated measurements, and SPSS software were used to determine the results. Mefenamic acid and vitex agnus significantly decreased bleeding. This decrease in month 4 was 52% in the mefenamic acid group and 47.6% in the vitex agnus group. The mean bleeding score changes was statistically significant between the two groups in the first three months and before the intervention. In the mefenamic acid group, the decreased bleeding was significantly more than the vitex agnus group. However, during the 4(th) month, the mean change was not statistically significant. Mefenamic acid and vitex agnus were both effective on IUD induced bleeding; however, mefenamic acid was more effective.

Comparing the Effect of Mefenamic Acid and Vitex Agnus on Intrauterine Device Induced Bleeding

PubMed Central

Yavarikia, Parisa; Shahnazi, Mahnaz; Hadavand Mirzaie, Samira; Javadzadeh, Yousef; Lutfi, Razieh

2013-01-01

Introduction: Increased bleeding is the most common cause of intrauterine device (IUD) removal. The use of alternative therapies to treat bleeding has increased due to the complications of medications. But most alternative therapies are not accepted by women. Therefore, conducting studies to find the right treatment with fewer complications and being acceptable is necessary. This study aimed to compare the effect of mefenamic acid and vitex agnus castus on IUD induced bleeding. Methods: This was a double blinded randomized controlled clinical trial. It was conducted on 84 women with random allocation in to two groups of 42 treated with mefenamic acid and vitex agnus capsules taking three times a day during menstruation for four months. Data were collected by demographic questionnaire and Higham 5 stage chart (1 month before the treatment and 4 months during the treatment)., Paired t-test, independent t-test, chi-square test, analysis of variance (ANOVA) with repeated measurements, and SPSS software were used to determine the results. Results: Mefenamic acid and vitex agnus significantly decreased bleeding. This decrease in month 4 was 52% in the mefenamic acid group and 47.6% in the vitex agnus group. The mean bleeding score changes was statistically significant between the two groups in the first three months and before the intervention. In the mefenamic acid group, the decreased bleeding was significantly more than the vitex agnus group. However, during the 4th month, the mean change was not statistically significant. Conclusion: Mefenamic acid and vitex agnus were both effective on IUD induced bleeding; however, mefenamic acid was more effective. PMID:25276733

Association of Short-term Bleeding and Cramping Patterns with Long-Acting Reversible Contraceptive Method Satisfaction

PubMed Central

Diedrich, Justin T.; Desai, Sanyukta; Zhao, Qiuhong; Secura, Gina; Madden, Tessa; Peipert, Jeffrey F.

2014-01-01

Objectives To examine the short-term (3 and 6-month), self-reported bleeding and cramping patterns with intrauterine devices (IUDs) and the contraceptive implant, and the association of these symptoms with method satisfaction. Study Design We analyzed 3 and 6-month survey data from IUD and implant users in the Contraceptive CHOICE Project, a prospective cohort study. Participants who received a long-acting reversible contraceptive (LARC) method (levonorgestrel intrauterine system (LNG-IUS), copper IUD, or the etonogestrel implant) and completed their 3- and 6-month surveys were included. Univariable and multivariable analyses were performed to examine the association of bleeding and cramping patterns with short-term satisfaction. Results Our analytic sample included 5,011 CHOICE participants: 3001 LNG-IUS users, 826 copper IUD users, and 1184 implant users. At 3 months, over 65% of LNG-IUS and implant users reported no change or decreased cramping, while 63% of copper IUD users reported increased menstrual cramping. Lighter bleeding was reported by 67% of LNG-IUS users, 58% of implant users, and 8% of copper IUD users. Satisfaction of all LARC methods was high (≥90%) and significantly higher than non-LARC methods (p<0.001). LARC users with increased menstrual cramping (HR 0.96, 95% CI 0.92 – 0.99), heavier bleeding (HR 0.91, 95% CI 0.87 – 0.96), and increased bleeding frequency (HR 0.92, 95% CI 0.89 – 0.96) were less likely to report being very satisfied at 6 months. Conclusion Regardless of the LARC method, satisfaction at 3 and 6 months is very high. Changes in self-reported bleeding and cramping are associated with short-term LARC satisfaction. PMID:25046805

Association of short-term bleeding and cramping patterns with long-acting reversible contraceptive method satisfaction.

PubMed

Diedrich, Justin T; Desai, Sanyukta; Zhao, Qiuhong; Secura, Gina; Madden, Tessa; Peipert, Jeffrey F

2015-01-01

We sought to examine the short-term (3- and 6-month), self-reported bleeding and cramping patterns with intrauterine devices (IUDs) and the contraceptive implant, and the association of these symptoms with method satisfaction. We analyzed 3- and 6-month survey data from IUD and implant users in the Contraceptive CHOICE Project, a prospective cohort study. Participants who received a long-acting reversible contraceptive (LARC) method (levonorgestrel-releasing intrauterine system [LNG-IUS], copper IUD, or the etonogestrel implant) and completed their 3- and 6-month surveys were included. Univariable and multivariable analyses were performed to examine the association of bleeding and cramping patterns with short-term satisfaction. Our analytic sample included 5011 Contraceptive CHOICE Project participants: 3001 LNG-IUS users, 826 copper IUD users, and 1184 implant users. At 3 months, >65% of LNG-IUS and implant users reported no change or decreased cramping, while 63% of copper IUD users reported increased menstrual cramping. Lighter bleeding was reported by 67% of LNG-IUS users, 58% of implant users, and 8% of copper IUD users. Satisfaction of all LARC methods was high (≥90%). LARC users with increased menstrual cramping (relative risk adjusted [RRadj], 0.78; 95% confidence interval [CI], 0.72-0.85), heavier bleeding (RRadj, 0.83; 95% CI, 0.76-0.92), and increased bleeding frequency (RRadj, 0.73; 95% CI, 0.67-0.80) were less likely to report being very satisfied at 6 months. Regardless of the LARC method, satisfaction at 3 and 6 months is very high. Changes in self-reported bleeding and cramping are associated with short-term LARC satisfaction. Copyright © 2015 Elsevier Inc. All rights reserved.

Low-Molecular-Weight Heparin and the Relative Risk of Surgical Site Bleeding Complications: Results of a Systematic Review and Meta-Analysis of Randomized Controlled Trials of Venous Thromboprophylaxis in Patients After Total Joint Arthroplasty.

PubMed

Suen, Kary; Westh, Roger N; Churilov, Leonid; Hardidge, Andrew J

2017-09-01

Venous thromboembolism causes significant morbidity and mortality in patients after total joint arthroplasty. Although network meta-analyses have demonstrated a benefit of various thromboprophylactic agents, there remains a concern in the surgical community regarding the resulting wound complications. There is currently no systematic review of the surgical site bleeding complications of thromboprophylactic agents. The aim of this study was to systematically review the surgical site bleeding outcomes of venous thromboembolism prophylaxis in this population. A systematic review and meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials comparing more than one of low-molecular-weight heparin (LMWH), warfarin, rivaroxaban, apixaban, dabigatran, aspirin, or no pharmacologic treatment in patients after total hip or knee arthroplasty were selected for inclusion. Five meta-analyses were performed to compare LMWH with control, warfarin, apixaban, rivaroxaban, and dabigatran. Forty-five randomized controlled trials of 56,730 patients were included. LMWH had a significantly increased relative risk of surgical site bleeding in comparison with control (relative risk, 2.32; 95% confidence interval, 1.40-3.85) and warfarin (1.54; 1.23-1.94). The relative risk of LMWH trended higher than apixaban (1.27; 1.00-1.63) and was similar to rivaroxaban (0.95; 0.74-1.23). Only 1 study reported the risk of surgical site bleeding in LMWH vs dabigatran (5.97; 2.08-17.11). LMWH increased the risk of surgical site bleeding compared with control, warfarin. and dabigatran and trended toward an increased risk compared with apixaban. The risk of surgical site bleeding was similar with LMWH and rivaroxaban. Copyright © 2017 Elsevier Inc. All rights reserved.

Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk.

PubMed

Allende, Mikel; Molina, Eva; Guruceaga, Elisabet; Tamayo, Ibai; González-Porras, José Ramón; Gonzalez-López, Tomás José; Toledo, Estefanía; Rabal, Obdulia; Ugarte, Ana; Roldán, Vanesa; Rivera, José; Oyarzabal, Julen; Montes, Ramón; Hermida, José

2016-06-01

Atrial fibrillation (AF) is a major risk factor for cardio-embolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern. This study sought to identify new targets to develop safer antithrombotic therapies. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke brought to light a stroke-related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was down-regulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. Remarkably, the tail bleeding time was unchanged. Accordingly, both TRC051384 and tubastatin A, i.e. two Hsp70 inducers via different pathways, delayed thrombus formation in WT mice, the tail bleeding time still being unaltered. Most interestingly, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression and higher circulating levels of activated protein C upon thrombotic stimulus. Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, and is especially promising for treating AF patients and in other situations where there is also a major bleeding hazard. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding. A risk modelling analysis.

PubMed

Majeed, Ammar; Wallvik, Niklas; Eriksson, Joakim; Höijer, Jonas; Bottai, Matteo; Holmström, Margareta; Schulman, Sam

2017-02-28

The optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the 'total risk', based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58 %) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2-3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07-0.55) and death (HR 0.61; 95 % CI, 0.39-0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95 % CI, 1.4-4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3-6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

Defective endomitosis during megakaryopoiesis leads to thrombocytopenia in Fanca−/− mice

PubMed Central

Pawlikowska, Patrycja; Fouchet, Pierre; Vainchenker, William; Rosselli, Filippo

2014-01-01

Fanconi anemia (FA) is an inherited chromosomal instability syndrome that is characterized by progressive bone marrow failure. One of the main causes of morbidity and mortality in FA is a bleeding tendency, resulting from low platelet counts. Platelets are the final products of megakaryocyte (MK) maturation. Here, we describe a previously unappreciated role of Fanconi anemia group A protein (Fanca) during the endomitotic process of MK differentiation. Fanca deficiency leads to the accumulation of MKs with low nuclear ploidy and to decreased platelet production. We show, for the first time, that Fanca−/− mice are characterized by limited number and proliferative capacity of MK progenitors. Defective megakaryopoiesis of Fanca−/− cells is associated with the formation of nucleoplasmic bridges and increased chromosomal instability, indicating that inaccurate endoreplication and karyokinesis occur during MK polyploidization. Sustained DNA damage forces Fanca−/− MKs to enter a senescence-like state. Furthermore, inhibition of the Rho-associated kinase, a regulator of cytokinesis, improves the polyploidization of Fanca−/− MKs but greatly increases their genomic instability and diminishes their differentiation potential, supporting the notion that accumulation of DNA damage through endomitotic cycles affects MK maturation. Our study indicates that Fanca expression during endomitosis is crucial for normal megakaryopoiesis and platelet production. PMID:25261197

Defective endomitosis during megakaryopoiesis leads to thrombocytopenia in Fanca-/- mice.

PubMed

Pawlikowska, Patrycja; Fouchet, Pierre; Vainchenker, William; Rosselli, Filippo; Naim, Valeria

2014-12-04

Fanconi anemia (FA) is an inherited chromosomal instability syndrome that is characterized by progressive bone marrow failure. One of the main causes of morbidity and mortality in FA is a bleeding tendency, resulting from low platelet counts. Platelets are the final products of megakaryocyte (MK) maturation. Here, we describe a previously unappreciated role of Fanconi anemia group A protein (Fanca) during the endomitotic process of MK differentiation. Fanca deficiency leads to the accumulation of MKs with low nuclear ploidy and to decreased platelet production. We show, for the first time, that Fanca(-/-) mice are characterized by limited number and proliferative capacity of MK progenitors. Defective megakaryopoiesis of Fanca(-/-) cells is associated with the formation of nucleoplasmic bridges and increased chromosomal instability, indicating that inaccurate endoreplication and karyokinesis occur during MK polyploidization. Sustained DNA damage forces Fanca(-/-) MKs to enter a senescence-like state. Furthermore, inhibition of the Rho-associated kinase, a regulator of cytokinesis, improves the polyploidization of Fanca(-/-) MKs but greatly increases their genomic instability and diminishes their differentiation potential, supporting the notion that accumulation of DNA damage through endomitotic cycles affects MK maturation. Our study indicates that Fanca expression during endomitosis is crucial for normal megakaryopoiesis and platelet production. © 2014 by The American Society of Hematology.

Risk of Ischemic Stroke, Hemorrhagic Stroke, Bleeding, and Death in Patients Switching from Vitamin K Antagonist to Dabigatran after an Ablation.

PubMed

Pallisgaard, Jannik Langtved; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian; Lee, Christina Ji-Young; Sindet-Pedersen, Caroline; Staerk, Laila; Olesen, Jonas Bjerring; Lindhardt, Tommi Bo

2016-01-01

Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation. Through the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference. In total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72-3.75) for bleeding and of 1.41 (0.66-3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40-14.5). Shifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding.

A bleeding assessment tool correlates with intraoperative blood loss in children and adolescents undergoing major spinal surgery.

PubMed

Anadio, Jennifer M; Sturm, Peter F; Forslund, Johan M; Agarwal, Sunil; Lane, Adam; Tarango, Cristina; Palumbo, Joseph S

2017-04-01

Screening laboratory studies for bleeding disorders are of little predictive value for operative bleeding risk in adults. Predicting perioperative bleeding in pediatric patients is particularly difficult as younger patients often have not had significant hemostatic challenges. This issue is distinctly important for high bleeding risk surgeries, such as major spinal procedures. The aim of this study was to determine if the score of a detailed bleeding questionnaire (BQ) correlated with surgical bleeding in pediatric patients undergoing major spinal surgery. A total of 220 consecutive pediatric patients (mean age 14.2years) undergoing major spinal surgery were administered the BQ preoperatively, as well as having routine screening laboratory studies (i.e., PT, aPTT, PFA) drawn. A retrospective analysis was conducted to determine if there was a correlation between either the results of the BQ and/or laboratory studies with operative outcomes. A BQ score>2 showed a strong positive correlation with intraoperative bleeding based on both univariate and multivariate analyses. In contrast, abnormalities in screening laboratory studies showed no significant correlation with operative bleeding outcomes. Relying on screening laboratory studies alone is inadequate. The BQ used here correlated with increased intraoperative hemorrhage, suggesting this tool may be useful for assessing pediatric surgical bleeding risk, and may also be useful in identifying a subset of patients with a very low bleeding risk that may not require laboratory screening. Copyright © 2017 Elsevier Ltd. All rights reserved.

Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications.

PubMed

Serebruany, Victor; Rao, Sunil V; Silva, Matthew A; Donovan, Jennifer L; Kannan, Abir O; Makarov, Leonid; Goto, Shinya; Atar, Dan

2010-01-01

To correlate inhibition of platelet aggregation (IPA) with bleeding events assessed by TIMI, GUSTO, and BleedScore scales in a large cohort of patients with coronary artery disease (CAD) and ischaemic stroke (IS) treated with chronic low-dose aspirin plus clopidogrel. Data from recent trials and registries suggest a link between increased risk of bleeding and cardiovascular mortality. However, the potential association of bleeding risk and IPA is not established. It may play a critical role for the safety of more aggressive platelet inhibition or/and individual tailoring of antiplatelet strategies. Secondary post hoc analyses of 5 microM ADP-induced IPA and bleeding complications assessed by TIMI, GUSTO, and BleedScore scales in a combined data set consisting of patients with documented CAD (n = 246) and previous IS (n = 117). Demographic characteristics differ substantially depending on the underlying vascular disease; however, IPA and bleeding risks were similar between CAD and IS. All three bleeding scales adequately captured serious haemorrhagic events, where the TIMI scale was the most exclusive, whereas BleedScore was the most inclusive. Over half of all patients experienced superficial event(s), most commonly occurring during two to three distinct bleeding episodes. There was no correlation between IPA and duration of antiplatelet therapy. Inhibition of platelet aggregation >50% strongly correlates with minor (r(2) = 0.58, P < 0.001; c-statistic = 0.92), but not severe (r(2) = 0.11, P = 0.038; c-statistic = 0.57), bleeding events. Chronic oral combination antiplatelet regimens are associated with a very high (56.5-60.7%) prevalence of superficial bleeding episodes, which are grossly underestimated in trials and registries. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. Although IPA is well suited for defining the risk of minor complications, prediction of more severe bleeding events may be challenging.

Cycle control with an extended-regimen oral contraceptive combining levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl estradiol instead of the traditional hormone-free interval.

PubMed

Nappi, Rossella E; Lobo Abascal, Paloma; Hsieh, Jennifer; Micheletti, Marie-Christine

2017-01-01

To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous low-dose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI). This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 µg EE/150 µg levonorgestrel (LNG) for 84 days and EE 10 µg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs. There was a 10% increase (OR =1.102; 95% CI: 1.006-1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), ≥45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393-1.683) and 31% (OR =1.307; 95% CI: 1.205-1.418) in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or ≤6 days of unscheduled bleeding during each 91-day cycle. Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/spotting in future cycles.

Cycle control with an extended-regimen oral contraceptive combining levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl estradiol instead of the traditional hormone-free interval

PubMed Central

Nappi, Rossella E; Lobo Abascal, Paloma; Hsieh, Jennifer; Micheletti, Marie-Christine

2017-01-01

Purpose To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous low-dose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI). Patients and methods This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 µg EE/150 µg levonorgestrel (LNG) for 84 days and EE 10 µg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs. Results There was a 10% increase (OR =1.102; 95% CI: 1.006–1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), ≥45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393–1.683) and 31% (OR =1.307; 95% CI: 1.205–1.418) in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or ≤6 days of unscheduled bleeding during each 91-day cycle. Conclusion Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/spotting in future cycles. PMID:29042818

Guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding.

PubMed

Fujishiro, Mitsuhiro; Iguchi, Mikitaka; Kakushima, Naomi; Kato, Motohiko; Sakata, Yasuhisa; Hoteya, Shu; Kataoka, Mikinori; Shimaoka, Shunji; Yahagi, Naohisa; Fujimoto, Kazuma

2016-05-01

Japan Gastroenterological Endoscopy Society (JGES) has compiled a set of guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding using evidence-based methods. The major cause of non-variceal upper gastrointestinal bleeding is peptic gastroduodenal ulcer bleeding. As a result, these guidelines mainly focus on peptic gastroduodenal ulcer bleeding, although bleeding from other causes is also overviewed. From the epidemiological aspect, in recent years in Japan, bleeding from drug-related ulcers has become predominant in comparison with bleeding from Helicobacter pylori (HP)-related ulcers, owing to an increase in the aging population and coverage of HP eradication therapy by national health insurance. As for treatment, endoscopic hemostasis, in which there are a variety of methods, is considered to be the first-line treatment for bleeding from almost all causes. It is very important to precisely evaluate the severity of the patient's condition and stabilize the patient's vital signs with intensive care for successful endoscopic hemostasis. Additionally, use of antisecretory agents is recommended to prevent rebleeding after endoscopic hemostasis, especially for gastroduodenal ulcer bleeding. Eighteen statements with evidence and recommendation levels have been made by the JGES committee of these guidelines according to evidence obtained from clinical research studies. However, some of the statements that are supported by a low level of evidence must be confirmed by further clinical research. © 2016 Japan Gastroenterological Endoscopy Society.

Menstrual Bleeding Patterns Among Regularly Menstruating Women

PubMed Central

Dasharathy, Sonya S.; Mumford, Sunni L.; Pollack, Anna Z.; Perkins, Neil J.; Mattison, Donald R.; Wactawski-Wende, Jean; Schisterman, Enrique F.

2012-01-01

Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005–2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (β = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (β = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle. PMID:22350580

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

PubMed Central

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E.; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-01-01

Background Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. Design and Methods We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. Results All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. Conclusions The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms. PMID:20179087

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function.

PubMed

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-06-01

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms.

Etiology and outcome in patients with upper gastrointestinal bleeding: Study on 4747 patients in the central region of Iran.

PubMed

Minakari, Mohammad; Badihian, Shervin; Jalalpour, Pooyan; Sebghatollahi, Vahid

2017-04-01

Upper gastrointestinal bleeding (UGIB) is a threatening condition leading to urgent hospitalization. This study aims to investigate etiology and outcome in UGIB patients in Iran. Medical records of GIB patients admitted to Alzahra referral hospital (in Isfahan) during 2010-2015 were retrospectively reviewed for demographic data, comorbidities, history of smoking and taking non-steroidal anti-inflammatory drugs (NSAIDs), presenting symptoms, endoscopic findings, therapeutic endoscopy, blood products' infusion, surgical intervention, rebleeding, and mortality. A total of 4747 patients were enrolled in the study (69.2% men, mean age = 55.46 ± 21.98 years). Hematemesis was the most frequent presenting symptom (63.5%). Peptic ulcer (duodenal ulcer in most cases) was seen as the main reason for UGIB (42.4%). Rebleeding (present in 16.5% of patients) was found to be more frequent in patients with older age, presenting sign of hematochezia and hypotension, history of taking NSAIDs and smoking, presence of comorbidities, history of bleeding because of UGI tract neoplasm and esophageal varices, history of needing blood products' infusion, and history of therapeutic endoscopy or surgical intervention (P < 0.005). We found that mortality (5.5% in total) was also higher in the same group of patients that were seen to have a higher tendency for rebleeding (P < 0.005). Peptic ulcers are the most common cause of UGIB. Comorbidities, hemodynamic instability, high-risk endoscopic stigmata, history of smoking and taking NSAIDs, gastric and esophageal malignancies, may be important predisposing factors for rebleeding and mortality in patients with UGIB. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Clinical utility of new bleeding criteria: a prospective study of evaluation for the Bleeding Academic Research Consortium definition of bleeding in patients undergoing percutaneous coronary intervention.

PubMed

Choi, Jae-Hyuk; Seo, Jeong-Min; Lee, Dong Hyun; Park, Kyungil; Kim, Young-Dae

2015-04-01

The aim of this study was to evaluate the clinical utility of the new bleeding criteria, proposed by the Bleeding Academic Research Consortium (BARC), compared with the old criteria for determining the action of physicians in contact with bleeding events, after percutaneous coronary intervention (PCI). The BARC criteria were independently associated with an increased risk of 1-year mortality after PCI, and provided a predictive value, in regard to 1-year mortality. The standardized bleeding definitions will be expected to help the physician to correctly analyze the bleeding events, to select an optimal treatment, and to objectively compare the results of multiple trials and registries. All the patients undergoing PCI from June to September 2012 were prospectively enrolled. Patients who experienced a bleeding event were further classified, based on three different bleeding severity criteria: BARC, Thrombolysis In Myocardial Infarction (TIMI), and Global Use of Strategies To Open coronary arteries (GUSTO). The primary outcome was the occurrence of bleeding events requiring interruption of antiplatelet therapy (IAT) by physicians. A total of 376 consecutive patients were included in this study. Total bleeding events occurred in 46 patients (12.2%). BARC type ≥2 bleeding occurred in 30 patients (8.0%); however, TIMI major or minor bleeding, and GUSTO moderate or severe bleeding occurred in 6 (1.6%) and 11 patients (2.9%), respectively. Of the 46 patients, 28 (60.9% of patients) required IAT. On receiver-operating characteristic curve analysis, bleeding defined BARC type ≥2 effectively predicted IAT, with a sensitivity of 89.3%, and a specificity of 98.5% (p<0.001), compared with TIMI (sensitivity, 21.4%; specificity, 100%; p<0.001), and GUSTO (sensitivity, 39.3%; specificity, 100%; p<0.001). Compared with TIMI and GUSTO, the BARC definition may be a more useful tool for the detection of bleeding with clinical relevance, for patients undergoing PCI. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Vitamin K deficiency bleeding and early infant male circumcision in Africa.

PubMed

Plank, Rebeca M; Steinmetz, Tara; Sokal, David C; Shearer, Martin J; Data, Santorino

2013-08-01

Early infant (1-60 days of life) male circumcision is being trialed in Africa as a human immunodeficiency virus prevention strategy. Postcircumcision bleeding is particularly concerning where most infants are breastfed, and thus these infants are at increased risk of vitamin K deficiency bleeding. During a circumcision trial, one infant bled for 90 minutes postprocedure. After discovering he had not received standard prophylactic vitamin K, we gave 2 mg phytomenadione (vitamin K1) intramuscularly; bleeding stopped within 30 minutes. Vitamin K's extremely rapid action is not commonly appreciated. Neonatal vitamin K has been shown to be cost-effective. To increase availability and promote awareness of its importance, especially in low-resource settings where blood products and transfusions are limited, vitamin K should be included in the World Health Organization's Model List of Essential Medicines for Children.

Quebec platelet disorder: update on pathogenesis, diagnosis, and treatment.

PubMed

Blavignac, Jessica; Bunimov, Natalia; Rivard, Georges E; Hayward, Catherine P M

2011-09-01

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with reduced platelet counts and a unique gain-of-function defect in fibrinolysis due to increased expression and storage of urokinase plasminogen activator (uPA) by megakaryocytes. QPD increases risks for bleeding and its key clinical feature is delayed-onset bleeding, following surgery, dental procedures or trauma, which responds only to treatment with fibrinolytic inhibitors. The genetic cause of the disorder is a tandem duplication mutation of the uPA gene, PLAU, which upregulates uPA expression in megakaryocytes by an unknown mechanism. The increased platelet stores of uPA trigger plasmin-mediated degradation of QPD α-granule proteins. The gain-of-function defect in fibrinolysis is thought to be central to the pathogenesis of QPD bleeding as the activation of QPD platelets leads to release of uPA from α-granules and accelerated clot lysis. The purpose of this review is to summarize current knowledge on QPD pathogenesis and the recommended approaches to QPD diagnosis and treatment. Thieme Medical Publishers.

Concurrent immune-mediated haemolytic anaemia and severe thrombocytopenia in 21 dogs.

PubMed

Goggs, R; Boag, A K; Chan, D L

2008-09-13

The medical records of 21 dogs with concurrent immune-mediated haemolytic anaemia (imha) and severe thrombocytopenia (defined as an automated platelet count of less than 50x10(9)/l, confirmed by the examination of a blood smear) were reviewed. Their mean (sd) age was 5.8 (2.5) years. When compared with the 24,759 dogs in the hospital population for the same period Airedale terriers and dobermanns appeared to be over-represented with odds ratios of 22.5 (95 per cent confidence interval [ci] 5.2 to 97.9) and 7.6 (95 per cent ci 1.8 to 32.7) respectively. The median duration of the dogs' clinical signs was seven days, with a range from one to 17 days. Eleven of the dogs had a history of a tendency to bleed, and 15 had evidence of bleeding when examined. Twenty of the 21 dogs had been treated with glucocorticoids, nine with vincristine, and seven with azathioprine. Their median stay in hospital was four days, with a range from one to 17 days. The median period for which they survived after admission to hospital was five days, with a range from one to 558 days, and 16 of the 21 dogs had died or been euthanased within 30 days of their admission.

Purified polysaccharides of Geoffroea spinosa barks have anticoagulant and antithrombotic activities devoid of hemorrhagic risks.

PubMed

Souza, Racquel O S; Assreuy, Ana M S; Madeira, Juliana C; Chagas, Francisco D S; Parreiras, Luane A; Santos, Gustavo R C; Mourão, Paulo A S; Pereira, Maria G

2015-06-25

Polysaccharides were extracted from the barks of Geoffroea spinosa, purified using anion exchange chromatography and characterized by chemical and methylation analysis, complemented by infrared and NMR spectroscopies. These polysaccharides were tested for their anticoagulant, antithrombotic and antiplatelet activities and also for their effects on bleeding. Unfractionated polysaccharide contains low levels of protein and high levels of carbohydrate (including hexuronic acid). The purified polysaccharides (fractions FII and FIII) are composed of arabinose (Ara), rhamnose (Rha), hexuronic acid, small amounts of galactose, but no sulfate ester. They have highly complex structure, which was partially characterized. NMR and methylation analysis indicate that the polysaccharides have a core of α-Rhap and branches of 5-linked α-Araf. Residues of 4-linked α-GalpA are also found in the structure. The unfractionated (TPL) and fraction FIII, but not fractions FI and FII, prolonged the activated partial thromboplastin time (aPTT). TPL, FII and FIII inhibited the platelet aggregation induced by ADP. More significantly, both unfractionated and purified fractions exhibited potent antithrombotic effect (31-60%) and the fractions did not modify the bleeding tendency. These plant polysaccharides could be alternative source of new anticoagulant, antiplatelet and antithrombotic compounds devoid of the undesirable risk of hemorrhage. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Unusual Cause of GI Bleeding in a Quadriplegic: Report of a Case and Review of the Literature

PubMed Central

Joseph, Raymond E.; Epsten, Robert; Kowlessar, O. Dhodanand

1982-01-01

The authors report a case of upper gastrointestinal hemorrhage in a quadriplegic. The cause was a Mallory-Weiss tear, a previously unrecognized problem in these patients. The incidence of bleeding in patients with spinal cord injury is as high as 25 percent in the few reported series. We feel that with the increased risk of gastrointestinal bleeding in the spinal cord patient and the accompanying significant mortality, early endoscopy is essential for accurate diagnosis since clues to the presence, etiology, and severity of the bleeding are often lacking. PMID:6981707

Flavocoxid, an anti-inflammatory agent of botanical origin, does not affect coagulation or interact with anticoagulation therapies.

PubMed

Pillai, Lakshmi; Levy, Robert M; Yimam, Mesfin; Zhao, Yuan; Jia, Qi; Burnett, Bruce P

2010-06-01

Flavocoxid, a botanical, anti-inflammatory agent, nonspecifically inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase (5-LOX). Due to the concomitant use of aspirin or warfarin in many osteoarthritis (OA) patients with increased cardiovascular risk, we felt it necessary to assess the anticoagulation properties of flavocoxid. Three different studies were used: 1) a mouse model to assess effects on bleeding times when combined with aspirin; 2) the effect on platelet function as evaluated by platelet aggregation and bleed times in healthy human subjects; and 3) the effect on international normalized ratio in previously warfarinized patients with OA. Flavocoxid at a human equivalent dose (HED) of 569 mg (within the standard human dosing range of 500 mg) produced no significant increases in bleeding time in mice. There was also no inhibition or synergistic increase in bleed times when flavocoxid was combined with aspirin (370 mg HED). Flavocoxid did not significantly inhibit thromboxane production or platelet aggregation, and did not increase bleeding times in healthy volunteers. Finally, flavocoxid did not inhibit or potentiate the anticoagulant effect of warfarin. These results suggest that flavocoxid does not affect the primary or extrinsic pathways of secondary hemostasis and, by not inhibiting the anticoagulation effects of aspirin, may have utility in cardiovascular patients with OA.

Upper Gastrointestinal Bleeding in Japanese Patients Prescribed Antithrombotic Drugs: Differences in Trends over Time.

PubMed

Yamaguchi, Daisuke; Sakata, Yasuhisa; Tsuruoka, Nanae; Shimoda, Ryo; Higuchi, Toru; Sakata, Hiroyuki; Fujimoto, Kazuma; Iwakiri, Ryuichi

2014-06-01

We studied the features of upper gastrointestinal bleeding (UGIB) in patients taking antithrombotic drugs. The records of 430 patients taking antithrombotic drugs who underwent emergency endoscopy for UGIB in Saga Medical School Hospital between 2002 and 2011 were studied. We also compared the characteristics of our cohort of 11,919 patients prescribed antithrombotic drugs in our hospital between 2002 and 2011. UBGI patients of variceal bleeding were not included in this study. 186 patients presented with UGIB in the first period (2002-2006) and 244 in the second period (2007-2011). The proportion of patients infected with Helicobacter pylori was lower in the second period, while the proportion taking antithrombotic drugs rose significantly. Peptic ulcer disease was responsible for the majority of bleeding episodes; however, bleeding from other sources is increasing. In the whole cohort, the risk of UGIB was 1.08%; however, of the 31.8% who also took an acid-secretion inhibitor only 18 (0.28%) developed bleeding. In contrast, 102 (1.87%) of those not taking an acid-secretion inhibitor developed UGIB, a statistically significant difference. Risk of UGIB in Japanese patients taking antithrombotics was 1.01% and the incidence is increasing. Acid-secretion inhibitors reduced the risk of antithrombotic drug-related UGIB.

Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits.

PubMed

Lué, Alberto; Lanas, Angel

2016-12-28

Proton pump inhibitors (PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding (LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.

Bleeding complications with dual antiplatelet therapy among patients with stable vascular disease or risk factors for vascular disease: results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.

PubMed

Berger, Peter B; Bhatt, Deepak L; Fuster, Valentin; Steg, P Gabriel; Fox, Keith A A; Shao, Mingyuan; Brennan, Danielle M; Hacke, Werner; Montalescot, Gilles; Steinhubl, Steven R; Topol, Eric J

2010-06-15

Uncertainty exists about the frequency, correlates, and clinical significance of bleeding with dual antiplatelet therapy (DAPT), particularly over an extended period in a stable population. We sought to determine the frequency and time course of bleeding with DAPT in patients with established vascular disease or risk factors only; identify correlates of bleeding; and determine whether bleeding is associated with mortality. We analyzed 15 603 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, a double-blind, placebo-controlled, randomized trial comparing long-term clopidogrel 75 mg/d versus placebo; all patients received aspirin (75 to 162 mg) daily. Patients had either established stable vascular disease or multiple risk factors for vascular disease without established disease. Median follow-up was 28 months. Bleeding was assessed with the use of the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria. Severe bleeding occurred in 1.7% of the clopidogrel group versus 1.3% on placebo (P=0.087); moderate bleeding occurred in 2.1% versus 1.3%, respectively (P<0.001). The risk of bleeding was greatest the first year. Patients without moderate or severe bleeding during the first year were no more likely than placebo-treated patients to have bleeding thereafter. The frequency of bleeding was similar in patients with established disease and risk factors only. In multivariable analysis, the relationship between moderate bleeding and all-cause mortality was strong (hazard ratio, 2.55; 95% confidence interval, 1.71 to 3.80; P<0.0001), along with myocardial infarction (hazard ratio, 2.92; 95% confidence interval, 2.04 to 4.18; P<0.0001) and stroke (hazard ratio, 4.20; 95% confidence interval, 3.05 to 5.77; P<0.0001). In CHARISMA, there was an increased risk of bleeding with long-term clopidogrel. The incremental risk of bleeding was greatest in the first year and similar thereafter. Moderate bleeding was strongly associated with mortality. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00050817.

Bleeding symptoms and laboratory correlation in patients with severe von Willebrand disease.

PubMed

Metjian, A D; Wang, C; Sood, S L; Cuker, A; Peterson, S M; Soucie, J M; Konkle, B A

2009-07-01

Type 3 von Willebrand disease (VWD) is a rare bleeding disorder with markedly decreased or absent von Willebrand factor (VWF) protein, accompanied by a parallel decrease in VWF function and factor VIII (FVIII) activity. The goal of this study was to describe the population of patients enrolled in the USA Centers for Disease Control Universal Data Collection (UDC) study with type 3 VWD, defined as a VWF:Ag of <10%, and to correlate bleeding symptoms with VWF and FVIII levels. Data on 150 patients were analysed. Almost all patients experienced bleeding episodes (98%) and required blood and/or factor product treatment (92%). While oral mucosal bleeding (the site of first bleed in 54%) was most common, subsequent muscle and joint bleeds were also seen (28%, 45%, respectively), and intracranial haemorrhage occurred in 8% of individuals. Mean age of first bleed was lower in those with either a FVIII < or =5% or a VWF:Ag <1%. Univariate marginal model analysis showed lower levels of FVIII and VWF:Ag both predicted a higher risk of joint bleeding. Longitudinal multivariate analysis found a lower FVIII level (P = 0.03), increasing age (P < 0.0001), history of joint bleeding (P = 0.001), higher body mass index (BMI) (P < 0.0001), and use of home infusion (P = 0.02) were all negatively associated with joint mobility. Low levels of VWF:Ag (P = 0.003) and male sex (P = 0.007) were also negatively associated with joint function. This study documents the strong bleeding phenotype in severe VWD and provides data to help target therapy, including prophylaxis, for patients most at risk of bleeding complications.

Meta-analysis shows similar re-bleeding rates among Western and Eastern populations after index video capsule endoscopy.

PubMed

Tziatzios, Georgios; Gkolfakis, Paraskevas; Hassan, Cesare; Toth, Ervin; Zullo, Angelo; Koulaouzidis, Anastasios; Dimitriadis, George D; Triantafyllou, Konstantinos

2018-03-01

Video capsule endoscopy (VCE) is the first-line diagnostic procedure for investigating obscure gastrointestinal bleeding (OGIB). Different re-bleeding rates following index VCE have been reported among Western and Eastern studies. We conducted a comprehensive literature search to identify studies examining re-bleeding rates after VCE for OGIB. Meta-analysis assessed the pooled proportion of re-bleeding events after VCE for OGIB according to study's origin (Western vs. Eastern) and according to the length of follow-up (≥24 months vs. <24 months). We also calculated the re-bleeding odds ratios (OR; 95% CI) after positive vs. negative index VCE, overt vs. occult initial presentation of bleeding and after interventional treatment for positive index cases, according to the study's origin. We included 46 (30 Western and 16 Eastern) studies with 5796 patients. Significant heterogeneity was detected among meta-analyzed studies. Overall, the pooled re-bleeding rate was similar between Western (29%; 95% CI: 23-34) and Eastern (21%; 95% CI: 15-27) populations, irrespective of the length of follow-up. The odds of re-bleeding was significantly higher after positive as compared to negative index VCE in Eastern studies (OR: 1.77; 95% CI: 1.07-2.94). Application of specific treatment after positive index VCE was associated with lower re-bleeding odds in both Western (OR: 0.37; 95% CI: 0.16-0.87) and Eastern (OR: 0.39; 95% CI: 0.21-0.72) populations. Patients undergoing VCE for OGIB have similar re-bleeding rates in the East and the West, regardless of the length of follow-up. However, increased re-bleeding odds after positive index VCE is observed in Eastern studies. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Association between gastrointestinal bleeding and 3-year mortality in patients with acute, first-ever ischemic stroke.

PubMed

Chou, Yu-Fang; Weng, Wei-Chieh; Huang, Wen-Yi

2017-10-01

The influence of gastrointestinal bleeding on clinical presentation and outcomes of patients with acute ischemic stroke remains controversial. We investigate the effect of gastrointestinal bleeding on the outcomes of patients with acute, first-ever ischemic stroke. We enrolled 934 patients with acute, first-ever ischemic stroke and followed up them for 3years. Patients were divided into 2 groups according to the presence or absence of gastrointestinal bleeding during acute stroke stage. Clinical presentation, stroke risk factors, laboratory data, co-morbidities, and outcomes were recorded. Seventy-six (8.1%) patients had gastrointestinal bleeding at admission. The prevalence of old age, atrial fibrillation, and previous transient ischemic attack was higher in patients with gastrointestinal bleeding (P<0.001, P=0.038, and P=0.018, respectively). Total anterior circulation syndrome occurred more frequently among patients with gastrointestinal bleeding (P<0.001). The mean length of acute ward stay, initial impaired consciousness, and stroke in evolution were higher in patients with gastrointestinal bleeding (P<0.001, P<0.001, and P<0.001, respectively). The occurrence of pneumonia and dependent functional outcome were higher in patients with gastrointestinal bleeding (P<0.001 and P<0.001, respectively). A multivariate Cox regression analysis revealed that gastrointestinal bleeding is a significant risk factor for 3-year all-cause mortality (hazard ratio=2.76; 95% confidence interval=1.61-4.72; P<0.001). In conclusion, gastrointestinal bleeding is associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke. Prophylactic therapies for gastrointestinal bleeding might improve ischemic stroke outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Red blood cell transfusion is associated with further bleeding and fresh-frozen plasma with mortality in nonvariceal upper gastrointestinal bleeding.

PubMed

Subramaniam, Kavitha; Spilsbury, Katrina; Ayonrinde, Oyekoya T; Latchmiah, Faye; Mukhtar, Syed A; Semmens, James B; Leahy, Michael F; Olynyk, John K

2016-04-01

Blood products are commonly transfused for patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). While concerns exist about further bleeding and mortality in subsets of patients receiving red blood cell (RBC) transfusion, the impact of non-RBC blood products has not previously been systematically investigated. The aim of the study was to investigate the associations between blood products transfusion, further bleeding, and mortality after acute NVUGIB. A retrospective cohort study examined further bleeding and 30-day and 1-year mortality in adult patients who underwent gastroscopy for suspected acute NVUGIB between 2008 and 2010 in three tertiary hospitals in Western Australia. Survival analysis was performed. A total of 2228 adults (63% male) with 2360 hospital admissions for NVUGIB met the inclusion criteria. Median age at presentation was 70 years (range, 19-99 years). Thirty-day mortality was 4.9% and 1-year mortality was 13.9%. Transfusion of 4 or more units of RBCs was associated with greater than 10 times the odds of further bleeding in patients with a hemoglobin level of more than 90 g/L (odds ratio, 11.9; 95% confidence interval [CI], 3.1-45.7; p ≤ 0.001), but was not associated with mortality. Administration of 5 or more units of fresh-frozen plasma (FFP) was associated with increased 30-day (hazard ratio, 2.8; 95% CI, 1.3-5.9; p = 0.008) and 1-year (hazard ratio, 2.6; 95% CI, 1.3-5.0; p = 0.005) mortality after adjusting for coagulopathy, comorbidity, Rockall score, and other covariates. In this large, multicenter study of NVUGIB, RBC transfusion was associated with further bleeding but not mortality, while FFP transfusion was associated with increased mortality in a subset of patients. © 2015 AABB.

Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry

PubMed Central

Förster, Kati; Pannach, Sven; Ebertz, Franziska; Gelbricht, Vera; Thieme, Christoph; Michalski, Franziska; Köhler, Christina; Werth, Sebastian; Sahin, Kurtulus; Tittl, Luise; Hänsel, Ulrike; Weiss, Norbert

2014-01-01

Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, but little is known about rivaroxaban-related bleeding complications in daily care. Using data from a prospective, noninterventional oral anticoagulation registry of daily care patients (Dresden NOAC registry), we analyzed rates, management, and outcome of rivaroxaban-related bleeding. Between October 1, 2011, and December 31, 2013, 1776 rivaroxaban patients were enrolled. So far, 762 patients (42.9%) reported 1082 bleeding events during/within 3 days after last intake of rivaroxaban (58.9% minor, 35.0% of nonmajor clinically relevant, and 6.1% major bleeding according to International Society on Thrombosis and Haemostasis definition). In case of major bleeding, surgical or interventional treatment was needed in 37.8% and prothrombin complex concentrate in 9.1%. In the time-to-first-event analysis, 100-patient-year rates of major bleeding were 3.1 (95% confidence interval 2.2-4.3) for stroke prevention in atrial fibrillation and 4.1 (95% confidence interval 2.5-6.4) for venous thromboembolism patients, respectively. In the as-treated analysis, case fatality rates of bleeding leading to hospitalizations were 5.1% and 6.3% at days 30 and 90 after bleeding, respectively. Our data indicate that, in real life, rates of rivaroxaban-related major bleeding may be lower and that the outcome may at least not be worse than that of major vitamin K antagonist bleeding, and probably better. This trial was registered at www.clinicaltrials.gov as identifier #NCT01588119. PMID:24859362

Continuous Aspirin Use Does Not Increase Bleeding Risk of Split-Thickness Skin Transplantation Repair to Chronic Wounds.

PubMed

Sun, Yanwei; Wang, Yibing; Li, Liang; Zhang, Zheng; Wang, Ning; Wu, Dan

Discontinuation of aspirin therapy before cutaneous surgery may cause serious complications. The aim of this prospective study was to evaluate the bleeding risk of split-thickness skin transplantation repair to chronic wounds in patients on aspirin therapy. A total of 97 patients who underwent split-thickness skin transplantation surgery of chronic wounds during a 2-year period were enrolled. They were categorized on the basis of aspirin therapies. The primary outcome was postoperative bleeding and bleeding complications. Univariate analysis was performed to examine the association between aspirin and bleeding complications. Among the 26 patients taking aspirin continuously in group A, there were 5 bleeding complications (19.23%). Among the 55 nonusers in group B, there were 10 bleeding complications (18.18%). Among the 16 discontinuous patients in group C, there were 3 bleeding complications (18.75%). No statistical differences were found among the groups ( P = .956). Univariate analysis showed that continuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.933; 95% confidence interval, 0.283-3.074; P = .910 in the aspirin and control groups) and that discontinuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.963; 95% confidence interval, 0.230-4.025; P = .959 in the aspirin and control groups; odds ratio, 0.969; 95% confidence interval, 0.198-4.752; P = .969 in the aspirin and discontinuous groups). Continuous aspirin use does not produce an additional bleeding risk in patients who undergo split-thickness skin transplantation repair of chronic wounds.

Evaluation of bleeding in patients receiving direct oral anticoagulants

PubMed Central

Hellenbart, Erika L; Faulkenberg, Kathleen D; Finks, Shannon W

2017-01-01

Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants. PMID:28860793

Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

PubMed

DiMarco, John P; Flaker, Gregory; Waldo, Albert L; Corley, Scott D; Greene, H Leon; Safford, Robert E; Rosenfeld, Lynda E; Mitrani, Gladys; Nemeth, Margit

2005-04-01

Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation. The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates. The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits. Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.

Potential Harm of Prophylactic Platelet Transfusion in Adult Dengue Patients.

PubMed

Lee, Tau-Hong; Wong, Joshua G X; Leo, Yee-Sin; Thein, Tun-Linn; Ng, Ee-Ling; Lee, Linda K; Lye, David C

2016-03-01

Thrombocytopenia is a hallmark of dengue infection, and bleeding is a dreaded complication of dengue fever. Prophylactic platelet transfusion has been used to prevent bleeding in the management of dengue fever, although the evidence for its benefit is lacking. In adult dengue patients with platelet count <20,000/mm3 without bleeding, we aimed to assess if prophylactic platelet transfusion was effective in reducing clinical bleeding and other outcomes. We conducted a retrospective non-randomised observational study of dengue patients with platelet count < 20,000/mm3 without bleeding (except petechiae) admitted to Tan Tock Seng Hospital from January 2005 to December 2008. Baseline characteristics and clinical outcomes were compared between the non-transfused vs. transfused groups. Outcomes studied were clinical bleeding, platelet increment, hospital length of stay, intensive care unit admission and death. Of the 788 patients included, 486 received prophylactic platelet transfusion. There was no significant difference in the presence of clinical bleeding in the two groups (18.2% in non-transfused group vs. 23.5% in transfused group; P = 0.08). Patients in the transfused group took a median of 1 day longer than the non-transfused group to increase their platelet count to 50,000/mm3 or more (3 days vs. 2 days, P <0.0001). The median duration of hospital stay in the non-transfused group was 5 days vs. 6 days in the transfused group (P< 0.0001). There was no significant difference in the proportion requiring ICU admission (non-transfused 0.66% vs. transfused 1.23%, P = 0.44) and death (non-transfused 0% vs. transfused 0.2%, P = 0.43). Platelet transfusion in absence of bleeding in adult dengue with platelet count <20,000/mm3 did not reduce bleeding or expedite platelet recovery. There was potential harm by slowing recovery of platelet count to >50,000/mm3 and increasing length of hospitalization.

Routine perioperative ketorolac administration is not associated with hemorrhage in pediatric neurosurgery patients.

PubMed

Richardson, Marlin Dustin; Palmeri, Nicholas O; Williams, Sarah A; Torok, Michelle R; O'Neill, Brent R; Handler, Michael H; Hankinson, Todd C

2016-01-01

OBJECT NSAIDs are effective perioperative analgesics. Many surgeons are reluctant to use NSAIDs perioperatively because of a theoretical increase in the risk for bleeding events. The authors assessed the effect of routine perioperative ketorolac use on intracranial hemorrhage in children undergoing a wide range of neurosurgical procedures. METHODS A retrospective single-institution analysis of 1451 neurosurgical cases was performed. Data included demographics, type of surgery, and perioperative ketorolac use. Outcomes included bleeding events requiring return to the operating room, bleeding seen on postoperative imaging, and the development of renal failure or gastrointestinal tract injury. Variables associated with both the exposure and outcomes (p < 0.20) were evaluated as potential confounders for bleeding on postoperative imaging, and multivariable logistic regression was performed. Bivariable analysis was performed for bleeding events. Odds ratios and 95% CIs were estimated. RESULTS Of the 1451 patients, 955 received ketorolac. Multivariate regression analysis demonstrated no significant association between clinically significant bleeding events (OR 0.69; 95% CI 0.15-3.1) or radiographic hemorrhage (OR 0.81; 95% CI 0.43-1.51) and the perioperative administration of ketorolac. Treatment with a medication that creates a known bleeding risk (OR 3.11; 95% CI 1.01-9.57), surgical procedure (OR 2.35; 95% CI 1.11-4.94), and craniotomy/craniectomy (OR 2.43; 95% CI 1.19-4.94) were associated with a significantly elevated risk for radiographically identified hemorrhage. CONCLUSIONS Short-term ketorolac therapy does not appear to be associated with a statistically significant increase in the risk of bleeding documented on postoperative imaging in pediatric neurosurgical patients and may be considered as part of a perioperative analgesic regimen. Although no association was found between ketorolac and clinically significant bleeding events, a larger study needs to be conducted to control for confounding factors, because of the rarity of these events.

Statins are associated with lower risk of gastrointestinal bleeding in patients with unstable coronary syndromes: analysis of the Orbofiban in Patients with Unstable coronary Syndromes-Thrombolysis In Myocardial Infarction 16 (OPUS-TIMI 16) trial.

PubMed

Atar, Shaul; Cannon, Christopher P; Murphy, Sabina A; Rosanio, Salvatore; Uretsky, Barry F; Birnbaum, Yochai

2006-05-01

It has recently been shown that statins increase the myocardial content of prostaglandin (PG) I2 (prostacyclin) and PGE2. A systemic increase of PG production may protect the gastric mucosa and prevent gastrointestinal (GI) bleeding. We hypothesized that statins would lower the risk of GI bleeding associated with antiplatelet therapy in patients with acute coronary syndromes (ACS). We retrospectively analyzed data on 10288 patients with ACS included in the OPUS-TIMI 16 trial and received aspirin and either the oral IIb/IIIa inhibitor orbofiban or placebo. Inhospital GI bleeding rate was significantly lower in patients who were receiving lipid-lowering drugs before admission compared with those who were not (0.2% vs 0.6%, P = .031). Throughout 10 months of follow-up, GI bleeding occurred in 1.8% of non-statin users compared with 1.0% of statin users (P = .001). Statin use was associated with less overall bleeding in both the orbofiban (1.4% vs 2.4%, P = .006) and the placebo groups (0.2% vs 0.8%, P = .047). Severe and major bleeding occurred less frequently with statin use (0.8% vs 1.5%, P = .001) in both the orbofiban (1.1% vs 2.0%, P = .006) and the placebo groups (0.1% vs 0.5%, P = .119). Logistic regression analysis showed that age > 65 years, orbofiban treatment, Killip class > 1, history of cerebrovascular disease, and calcium-channel blocker use were associated with higher risk of GI bleeding, whereas statin therapy was associated with a lower risk (odds ratio 0.68, 95% CI 0.45-1.04, P = .079). Statins may exert protective effect against GI bleeding in patients with ACS. Additional studies are warranted to explore this additional potential benefit of statins.

Association of preoperative plasma fibrinogen level with postoperative bleeding after on-pump coronary bypass surgery: does plasma fibrinogen level affect the amount of postoperative bleeding?

PubMed

Alagha, Sameh; Songur, Murat; Avci, Tugba; Vural, Kerem; Kaplan, Sadi

2018-05-15

Our primary aim was to investigate the association between the preoperative concentration of plasma fibrinogen and the volume of postoperative bleeding. Our secondary aim was to identify whether there is a possible correlation between the patients' different characteristics and haemostatic laboratory variables and the postoperative amount of bleeding after on-pump coronary artery bypass grafting procedures. A total of 550 adult patients undergoing isolated coronary artery bypass grafting on cardiopulmonary bypass in our hospital were enrolled and investigated retrospectively. The total amount of chest tube drainage within the first 24 postoperative hours or until the patient was re-explored for bleeding was assessed. Excessive bleeding was defined as more than 500 ml drainage in the first 24 h. The patients were divided into 2 groups: Group 1: the patients who bled ≤500 ml in the first 24 h and Group 2: the patients who bled >500 ml in the first 24 h. A preoperative fibrinogen threshold associated with excessive bleeding was investigated by receiver operating characteristic curve analyses, revealing a calculated cutoff value of 3.1 g/l. Risk factors for increased bleeding were analysed by a logistic regression model that revealed male gender (P < 0.001), body mass index ≤28.3 kg/m2 (P < 0.001), platelet count ≤233 × 103/µl (P < 0.001), estimated glomerular filtration rate ≤90.8 ml/min (P < 0.001) and fibrinogen ≤3.1 g/l (P = 0.01) as significant predictors. A preoperative plasma fibrinogen concentration <3.1 g/l was associated with increased risk of excessive bleeding in patients undergoing on-pump coronary artery bypass grafting. The amount of postoperative blood loss can be roughly predicted with simple preoperative blood tests.

Bleeding risks of herbal, homeopathic, and dietary supplements: a hidden nightmare for plastic surgeons?

PubMed

Wong, Wendy W; Gabriel, Allen; Maxwell, G Patrick; Gupta, Subhas C

2012-03-01

The utilization of complementary and alternative medicine has increased tremendously in the last two decades. Herbal products, homeopathic medicines, and dietary supplements are extremely popular and are available without a prescription (which likely contributes to their popularity). Despite their "natural" characteristics, these remedies have the potential to cause bleeding in patients who undergo surgery. The high use of these supplements among cosmetic surgery patients, coupled with increasing reports of hematomas associated with herbal and homeopathic medicines, prompted the authors to conduct a comprehensive review focused on bleeding risks of such products in an effort to raise awareness among plastic surgeons. This review focuses on 19 herbs, three herbal formulas, two herbal teas, and several other supplements that can cause bleeding perioperatively and postoperatively. In addition to being aware of such adverse effects, plastic surgeons must adequately screen all patients and educate them on the possible dangers associated with these treatments.

Advances in gastrointestinal bleeding.

PubMed

Lanas, Ángel

2016-09-01

The main innovations of the latest meeting of the Gastroenterological Association (2016) concerning upper gastrointestinal bleeding from the clinician's perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the best accuracy in predicting the need for surgical intervention and hospital mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest that treatment with hemospray does not seem to be superior to current standard treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a proton pump inhibitor may be effective in preventing haemorrhagic recurrence in patients taking aspirin, but this finding needs to be confirmed in further studies; e) There was confirmation of the need to re-introduce antiplatelet therapy as early as possible in patients with antiplatelet-associated gastrointestinal bleeding in order to prevent cardiovascular mortality; f) Routine clinical practice suggests that gastrointestinal or cardiovascular complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is associated with an increased incidence of gastrointestinal bleeding compared with apixaban or warfarin. At least half of the episodes are located in the lower gastrointestinal tract; h) Implant devices for external ventricular circulatory support are associated with early gastrointestinal bleeding in up to one third of patients; the bleeding is often secondary to arteriovenous malformations. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Risk factors for adverse in-hospital outcomes in acute colonic diverticular hemorrhage

PubMed Central

Nagata, Naoyoshi; Niikura, Ryota; Aoki, Tomonori; Moriyasu, Shiori; Sakurai, Toshiyuki; Shimbo, Takuro; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Yokoi, Chizu; Akiyama, Junichi; Yanase, Mikio; Mizokami, Masashi; Fujimoto, Kazuma; Uemura, Naomi

2015-01-01

AIM: To investigate the factors associated with transfusion, further bleeding, and prolonged length of stay. METHODS: In total, 153 patients emergently hospitalized for diverticular bleeding who were examined by colonoscopy were prospectively enrolled. Patients in whom the bleeding source was identified received endoscopic treatment such as clipping or endoscopic ligation. After spontaneous cessation of bleeding with conservative treatment or hemostasis with endoscopic treatment, all patients were started on a liquid food diet and gradually progressed to a solid diet over 3 d, and were discharged. At enrollment, we assessed smoking, alcohol, medications [non-steroidal anti-inflammatory drugs (NSAIDs)], low-dose aspirin, and other antiplatelets, warfarin, acetaminophen, and oral corticosteroids), and co-morbidities [hypertension, diabetes mellitus, dyslipidemia, cerebro-cardiovascular disease, chronic liver disease, and chronic kidney disease (CKD)]. The in-hospital outcomes were need for transfusion, further bleeding after spontaneous cessation of hemorrhage, and length of hospital stay. The odds ratio (OR) for transfusion need, further bleeding, and prolonged length of stay were estimated by logistic regression analysis. RESULTS: No patients required angiographic embolization or surgery. Stigmata of bleeding occurred in 18% of patients (27/153) and was treated by endoscopic procedures. During hospitalization, 40 patients (26%) received a median of 6 units of packed red blood cells. Multivariate analysis revealed that female sex (OR = 2.5, P = 0.02), warfarin use (OR = 9.3, P < 0.01), and CKD (OR = 5.9, P < 0.01) were independent risk factors for transfusion need. During hospitalization, 6 patients (3.9%) experienced further bleeding, and NSAID use (OR = 5.9, P = 0.04) and stigmata of bleeding (OR = 11, P < 0.01) were significant risk factors. Median length of hospital stay was 8 d. Multivariate analysis revealed that age > 70 years (OR = 2.1, P = 0.04) and NSAID use (OR = 2.7, P = 0.03) were independent risk factors for prolonged hospitalization (≥ 8 d). CONCLUSION: In colonic diverticular bleeding, female sex, warfarin, and CKD increased the risk of transfusion requirement, while advanced age and NSAID increased the risk of prolonged hospitalization. PMID:26457031

Pentasaccharides in the prophylaxis and treatment of venous thromboembolism: a systematic review.

PubMed

Nijkeuter, M; Huisman, M V

2004-09-01

The aim of this review is to perform a critical analysis of all completed studies evaluating pentasaccharides-synthetically derived, selective inhibitors of activated factor X-in prophylaxis in major orthopedic surgery and the treatment of venous thromboembolism. Venous thromboembolism is a disorder with considerable morbidity when left untreated. New antithrombotic agents have been developed that selectively inhibit components of the coagulation system, thereby avoiding the difficulties associated with current anticoagulants. The pentasaccharides fondaparinux and idraparinux are the first of a new class of synthetic selective inhibitors of activated factor X. Fondaparinux has been extensively investigated in two areas: orthopedic surgery and venous thromboembolism. It is clear from four thromboprophylaxis studies in major orthopedic surgery that fondaparinux is 50% more effective in reducing venous thromboembolism than enoxaparin. This superior efficacy led to an overall increase in major bleeding, which was however primarily due to more fondaparinux-treated patients with bleeding indexes of 2 or greater. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two groups. In the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, fondaparinux was equally effective as low molecular weight heparins and unfractionated heparin, respectively, without a different incidence in major bleeding in fondaparinux and comparator heparin groups. Fondaparinux, one of the first of a new class of synthetic selective factor Xa inhibitors, is overall 50% more effective in reducing venous thromboembolism than enoxaparin in major orthopedic surgery, with an overall 1% increased rate of major bleeding, when compared with enoxaparin. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two treatment groups. Fondaparinux is equally effective as low molecular weight heparins and unfractionated heparin in the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, respectively. Finally, as with any new drug, fondaparinux should be used cautiously and only in patients who reflect the population of the clinical trials in which the drug was evaluated.

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

PubMed Central

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin in prevention of cardiovascular events. PMID:27490468

A genetically-engineered von Willebrand disease type 2B mouse model displays defects in hemostasis and inflammation.

PubMed

Adam, Frédéric; Casari, Caterina; Prévost, Nicolas; Kauskot, Alexandre; Loubière, Cécile; Legendre, Paulette; Repérant, Christelle; Baruch, Dominique; Rosa, Jean-Philippe; Bryckaert, Marijke; de Groot, Philip G; Christophe, Olivier D; Lenting, Peter J; Denis, Cécile V

2016-05-23

von Willebrand disease (VWD)-type 2B is characterized by gain-of-function mutations in the von Willebrand factor (VWF) A1-domain, leading to increased affinity for its platelet-receptor, glycoprotein Ibα. We engineered the first knock-in (KI) murine model for VWD-type 2B by introducing the p.V1316M mutation in murine VWF. Homozygous KI-mice replicated human VWD-type 2B with macrothrombocytopenia (platelet counts reduced by 55%, platelet volume increased by 44%), circulating platelet-aggregates and a severe bleeding tendency. Also, vessel occlusion was deficient in the FeCl3-induced thrombosis model. Platelet aggregation induced by thrombin or collagen was defective for KI-mice at all doses. KI-mice manifested a loss of high molecular weight multimers and increased multimer degradation. In a model of VWF-string formation, the number of platelets/string and string-lifetime were surprisingly enhanced in KI-mice, suggesting that proteolysis of VWF/p.V1316M is differentially regulated in the circulation versus the endothelial surface. Furthermore, we observed increased leukocyte recruitment during an inflammatory response induced by the reverse passive Arthus reaction. This points to an active role of VWF/p.V1316M in the exfiltration of leukocytes under inflammatory conditions. In conclusion, our genetically-engineered VWD-type 2B mice represent an original model to study the consequences of spontaneous VWF-platelet interactions and the physiopathology of this human disease.

Preoperative platelet transfusions to reverse antiplatelet therapy for urgent non-cardiac surgery: an observational cohort study.

PubMed

Baschin, M; Selleng, S; Hummel, A; Diedrich, S; Schroeder, H W; Kohlmann, T; Westphal, A; Greinacher, A; Thiele, T

2018-04-01

Essentials An increasing number of patients requiring surgery receive antiplatelet therapy (APT). We analyzed 181 patients receiving presurgery platelet transfusions to reverse APT. No coronary thrombosis occurred after platelet transfusion. This justifies a prospective trial to test preoperative platelet transfusions to reverse APT. Background Patients receiving antiplatelet therapy (APT) have an increased risk of perioperative bleeding and cardiac adverse events (CAE). Preoperative platelet transfusions may reduce the bleeding risk but may also increase the risk of CAE, particularly coronary thrombosis in patients after recent stent implantation. Objectives To analyze the incidence of perioperative CAE and bleeding in patients undergoing non-cardiac surgery using a standardized management of transfusing two platelet concentrates preoperatively and restart of APT within 24-72 h after surgery. Methods A cohort of consecutive patients on APT treated with two platelet concentrates before non-cardiac surgery between January 2012 and December 2014 was retrospectively identified. Patients were stratified by the risk of major adverse cardiac and cerebrovascular events (MACCE). The primary objective was the incidence of CAE (myocardial infarction, acute heart failure and cardiac troponine T increase). Secondary objectives were incidences of other thromboembolic events, bleedings, transfusions and mortality. Results Among 181 patients, 88 received aspirin, 21 clopidogrel and 72 dual APT. MACCE risk was high in 63, moderate in 103 and low in 15 patients; 67 had cardiac stents. Ten patients (5.5%; 95% CI, 3.0-9.9%) developed a CAE (three myocardial infarctions, four cardiac failures and three troponin T increases). None was caused by coronary thrombosis. Surgery-related bleeding occurred in 22 patients (12.2%; 95% CI, 8.2-17.7%), making 12 re-interventions necessary (6.6%; 95% CI, 3.8-11.2%). Conclusion Preoperative platelet transfusions and early restart of APT allowed urgent surgery and did not cause coronary thromboses, but non-thrombotic CAEs and re-bleeding occurred. Randomized trials are warranted to test platelet transfusion against other management strategies. © 2018 International Society on Thrombosis and Haemostasis.

Pooled analysis of two randomized, open-label studies comparing the effects of nomegestrol acetate/17β-estradiol and drospirenone/ethinyl estradiol on bleeding patterns in healthy women.

PubMed

Mansour, Diana; Westhoff, Carolyn; Kher, Uma; Korver, Tjeerd

2017-04-01

To obtain more precise and detailed information regarding the bleeding patterns of nomegestrol acetate (NOMAC)/17β-estradiol (E2) and drospirenone/ethinyl estradiol (DRSP/EE) and to identify whether baseline demographic characteristics were associated with unscheduled bleeding, absent scheduled bleeding, or amenorrhea. This analysis pooled results from two pivotal open-label, randomized trials that compared bleeding patterns of NOMAC/E2 and DRSP/EE. In the two studies 4317 women aged 18-50 years from 24 countries across the Americas, Europe, and Asia underwent treatment. 2835 women taking NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen and 938 women taking DRSP/EE (3 mg/30 μg) in a 21/7-day regimen had at least 1 evaluable cycle for vaginal bleeding analyses. The frequency of absent scheduled bleeding was higher (p<.0001) for women using NOMAC/E2 than DRSP/EE across all 11 cycles (cycles 2-12), ranging between 17.6% and 31.6% and between 3.4% and 5.8%, respectively. For women who had absent scheduled bleeding in cycles 2, 3, or 4 the incidence of absent scheduled bleeding in subsequent cycles was high and ranged between approximately 50%-60% for NOMAC/E2 and approximately 40%-50% for DRSP/EE. Amenorrhea increased over time with both regimens, being higher with NOMAC/E2. Both absent scheduled bleeding and amenorrhea with NOMAC/E2 were more common in older women, overweight women, switchers, and smokers; unscheduled bleeding was more common in starters, but had no association with age, body mass index, and smoking. NOMAC/E2 is associated with a higher prevalence of absent scheduled bleeding compared with DRSP/EE. Absent scheduled bleeding and amenorrhea were associated with age, body weight, switching and smoking. Unscheduled bleeding was more common in starters. Information about the factors associated with bleeding patterns may help clinicians provide guidance to women considering use of the NOMAC/E2 oral contraceptive. Copyright © 2016 Elsevier Inc. All rights reserved.

Cancer in heart disease patients: what are the limitations in the treatment strategy?

PubMed

Mistiaen, Wilhelm P

2013-07-01

Cardiovascular disease and cancer are leading causes of morbidity and mortality, and can both be present in one patient. In patients with simultaneous disease, the most threatening disease should be treated first. This is usually heart disease, but this can pose specific problems. If percutaneous coronary intervention is preferred, bleeding and thrombotic tendencies have to be taken into account in the subsequent treatment of the malignancy. With coronary artery bypass grafting, the advantages and disadvantages of one- or two-stage procedures, and the use of extracorporeal circulation have to be balanced. Development of heart disease after treatment of malignancy could be due to radiotherapy and chemotherapy. The effects of these cancer treatments have to be taken into account for the treatment options of the heart disease and the postoperative prognosis.

Growth differentiation factor-15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes: results from the PLATO study.

PubMed

Hagström, Emil; James, Stefan K; Bertilsson, Maria; Becker, Richard C; Himmelmann, Anders; Husted, Steen; Katus, Hugo A; Steg, Philippe Gabriel; Storey, Robert F; Siegbahn, Agneta; Wallentin, Lars

2016-04-21

Growth differentiation factor-15 (GDF-15) predicts death and composite cardiovascular (CV) events in patients with acute coronary syndrome (ACS). We investigated the independent associations between GDF-15 levels and major bleeding, the extent of coronary lesions and individual CV events in patients with ACS. Growth differentiation factor-15 was analysed at baseline ( ITALIC! n = 16 876) in patients with ACS randomized to ticagrelor or clopidogrel in the PLATO (PLATelet inhibition and patient Outcomes) trial. Growth differentiation factor-15 levels were related to extent of coronary artery disease (CAD) and to all types of non-coronary artery bypass grafting (CABG)-related major bleeding, spontaneous myocardial infarction (MI), stroke, and death during 12-month follow-up. In Cox proportional hazards models adjusting for established risk factors for CV disease and prognostic biomarkers (N-terminal pro B-type natriuretic peptide, cystatin C, high-sensitive C-reactive protein, and high-sensitive troponin T), 1 SD increase in ln GDF-15 was associated with increased risk of major bleeding with a hazard ratio (HR) 1.37 (95% confidence interval: 1.25-1.51) and with a similar increase in risk across different bleeding locations. For the same increase in ln GDF-15, the HR for the composite of CV death, spontaneous MI, and stroke was 1.29 (1.21-1.37), CV death 1.41 (1.30-1.53), all-cause death 1.41 (1.31-1.53), spontaneous MI 1.15 (1.05-1.26), and stroke 1.19 (1.01-1.42). The ITALIC! C-statistic improved for the prediction of CV death and non-CABG-related major bleeding when adding GDF-15 to established risk factors. In patients with ACS, higher levels of GDF-15 are associated with raised risks of all types of major non-CABG-related bleeding, spontaneous MI, and stroke as well as CV and total mortality and seem to improve risk stratification for CV-mortality and major bleeding beyond established risk factors. www.clinicaltrials.gov; NCT00391872. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Agonist-induced platelet reactivity correlates with bleeding in haemato-oncological patients.

PubMed

Batman, B; van Bladel, E R; van Hamersveld, M; Pasker-de Jong, P C M; Korporaal, S J A; Urbanus, R T; Roest, M; Boven, L A; Fijnheer, R

2017-11-01

Prophylactic platelet transfusions are administered to prevent bleeding in haemato-oncological patients. However, bleeding still occurs, despite these transfusions. This practice is costly and not without risk. Better predictors of bleeding are needed, and flow cytometric evaluation of platelet function might aid the clinician in identifying patients at risk of bleeding. This evaluation can be performed within the hour and is not hampered by low platelet count. Our objective was to assess a possible correlation between bleeding and platelet function in thrombocytopenic haemato-oncological patients. Inclusion was possible for admitted haemato-oncology patients aged 18 years and above. Furthermore, an expected need for platelet transfusions was necessary. Bleeding was graded according to the WHO bleeding scale. Platelet reactivity to stimulation by either adenosine diphosphate (ADP), cross-linked collagen-related peptide (CRP-xL), PAR1- or PAR4-activating peptide (AP) was measured using flow cytometry. A total of 114 evaluations were available from 21 consecutive patients. Platelet reactivity in response to stimulation by all four studied agonists was inversely correlated with significant bleeding. Odds ratios (OR) for bleeding were 0·28 for every unit increase in median fluorescence intensity (MFI) [95% confidence interval (CI) 0·11-0·73] for ADP; 0·59 [0·40-0·87] for CRP-xL; 0·59 [0·37-0·94] for PAR1-AP; and 0·43 [0·23-0·79] for PAR4-AP. The platelet count was not correlated with bleeding (OR 0·99 [0·96-1·02]). Agonist-induced platelet reactivity was significantly correlated to bleeding. Platelet function testing could provide a basis for a personalized transfusion regimen, in which platelet transfusions are limited to those at risk of bleeding. © 2017 International Society of Blood Transfusion.

Post-tonsillectomy hemorrhagic outcomes in children with bleeding disorders at a single institution.

PubMed

Patel, Priyesh N; Arambula, Alexandra M; Wheeler, Allison P; Penn, Edward B

2017-09-01

To report on the post-tonsillectomy bleeding outcomes and factors associated with hemorrhage among children with pre- or post-operatively diagnosed bleeding disorders treated with an institutional protocol. Retrospective cohort study of patients with hematologic disorders who underwent tonsillectomy between 2003 and 2016 and were treated with perioperative desmopressin or factor replacement and/or aminocaproic acid. Postoperative outcomes were compared to controls matched for age, sex, and indication for surgery. Analysis of factors associated with hemorrhage was performed in patients with bleeding disorders using Mann-Whitney U or chi-squared tests. 45 patients with hematologic disorders met inclusion criteria. Platelet dysfunction, including von Willebrand Disease (vWD), was the most common diagnosis (77.8%). Most patients had a preoperative diagnosis of a bleeding disorder and received perioperative hematologic medications (86.7%). Compared to matched controls, patients with hematologic disorders experienced more postoperative bleeding (15.5%; 12 bleeds, 7 patients vs. 1.7%; 1 bleed, 1 patient, p = 0.05) and had longer postoperative stays (1.3 days vs. 0.4 days, p < 0.001). Among the patients with hematologic disorders, patients who experienced a postoperative bleed were significantly more likely to have a factor deficiency (e.g. Hemophilia over vWD) and have a postoperative diagnosis (compared to preoperative diagnosis) for which they did not receive perioperative hematologic medication. Of patients with a postoperative bleed, all those diagnosed postoperatively required at least one surgical intervention to control bleeding compared to 33% of patients with a preoperative diagnosis. A history of post-surgical bleeding, male sex, age at surgery, and pharyngitis as surgical indication were not associated with higher hemorrhage rates in this group. This study suggests a clinically important magnitude of increased bleeding risk in patients with hematologic disease. This risk appears to decrease with the use of an institutional protocol consisting of desmopressin or factor replacement and an antifibrinolytic agent extending through postoperative day 10. Copyright © 2017 Elsevier B.V. All rights reserved.

[Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients].

PubMed

Nantes, Óscar; Zozaya, José Manuel; Montes, Ramón; Hermida, José

2014-01-01

In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Pantoprazole for the treatment of peptic ulcer bleeding and prevention of rebleeding.

PubMed

van Rensburg, Christo J; Cheer, Susan

2012-01-01

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers.

Pantoprazole for the Treatment of Peptic Ulcer Bleeding and Prevention of Rebleeding

PubMed Central

van Rensburg, Christo J.; Cheer, Susan

2012-01-01

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers. PMID:24833934

Increasing numbers of nonaneurysmal subarachnoid hemorrhage in the last 15 years: antithrombotic medication as reason and prognostic factor?

PubMed

Konczalla, Juergen; Kashefiolasl, Sepide; Brawanski, Nina; Senft, Christian; Seifert, Volker; Platz, Johannes

2016-06-01

OBJECT Subarachnoid hemorrhage (SAH) is usually caused by a ruptured intracranial aneurysm, but in some patients no source of hemorrhage can be detected. More recent data showed increasing numbers of cases of spontaneous nonaneurysmal SAH (NASAH). The aim of this study was to analyze factors, especially the use of antithrombotic medications such as systemic anticoagulation or antiplatelet agents (aCPs), influencing the increasing numbers of cases of NASAH and the clinical outcome. METHODS Between 1999 and 2013, 214 patients who were admitted to the authors' institution suffered from NASAH, 14% of all patients with SAH. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months. Risk factors were identified based on the outcome. RESULTS The number of patients with NASAH increased significantly in the last 15 years of the study period. There was a statistically significant increase in the rate of nonperimesencephalic (NPM)-SAH occurrence and aCP use, while the proportion of elderly patients remained stable. Favorable outcome (mRS 0-2) was achieved in 85% of cases, but patients treated with aCPs had a significantly higher risk for an unfavorable outcome. Further analysis showed that elderly patients, and especially the subgroup with a Fisher Grade 3 bleeding pattern, had a high risk for an unfavorable outcome, whereas the subgroup of NPM-SAH without a Fisher Grade 3 bleeding pattern had a favorable outcome, similar to perimesencephalic (PM)-SAH. CONCLUSIONS Over the years, a significant increase in the number of patients with NASAH has been observed. Also, the rate of aCP use has increased significantly. Risk factors for an unfavorable outcome were age > 65 years, Fisher Grade 3 bleeding pattern, and aCP use. Both "PM-SAH" and "NPM-SAH without a Fisher Grade 3 bleeding pattern" had excellent outcomes. Patients with NASAH and a Fisher Grade 3 bleeding pattern had a significantly higher risk for an unfavorable outcome and death. Therefore, for further investigations, NPM-SAH should be stratified into patients with or without a Fisher Grade 3 bleeding pattern. Also, cases of spontaneous SAH should be stratified into NASAH and aneurysmal SAH.

Flowfield analysis for successive oblique shock wave-turbulent boundary layer interactions

NASA Technical Reports Server (NTRS)

Sun, C. C.; Childs, M. E.

1976-01-01

A computation procedure is described for predicting the flowfields which develop when successive interactions between oblique shock waves and a turbulent boundary layer occur. Such interactions may occur, for example, in engine inlets for supersonic aircraft. Computations are carried out for axisymmetric internal flows at M 3.82 and 2.82. The effect of boundary layer bleed is considered for the M 2.82 flow. A control volume analysis is used to predict changes in the flow field across the interactions. Two bleed flow models have been considered. A turbulent boundary layer program is used to compute changes in the boundary layer between the interactions. The results given are for flows with two shock wave interactions and for bleed at the second interaction site. In principle the method described may be extended to account for additional interactions. The predicted results are compared with measured results and are shown to be in good agreement when the bleed flow rate is low (on the order of 3% of the boundary layer mass flow), or when there is no bleed. As the bleed flow rate is increased, differences between the predicted and measured results become larger. Shortcomings of the bleed flow models at higher bleed flow rates are discussed.

Reversal of Direct Oral Anticoagulants: Current Status and Future Directions.

PubMed

Weitz, Jeffrey I

2017-02-01

Direct oral anticoagulants (DOACs) are increasingly used for prevention and treatment of venous thromboembolism and for prevention of stroke in patients with nonvalvular atrial fibrillation. In phase III clinical trials that included more than 100,000 patients, the DOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with less serious bleeding, particularly less intracranial bleeding. Real-world evidence supports these outcomes. Despite this, some physicians and patients are concerned about serious bleeding or emergencies unless specific reversal agents for the DOACs are available. However, in clinical trials performed without reversal agents, the outcome of major bleeds was similar or better in patients receiving DOACs than in those taking VKAs. Because of their short half-lives, supportive measures are sufficient to manage most bleeds in patients receiving DOACs. Anticoagulant reversal should only be considered with life-threatening bleeds, with bleeds that fail to respond to usual measures and in patients requiring urgent surgery. Idarucizumab is licensed for dabigatran reversal and andexanet alfa is likely to be soon licensed for reversal of rivaroxaban, apixaban, and edoxaban. To ensure responsible use of these agents, every hospital needs a bleeding management algorithm that identifies patients eligible for reversal and outlines appropriate dosing regimens. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Late complications of liver cirrhosis - management of gastrointestinal bleeding in the presence of portal hypertension].

PubMed

Hejda, Václav

Cirrhosis is the end stage of progressive development of different liver diseases and is associated with significant morbidity and mortality rates. Cirrhosis is associated with a number of potential complications, in particular with development of portal hypertension. Portal hypertension with the production of ascites, hepatic and gastric varices bleeding in the upper part of the gastrointestinal tract, presents the breakpoint in the natural course of cirrhosis, and it is associated with a considerably worse prognosis of patients, with a dramatically increased risk of mortality. A major progress was reached during the past 10-20 years in diagnosing liver cirrhosis (including non-invasive methods), in primary prevention of the initial episode of upper gastrointestinal bleeding and in the therapy of acute bleeding due to modern pharmacotherapy, with regard to expanding possibilities of therapeutic endoscopy and relatively new options for management of acute bleeding (esophageal stents, TIPS and suchlike). However acute upper gastrointestinal bleeding associated with portal hypertension still presents a considerable risk of premature death (15-20 %). Early diagnosing and causal treatment of numerous liver diseases may lead to slowing or regression of fibrosis and cirrhosis and possibly even of the degree of portal hypertension and thereby also the risk of bleeding.Key words: cirrhosis - esophageal varices - treatment of bleeding - portal hypertension.

Gastrointestinal Bleeding Following LVAD Placement from Top to Bottom.

PubMed

Cushing, Kelly; Kushnir, Vladimir

2016-06-01

Left ventricular assist devices (LVADs) are an increasingly prevalent form of mechanical support for patients with end-stage heart failure. These devices can be implanted both as a bridge to transplant and as definitive/destination therapy. Gastrointestinal (GI) bleeding is one of the most common and recalcitrant long-term complications following LVAD implantation, with an incidence approaching 30 %. This review will discuss what is known about the pathophysiology of GI bleeding in LVADs and the currently available options for medical and/or endoscopic management. The pathophysiology of bleeding is multifactorial, with hemodynamic alterations, acquired von Willebrand factor deficiency, and coagulopathy being most often implicated. The majority of bleeding events in this population result from angioectasias and gastroduodenal erosive disease. While these bleeding events are significant and often require transfusion therapy, they are rarely life threatening. Endoscopy remains the standard of care with upper endoscopy offering the highest diagnostic yield in these patients. However, the effectiveness of endoscopic hemostasis in this population is not well established. A small number of studies have evaluated medical therapy and alterations in LVAD settings as a means of preventing or treating bleeding with variable results. In summary, GI bleeding with LVADs is a common occurrence and will continue to be as more LVADs are being performed for destination therapy.

Distinctive aspects of peptic ulcer disease, Dieulafoy's lesion, and Mallory-Weiss syndrome in patients with advanced alcoholic liver disease or cirrhosis

PubMed Central

Nojkov, Borko; Cappell, Mitchell S

2016-01-01

AIM: To systematically review the data on distinctive aspects of peptic ulcer disease (PUD), Dieulafoy’s lesion (DL), and Mallory-Weiss syndrome (MWS) in patients with advanced alcoholic liver disease (aALD), including alcoholic hepatitis or alcoholic cirrhosis. METHODS: Computerized literature search performed via PubMed using the following medical subject heading terms and keywords: “alcoholic liver disease”, “alcoholic hepatitis”,“ alcoholic cirrhosis”, “cirrhosis”, “liver disease”, “upper gastrointestinal bleeding”, “non-variceal upper gastrointestinal bleeding”, “PUD”, ‘‘DL’’, ‘‘Mallory-Weiss tear”, and “MWS’’. RESULTS: While the majority of acute gastrointestinal (GI) bleeding with aALD is related to portal hypertension, about 30%-40% of acute GI bleeding in patients with aALD is unrelated to portal hypertension. Such bleeding constitutes an important complication of aALD because of its frequency, severity, and associated mortality. Patients with cirrhosis have a markedly increased risk of PUD, which further increases with the progression of cirrhosis. Patients with cirrhosis or aALD and peptic ulcer bleeding (PUB) have worse clinical outcomes than other patients with PUB, including uncontrolled bleeding, rebleeding, and mortality. Alcohol consumption, nonsteroidal anti-inflammatory drug use, and portal hypertension may have a pathogenic role in the development of PUD in patients with aALD. Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients. The frequency of bleeding from DL appears to be increased in patients with aALD. DL may be associated with an especially high mortality in these patients. MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism, and is associated with aALD. Patients with aALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics. Pre-endoscopic management of acute GI bleeding in patients with aALD unrelated to portal hypertension is similar to the management of aALD patients with GI bleeding from portal hypertension, because clinical distinction before endoscopy is difficult. Most patients require intensive care unit admission and attention to avoid over-transfusion, to correct electrolyte abnormalities and coagulopathies, and to administer antibiotic prophylaxis. Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal. Prompt endoscopy, after initial resuscitation, is essential to diagnose and appropriately treat these patients. Generally, the same endoscopic hemostatic techniques are used in patients bleeding from PUD, DL, or MWS in patients with aALD as in the general population. CONCLUSION: Nonvariceal upper GI bleeding in patients with aALD has clinically important differences from that in the general population without aALD, including: more frequent and more severe bleeding from PUD, DL, or MWS. PMID:26755890

Anti-thrombotic efficacy of S007-867: Pre-clinical evaluation in experimental models of thrombosis in vivo and in vitro.

PubMed

Misra, Ankita; Prakash, Prem; Aggarwal, Hobby; Dhankani, Priyanka; Kumar, Sachin; Pandey, Chandra Prakash; Pugh, Nicholas; Bihan, Dominique; Barthwal, Manoj Kumar; Farndale, Richard W; Dikshit, Dinesh Kumar; Dikshit, Madhu

2018-02-01

Pharmacological inhibition of platelet collagen interaction is a promising therapeutic strategy to treat intra-vascular thrombosis. S007-867 is a novel synthetic inhibitor of collagen-induced platelet aggregation. It has shown better antithrombotic protection than aspirin and clopidogrel with minimal bleeding tendency in mice. The present study is aimed to systematically investigate the antithrombotic efficacy of S007-867 in comparison to aspirin and clopidogrel in vivo and to delineate its mechanism of action in vitro. Aspirin, clopidogrel, and S007-867 significantly reduced thrombus weight in arterio-venous (AV) shunt model in rats. In mice, following ferric chloride induced thrombosis in either carotid or mesenteric artery; S007-867 significantly prolonged the vessel occlusion time (1.2-fold) and maintained a sustained blood flow velocity for >30 min. Comparatively, clopidogrel showed significant prolongation in TTO (1.3-fold) while aspirin remained ineffective. Both S007-867 and aspirin did not alter bleeding time in either kidney or spleen injury models, and thus maintained hemostasis, while clopidogrel showed significant increase in spleen bleeding time (1.7-fold). The coagulation parameters namely thrombin time, prothrombin time or activated partial thromboplastin time remained unaffected even at high concentration of S007-867 (300 µM), thus implying its antithrombotic effect to be primarily platelet mediated. S007-867 significantly inhibited collagen-mediated platelet adhesion and aggregation in mice ex-vivo. Moreover, when blood was perfused over a highly thrombogenic combination of collagen mimicking peptides like CRP-GFOGER-VWF-III, S007-867 significantly reduced total thrombus volume or ZV 50 (53.4 ± 5.7%). Mechanistically, S007-867 (10-300 μM) inhibited collagen-induced ATP release, thromboxane A 2 (TxA 2 ) generation, intra-platelet [Ca +2 ] flux and global tyrosine phosphorylation including PLCγ2. Collectively the present study highlights that S007-867 is a novel synthetic inhibitor of collagen induced platelet activation, that effectively maintains blood flow velocity and delays vascular occlusion. It inhibits thrombogenesis without compromising hemostasis. Therefore, S007-867 may be further developed for the treatment of thrombotic disorders in clinical settings. Copyright © 2018 Elsevier Inc. All rights reserved.

Tisseel utilized as hemostatic in spine surgery impacts time to drain removal and length of stay.

PubMed

Epstein, Nancy E

2014-01-01

Although fibrin sealants (FSs) and fibrin glues (FGs) are predominantly utilized to strengthen repairs of cerebrospinal fluid (CSF) fistulas (deliberate/traumatic) during spinal surgery, they are also increasingly utilized to achieve hemostasis. Here, we investigated whether adding Tisseel (Baxter International Inc., Westlake Village, CA, USA), utilized to address increased bleeding during multilevel lumbar laminectomies with non-instrumented fusions, would reduce or equalize the time to drain removal and length of stay (LOS) without contributing to infections or prolonging time to fusion. Prospectively, 39 patients underwent multilevel laminectomies and 1-2 level non-instrumented (in situ) fusions to address stenosis/olisthesis; 22 who demonstrated increased intraoperative bleeding received Tisseel, while 17 without such bleeding did not. The 22 receiving versus 17 not receiving Tisseel, with similar clinical parameters, underwent comparable average multilevel laminectomies (4.36 and 4.25) and 1-2 level fusions (1.4 vs. 1.29 levels). As anticipated, for those receiving Tisseel, the average intraoperative estimated blood loss (EBL), total postoperative blood loss, and total perioperative transfusion requirements [red blood cells (RBC), fresh frozen plasma (FFP), platelets] were higher. However, Tisseel had the added benefit of equalizing the time to postoperative drain removal [e.g. 3.41 days (with) vs. 3.38 days (without)] and LOS [e.g. 5.86 days (with) vs. 5.82 days (without)] without increasing the infection rates (e.g. one superficial infection per group) or average times to fusion (e.g. 5.9 vs. 5.5 months). Adding Tisseel for increased bleeding during multilevel laminectomies/in situ fusions contributed to hemostasis by equalizing the average times to drain removal/LOS compared to patients without increased bleeding and not requiring Tisseel.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy.

PubMed

Gjeorgjievski, Mihajlo; Cappell, Mitchell S

2016-02-08

To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.

Oral contraception following abortion

PubMed Central

Che, Yan; Liu, Xiaoting; Zhang, Bin; Cheng, Linan

2016-01-01

Abstract Oral contraceptives (OCs) following induced abortion offer a reliable method to avoid repeated abortion. However, limited data exist supporting the effective use of OCs postabortion. We conducted this systematic review and meta-analysis in the present study reported immediate administration of OCs or combined OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies. A total of 8 major authorized Chinese and English databases were screened from January 1960 to November 2014. Randomized controlled trials in which patients had undergone medical or surgical abortions were included. Chinese studies that met the inclusion criteria were divided into 3 groups: administration of OC postmedical abortion (group I; n = 1712), administration of OC postsurgical abortion (group II; n = 8788), and administration of OC in combination with traditional Chinese medicine postsurgical abortion (group III; n = 19,707). In total, 119 of 6160 publications were included in this analysis. Significant difference was observed in group I for vaginal bleeding time (P = 0.0001), the amount of vaginal bleeding (P = 0.03), and menstruation recovery period (P < 0.00001) compared with the control groups. Group II demonstrated a significant difference in vaginal bleeding time (P < 0.00001), the amount of vaginal bleeding (P = 0.0002), menstruation recovery period (P < 0.00001), and endometrial thickness at 2 (P = 0.003) and 3 (P < 0.00001) weeks postabortion compared with the control group. Similarly, a significant difference was observed in group III for reducing vaginal bleeding time (P < 0.00001) and the amount of vaginal bleeding (P < 0.00001), shortening the menstruation recovery period (P < 0.00001), and increasing endometrial thickness 2 and 3 weeks after surgical abortion (P < 0.00001, all). Immediate administration of OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies. PMID:27399060

The impact of early outcome events on the effect of tranexamic acid in post-partum haemorrhage: an exploratory subgroup analysis of the WOMAN trial.

PubMed

Brenner, Amy; Shakur-Still, Haleema; Chaudhri, Rizwana; Fawole, Bukola; Arulkumaran, Sabaratnam; Roberts, Ian

2018-06-07

In severe post-partum haemorrhage, death can occur within hours of bleeding onset so interventions to control the bleeding must be given immediately. In clinical trials of treatments for life-threatening bleeding, established treatments are given priority and the trial treatment is usually given last. However, enrolling patients in whom severe maternal morbidity or death is imminent or inevitable at the time of randomisation may dilute the effects of a trial treatment. We conducted an exploratory analysis of data from the WOMAN trial, an international, randomised placebo-controlled trial of the effects of tranexamic acid on death and surgical intervention in 20,060 women with post-partum haemorrhage. We assessed the impact of early maternal death or hysterectomy due to exsanguination on the effect of tranexamic acid on each of these respective outcomes. We conducted repeated analyses excluding patients with these outcomes at increasing intervals from the time of randomisation. We quantified treatment effects using risk ratios (RR) and 99% confidence intervals (CI) and prepared cumulative failure plots. Among 14,923 women randomised within 3 h of delivery (7518 tranexamic acid and 7405 placebo), there were 216 bleeding deaths (1.5%) and 383 hysterectomies due to bleeding (2.8%). After excluding deaths from exsanguination at increasing time intervals following randomization, there was a significant reduction in the risk of death due to bleeding with tranexamic acid (RR = 0.41; 99% CI 0.19-0.89). However, after excluding hysterectomies at increasing time intervals post-randomization, there was no reduction in the risk of hysterectomy due to bleeding with tranexamic acid (RR = 0.79; 99% CI 0.33-1.86). Findings from this analysis provide further evidence that tranexamic acid reduces the risk of death from exsanguination in women who experience postpartum haemorrhage. It is uncertain whether tranexamic acid reduces the risk of hysterectomy for bleeding after excluding early hysterectomies. ISRCTN trial registration number ISRCTN76912190, 8 Dec 2008; ClinicalTrials.gov number NCT00872469, 30 March 2009; PACTR number PACTR201007000192283, 9 Feb 2010; EudraCT number 2008-008441-38, 8 Dec 2010 (retrospectively registered).

Clinical significance of residual platelet reactivity in patients treated with platelet P2Y12 inhibitors.

PubMed

Thomas, Mark R; Storey, Robert F

2016-09-01

Platelet P2Y12 inhibitors have become an essential component of the treatment strategy for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. It is now well-established that approximately 30% of patients treated with the P2Y12 inhibitor clopidogrel display high residual platelet reactivity despite treatment. Patients with high on-treatment platelet reactivity have approximately 2-3-fold greater risk of adverse cardiovascular events and stent thrombosis than those without high platelet reactivity. Conversely, clopidogrel-treated patients with low platelet reactivity display approximately 1.7-fold increased risk of major bleeding. High platelet reactivity is uncommon during treatment with prasugrel and ticagrelor, which achieve a greater reduction in adverse cardiovascular events compared to clopidogrel in ACS patients treated with PCI. This is at the expense of an increase in spontaneous bleeding, however. Minor bleeding events, such as skin haematomas, are more common in prasugrel- and ticagrelor-treated patients that have particularly low platelet reactivity values. These minor bleeding events may occasionally prompt discontinuation of therapy, but their overall prognostic impact is uncertain. However, risk factors for bleeding tend to overlap with risk factors for adverse cardiovascular events. Therefore, patients with these minor bleeding events may also be at higher risk of adverse cardiovascular events, conferring a benefit from low platelet reactivity. Further work is needed to determine the optimal level of platelet reactivity in individuals by taking into account their risk of subsequent adverse cardiovascular events and bleeding. Copyright © 2016 Elsevier Inc. All rights reserved.

Recombinant activated factor VII for bleeding in patients without inherited bleeding disorders.

PubMed

Selin, S; Tejani, A

2006-03-01

(1) Recombinant activated factor VII (rFVIIa) is licensed in Canada for the prevention and treatment of bleeding in hemophiliacs, but it is increasingly used to control bleeding in non-hemophilic patients during surgery, or during treatment for severe trauma or intracerebral hemorrhage (ICH). (2) In one clinical trial, there was a significant reduction in mortality among patients with ICH treated with rFVIIa. In another trial, administration of rFVIIa significantly reduced the number of trauma patients needing massive blood transfusions although there was no significant difference in mortality. (3) Adequately powered randomized controlled trials are needed to clarify the efficacy and safety of rFVIIa for non-bleeding disorder indications. Phase III trials in ICH and trauma are underway. (4) There is potential for non-hemophilic use, particularly if clinical efficacy and cost effectiveness are established.

Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists. An individual patient data meta-analysis.

PubMed

Bleker, Suzanne M; Brekelmans, Marjolein P A; Eerenberg, Elise S; Cohen, Alexander T; Middeldorp, Saskia; Raskob, Gary; Büller, Harry R

2017-10-05

Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35 % and 48 % of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95 % CI 0.36-0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22 % of the fXa inhibitor and 25 % of the VKA associated bleeds (OR 0.83, 95 % CI 0.47-1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

"If it bleeds it leads"? Attributes of TV health news stories that drive viewer attention.

PubMed Central

Cooper, C P; Roter, D L

2000-01-01

OBJECTIVE: Health advocates increasing y use the news media to educate the public. However, little is known about what motivates individuals to pay attention to health news. This study investigated which characteristics of TV health news stories attract viewer interest. METHODS: The authors surveyed airport patrons, the audience of a public health symposium, and municipal jurors, asking which attributes of TV heath news stories encouraged interest and which attributes discouraged interest. The authors ranked mean responses and compared them using Spearman rank correlations, RESULTS: The rankings assigned by the three samples were highly correlated. Respondents reported being most attracted to health stories about personally relevant topics. Interestingly, they also reported that sensational story elements such as "showing a bloody or injured person" and "being action packed" did not substantially influence their attention. CONCLUSIONS: This study suggests that viewers, regardless of their level of health knowledge, value the same attributes in TV health news stories. Emphasizing the personal relevance of health topics appears to be a viable strategy to capture viewer interest. Conversely, the tendency of broadcast news to sensationalize stories may be distracting in the case of health news. PMID:11059426

[Spleen-preserving surgery after blunt abdominal trauma with splenic hilum involvement].

PubMed

Navas-Cuéllar, José Aurelio; Cañete-Gómez, Jesús; López-Bernal, Francisco; García-Rivera, Carla; Pareja-Ciuró, Felipe; Padillo-Ruiz, Javier

2015-01-01

Splenic involvement secondary to blunt abdominal trauma is often treated by performing a splenectomy. The severity of the post-splenectomy syndrome is currently well known (blood loss, sepsis), so there is an increasing tendency to preserve the spleen. The case is presented of splenic preservation after blunt abdominal trauma with hilum involvement, emphasising the role of Floseal as a haemostatic agent, as well as the use of resorbable meshes to preserve the spleen. A 22-year-old woman presenting with a grade IV splenic lesion secondary to a blunt abdominal trauma after a traffic accident. Partial splenic resection was performed and bleeding was controlled with Floseal and use of a reinforcing polyglycolic acid mesh. No postoperative complications occurred, being discharged on day 5. The long-term follow-up has been uneventful. The use of haemostatic agents such as thrombin and the gelatine gel (FloSeal) and the use of polyglycolic acid meshes enable spleen-preserving surgery, making it a feasible and reproducible procedure and an alternative to classical splenectomy. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

"If it bleeds it leads"? Attributes of TV health news stories that drive viewer attention.

PubMed

Cooper, C P; Roter, D L

2000-01-01

Health advocates increasing y use the news media to educate the public. However, little is known about what motivates individuals to pay attention to health news. This study investigated which characteristics of TV health news stories attract viewer interest. The authors surveyed airport patrons, the audience of a public health symposium, and municipal jurors, asking which attributes of TV heath news stories encouraged interest and which attributes discouraged interest. The authors ranked mean responses and compared them using Spearman rank correlations, The rankings assigned by the three samples were highly correlated. Respondents reported being most attracted to health stories about personally relevant topics. Interestingly, they also reported that sensational story elements such as "showing a bloody or injured person" and "being action packed" did not substantially influence their attention. This study suggests that viewers, regardless of their level of health knowledge, value the same attributes in TV health news stories. Emphasizing the personal relevance of health topics appears to be a viable strategy to capture viewer interest. Conversely, the tendency of broadcast news to sensationalize stories may be distracting in the case of health news.

Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran.

PubMed

Kolb, Jennifer M; Flack, Kathryn Friedman; Chatterjee-Murphy, Prapti; Desai, Jay; Wallentin, Lars C; Ezekowitz, Michael; Connolly, Stuart; Reilly, Paul; Brueckmann, Martina; Ilgenfritz, John; Aisenberg, James

2018-03-27

Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.

Risk of vaginal bleeding and postpartum hemorrhage after use of antidepressants in pregnancy: a study from the Norwegian Mother and Child Cohort Study.

PubMed

Lupattelli, Angela; Spigset, Olav; Koren, Gideon; Nordeng, Hedvig

2014-02-01

This study aimed to examine obstetric bleeding outcomes after exposure during pregnancy to selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic (TCAs), and other antidepressants (OADs).The Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway constituted the data source for the present study. We included 57,279 pregnant women, of which 1.02% reported use of antidepressants during pregnancy, mostly SSRIs/SNRIs (0.92%). We categorized exposure according to antidepressant use in pregnancy (SSRIs/SNRIs, n = 527; TCAs/OADs, n = 59; nonexposed, nondepressed, n = 55,411) with inclusion of a disease comparison group (nonexposed, depressed, n = 1282). We used logistic regression to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI) for vaginal bleeding outcomes in pregnancy and postpartum hemorrhage.Compared with nonexposed subjects, first trimester exposure to SSRIs/SNRIs or TCAs/OADs did not confer any increased risk of vaginal bleeding in early pregnancy (aOR, 0.91; 95% CI, 0.72-1.16 and aOR, 0.83; 95% CI, 0.36-1.92, respectively). No increased risk for vaginal bleeding in midpregnancy was observed among users of SSRIs/SNRIs (aOR, 0.81; 95% CI, 0.50-1.31) or TCAs/OADs (aOR, 0.96; 95% CI, 0.26-3.53) in second trimester. Exposure to SSRIs/SNRIs during gestational week 30 to childbirth did not confer any increased risk of postpartum hemorrhage after vaginal (aOR, 0.90; 95% CI, 0.47-1.74) or cesarean (aOR, 1.47; 95% CI, 0.51-4.22) delivery. Women in the disease comparison group presented a significant moderate increased risk of vaginal bleeding in early pregnancy (aOR, 1.22; 95% CI, 1.06-1.39) and midpregnancy (aOR, 1.28; 95% CI, 1.07-1.55) but not postpartum.Among this Norwegian cohort of pregnant women, use of antidepressants in pregnancy was not associated with any obstetrical bleeding outcome.

Risk of bleeding with dabigatran in atrial fibrillation.

PubMed

Hernandez, Inmaculada; Baik, Seo Hyon; Piñera, Antonio; Zhang, Yuting

2015-01-01

It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice. To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data. In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011. Dabigatran users (n = 1302) and warfarin users (n = 8102). We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities. Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease. Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

Incident Risk Factors and Major Bleeding in Patients with Atrial Fibrillation Treated with Oral Anticoagulants: A Comparison of Baseline, Follow-up and Delta HAS-BLED Scores with an Approach Focused on Modifiable Bleeding Risk Factors.

PubMed

Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

2018-04-01

 When assessing bleeding risk in patients with atrial fibrillation (AF), risk stratification is often based on the baseline risks. We aimed to investigate changes in bleeding risk factors and alterations in the HAS-BLED score in AF patients. We hypothesized that a follow-up HAS-BLED score and the 'delta HAS-BLED score' (reflecting the change in score between baseline and follow-up) would be more predictive of major bleeding, when compared with baseline HAS-BLED score.  A total of 19,566 AF patients receiving warfarin and baseline HAS-BLED score ≤2 were studied. After a follow-up of 93,783 person-years, 3,032 major bleeds were observed. The accuracies of baseline, follow-up, and delta HAS-BLED scores as well as cumulative numbers of baseline modifiable bleeding risk factors, in predicting subsequent major bleeding, were analysed and compared. The mean baseline HAS-BLED score was 1.43 which increased to 2.45 with a mean 'delta HAS-BLED score' of 1.03. The HAS-BLED score remained unchanged in 38.2% of patients. Of those patients experiencing major bleeding, 76.6% had a 'delta HAS-BLED' score ≥1, compared with only 59.0% in patients without major bleeding ( p  < 0.001). For prediction of major bleeding, AUC was significantly higher for the follow-up HAS-BLED (0.63) or delta HAS-BLED (0.62) scores, compared with baseline HAS-BLED score (0.54). The number of baseline modifiable risk factors was non-significantly predictive of major bleeding (AUC = 0.49).  In this 'real-world' nationwide AF cohort, follow-up HAS-BLED or 'delta HAS-BLED score' was more predictive of major bleeding compared with baseline HAS-BLED or the simple determination of 'modifiable bleeding risk factors'. Bleeding risk in AF is a dynamic process and use of the HAS-BLED score should be to 'flag up' patients potentially at risk for more regular review and follow-up, and to address the modifiable bleeding risk factors during follow-up visits. Schattauer GmbH Stuttgart.

The influence of the full moon on the number of admissions related to gastrointestinal bleeding.

PubMed

Román, Eva María; Soriano, Germán; Fuentes, Mercedes; Gálvez, María Luz; Fernández, Clotilde

2004-12-01

The objective of this study was to analyse whether the number of admissions for gastrointestinal bleeding to our bleeding unit increases during the full moon. In a prospective study, we included 447 consecutive patients with gastrointestinal haemorrhage admitted to our bleeding unit during a period of two years. The number of admissions was allocated to the corresponding day of the lunar cycle, and full moon and non-full moon days were compared. A wide variation in the number of admissions throughout the lunar cycle was observed. There were 26 admissions on the 25 days of full moon and 421 admissions in the remaining 713 days of non-full moon. This difference was mainly related to a higher incidence of haemorrhage in men and variceal haemorrhage at full moon. The results of this study suggest an increase in the number of admissions related to gastrointestinal haemorrhage in our bleeding unit during the full moon, especially in men and in patients experiencing variceal haemorrhage. However, the wide variation in the number of admissions throughout the lunar cycle could limit interpretation of the results. Therefore, further studies are needed to clarify the possible influence of the moon on gastrointestinal haemorrhage.

[Changes in PCO2 and pH gradients in a canine model of experimental acute hemorrhage].

PubMed

Rabanal, J M; Mons, R; Galindo, M; Solares, G; Seco, I; García-Castrillo, L

1999-01-01

To study changes in arterial-venous PCO2 pressures (Da-vPCO2) and in pH (Da-vpH) in an experimental dog model of acute bleeding. To emphasize the utility of monitoring these variables in situations of acute bleeding. ANIMALS AND METHOD: Eighteen dogs were anesthesized and monitored while being subjected to gradual bleeding. Gasometric and hemodynamic variables were recorded at the following moments: baseline, stage I (15% of volemic loss), stage Ib (20%), stage II (25%), stage IIb (30%) and stage III (35%). No significant differences in pH or PCO2 in either arterial or mixed venous blood were found. Bleeding induced a constant and progressive increase in Da-vPCO2 that correlated with changes in volume (r = -0.56, p < 0.001), SvO2 (r = 0.71; p < 0.001), Da-vO2 gradient (r = 0.62; p < 0.001) and cardiac output (r = 0.63; p < 0.001). Gradual bleeding caused a constant and significant increase of Da-vPCO2. Monitoring such changes in states of circulatory insufficiency may be useful for evaluating tissue ischemia.

Risk of bleeding in surgical patients treated with topical bovine thrombin sealants: a review of the literature

PubMed Central

Reynolds, Matthew W; Clark, John; Crean, Sheila; Samudrala, Srinath

2008-01-01

Background One of the most anticipated, but potentially serious complications during or after surgery are bleeding events. Among the many potential factors associated with bleeding complications in surgery, the use of bovine thrombin has been anecdotally identified as a possible cause of increased bleeding risk. Most of these reports of bleeding events in association with the use of topical bovine thrombin have been limited to case reports lacking clear cause and effect relationship determination. Recent studies have failed to establish significant differences in the rates of bleeding events between those treated with bovine thrombin and those treated with either human or recombinant thrombin. Methods We conducted a search of MEDLINE for the most recent past 10 years (1997–2007) and identified all published studies that reported a study of surgical patients with a clear objective to examine the risk of bleeding events in surgical patients. We also specifically noted the reporting of any topical bovine thrombin used during surgical procedures. We aimed to examine whether there were any differences in the risk of bleeds in general surgical populations as compared to those studies that reported exposure to topical bovine thrombin. Results We identified 21 clinical studies that addressed the risk of bleeding in surgery. Of these, 5 studies analyzed the use of bovine thrombin sealants in surgical patients. There were no standardized definitions for bleeding events employed across these studies. The rates of bleeds in the general surgery studies ranged from 0.1%–20.2%, with most studies reporting rates between 2.6%–4%. The rates of bleeding events ranged from 0.0%–13% in the bovine thrombin studies with most studies reporting between a 2%–3% rate. Conclusion The risk of bleeds was not clearly different in those studies reporting use of bovine thrombin in all patients compared to the other surgical populations studied. A well-designed and well-controlled study is needed to accurately examine the bleeding risks in surgical patients treated and unexposed to topical bovine thrombin, and to evaluate the independent risk associated with topical bovine thrombin as well as other risk factors. PMID:18348725

Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial.

PubMed

Sherwood, Matthew W; Nessel, Christopher C; Hellkamp, Anne S; Mahaffey, Kenneth W; Piccini, Jonathan P; Suh, Eun-Young; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hankey, Graeme J; Berkowitz, Scott D; Fox, Keith A A; Patel, Manesh R

2015-12-01

Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Liquefied Bleed for Stability and Efficiency of High Speed Inlets

NASA Technical Reports Server (NTRS)

Saunders, J. David; Davis, David; Barsi, Stephen J.; Deans, Matthew C.; Weir, Lois J.; Sanders, Bobby W.

2014-01-01

A mission analysis code was developed to perform a trade study on the effectiveness of liquefying bleed for the inlet of the first stage of a TSTO vehicle. By liquefying bleed, the vehicle weight (TOGW) could be reduced by 7 to 23%. Numerous simplifying assumptions were made and lessons were learned. Increased accuracy in future analyses can be achieved by: Including a higher fidelity model to capture the effect of rescaling (variable vehicle TOGW). Refining specific thrust and impulse models ( T m a and Isp) to preserve fuel-to-air ratio. Implementing LH2 for T m a and Isp. Correlating baseline design to other mission analyses and correcting vehicle design elements. Implementing angle-of-attack effects on inlet characteristics. Refining aerodynamic performance (to improve L/D ratio at higher Mach numbers). Examining the benefit with partial cooling or densification of the bleed air stream. Incorporating higher fidelity weight estimates for the liquefied bleed system (heat exchange and liquid storage versus bleed duct weights) could be added when more fully developed. Adding trim drag or 6-degree-of-freedom trajectory analysis for higher fidelity. Investigating vehicle optimization for each of the bleed configurations.

Quebec platelet disorder: features, pathogenesis and treatment.

PubMed

Diamandis, Maria; Veljkovic, D Kika; Maurer-Spurej, Elisabeth; Rivard, Georges E; Hayward, Catherine P M

2008-03-01

Quebec platelet disorder (QPD) is a rare, autosomal-dominant, inherited bleeding disorder that is associated with unique abnormalities in fibrinolysis. Its hallmark features are delayed-onset bleeding following hemostatic challenges that responds to fibrinolytic inhibitor therapy and increased expression and storage of the fibrinolytic enzyme urokinase plasminogen activator in platelets, without increased plasma urokinase plasminogen activator or systemic fibrinolysis. The increased urokinase plasminogen activator in QPD platelets is only partially inhibited, and, as a result, there is intraplatelet generation of plasmin, and secondary degradation of many platelet alpha-granule proteins. During clot formation, the urokinase plasminogen activator released by QPD platelets leads to platelet-dependent increased fibrinolysis, and this is postulated to be a major contributor to QPD bleeding. The focus of the present review is to summarize the current state of knowledge on QPD, including the history of this disorder, its clinical and laboratory features, and recommended approaches for its diagnosis and treatment.

Unscheduled vaginal bleeding with progestin-only contraceptive use.

PubMed

Zigler, Rachel E; McNicholas, Colleen

2017-05-01

Nearly 20% of women using contraception are using progestin-only contraception, including progestin-only pills, depot-medroxyprogesterone acetate, subdermal etonogestrel implants, and levonorgestrel intrauterine devices. This number will continue to grow with the increased provision of long-acting reversible contraception. Although overall satisfaction among women using progestin-only contraception is high, dissatisfaction and discontinuation may be associated with unscheduled bleeding and spotting. The exact etiology of irregular bleeding associated with progestin-containing contraceptives is not completely understood, yet several mechanisms have been suggested. Several therapies targeting these mechanisms have been evaluated with mixed results. This paper will review the physiology and management of unscheduled bleeding with progestin-containing contraceptives. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic Value of the Amount of Bleeding After Aneurysmal Subarachnoid Hemorrhage: A Quantitative Volumetric Study.

PubMed

Lagares, Alfonso; Jiménez-Roldán, Luis; Gomez, Pedro A; Munarriz, Pablo M; Castaño-León, Ana M; Cepeda, Santiago; Alén, José F

2015-12-01

Quantitative estimation of the hemorrhage volume associated with aneurysm rupture is a new tool of assessing prognosis. To determine the prognostic value of the quantitative estimation of the amount of bleeding after aneurysmal subarachnoid hemorrhage, as well the relative importance of this factor related to other prognostic indicators, and to establish a possible cut-off value of volume of bleeding related to poor outcome. A prospective cohort of 206 patients consecutively admitted with the diagnosis of aneurysmal subarachnoid hemorrhage to Hospital 12 de Octubre were included in the study. Subarachnoid, intraventricular, intracerebral, and total bleeding volumes were calculated using analytic software. For assessing factors related to prognosis, univariate and multivariate analysis (logistic regression) were performed. The relative importance of factors in determining prognosis was established by calculating their proportion of explained variation. Maximum Youden index was calculated to determine the optimal cut point for subarachnoid and total bleeding volume. Variables independently related to prognosis were clinical grade at admission, age, and the different bleeding volumes. The proportion of variance explained is higher for subarachnoid bleeding. The optimal cut point related to poor prognosis is a volume of 20 mL both for subarachnoid and total bleeding. Volumetric measurement of subarachnoid or total bleeding volume are both independent prognostic factors in patients with aneurysmal subarachnoid hemorrhage. A volume of more than 20 mL of blood in the initial noncontrast computed tomography is related to a clear increase in poor outcome risk. : aSAH, aneurysmal subarachnoid hemorrhage.

Randomized comparison of bleeding patterns in women using a combined contraceptive vaginal ring or a low-dose combined oral contraceptive on a menstrually signaled regimen.

PubMed

Weisberg, Edith; Merki-Feld, Gabriele S; McGeechan, Kevin; Fraser, Ian S

2015-02-01

To compare bleeding patterns for 12 months continuous use of a contraceptive ring [contraceptive vaginal ring (CVR)] and pill [combined oral contraceptive (COC)] on a menstrually signaled regimen and the effectiveness of 4 days "treatment withdrawal" to stop bleeding. Women, 66 to each group, were randomized to continuous use of a CVR (15 mcg ethinyl estradiol/150 mcg etonogestrel) or a low-dose pill (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for 360 days on a menstrually signaled regimen. Bleeding/spotting days, daily use of ring or pill, was recorded. Endpoint was the total number of bleeding/spotting days for each method over four 90-day reference periods (RP) plus the analysis of bleeding patterns using modified World Health Organization criteria. There was a reduction in the mean (±S.D.) number of bleeding/spotting days from RP1 (CVR 14.2±10; pill 16.6±10.9) to RP4 (CVR 8.8±9.6; pill 8.8±9.1). Fifteen percent of CVR and 4% COC users experienced amenorrhea or infrequent bleeding throughout the study. Amenorrhea increased over time (RP1 vs. RP4: CVR 10% vs. 21% and COC 2% vs. 30%). Compliance with the menstrually signaled regimen was poor. Ceasing hormones for 4 days stopped a bleeding episode within 5 days in the majority of episodes and many stopped spontaneously. Bleeding patterns with continuous use of the CVR and COC are similar and improve over 1 year of use. The unpredictability, but short duration, of bleeding episodes should be stressed during counseling. This information for clinicians and women about breakthrough bleeding patterns with use of a CVR or combined pill over 12 months using a menstrually signaled regimen will give women an indication of what to expect with continuous use. Copyright © 2015 Elsevier Inc. All rights reserved.

Bleeding rates in Veterans Affairs patients with atrial fibrillation who switch from warfarin to dabigatran.

PubMed

Vaughan Sarrazin, Mary S; Jones, Michael; Mazur, Alexander; Chrischilles, Elizabeth; Cram, Peter

2014-12-01

Clinical trial data suggest that dabigatran and warfarin have similar rates of major bleeding but higher rates of gastrointestinal bleeding. These findings have not been evaluated outside of a clinical trial. We evaluated the relative risks of any, gastrointestinal, intracranial, and other bleeding for Veterans Affairs patients who switched to dabigatran after at least 6 months on warfarin, compared with patients who continued on warfarin. We used national Veterans Affairs administrative encounter and pharmacy data from fiscal years 2010-2012 to identify 85,344 patients with atrial fibrillation who had been taking warfarin for at least 180 days before June 2011, of whom 1394 (1.7%) received dabigatran (150 mg) during the next 15 months. Dates of the first occurrence of each type of bleed and dates of death from June 2011 to September 2012 were determined. Baseline and time-dependent patient characteristics were identified, including comorbid conditions, stroke and bleeding risk scores, and time in therapeutic range for international normalized ratios. Marginal structural models were used to address selection bias in the longitudinal observational data. Weighted logistic regression models were fit using generalized estimating equations and reflected baseline and time-dependent covariates and weekly indicators of anticoagulant type (warfarin or dabigatran). Compared with patients who never used dabigatran, patients who used dabigatran at least once were younger, were more likely to be white, had lower international normalized ratio time in therapeutic range on warfarin, had lower stroke risk scores, and had similar bleeding risk scores. Overall, 10,734 patients experienced bleeding events, including 131 events after dabigatran use. The risk-adjusted rate of any bleeding was higher with dabigatran compared with warfarin, which was largely driven by a 54% higher risk of gastrointestinal bleeding with dabigatran. Rates of intracranial, other bleeding, and death were similar for dabigatran and warfarin. Dabigatran may increase the likelihood of gastrointestinal bleeds. Published by Elsevier Inc.

Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials.

PubMed

Amin, Alpesh; Deitelzweig, Steve; Jing, Yonghua; Makenbaeva, Dinara; Wiederkehr, Daniel; Lin, Jay; Graham, John

2014-01-01

Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (-0.035%/py, p = 0.63). As warfarin's TTR increased from 30 to 90% the estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

Predicting the Occurrence of Hypotension in Stable Patients With Nonvariceal Upper Gastrointestinal Bleeding: Point-of-Care Lactate Testing.

PubMed

Ko, Byuk Sung; Kim, Won Young; Ryoo, Seung Mok; Ahn, Shin; Sohn, Chang Hwan; Seo, Dong Woo; Lee, Yoon-Seon; Lim, Kyoung Soo; Jung, Hwoon-Yong

2015-11-01

It is difficult to assess risk in normotensive patients with upper gastrointestinal bleeding. The aim of this study was to evaluate whether the initial lactate value can predict the in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. Retrospective, observational, single-center study. Emergency department of a tertiary-care, university-affiliated hospital during a 5-year period. Medical records of 3,489 patients with acute upper gastrointestinal bleeding who were normotensive at presentation to the emergency department. We analyzed the ability of point-of-care testing of lactate at emergency department admission to predict hypotension development (defined as systolic blood pressure <90 mm Hg) within 24 hours after emergency department admission. None. Of the 1,003 patients with acute nonvariceal upper gastrointestinal bleeding, 157 patients experienced hypotension within 24 hours. Lactate was independently associated with hypotension development (odds ratio, 1.6; 95% CI, 1.4-1.7), and the risk of hypotension significantly increased as the lactate increased from 2.5-4.9 mmol/L (odds ratio, 2.2) to 5.0-7.4 mmol/L (odds ratio, 4.0) and to greater than or equal to 7.5 mmol/L (odds ratio, 39.2) (p<0.001). Lactate elevation (≥2.5 mmol/L) was associated with 90% specificity and an 84% negative predictive value for hypotension development. When the lactate levels were greater than 5.0 mmol/L, the specificity and negative predictive value increased to 98% and 87%, respectively. Point-of-care testing of lactate can predict in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. However, subsequently, prospective validate research will be required to clarify this.

Relationship between activated clotting time and ischemic or hemorrhagic complications: analysis of 4 recent randomized clinical trials of percutaneous coronary intervention.

PubMed

Brener, Sorin J; Moliterno, David J; Lincoff, A Michael; Steinhubl, Steven R; Wolski, Kathy E; Topol, Eric J

2004-08-24

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time (ACT) for prevention of ischemic or hemorrhagic complications. We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively (P=0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds (P=0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg, P=0.001). In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.

Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.

PubMed

Gobble, Ryan M; Hoang, Han L T; Kachniarz, Bart; Orgill, Dennis P

2014-03-01

Postoperative pain control is essential for optimal patient outcomes. Ketorolac is an attractive alternative for achieving pain control postoperatively, but concerns over postoperative bleeding have limited its use. Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases were performed. Twenty-seven double-blind, randomized, controlled studies were reviewed by two independent investigators for the incidence of adverse events, including postoperative bleeding. Comprehensive meta-analysis software was used to evaluate the differences between ketorolac and control groups. Twenty-seven studies with 2314 patients were analyzed. Postoperative bleeding occurred in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of 1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p = 0.72). Adverse events were similar in the groups, 31.7 percent in the control group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to 1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with ketorolac was superior to controls and equivalent to opioids. This is the first meta-analysis of randomized controlled trials examining whether there is increased postoperative bleeding with ketorolac. Postoperative bleeding was not significantly increased with ketorolac compared with controls, and adverse effects were not statistically different between the groups. Pain control was found to be superior with ketorolac compared with controls. Ketorolac should be considered for postoperative pain control, especially to limit the use of opioid pain medications. Therapeutic, II.

Assessment of Bleeding and Thrombosis Based on Aspirin Responsiveness after Continuous-Flow Left Ventricular Assist Device Placement.

PubMed

Floroff, Catherine K; Rieger, Krista L; Veasey, Tara M; Strout, Sara E; DeNino, Walter F; Meadows, Holly B; Stroud, Martha R; Toole, John M; Heyward, Dawn P; Brisco-Bacik, Meredith A; Cook, Jennifer L; Lazarchick, John; Uber, Walter E

Pump thrombosis (PT) is a severe complication of left ventricular assist device (LVAD) support. This study evaluated PT and bleeding after LVAD placement in patients responsive to a standard aspirin dose of 81 mg using platelet inhibition monitoring compared with initial nonresponders who were then titrated upward to achieve therapeutic response. Patients ≥ 18 years of age with initial placement of HeartMate II LVAD at our institution and at least one VerifyNow Aspirin test performed during initial hospitalization were included. The primary endpoints were bleeding and PT compared between initial aspirin responders and nonresponders. Of 85 patients, 19 (22%) were nonresponsive to initial aspirin therapy. Responders and nonresponders showed similar survival (p = 0.082), freedom from suspected/confirmed PT (p = 0.941), confirmed PT (p = 0.273), bleeding (p = 0.401), and incidence rates in PT and bleeding. Among the initial responders (<500 vs. 500-549 aspirin reaction units), there were no significant differences in survival (p = 0.177), freedom from suspected/confirmed PT (p = 0.542), confirmed PT (p = 0.159), bleeding (p = 0.879), and incidence of PT and bleeding. Platelet function testing may detect resistance to standard aspirin regimens used in LVAD patients. Dose escalation in initially nonresponsive patients to achieve responsiveness may confer a similar PT risk to patients initially responsive to standard aspirin dosing without increased bleeding risk.

The effect of tranexamic acid on the quality of life of women with heavy menstrual bleeding.

PubMed

Winkler, U H

2001-12-01

To investigate whether medical treatment with tranexamic acid would increase the quality of life of women with heavy menstrual bleeding. This open, uncontrolled usage study included 849 women diagnosed with heavy menstrual bleeding and considered eligible for tranexamic-acid treatment. The condition of the women was investigated at baseline and after the first and the third treated menstruation. Quality of life and subjectively experienced state of health were assessed with the aid of a questionnaire. Satisfaction with the treatment was registered. After the third menstruation, 80% of the women were satisfied with the treatment. Impairment of social activities and impairment at work were greatly reduced by the treatment. Substantial improvements were also recorded with regard to alertness, productivity, cleanliness, spirits, action radius and overall well-being. Adverse reactions to the drug used for the treatment were few and non-serious. Medical treatment with tranexamic acid increases quality of life for women with heavy menstrual bleeding.

Review: pharmacotherapeutic agents in the treatment of portal hypertension.

PubMed

Lebrec, D

1997-02-01

Certain vasoactive substances reduce portal pressure in patients or animals with portal hypertension by either inducing splanchnic vasoconstriction or reducing hepatic vascular resistance. Studies have shown that propranolol or nadolol significantly reduce the risk of a first episode of gastrointestinal (GI) bleeding and increase the survival rate in patients with cirrhosis and oesophageal varices. Isosorbide-5-mononitrate is also effective in the prevention of bleeding. The combination of beta-blockers and nitrates may be more effective than one drug alone. These results show that beta-adrenoceptor antagonists must be used to prevent the first episode of GI bleeding. Beta-blocker administration also significantly reduces the risk of recurrent GI bleeding and increases the survival rate in patients with cirrhosis. Studies have shown that propranolol is as effective as endoscopic sclerotherapy. The combination of a beta-blocker with endoscopic sclerotherapy may be more effective than pharmacological or endoscopic treatment alone for the prevention of rebleeding. Finally, new experimental and clinical studies are needed to improve the pharmacological treatment of portal hypertension.

Rivaroxaban Versus Dabigatran or Warfarin in Real-World Studies of Stroke Prevention in Atrial Fibrillation: Systematic Review and Meta-Analysis.

PubMed

Bai, Ying; Deng, Hai; Shantsila, Alena; Lip, Gregory Y H

2017-04-01

This study was designed to evaluate the effectiveness and safety of rivaroxaban in real-world practice compared with effectiveness and safety of dabigatran or warfarin for stroke prevention in atrial fibrillation through meta-analyzing observational studies. Seventeen studies were included after searching in PubMed for studies reporting the comparative effectiveness and safety of rivaroxaban versus dabigatran (n=3), rivaroxaban versus Warfarin (n=11), or both (n=3) for stroke prevention in atrial fibrillation. Overall, the risks of stroke/systematic thromboembolism with rivaroxaban were similar when compared with those with dabigatran (stroke/thromboembolism: hazard ratio, 1.02; 95% confidence interval, 0.91-1.13; I 2 =70.2%, N=5), but were significantly reduced when compared with those with warfarin (hazard ratio, 0.75; 95% confidence interval, 0.64-0.85; I 2 =45.1%, N=9). Major bleeding risk was significantly higher with rivaroxaban than with dabigatran (hazard ratio, 1.38; 95% confidence interval, 1.27-1.49; I 2 =26.1%, N=5), but similar to that with warfarin (hazard ratio, 0.99; 95% confidence interval, 0.91-1.07; I 2 =0.0%, N=6). Rivaroxaban was associated with increased all-cause mortality and gastrointestinal bleeding, but similar risk of acute myocardial infarction and intracranial hemorrhage when compared with dabigatran. When compared with warfarin, rivaroxaban was associated with similar risk of any bleeding, mortality, and acute myocardial infarction, but a higher risk of gastrointestinal bleeding and lower risk of intracranial hemorrhage. In this systematic review and meta-analysis, rivaroxaban was as effective as dabigatran, but was more effective than warfarin for the prevention of stroke/thromboembolism in atrial fibrillation patients. Major bleeding risk was significantly higher with rivaroxaban than with dabigatran, as was all-cause mortality and gastrointestinal bleeding. Rivaroxaban was comparable to warfarin for major bleeding, with an increased risk in gastrointestinal bleeding and decreased risk of intracranial hemorrhage. © 2017 American Heart Association, Inc.

Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding

PubMed Central

Delaney, Joseph A.; Opatrny, Lucie; Brophy, James M.; Suissa, Samy

2007-01-01

Background Anticoagulants and antiplatelet drugs (e.g., warfarin, clopidogrel and acetylsalicylic acid) are key therapeutic agents in the treatment of cardiovascular diseases. However, drug–drug interactions may lead to a greatly increased risk of gastrointestinal bleeding when these drugs are combined. We assessed whether antithrombotic drug combinations increased the risk of such bleeding in a general practice population. Methods We conducted a population-based, retrospective case–control study using records in the United Kingdom General Practice Research Database from 2000 through 2005. Cases were identified as patients over 18 years of age with a first-ever diagnosis of gastrointestinal bleeding. They were matched with controls by physician practice, patient age and index date (date of diagnosis of bleeding). All eligible patients had to have at least 3 years of follow-up data in the database. Drug exposure was considered to be any prescription issued in the 90 days before the index date. Results There were 4028 cases with a diagnosis of gastrointestinal bleeding and 40 171 matched controls. The prescribing of acetylsalicylic acid with either clopidogrel (adjusted rate ratio [RR] 3.90, 95% confidence interval [CI] 2.78–5.47) or warfarin (adjusted RR 6.48, 95% CI 4.25–9.87) was associated with a greater risk of gastrointestinal bleeding than that observed with each drug alone. The same was true when a nonsteroidal anti-inflammatory drug was combined with either clopidogrel (adjusted RR 2.93, 95% CI 1.74–4.93) or warfarin (RR 4.60, 95% CI 2.77–7.64). Interpretation Drug combinations involving antiplatelets and anticoagulants are associated with a high risk of gastrointestinal bleeding beyond that associated with each drug used alone. Physicians should be aware of these risks to better assess their patients' therapeutic risk–benefit profiles. PMID:17698822

Bleeding Risk and Antithrombotic Strategy in Patients with Sinus Rhythm Heart Failure with Reduced Ejection Fraction Treated with Warfarin or Aspirin

PubMed Central

Ye, Siqin; Cheng, Bin; Lip, Gregory Y. H.; Buchsbaum, Richard; Sacco, Ralph L.; Levin, Bruce; Di Tullio, Marco R.; Qian, Min; Mann, Douglas L.; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Mohr, J.P.; Graham, Susan; Labovitz, Arthur J.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Thompson, John L.P.; Homma, Shunichi

2015-01-01

We sought to assess the performance of existing bleeding risk scores, such as HAS-BLED or OBRI, in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell’s c-statistic and net-reclassification improvement (NRI) index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly higher c-statistic (0.72 vs 0.61; p=0.03) compared to HAS-BLED, though the NRI for comparing OBRI to HAS-BLED was not significant (0.32, 95% CI - 0.18-0.37). Performance of the OBRI and HAS-BLED risk scores were similar for the aspirin arm. For participants with OBRI score of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (HR 0.51, 95% CI 0.26-0.98, p=0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66-2.30, p=0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27-1.15, p=0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99-8.22, p<0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in HFrEF patients in SR, and could be tested for potentially identifying patients with a favorable risk / benefit profile for antithrombotic therapy with warfarin. PMID:26189039

Serious Bleeding Events due to Warfarin and Antibiotic Co-prescription In a Cohort of Veterans

PubMed Central

Lane, Michael A.; Zeringue, Angelique; McDonald, Jay R.

2014-01-01

Background Antibiotics may interact with warfarin, increasing the risk for significant bleeding events. Methods Retrospective cohort study of veterans prescribed warfarin for ≥ 30 days without interruption through the VA between October 1, 2002 and September 1, 2008. Antibiotics considered to be high-risk for interaction with warfarin include: trimethoprim/sulfamethoxazole (TMP/SMX), ciprofloxacin, levofloxacin, metronidazole, fluiconazole, azithromycin, and clarithromycin. Low-risk antibiotics include: clindamycin and cephalexin. Risk of bleeding event within 30 days of antibiotic exposure was measured using Cox proportional hazards regression, adjusted for demographic characteristics, comorbid conditions and receipt of other medications interacting with warfarin. Results A total of 22,272 patients met inclusion criteria with 14,078 and 8,194 receiving high- and low-risk antibiotics, respectively. There were 93 and 36 bleeding events in the high- and low-risk groups, respectively. Receipt of a high-risk antibiotic (HR 1.48, 95% CI 1.00-2.19) and azithromycin (HR 1.93, 95% CI 1.13-3.30) were associated with increased risk of bleeding as a primary diagnosis. TMP/SMX (HR 2.09, 95% CI 1.45-3.02), ciprofloxacin (HR 1.87, 95% CI 1.42-2.50), levofloxacin (HR 1.77, 95% CI 1.22-2.50), azithromycin (HR 1.64, 95% CI 1.16-2.33), and clarithromycin (HR 2.40, 95% CI 1.16-4.94) were associated with serious bleeding as a primary or secondary diagnosis. INR alterations were common; 9.7% of patients prescribed fluconazole had INR value >6. Patients who had INR performed 3-14 days of co-prescription were at a decrease risk of serious bleeding (HR 0.61, 95% CI 0.42-0.88). Conclusions Warfarin users who are prescribed high-risk antibiotics are at higher risk for serious bleeding events. Early INR evaluation may mitigate this risk. PMID:24657899

Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats.

PubMed

Takeuchi, Koji; Takayama, Shinichi; Hashimoto, Erika; Itayama, Misaki; Amagase, Kikuko; Izuhara, Chitose

2014-12-01

We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats. Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30 mg/kg) was given p.o. 24 h before the perfusion. Rebamipide (3-30 mg/kg) or other antiulcer drugs were given i.d. before the ASA perfusion. Slight gastric bleeding or damage was observed with the perfusion of ASA under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to ASA plus clopidogrel. Rebamipide had no effect on acid secretion, but dose-dependently prevented gastric bleeding in response to ASA plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs. These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by ASA under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Impact of COPD on outcome among patients with complicated peptic ulcer.

PubMed

Christensen, Steffen; Thomsen, Reimar W; Tørring, Marie Louise; Riis, Anders; Nørgaard, Mette; Sørensen, Henrik T

2008-06-01

COPD is associated with an increased risk of peptic ulcer disease, but limited data exist on whether COPD influences short-term mortality among patients with bleeding and a perforated peptic ulcer. We examined the association between COPD and 30-day mortality following bleeding and perforation of a peptic ulcer. We identified all patients who had been hospitalized with a first-time diagnosis of peptic ulcer perforation (n = 2,033) or bleeding (n = 7,486) in northern Denmark between 1991 and 2004. Information on COPD, comorbidities, and filled prescriptions was obtained from medical databases. Mortality was ascertained using the Danish Civil Registration System. We computed the cumulative 30-day mortality rates for ulcer patients with COPD and for other ulcer patients, and used regression analysis to obtain the 30-day mortality rate ratios (MRRs), controlling for potential confounding factors. Among patients who were hospitalized with perforated peptic ulcers, 218 (10.7%) had previously been hospitalized with COPD. The 30-day mortality rate was 44.0% among perforated ulcer patients with COPD vs 25.5% among other ulcer patients (adjusted MRR, 1.48; 95% confidence interval [CI], 1.18 to 1.85). Among patients hospitalized with a bleeding peptic ulcer, 759 (10.1%) had previously been hospitalized with COPD. The 30-day mortality rate was 16.5% among bleeding peptic ulcer patients with COPD vs 10.8% among other ulcer patients (adjusted MRR, 1.38; 95% CI, 1.14 to 1.68). The use of oral glucocorticoids among COPD patients was associated with higher MRRs for both perforated and bleeding peptic ulcers. COPD substantially increased 30-day mortality among patients with bleeding and perforated peptic ulcers.

Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use.

PubMed

Cheng, Hsiu-Chi; Yang, Er-Hsiang; Wu, Chung-Tai; Wang, Wen-Lun; Chen, Po-Jun; Lin, Meng-Ying; Sheu, Bor-Shyang

2018-04-01

Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use. The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin <28 g/L), 135 in the marginal hypoalbuminemia group (Margin-AG, serum albumin 28-34.9 g/L), and 212 in the normal albuminemia group (Normal-AG, serum albumin ≥35 g/L). Each subject received 72-h of intravenous infusion and then the oral form of proton pump inhibitors and were monitored for 84 days to assess all-cause mortality and recurrent bleeding. The primary outcome of all-cause mortality rates were increased in a stepwise fashion in a trend from Normal-AG, Margin-AG, to Hypo-AG (0-28th day: 1.9%, 2.2%, 12.8%, p < 0.001; 29th-84th day: 2.5%, 8.0%, 10.6%, p < 0.01). The secondary outcome of recurrent bleeding rates were also increased in the same fashion (0-28th day: 6.4%, 15.4%, 24.6%, p < 0.001; 29th-84th day: 0%, 3.0%, 4.2%, p = 0.01). Abnormal albuminemia was <30 g/L related to hemoglobin levels <70 g/L, nosocomial bleeding, cirrhosis, age ≥70 years, shock, and ulcer size ≥1.0 cm independently (p < 0.05). Hypoalbuminemia in patients with peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083). Copyright © 2017. Published by Elsevier B.V.

Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis.

PubMed

Burr, Nick; Lummis, Katie; Sood, Ruchit; Kane, John Samuel; Corp, Aaron; Subramanian, Venkataraman

2017-02-01

Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]). Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants. Leeds Teaching Hospitals Charitable Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acid-suppressive Medication Use and the Risk for Nosocomial Gastrointestinal Bleeding

PubMed Central

Herzig, Shoshana J.; Vaughn, Byron P.; Howell, Michael D.; Ngo, Long H.; Marcantonio, Edward R.

2011-01-01

Background Acid-suppressive medications are increasingly prescribed for non-critically ill hospitalized patients, although the incidence of nosocomial gastrointestinal bleeding and magnitude of potential benefit from this practice are unknown. We aimed to define the incidence of nosocomial gastrointestinal bleeding outside of the intensive care unit, and examine the association between acid-suppressive medication and this complication. Methods We conducted a pharmacoepidemiologic cohort study of patients admitted to an academic medical center from 2004 through 2007, at least 18 years of age and hospitalized for 3 or more days. Admissions with a primary diagnosis of gastrointestinal bleeding were excluded. Acid-suppressive medication use was defined as any order for a proton-pump inhibitor or histamine-2-receptor antagonist. The main outcome measure was nosocomial gastrointestinal bleeding. A propensity matched generalized estimating equation was used to control for confounders. Results The final cohort included 78,394 admissions (median age = 56 years; 41% men). Acid-suppressive medication was ordered in 59% of admissions and nosocomial gastrointestinal bleeding occurred in 224 admissions (0.29%). After matching on the propensity score, the adjusted odds ratio for nosocomial gastrointestinal bleeding in the group exposed to acid-suppressive medication relative to the unexposed group was 0.63 (95% CI 0.42 to 0.93). The number-needed-to-treat to prevent one episode of nosocomial gastrointestinal bleeding was 770. Conclusions Nosocomial gastrointestinal bleeding outside of the intensive care unit was rare. Despite a protective effect of acid-suppressive medication, the number-needed-to-treat to prevent one case of nosocomial gastrointestinal bleeding was relatively high, supporting the recommendation against routine use of prophylactic acid-suppressive medication in noncritically ill hospitalized patients. PMID:21321285

Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome.

PubMed

Guntipalli, Prathima; Chason, Rebecca; Elliott, Alan; Rockey, Don C

2014-12-01

We have recognized a unique clinical syndrome in patients with upper gastrointestinal bleeding who are found to have severe esophagitis. We aimed to more clearly describe the clinical entity of upper gastrointestinal bleeding in patients with severe esophagitis. We conducted a retrospective matched case-control study designed to investigate clinical features in patients with carefully defined upper gastrointestinal bleeding and severe esophagitis. Patient data were captured prospectively via a Gastrointestinal Bleeding Healthcare Registry, which collects data on all patients admitted with gastrointestinal bleeding. Patients with endoscopically documented esophagitis (cases) were matched with randomly selected controls that had upper gastrointestinal bleeding caused by other lesions. Epidemiologic features in patients with esophagitis were similar to those with other causes of upper gastrointestinal bleeding. However, hematemesis was more common in patients with esophagitis 86% (102/119) than in controls 55% (196/357) (p < 0.0001), while melena was less common in patients with esophagitis 38% (45/119) than in controls 68% (244/357) (p < 0.0001). Additionally, the more severe the esophagitis, the more frequent was melena. Patients with esophagitis had less abnormal vital signs, lesser decreases in hematocrit, and lesser increases in BUN. Both pre- and postRockall scores were lower in patients with esophagitis compared with controls (p = 0.01, and p < 0.0001, respectively). Length of hospital stay (p = 0.002), rebleeding rate at 42 days (p = 0.0007), and mortality were less in patients with esophagitis than controls. Finally, analysis of patients with esophagitis and cirrhosis suggested that this group of patients had more severe bleeding than those without cirrhosis. We have described a unique clinical syndrome in patients with upper gastrointestinal bleeding who have erosive esophagitis. This syndrome is manifest by typical clinical features and is associated with favorable outcomes.

Risks of postextraction bleeding after receiving direct oral anticoagulants or warfarin: a retrospective cohort study

PubMed Central

Yagyuu, Takahiro; Kawakami, Mao; Ueyama, Yoshihiro; Imada, Mitsuhiko; Kurihara, Miyako; Matsusue, Yumiko; Imai, Yuichiro; Yamamoto, Kazuhiko; Kirita, Tadaaki

2017-01-01

Objective The effect of direct oral anticoagulants (DOACs) on the risk of bleeding after tooth extraction remains unclear. This study aimed to evaluate the incidence of postextraction bleeding among patients who received DOAC and vitamin K antagonists (VKAs), such as warfarin. Design This study was a retrospective cohort analysis. Incidence rates and propensity score-matched regression models were used to compare the risks of bleeding after tooth extractions involving DOACs and VKAs. Setting The study took place in a single university hospital in Japan. Participants Between April 2013 and April 2015, 543 patients underwent a total of 1196 simple tooth extractions. Primary outcome measure The primary outcome measure was the occurrence of postextraction bleeding, which was defined as bleeding that could not be stopped by biting down on gauze and required medical treatment between 30 min and 7 days after the extraction. Results A total of 1196 tooth extractions (634 procedures) in 541 patients fulfilled the study criteria, with 72 extractions (41 procedures) involving DOACs, 100 extractions (50 procedures) involving VKAs and 1024 extractions (543 procedures) involving no anticoagulants. The incidences of postextraction bleeding per tooth for the DOAC, VKA and no anticoagulant extractions were 10.4%, 12.0% and 0.9%, respectively. The incidences of postextraction bleeding per procedure for DOACs, VKAs and no anticoagulants were 9.7%, 10.0% and 1.1%, respectively. In comparison to the VKA extractions, the DOAC extractions did not significantly increase the risk of postextraction bleeding (OR 0.69, 95% CIs 0.24 to 1.97; p=0.49). Conclusions The risk of postextraction bleeding was similar for DOAC and VKA extractions. PMID:28827248

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

PubMed Central

Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-01-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans. PMID:2789070

Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiraishi, Yutaka, E-mail: shiraishi@rad.med.keio.ac.jp; Hanada, Takashi; Ohashi, Toshio

2013-09-01

Purpose: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after {sup 125}I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. Methods and Materials: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose–volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUD{sub sum}) was determined by a summation ofmore » the brachytherapy and external-beam radiation therapy components. Results: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUD{sub sum} increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUD{sub sum} (P=.000) as risk factors for grade 2+ rectal bleeding. Conclusions: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.« less

IBUPROFEN DOES NOT INCREASE BLEEDING RISK IN PLASTIC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS

PubMed Central

Kelley, Brian P.; Bennett, Katelyn G.; Chung, Kevin C.; Kozlow, Jeffrey H.

2016-01-01

Background Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are common medications with multiple useful effects including pain relief and reduction of inflammation. However, surgeons commonly hold all NSAIDs peri-operatively because of bleeding concerns. However, not all NSAIDs irreversibly block platelet function. We hypothesized that the use of ibuprofen would have no effect on postoperative bleeding in plastic surgery patients. Methods A literature review was performed using Medline (PubMed), EMBASE, and the Cochrane Collaboration Library for primary research articles on ibuprofen and bleeding. Inclusion criteria were primary journal articles examining treatment of acute postoperative based on any modality. Data related to pain assessment, postoperative recovery, and complications were extracted. Bias assessment and meta-analysis were performed. Results A total of 881 publications were reviewed. Four primary randomized controlled trials were selected for full analysis. Articles were of high quality by bias assessment. No significant difference was noted regarding bleeding events (p = 0.32) and pain control was noted to be equivalent. Conclusion Ibuprofen is a useful medication in the setting of surgery with multiple beneficial effects. This meta-analysis represents a small set of high quality studies that suggests ibuprofen provides equivalent pain control to narcotics. Importantly, ibuprofen was not associated with an increased risk of bleeding. Further large studies will be necessary to elucidate this issue further, but ibuprofen is a safe postoperative analgesic in patients undergoing common plastic surgery soft tissue procedures. PMID:27018685

Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients

PubMed Central

Yang, Ju-Yeh; Lee, Tsung-Chun; Montez-Rath, Maria E.; Paik, Jane; Chertow, Glenn M.; Desai, Manisha

2012-01-01

Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial. PMID:22266666

Relevance of surgery after embolization of gastrointestinal and abdominal hemorrhage.

PubMed

Köhler, Gernot; Koch, Oliver Owen; Antoniou, Stavros A; Mayer, Franz; Lechner, Michael; Pallwein-Prettner, Leo; Emmanuel, Klaus

2014-09-01

Gastrointestinal and abdominal bleeding can lead to life-threatening situations. Embolization is considered a feasible and safe treatment option. The relevance of surgery has thus diminished in the past. The aim of the present study was to evaluate the role of surgery in the management of patients after embolization. We performed a retrospective single-center analysis of outcomes after transarterial embolization of acute abdominal and gastrointestinal hemorrhage between January 2009 and December 2012 at the Sisters of Charity Hospital, Linz. Patients were divided into three groups, as follows: upper gastrointestinal bleeding (UGIB), lower gastrointestinal bleeding (LGIB), and abdominal hemorrhage. Fifty-four patients with 55 bleeding events were included. The bleeding source could be localized angiographically in 80 %, and the primary clinical success rate of embolization was 81.8 % (45/55 cases). Early recurrent bleeding (<30 days) occurred in 18.2 % (10/55) of the patients, and delayed recurrent hemorrhage (>30 days) developed in 3.6 % (2/55). The mean follow-up was 8.4 months, and data were available for 85.2 % (46/54) of the patients. Surgery after embolization was required in 20.4 % of these patients (11/54). Failure to localize the bleeding site was identified as predictive of recurrent bleeding (p = 0.009). More than one embolization effort increased the risk of complications (p = 0.02) and rebleeding (p = 0.07). Surgery still has an important role after embolization in patients with gastrointestinal and abdominal hemorrhage. One of five patients required surgery in cases of early and delayed rebleeding or because of ischemic complications (2/55 both had ischemic damage of the gallbladder) and bleeding consequences.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

PubMed Central

Gjeorgjievski, Mihajlo; Cappell, Mitchell S

2016-01-01

AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS: Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: “portal” and “gastropathy”; or “portal” and “hypertensive”; or “congestive” and “gastropathy”; or “congestive” and “gastroenteropathy”. The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy. PMID:26855694

Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding

PubMed Central

Wang, Xi-Xu; Dong, Bo; Hong, Biao; Gong, Yi-Qun; Wang, Wei; Wang, Jue; Zhou, Zhen-Yu; Jiang, Wei-Jun

2017-01-01

AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the difference was compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups (70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8 (8.2%) vs 15 (21.7%), P < 0.05; 65 (66.3%) vs 13 (18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant (P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group (log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio (HR) for recurrent bleeding was 2.986 (95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216 (95%CI: 1.035-26.278, P = 0.028). CONCLUSION After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding. PMID:28216980

Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding.

PubMed

Wang, Xi-Xu; Dong, Bo; Hong, Biao; Gong, Yi-Qun; Wang, Wei; Wang, Jue; Zhou, Zhen-Yu; Jiang, Wei-Jun

2017-01-28

To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t - or χ 2 -test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the difference was compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups (70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8 (8.2%) vs 15 (21.7%), P < 0.05; 65 (66.3%) vs 13 (18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant ( P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group (log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio (HR) for recurrent bleeding was 2.986 (95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216 (95%CI: 1.035-26.278, P = 0.028). After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding.

Increasing biopsy number and sampling from gastric body improve the sensitivity of rapid urease test in patients with peptic ulcer bleeding.

PubMed

Lee, Tzong-Hsi; Lin, Chien-Chu; Chung, Chen-Shuan; Lin, Cheng-Kuan; Liang, Cheng-Chao; Tsai, Kuang-Chau

2015-02-01

Previous studies demonstrated that the sensitivity of rapid urease test (RUT) for diagnosis of Helicobacter pylori infection decreased during peptic ulcer bleeding. We designed this study and tried to find a better method to improve the detection rate of H. pylori infection at the same session of endoscopic diagnosis of peptic ulcer bleeding. We prospectively enrolled 116 patients with peptic ulcer bleeding. These patients received intravenous proton pump inhibitor and then received upper gastrointestinal endoscopy within 24 h after arrival. We took one piece of biopsy from gastric antrum (Group 1), four pieces from gastric antrum (Group 2), and one piece from the gastric body (Group 3) for three separate RUTs, respectively. (13)C-urease breath test was used as gold standard for diagnosis of H. pylori infection. There were 74 patients (64 %) with positive (13)C-urease breath test. Among these 74 patients, 45 patients had positive RUT (sensitivity: 61 %) in Group 1; 55 patients had positive RUT (sensitivity: 74 %) in Group 2; 54 patients had positive RUT (sensitivity: 73 %) in Group 3. There were significant differences between Group 1 and Group 2 (p = 0.02) and between Group 1 and Group 3 (p = 0.022). The sensitivity of RUT was 61 % during peptic ulcer bleeding. The sensitivity of RUT can be increased significantly by increased biopsy number from gastric antrum or biopsy from gastric body.

Diagnosis and therapy of non-variceal upper gastrointestinal bleeding

PubMed Central

Biecker, Erwin

2015-01-01

Non-variceal upper gastrointestinal bleeding (UGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of oesophageal, gastric or duodenal varices. The clinical presentation varies according to the intensity of bleeding from occult bleeding to melena or haematemesis and haemorrhagic shock. Causes of UGIB are peptic ulcers, Mallory-Weiss lesions, erosive gastritis, reflux oesophagitis, Dieulafoy lesions or angiodysplasia. After admission to the hospital a structured approach to the patient with acute UGIB that includes haemodynamic resuscitation and stabilization as well as pre-endoscopic risk stratification has to be done. Endoscopy offers not only the localisation of the bleeding site but also a variety of therapeutic measures like injection therapy, thermocoagulation or endoclips. Endoscopic therapy is facilitated by acid suppression with proton pump inhibitor (PPI) therapy. These drugs are highly effective but the best route of application (oral vs intravenous) and the adequate dosage are still subjects of discussion. Patients with ulcer disease are tested for Helicobacter pylori and eradication therapy should be given if it is present. Non-steroidal anti-inflammatory drugs have to be discontinued if possible. If discontinuation is not possible, cyclooxygenase-2 inhibitors in combination with PPI have the lowest bleeding risk but the incidence of cardiovascular events is increased. PMID:26558151

Ultrasound imaging in the management of bleeding and pain in early pregnancy.

PubMed

Knez, Jure; Day, Andrea; Jurkovic, Davor

2014-07-01

Bleeding and pain are experienced by 20% of women during the first trimester of pregnancy. Although most pregnancies complicated by pain and bleeding tend to progress normally, these symptoms are distressing for woman, and they are also associated with an increased risk of miscarriage and ectopic pregnancy. Ultrasound is the first and often the only diagnostic modality that is used to determine location of early pregnancy and to assess its health. Ultrasound is an accurate, safe, painless and relatively inexpensive diagnostic tool, which all contributed to its widespread use in early pregnancy. Pain and bleeding in early pregnancy are sometimes caused by concomitant gynaecological, gastrointestinal, and urological problems, which could also be detected on ultrasound scan. In women with suspected intra-abdominal bleeding, ultrasound scan can be used to detect the presence of blood and provide information about the extent of bleeding. In this chapter, we comprehensively review the use of ultrasound in the diagnosis and management of early pregnancy complications. We include information about the diagnosis of gynaecological and other pelvic abnormalities, which could cause pain or bleeding in pregnancy. We also provide a summary of the current views on the safety of ultrasound in early pregnancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Severe physical violence among intimate partners: a risk factor for vaginal bleeding during gestation in less privileged women?

PubMed

Moraes, Claudia Leite; Reichenheim, Michael; Nunes, Antônio Paulo

2009-01-01

To evaluate the role of severe physical violence within intimate partners on the occurrence of vaginal bleeding during gestation in less privileged women. Health service survey. Three large public maternities in the city of Rio de Janeiro, Brazil. Five hundred and twenty-eight women who gave birth to full-term newborn infants were selected at random among the births that took place during the six months of fieldwork. Information on vaginal bleeding during gestation was obtained from medical records, pre-natal cards, and by means of a questionnaire addressed to the women giving birth. To collect severe physical violence data, use was made of the Portuguese version of the instrument Revised Conflict Tactics Scales, formally adapted for use in Brazil. Vaginal bleeding during gestation. After accounting for socio-economic, demographic, reproductive, and pregnant women's life-style variables, women who had been victims of two or more acts of severe physical violence were 2.74 (95% CI: 1.37-5.48) times more liable to present with vaginal bleeding during pregnancy than those who did not. Our findings suggest that physical violence increases the risk of vaginal bleeding in pregnancy. This result should encourage studies on whether intervention in violent relationships can reduce the risk of vaginal bleeding and other pregnancy complications.

Risk factors for postpolypectomy bleeding in patients receiving anticoagulation or antiplatelet medications.

PubMed

Lin, David; Soetikno, Roy M; McQuaid, Kenneth; Pham, Chi; Doan, Gilbert; Mou, Shanshan; Shergill, Amandeep K; Somsouk, Ma; Rouse, Robert V; Kaltenbach, Tonya

2018-04-01

Balancing the risks for thromboembolism and postpolypectomy bleeding in patients requiring anticoagulation and antiplatelet agents is challenging. We investigated the incidence and risk factors for postpolypectomy bleeding on anticoagulation, including heparin bridge and other antithrombotic therapy. We performed a retrospective cohort and case control study at 2 tertiary-care medical centers from 2004 to 2012. Cases included male patients on antithrombotics with hematochezia after polypectomy. Nonbleeding controls were matched to cases 3 to 1 by antithrombotic type, study site, polypectomy technique, and year of procedure. Our outcomes were the incidence and risk factors for postpolypectomy bleeding. There were 59 cases and 174 matched controls. Postpolypectomy bleeding occurred in 14.9% on bridge anticoagulation. This was significantly higher than the overall incidence of bleeding on antithrombotics at 1.19% (95% confidence interval, 0.91%-1.54%) (59/4923). We identified similarly low rates of bleeding in patients taking warfarin (0.66%), clopidogrel (0.84%), and aspirin (0.92%). Patients who bled tended to have larger polyps (13.9 vs 7.3 mm; P < .001) and more polyps ≥2 cm (41% vs 10%; P < .001). Bleeding risk was increased with restarting antithrombotics within 1 week postpolypectomy (odds ratio [OR] 4.50; P < .001), having polyps ≥2 cm (OR 5.94; P < .001), performing right-sided cautery (OR 2.61; P = .004), and having multiple large polyps (OR 2.92; P = .001). Among patients on warfarin, the presence of bridge anticoagulation was an independent risk factor for postpolypectomy bleeding (OR 12.27; P = .0001). We conclude that bridge anticoagulation is associated with a high incidence of postpolypectomy bleeding and is an independent risk factor for hemorrhage compared with patients taking warfarin alone. A higher threshold to use bridge anticoagulation should be considered in patients with an elevated bleeding risk. Copyright © 2018. Published by Elsevier Inc.

Abnormal uterine bleeding in perimenopause.

PubMed

Goldstein, S R; Lumsden, M A

2017-10-01

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

Heparins from porcine and bovine intestinal mucosa: Are they similar drugs?

PubMed

Aquino, Rafael S; Pereira, Mariana S; Vairo, Bruno C; Cinelli, Leonardo P; Santos, Gustavo R C; Fonseca, Roberto J C; Mourão, Paulo A S

2010-05-01

Increasing reports of bleeding and peri- or post-operative blood dyscrasias in Brazil were possibly associated with the use of heparin from bovine instead of porcine intestine. These two pharmaceutical grade heparins were analysed for potential differences. NMR analyses confirmed that porcine heparin is composed of mainly trisulfated disaccharides -->4-alpha-IdoA2S-1-->4-alpha-GlcNS6S-1-->. Heparin from bovine intestine is also composed of highly 2-sulfated alpha-iduronic acid residues, but the sulfation of the alpha-glucosamine units vary significantly: approximately 50% are 6- and N -disulfated, as in porcine heparin, while approximately 36% are 6-desulfated and approximately 14% N -acetylated. These heparins differ significantly in their effects on coagulation, thrombosis and bleeding. Bovine heparin acts mostly through factor Xa. Compared to porcine heparin on a weight basis, bovine heparin exhibited approximately half of the anticoagulant and antithrombotic effects, but similar effect on bleeding. These two heparins also differ in their protamine neutralisation curves. The doses of heparin from bovine intestine required for effective antithrombotic protection and the production of adverse bleeding effects are closer than those for porcine heparin. This observation may explain the increasing bleeding observed among Brazilian patients. Our results suggest that these two types of heparin are not equivalent drugs.

Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in a rat model.

PubMed

Blum, Jared; Carreiro, Stephanie; Hack, Jason B

2013-10-01

The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36) = 33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36) = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5 seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95% CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5 seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55 seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased significantly at T15 to 237 seconds (95% CI = 161 to 313 seconds; p = 0.02). The anticoagulant effects of dabigatran are not reversed with ILE therapy. Although ILE itself significantly prolonged bleeding times, when administered to dabigatran-anticoagulated rats, bleeding times did not change significantly. There may be a complex interaction of ILE with dabigatran that this study was not able to elucidate. © 2013 by the Society for Academic Emergency Medicine.

The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study.

PubMed

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Siegbahn, Agneta; Yusuf, Salim; Granger, Christopher B; Wallentin, Lars

2016-06-04

The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation. We developed and internally validated a new biomarker-based risk score for major bleeding in 14,537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov, numbers NCT00412984 and NCT00262600, respectively. The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers [GDF-15, cTnT-hs, and haemoglobin], and clinical history [previous bleeding]) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0·68 [95% CI 0·66-0·70] vs 0·61 [0·59-0·63] vs 0·65 [0·62-0·67], respectively; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0·71 [95% CI 0·68-0·73] vs 0·62 [0·59-0·64] for HAS-BLED vs 0·68 [0·65-0·70] for ORBIT; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores. The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation. BMS, Pfizer, Boehringer Ingelheim, Roche Diagnostics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential roles of fibrinogen and von Willebrand factor on clot formation and platelet adhesion in reconstituted and immune thrombocytopenia.

PubMed

Misgav, Mudi; Shenkman, Boris; Budnik, Ivan; Einav, Yulia; Martinowitz, Uri

2011-05-01

Bleeding tendencies in immune thrombocytopenia (ITP) do not always correlate with the number of platelets, suggesting platelet function variation. We used a model of normal whole blood thrombocytopenia to compare platelet function and other hemostatic variables with ITP patients. We further investigated the effect of in vitro spiking with von Willebrand factor (vWF) and fibrinogen on platelet function and hemostatic variables. The Cone and Plate(let) Analyzer was used to measure platelet adhesion (surface coverage [SC], %) and aggregation (average size, μm(2)) under defined shear rate (1200 s(-1)). Rotational thromboelastometry was used to determine variables of clot formation triggered by CaCl(2) and tissue factor. In both the model of thrombocytopenia as well as in ITP, the SC and to some extent the average size were correlated to the platelet number over a range of 5 to 80 × 10(6)/mL. The results obtained for most ITP samples were within the boundaries of the lower and upper limits set by the whole blood model of thrombocytopenia. The addition of 2 U/mL vWF (Haemate-P) to whole blood (calculated to plasma volume) results in an increase in the SC and average size without affecting clot formation. Spiking with fibrinogen (100 and 300 mg/dL) did not affect platelet deposition but improved clot formation. Using a model of whole blood thrombocytopenia enables us to establish reference variables for the Cone and Plate(let) Analyzer and rotational thromboelastometry and to assess platelet function and clot formation in the presence of severe thrombocytopenia. We demonstrated that in most cases of ITP, platelet function is comparable to normal platelets. This work also suggests that vWF and fibrinogen differentially affect primary and secondary hemostasis and therefore both may perform a function in the bleeding phenotype and possibly may be considered for treatment in patients with ITP. © 2011 International Anesthesia Research Society

Successful treatment of life-threatening bleeding from a duodenal posterior bulb peptic ulcer by an over-the-scope-clip.

PubMed

Brechmann, Thorsten; Schmiegel, Wolff

2015-02-07

Bleeding of peptic ulcer at the posterior duodenal bulb still is a particular endoscopic challenge with increased risk of treatment failure and worse outcome. In this article, we report successful treatment of an actively bleeding peptic ulcer located at the posterior duodenal wall, using an over-the-scope-clip in the case of a 54-year-old male patient with hemorrhagic shock. Incident primary hemostasis was achieved and no adverse events occurred during a follow-up of 60 d.

Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

PubMed

Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

2017-08-01

Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

Telemetric real-time sensor for the detection of acute upper gastrointestinal bleeding.

PubMed

Schostek, Sebastian; Zimmermann, Melanie; Keller, Jan; Fode, Mario; Melbert, Michael; Schurr, Marc O; Gottwald, Thomas; Prosst, Ruediger L

2016-04-15

Acute upper gastrointestinal bleedings from ulcers or esophago-gastric varices are life threatening medical conditions which require immediate endoscopic therapy. Despite successful endoscopic hemostasis, there is a significant risk of rebleeding often requiring close surveillance of these patients in the intensive care unit (ICU). Any time delay to recognize bleeding may lead to a high blood loss and increases the risk of death. A novel telemetric real-time bleeding sensor can help indicate blood in the stomach: the sensor is swallowed to detect active bleeding or is anchored endoscopically on the gastrointestinal wall close to the potential bleeding source. By telemetric communication with an extra-corporeal receiver, information about the bleeding status is displayed. In this study the novel sensor, which measures characteristic optical properties of blood, has been evaluated in an ex-vivo setting to assess its clinical applicability and usability. Human venous blood of different concentrations, various fluids, and liquid food were tested. The LED-based sensor was able to reliably distinguish between concentrated blood and other liquids, especially red-colored fluids. In addition, the spectrometric quality of the small sensor (size: 6.5mm in diameter, 25.5mm in length) was comparable to a much larger and technically more complex laboratory spectrophotometer. The experimental data confirm the capability of a miniaturized sensor to identify concentrated blood, which could help in the very near future the detection of upper gastrointestinal bleeding and to survey high-risk patients for rebleeding. Copyright © 2015 Elsevier B.V. All rights reserved.

Placenta previa associated with severe bleeding leading to hospitalization and delivery: a retrospective population-based cohort study.

PubMed

Mastrolia, Salvatore Andrea; Baumfeld, Yael; Loverro, Giuseppe; Yohai, David; Hershkovitz, Reli; Weintraub, Adi Yehuda

2016-11-01

The aim of our study was to compare maternal and neonatal outcomes in women with placenta previa complicated with severe bleeding leading to hospitalization until delivery versus those without severe bleeding episodes. This is a population-based retrospective cohort study including all pregnant women with placenta previa who delivered at our medical center in the study period, divided into the following groups: 1) women with severe bleeding leading to hospitalization resulting with delivery (n = 32); 2) patients with placenta previa without severe bleeding episodes (n = 1217). Out of all women with placenta previa who delivered at our medical center, 2.6% (32/1249) had an episode of severe bleeding leading to hospitalization and resulting with delivery. The rate of anemia was lower (43.8% versus 63.7%, p = 0.02) while the need for blood transfusion higher (37.5% versus 21.1%, p = 0.03) in the study group. The rate of cesarean sections was significantly different between the groups, and a logistic regression model was constructed in order to find independent risk factors for cesarean section in our patients. To the best of our knowledge, this is the first study to evaluate the impact of severe bleeding on the outcome of pregnancies complicated with placenta previa. Our study demonstrates that, in women with placenta previa, severe bleeding does not lead to increased adverse maternal or neonatal outcomes.

[Comparison of the HAS-BLED and ATRIA scores for the risk of bleeding in patients aged 75 and over receiving vitamin K antagonist (VKA) therapy and educated VKA-management].

PubMed

Soave, Claire; Chidlovskii, Elena; Lebelhomme, Audrey; Gaboreau, Yoann; Pernod, Gilles; Bosson, Jean Luc; Couturier, Pascal

2015-09-01

Bleeding is the main complication on vitamin K antagonist treatment (VKA), particularly in elderly patients. However, the bleeding risk prediction in geriatric patients remains difficult. We evaluated the predictive value of the HAS-BLED and ATRIA bleeding scores in VKA-treated patients aged 75 and over. Various clinical bleeding risk factors in elderly were also studied. 208 patients were included in a case-control study: 52 hemorrhages cases were compared to 156 hemorrhage-free cases (controls), mean age 83.1 years in cases and 82.6 in controls. This elderly subgroup was provided from the prospective SCORE cohort study (study designed to validate the use of bleeding scores in an ambulatory population). The patients were included during a VKA-therapeutic education between May 2009 and May 2010 in 4 French hospitals, and followed for 1 year. The primary endpoint, collected prospectively, was the occurrence of severe and clinically relevant bleeding events. According to the Receiver operating characteristics (ROC), the ATRIA score was as effective as HAS- BLED to predict all bleeding (c-statistic: 0.59 [95% CI 0.50-0.68] vs 0.56 [0.48-0.65]) including severe bleeding (c-statistic: 0.64 [95% CI 0.49-0.79] vs 0.62 [0.49-0.75]). Multivariate Cox regression analysis showed increasing bleeding risk with anemia (OR = 2.6 [95% CI 1.34-5.23], p = 0.005), serotonin reuptake inhibitors (2.8 [1.08-7.47], 0.034), and family-management of VKA-treatment (2.8 [1.28-6.15], 0.01). ATRIA hemorrhage predictive value can be improved by adding such parameters as family-management of VKA-treatment and serotonin reuptake inhibitors treatment. ATRIA appears as relevant as HAS-BLED in predicting all bleeding including major hemorrhages in elderly patients educated VKA-management. The ATRIA bleeding score is improved by including items of serotonin reuptake inhibitors treatment and family-management of VKA-treatment.

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pourgholi, Leyla

Background: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. Methods: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0–3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restrictionmore » fragment length polymorphism (PCR-RFLP). Results: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P = 0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P = 0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. Conclusion: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations. - Highlights: • NQO1 C609T variant is associated with warfarin induced bleeding at therapeutic INR. • Haplotypes of CYP2C9 (1*2 or 1*3) are also associated with bleeding events. • VKORC1, Factor VII, and EPHX1 genotypes were not associated with bleeding risk.« less

Safety of continuing aspirin therapy during spinal surgery: A systematic review and meta-analysis.

PubMed

Zhang, Chenggui; Wang, Guodong; Liu, Xiaoyang; Li, Yang; Sun, Jianmin

2017-11-01

Questions whether to continue or discontinue aspirin administration in the perioperative period of spinal surgery has not been systematically evaluated. The present systematic review is carried out to assess the impact of continuing aspirin administration on the bleeding and cardiovascular events in perispinal surgery period. Studies were retrieved through MEDLINE, EMBASE, and Springer Link Databases (search terms, aspirin, continue or discontinue, and spinal fusion), bibliographies of the articles retrieved, and the authors' reference files. We included studies that enrolled patients who underwent spinal surgery who were anticoagulated with aspirin alone and that reported bleeding or cardiovascular events as an outcome. Study quality was assessed using a validated form. 95% confidence interval (95% CI) was pooled to give summary estimates of bleeding and cardiovascular risk. We identified 4 studies assessing bleeding risk associated with aspirin continuation or cardiovascular risk with aspirin discontinuation during spinal surgery. The continuation of aspirin will not increase the risk of blood loss during the spinal surgery (95% CI, -111.72 to -0.59; P = .05). Also, there was no observed increase in the operative time (95% CI, -33.29 to -3.89; P = .01) and postoperative blood transfusion (95% CI, 0.00-0.27; P = .05). But as for the cardiovascular risk without aspirin continuation and mean hospital length of stay with aspirin continuation, we did not get enough samples to make an accurate decision about their relations with aspirin. Patients undergoing spinal surgery with continued aspirin administration do not have an increased risk for bleeding. In addition, there is no observed increase in the operation time and postoperative blood transfusion.

Resuscitative endovascular balloon occlusion of the aorta may increase the bleeding of minor thoracic injury in severe multiple trauma patients: a case report.

PubMed

Maruhashi, Takaaki; Minehara, Hiroaki; Takeuchi, Ichiro; Kataoka, Yuichi; Asari, Yasushi

2017-12-14

The resuscitative endovascular balloon occlusion of the aorta, because of its efficacy and feasibility, has been widely used in treating patients with severe torso trauma. However, complications developing around the site proximal to the occlusion by resuscitative endovascular balloon occlusion of the aorta have almost never been studied. A 50-year-old Japanese woman fell from a height of approximately 10 m. At initial arrival, her respiratory rate was 24 breaths/minute, her blood oxygen saturation was 95% under 10 L/minute oxygenation, her pulse rate was 90 beats per minute, and her blood pressure was 180/120 mmHg. Mild lung contusion, hemopneumothorax, unstable pelvic fracture, and retroperitoneal bleeding with extravasation of contrast media were observed in initial computed tomography. As her vital signs had deteriorated during computed tomography, a 7-French aortic occlusion catheter (RESCUE BALLOON®, Tokai Medical Products, Aichi, Japan) was inserted and inflated for aortic occlusion at the first lumbar vertebra level and transcatheter arterial embolization was performed for the pelvic fracture. Her bilateral internal iliac arteries were embolized with a gelatin sponge; however, the embolized sites presented recanalization as coagulopathy appeared. Her bilateral internal iliac arteries were re-embolized by n-butyl-2-cyanoacrylate. The balloon was deflated 18 minutes later. After embolization, repeat computed tomography was performed and a massive hemothorax, which had not been captured on arrival, had appeared in her left pleural cavity. Thoracotomy hemostasis was performed and a hemothorax of approximately 2500 ml was aspirated to search for the source of bleeding. However, clear active bleeding was not captured; resuscitative endovascular balloon occlusion of the aorta may have been the cause of the increased bleeding of the thoracic injury at the proximal site of the aorta occlusion. It is necessary to note that the use of resuscitative endovascular balloon occlusion of the aorta may increase bleeding in sites proximal to occlusions, even in the case of minor injuries without active bleeding at the initial diagnosis.

Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study

PubMed Central

de Abajo, Francisco José; Rodríguez, Luis Alberto García; Montero, Dolores

1999-01-01

Objective To examine the association between selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding. Design Population based case-control study. Setting General practices included in the UK general practice research database. Subjects 1651 incident cases of upper gastrointestinal bleeding and 248 cases of ulcer perforation among patients aged 40 to 79 years between April 1993 and September 1997, and 10 000 controls matched for age, sex, and year that the case was identified. Interventions Review of computer profiles for all potential cases, and an internal validation study to confirm the accuracy of the diagnosis on the basis of the computerised information. Main outcome measures Current use of selective serotonin reuptake inhibitors or other antidepressants within 30 days before the index date. Results Current exposure to selective serotonin reuptake inhibitors was identified in 3.1% (52 of 1651) of patients with upper gastrointestinal bleeding but only 1.0% (95 of 10 000) of controls, giving an adjusted rate ratio of 3.0 (95% confidence interval 2.1 to 4.4). This effect measure was not modified by sex, age, dose, or treatment duration. A crude incidence of 1 case per 8000 prescriptions was estimated. A small association was found with non-selective serotonin reuptake inhibitors (relative risk 1.4, 1.1 to 1.9) but not with antidepressants lacking this inhibitory effect. None of the groups of antidepressants was associated with ulcer perforation. The concurrent use of selective serotonin reuptake inhibitors with non-steroidal anti-inflammatory drugs increased the risk of upper gastrointestinal bleeding beyond the sum of their independent effects (15.6, 6.6 to 36.6). A smaller interaction was also found between selective serotonin reuptake inhibitors and low dose aspirin (7.2, 3.1 to 17.1). Conclusions Selective serotonin reuptake inhibitors increase the risk of upper gastrointestinal bleeding. The absolute effect is, however, moderate and about equivalent to low dose ibuprofen. The concurrent use of non-steroidal anti-inflammatory drugs or aspirin with selective serotonin reuptake inhibitors greatly increases the risk of upper gastrointestinal bleeding. PMID:10531103

What is the impact of preoperative aspirin administration on patients undergoing coronary artery bypass grafting?

PubMed

Aboul-Hassan, Sleiman Sebastian; Stankowski, Tomasz; Marczak, Jakub; Cichon, Romuald

2017-02-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether continuation of administration of preoperative aspirin until the day of coronary artery bypass grafting (CABG) could minimize postoperative mortality, prevalence of postoperative myocardial infarction (MI) with or without influence on postoperative bleeding, packed red blood cell (PRBC) transfusion and reoperation for bleeding. Altogether, 662 papers were found using the reported search, 7 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Seven studies, included in this review, consisted of five meta-analyses and two randomized controlled trials. One meta-analysis, involving 27 533 patients submitted to CABG, showed that the administration of preoperative aspirin decreased postoperative 30-day mortality by 27%. Another meta-analysis, including 1437 patients, showed that preoperative aspirin decreased the incidence of perioperative MI by 44%, the effect being even more pronounced with low-dose aspirin, which reduced the prevalence of perioperative MI by 63%. One RCT showed that preoperative aspirin is associated with reduced long-term hazard of MI or repeated revascularization. Four meta-analyses and two RCTs showed that preoperative aspirin is associated with increased postoperative bleeding, PRBC transfusion and reoperation for bleeding. However, this was not the case with preoperative administration of low-dose aspirin. The results presented in these studies suggest that preoperative aspirin administration in patients undergoing CABG has a significant benefit in reducing the incidence of perioperative MI and 30-day mortality rate, as well as reduced long-term hazard of MI or repeated revascularization. At a higher dose (>100 mg/day), postoperative bleeding, PRBC transfusion and reoperation for bleeding increased. However, with low-dose aspirin (≤100 mg/day), these benefits were not at the expense of increased postoperative bleeding or transfusion. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Heparin monotherapy or bivalirudin during percutaneous coronary intervention in patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease: results from the Evaluation of Drug-Eluting Stents and Ischemic Events registry.

PubMed

Bangalore, Sripal; Pencina, Michael J; Kleiman, Neal S; Cohen, David J

2014-06-01

The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined. The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy. Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use during percutaneous coronary intervention when compared with unfractionated heparin monotherapy was associated with lower bleeding without significant increase in ischemic outcomes or stent thrombosis. © 2014 American Heart Association, Inc.

Detection of the source of hemorrhage using postmortem computerized tomographic angiography in a case of a giant juvenile nasopharyngeal angiofibroma after surgical treatment.

PubMed

do Nascimento, Felipe Barjud Pereira; dos Santos, Glaucia Aparecida Bento; Melo, Nelson Almeida d'Ávila; Damasceno, Eduarda Bittencourt; Mauad, Thais

2015-09-01

Postmortem computerized tomographic angiography (PMCTA) has been increasingly used in forensic medicine to detect and locate the source of bleeding in cases of fatal acute hemorrhage. In this paper, we report a case of postoperative complication in a patient with a giant juvenile nasopharyngeal angiofibroma in which the source of bleeding was detected by PMCTA. A case description and evaluations of the pre- and postoperative exams, postmortem CT angiogram, and conventional autopsy results are provided. The source of bleeding was identified by postmortem CT angiography but not by conventional autopsy. The established protocol, injecting contrast medium into the femoral artery, was effective in identifying the source of bleeding. Postoperative bleeding is a rare and frequently fatal complication of juvenile nasopharyngeal angiofibroma. As a complement to conventional autopsy, postmortem angiography is a valuable tool for the detection of lethal acute hemorrhagic foci, and establishing a routine procedure for PMCTA may improve its efficiency.

Diagnosis, Treatment, and Outcome in Patients with Bleeding Peptic Ulcers and Helicobacter pylori Infections

PubMed Central

2014-01-01

Upper gastrointestinal (UGI) bleeding is the most frequently encountered complication of peptic ulcer disease. Helicobacter pylori (Hp) infection and nonsteroidal anti-inflammatory drug (NSAID) administration are two independent risk factors for UGI bleeding. Therefore, testing for and diagnosing Hp infection are essential for every patient with UGI hemorrhage. The presence of the infection is usually underestimated in cases of bleeding peptic ulcers. A rapid urease test (RUT), with or without histology, is usually the first test performed during endoscopy. If the initial diagnostic test is negative, a delayed 13C-urea breath test (UBT) or serology should be performed. Once an infection is diagnosed, antibiotic treatment is advocated. Sufficient evidence supports the concept that Hp infection eradication can heal the ulcer and reduce the likelihood of rebleeding. With increased awareness of the effects of Hp infection, the etiologies of bleeding peptic ulcers have shifted to NSAID use, old age, and disease comorbidity. PMID:25101293

Upper Gastrointestinal Bleeding in Chinese Children: A Multicenter 10-Year Retrospective Study.

PubMed

Yu, Yi; Wang, Baoxiang; Yuan, Lan; Yang, Hui; Wang, Xinqiong; Xiao, Yuan; Mei, Hong; Xu, Chundi

2016-08-01

Objective This study aims to analyze the clinical and endoscopic presentations of upper gastrointestinal bleeding (UGIB) in the Chinese children. Methods A 10-year retrospective study was made on children with UGIB and undertaken esophagogastroduodenoscopy (EGD) from 4 tertiary referral centers in China. Results Of the 1218 children studied, the bleeding source was found in 76.4%. Erosive gastritis was the most common endoscopic finding (33.5%), followed by duodenal ulcer (23.2%). The proportion of erosive gastritis decreased with age (correlation coefficient = -0.787), and duodenal ulcer increased with age (correlation coefficient = 0.958). The bleeding source was more likely to be determined in children having EGDs within 48 hours (80.6% vs 67.9%). Conclusions In Chinese children with UGIB, erosive gastritis and duodenal ulcer were the leading causes, and their proportions varied with age. EGDs performed within 48 hours may improve the possibility of finding the source of bleeding. © The Author(s) 2015.

Efficient halal bleeding, animal handling, and welfare: A holistic approach for meat quality.

PubMed

Aghwan, Z A; Bello, A U; Abubakar, A A; Imlan, J C; Sazili, A Q

2016-11-01

Traditional halal slaughter and other forms of religious slaughter are still an issue of debate. Opposing arguments related to pre-slaughter handling, stress and pain associated with restraint, whether the incision is painful or not, and the onset of unconsciousness have been put forward, but no consensus has been achieved. There is a need to strike a balance between halal bleeding in the light of science and animal welfare. There is a paucity of scientific data with respect to animal welfare, particularly the use of restraining devices, animal handling, and efficient halal bleeding. However, this review found that competent handling of animals, proper use of restraining devices, and the efficient bleeding process that follows halal slaughter maintains meat eating quality. In conclusion, halal bleeding, when carried out in accordance with recommended animal welfare procedures, will not only maintain the quality and wholesomeness of meat but could also potentially reduce suffering and pain. Maintained meat quality increases consumer satisfaction and food safety. Copyright © 2016. Published by Elsevier Ltd.

Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin.

PubMed

Gasse, Christiane; Hollowell, Jennifer; Meier, Christoph R; Haefeli, Walter E

2005-09-01

Although drug interactions with warfarin are an important cause of excessive anticoagulation, their impact on the risk of serious bleeding is unknown. We therefore performed a cohort study and a nested case-control analysis to determine the risk of serious bleeding in 4152 patients (aged 40-84 years) with nonvalvular atrial fibrillation (AF) taking long-term warfarin (> 3 months). The study population was drawn from the UK General Practice Research Database. More than half (58%) of eligible patients used potentially interacting drugs during continuous warfarin treatment. Among 45 identified cases of incident idiopathic bleeds (resulting in hospitalisation within 30 days or death within 7 days) and 143 matched controls, more cases than controls took > or = 1 potentially interacting drug within the preceding 30 days (62.2% vs. 35.7%) and used > 4 drugs (polypharmacy) within the preceding 90 days (80.0% vs. 66.4%). Conditional logistic regression analysis yielded an odds ratio (OR) of 3.4 (95% confidence interval [CI]: 1.4-8.5) for the risk of serious bleeding in patients treated with warfarin and > or = 1 drugs potentially increasing the effect of warfarin vs. warfarin alone adjusted for polypharmacy, diabetes, hypertension, heart failure, and thyroid disease; the adjusted OR for the combined use of warfarin and aspirin vs. warfarin alone was 4.5 (95% CI: 1.1-18.1). We conclude that concurrent use of potentially interacting drugs with warfarin is associated with a 3 to 4.5-fold increased risk of serious bleeding in long-term warfarin users.

Management of Acute Lower Gastrointestinal Bleeding.

PubMed

Speir, Ethan J; Ermentrout, R Mitchell; Martin, Jonathan G

2017-12-01

Acute lower gastrointestinal bleeding (LGIB), defined as hemorrhage into the gastrointestinal tract distal to the ligament of Treitz, is a major cause of morbidity and mortality among adults. Overall, mortality rates are estimated between 2.4% and 3.9%. The most common etiology for LGIB is diverticulosis, implicated in approximately 30% of cases, with other causes including hemorrhoids, ischemic colitis, and postpolypectomy bleeding. Transcatheter visceral angiography has begun to play an increasingly important role in both the diagnosis and treatment of LGIB. Historically, transcatheter visceral angiography has been used to direct vasopressin infusion with embolization reserved for treatment of upper gastrointestinal bleeding. However, advances in microcatheter technology and embolotherapy have enabled super-selective embolization to emerge as the treatment of choice for many cases of LGIB. Copyright © 2017 Elsevier Inc. All rights reserved.

Implementation of a Multidisciplinary Bleeding and Transfusion Protocol Significantly Decreases Perioperative Blood Product Utilization and Improves Some Bleeding Outcomes.

PubMed

Timpa, Joseph G; O'Meara, L Carlisle; Goldberg, Kellen G; Phillips, Jay P; Crawford, Jack H; Jackson, Kimberly W; Alten, Jeffrey A

2016-03-01

Perioperative transfusion of blood products is associated with increased morbidity and mortality after pediatric cardiac surgery. We report the results of a quality improvement project aimed at decreasing perioperative blood product administration and bleeding after pediatric cardiopulmonary bypass (CPB) surgery. A multidisciplinary team evaluated baseline data from 99 consecutive CPB patients, focusing on the variability in transfusion management and bleeding outcomes, to create a standardized bleeding and transfusion management protocol. A total of 62 subsequent patients were evaluated after implementation of the protocol: 17 with single pass hemoconcentrated (SPHC) blood transfusion and 45 with modified ultrafiltration (MUF). Implementation of the protocol with SPHC blood led to significant decrease in transfusion of every blood product in the cardiovascular operating room and first 6 hours in cardiovascular intensive care unit ([CVICU] p < .05). Addition of MUF to the protocol led to further decrease in transfusion of all blood products compared to preprotocol. Patients <2 months old had 49% decrease in total blood product administration: 155 mL/kg preprotocol, 117 mL/kg protocol plus SPHC, and 79 mL/kg protocol plus MUF (p < .01). There were significant decreases in postoperative bleeding in the first hour after CVICU admission: 6 mL/kg preprotocol, 3.8 mL/kg protocol plus SPHC, and 2 mL/kg protocol plusMUF (p = .02). There was also significantly decreased incidence of severe postoperative bleeding (>10 mL/kg) in the first CVICU hour for protocol plus MUF patients (p < .01). Implementation of a multidisciplinary bleeding and transfusion protocol significantly decreases perioperative blood product transfusion and improves some bleeding outcomes.

Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis.

PubMed

Valentino, L A; Pipe, S W; Collins, P W; Blanchette, V S; Berntorp, E; Fischer, K; Ewenstein, B M; Oh, M; Spotts, G

2016-07-01

We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been investigated. The aim of this study was to analyse data from the PKP arm to determine whether peak FVIII levels, AUC and time with FVIII levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis. Post hoc analysis of the association of FVIII levels and AUC with annualized bleeding rate in 34 patients on PKP. During 1 year of PKP, 131 bleeding episodes occurred in 24/34 patients. Average peak FVIII levels ranged from 24 to 168 IU dL(-1) , with higher values associated with a decreased risk for all bleeding (joint and non-joint; P < 0.01) and joint bleeding (P < 0.01). Following rFVIII infusion, median percent of time spent with FVIII levels >20 IU dL(-1) was 22%; median AUC was 1363. Both values were significantly associated with a lower ABR when targeting a 1% trough at 72 h. When PKP was administered every third day, higher peak FVIII levels, higher AUC and more time spent per week with FVIII levels >20 IU dL(-1) provided increased protection from joint and non-joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and AUC in some patients treated every third day. The findings do not necessarily apply to alternate-day or other prophylactic dosing regimens. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Single nucleotide polymorphism markers for low-dose aspirin-associated peptic ulcer and ulcer bleeding.

PubMed

Shiotani, Akiko; Murao, Takahisa; Fujita, Yoshihiko; Fujimura, Yoshinori; Sakakibara, Takashi; Nishio, Kazuto; Haruma, Ken

2014-12-01

In our previous study, the SLCO1B1 521TT genotype and the SLCO1B1*1b haplotype were significantly associated with the risk of peptic ulcer in patients taking low-dose aspirin (LDA). The aim of the present study was to investigate pharmacogenomic profile of LDA-induced peptic ulcer and ulcer bleeding. Patients taking 100 mg of enteric-coated aspirin for cardiovascular diseases and with a peptic ulcer or ulcer bleeding and patients who also participated in endoscopic surveillance were studied. Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DME Plus Premier Pack. SLCO1B1*1b haplotype and candidate genotypes of genes associated with ulcer bleeding or small bowel bleeding identified by genome-wide analysis were determined using TaqMan SNP Genotyping Assay kits, polymerase chain reaction-restriction fragment length polymorphism, and direct sequencing. Of 593 patients enrolled, 111 patients had a peptic ulcer and 45 had ulcer bleeding. The frequencies of the SLCO1B1*1b haplotype and CHST2 2082 T allele were significantly greater in patients with peptic ulcer and ulcer bleeding compared to the controls. After adjustment for significant factors, the SLCO1B1*1b haplotype was associated with peptic ulcer (OR 2.20, 95% CI 1.24-3.89) and CHST2 2082 T allele with ulcer bleeding (2.57, 1.07-6.17). The CHST2 2082 T allele as well as SLCO1B1*1b haplotype may identify patients at increased risk for aspirin-induced peptic ulcer or ulcer bleeding. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study.

PubMed

Tseng, C-L; Chen, Y-T; Huang, C-J; Luo, J-C; Peng, Y-L; Huang, D-F; Hou, M-C; Lin, H-C; Lee, F-Y

2015-09-01

Controversy exists regarding glucocorticoids therapy and the risk of peptic ulcer bleeding (PUB). The present study was undertaken to determine whether short-term use of glucocorticoids is associated with the occurrence of peptic ulcer bleeding. The records of adult patients hospitalised for newly diagnosed peptic ulcer bleeding from 2000 to 2012 were retrieved from the Taiwan National Health Insurance Research Database, a nationwide population-based registry system. The association between systemic glucocorticoids usage and peptic ulcer bleeding was determined with a conditional logistic regression model comparing cases and controls during time windows of 7, 14 and 28 days using a case-crossover design. Of the 8894 enrolled patients, the adjusted self-matched odds ratios for peptic ulcer bleeding after exposure to the glucocorticoids were 1.37 (95% CI: 1.12-1.68, P = 0.003) for the 7-day window, 1.66 (95% CI: 1.38-2.00, P < 0.001) for the 14-day window and 1.84 (95% CI: 1.57-2.16, P < 0.001) for the 28-day window. Moderate to high, but not low dose glucocorticoids (methylprednisolone <4 mg/day or its equivalence) were associated with an increased risk of peptic ulcer bleeding. Concomitant use of a nonselective nonsteroidal anti-inflammatory drug (NSAID) or aspirin further elevated the risk. However, it does not eliminate the effect of underlying diseases flare-up that may have placed the patients at risk for peptic ulcer bleeding in this kind of study design. Short-term (7-28 days) exposure to glucocorticoids is significantly associated with peptic ulcer bleeding; this risk seems dose-dependent and is higher when nonselective NSAIDs or aspirin are used concurrently. © 2015 John Wiley & Sons Ltd.

Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue

PubMed Central

Cocero, Nadia; Pucci, Fabrizio; Messina, Maria; Pollio, Berardino; Mozzati, Marco; Bergamasco, Laura

2015-01-01

Background Dental extractions in haemophiliacs may cause secondary bleeding, requiring repeated surgical and haematological interventions. As a local haemostatic, fibrin glue has recognised efficacy but, as a plasma-derived product, it carries the risk of viral infections. We, therefore, compared fibrin glue with an autologous haemostatic, plasma rich in growth factors (PRGF), in a controlled trial. Material and methods One hundred and twenty patients with different blood disorders were randomised into two cohorts to undergo dental extraction procedures without hospitalisation. Prior to the extractions, patients underwent systemic haematological treatment. Complications were defined as secondary bleeding after the 7-day follow-up period or protracting after the repair procedure. Results There were 106 extractions (7 retained 3rd molars) in the group managed with fibrin glue: secondary bleeding affected 3/60 patients (5%) on the third day after extraction and necessitated additional surgery and systemic treatment (in one case the procedure had to be repeated on the 7th day). In the PRGF arm there were 98 extractions (23 retained 3rd molars): secondary bleeding affected two patients (3.3%) on the first day after extraction and was arrested with surgery without systemic treatment. Four out of the five secondary bleeds occurred in patients with haemophilia A. Concomitant diabetes or liver disease significantly increased the bleeding risk. Discussion The bleeding rates in the study and control arm prove that PRGF works as well as fibrin glue as a local haemostatic. Further assets are that PRGF has autologous origin, does not require additional systemic treatment in post-extraction repair surgery, is associated with an earlier onset of neo-angiogenesis and, overall, can reduce patients’ distress and costs to the health system. PMID:25369587

Risk factors and outcomes of acute lower gastrointestinal bleeding in intestinal Behçet's disease.

PubMed

Park, Jihye; Cheon, Jae Hee; Park, Yong Eun; Lee, Yoon Jee; Lee, Hyun Jung; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho

2017-05-01

Intestinal Behçet's disease (BD) can cause acute lower gastrointestinal bleeding, which is sometimes fatal. We aimed to identify the risk factors and outcomes of acute lower gastrointestinal bleeding and factors associated with rebleeding in intestinal BD patients. Of the total of 588 intestinal BD patients, we retrospectively reviewed the medical records of 66 (11.2%) patients with acute lower gastrointestinal bleeding and compared them with those of 132 matched patients without bleeding. The baseline characteristics were comparable between the bleeding group (n = 66) and the non-bleeding group (n = 132). On multivariate analysis, the independent factors significantly associated with lower gastrointestinal bleeding were older age (>52 years) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.058-4.684, p = 0.035) and a nodular ulcer margin (HR 7.1, 95% CI 2.084-24.189, p = 0.002). Rebleeding occurred in 23 patients (34.8%). Female patients (p = 0.044) and those with previous use of corticosteroids or azathioprine (p = 0.034) were more likely to develop rebleeding. On multivariate analysis, only use of steroids or azathioprine was significantly associated with rebleeding (HR 3.2, 95% CI 1.070-9.462, p = 0.037). Age >52 years and the presence of a nodular margin of the ulcer were found to be related to increased risk of bleeding in patients with intestinal BD. Rebleeding is not uncommon and not effectively prevented with currently available medications. Further studies are warranted to identify effective measures to decrease rebleeding in intestinal BD.

Plate-clearing tendencies and portion size are independently associated with main meal food intake in women: A laboratory study.

PubMed

Sheen, Florence; Hardman, Charlotte A; Robinson, Eric

2018-08-01

Larger portion sizes of food promote increased food intake, although the mechanisms explaining the portion size effect are unclear. In the present study we examined whether the tendency to clear one's plate when eating is associated with greater food intake in response to larger portion size. We recruited female participants who were either self-reported habitual plate clearers (N = 48) or non-plate clearers (N = 41) into a laboratory study. In a between-subjects design, participants were served either a 'normal' (500 g) or 'large' (1000 g) portion of pasta for lunch and ate as much as they desired. There was no significant interaction found between portion size and plate-clearing tendencies; portion size had a similar sized effect on food intake in both plate clearers and non-plate clearers. A significant main effect of portion size was found, whereby participants consumed significantly more when served the large versus the normal portion (100.55 g difference, p < .001, η p 2  = 0.16). There was also a significant main effect of plate clearing; participants with a tendency to clear their plate when eating consumed significantly more than non-plate clearers (68.21 g difference, p = .006, η p 2  = 0.08). The tendency to clear one's plate when eating was associated with increased food intake during a lunchtime meal. Increasing the portion size of the lunchtime meal increased food intake, although the tendency for a larger portion size to increase food intake was observed irrespective of participant plate-clearing tendencies. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Using narrow-band imaging with conventional hysteroscopy increases the detection of chronic endometritis in abnormal uterine bleeding and postmenopausal bleeding.

PubMed

Ozturk, Mustafa; Ulubay, Mustafa; Alanbay, Ibrahim; Keskin, Uğur; Karasahin, Emre; Yenen, Müfit Cemal

2016-01-01

A preliminary study was designed to evaluate whether a narrow-band imaging (NBI) endoscopic light source could detect chronic endometritis that was not identifiable with a white light hysteroscope. A total of 86 patients with endometrial pathology (71 abnormal uterine bleeding and 15 postmenopausal bleeding) were examined by NBI endoscopy and white light hysteroscopy between February 2010 and February 2011. The surgeon initially observed the uterine cavity using white light hysteroscopy and made a diagnostic impression, which was recorded. Subsequently, after pressing a button on the telescope, NBI was used to reevaluate the endometrial mucosa. The median age of the patients was 40 years (range: 30-60 years). Endometritis was diagnosed histologically. Six cases of abnormal uterine bleeding (6/71, 8.4%, 95% confidence interval [CI] 0.03-0.17) and one case of postmenopausal bleeding (1/15, 6%, 95%CI 0.01-0.29) were only diagnosed with chronic endometritis by NBI (7/86, 8.1%, 95%CI 0.04-0.15). Capillary patterns of the endometrium can be observed by NBI and this method can be used to assess chronic endometritis. © 2015 Japan Society of Obstetrics and Gynecology.

Association of past and recent major depression and menstrual characteristics in midlife: Study of Women's Health Across the Nation.

PubMed

Bromberger, Joyce T; Schott, Laura L; Matthews, Karen A; Kravitz, Howard M; Randolph, John F; Harlow, Sioban; Crawford, Sybil; Green, Robin; Joffe, Hadine

2012-09-01

The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women. Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors. One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD. Midlife women with a history of MD are more likely to report heavy bleeding.

Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies.

PubMed

Shatzel, J J; Olson, S R; Tao, D L; McCarty, O J T; Danilov, A V; DeLoughery, T G

2017-05-01

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib. © 2017 International Society on Thrombosis and Haemostasis.

Agents of Reconciliation: Agency-Affirmation Promotes Constructive Tendencies Following Transgressions in Low-Commitment Relationships.

PubMed

SimanTov-Nachlieli, Ilanit; Shnabel, Nurit; Mori-Hoffman, Anael

2017-02-01

Conflicting parties experience threats to both their agency and morality, but the experience of agency-threat exerts more influence on their behavior, leading to relationship-destructive tendencies. Whereas high-commitment relationships facilitate constructive tendencies despite the conflict, we theorized that in low-commitment relationships, affirming the adversary's agency is a prerequisite for facilitating more constructive tendencies. Focusing on sibling conflicts, Study 1 found that when commitment was low (rather than high), agency-affirmation increased participants' constructive tendencies toward their brother/sister compared with a control/no-affirmation condition. A corresponding morality-affirmation did not affect participants' tendencies. Study 2 replicated these results in workplace conflicts and further found that the positive effect of agency-affirmation in low-commitment relationships was mediated by participants' wish to restore their morality. Study 3 induced a conflict between lab participants and manipulated their commitment. Again, in the low- (rather than high-) commitment condition, agency-affirmation increased participants' wish to restore their morality, leading to constructive behavior.

Warfarin - Fluoroquinolones, Sulfonamides, or Azole Antifungals Interactions and the Risk of Hospitalization for Gastrointestinal Bleeding

PubMed Central

Schelleman, Hedi; Bilker, Warren B.; Brensinger, Colleen M.; Han, Xiaoyan; Kimmel, Stephen E.; Hennessy, Sean

2008-01-01

Objective To determine whether a potential pharmacokinetic interaction between warfarin and orally administered anti-infectives increases the risk of hospitalization for gastrointestinal (GI) bleeding in warfarin users. Methods We conducted a nested case-control and case-crossover study in US Medicaid data. Logistic regression was used to determine the association between GI bleeding and prior use of ciprofloxacin, levofloxacin, gatifloxacin, cotrimoxazole, or fluconazole, all versus no exposure and versus cephalexin, which would not be expected to interact with warfarin. Results All anti-infectives examined exhibited an elevated odds ratio (OR) vs. no exposure. Using cephalexin as the reference category, ORs for cotrimoxazole (OR:1.68 [95% CI:1.21–2.33] in the prior 6–10 days) and fluconazole (OR:2.09 [95% CI:1.34–3.26] in the prior 11–15 days) were significantly elevated. Conclusions Warfarin users who had received an anti-infective agent showed a substantially increased risk of GI bleeding. Nonetheless, a drug-drug interaction with warfarin was evident only for cotrimoxazole and fluconazole. PMID:18685566

Oxytocin Receptor (OXTR) Single Nucleotide Polymorphisms Indirectly Predict Prosocial Behavior Through Perspective Taking and Empathic Concern.

PubMed

Christ, Christa C; Carlo, Gustavo; Stoltenberg, Scott F

2016-04-01

Engaging in prosocial behavior can provide positive outcomes for self and others. Prosocial tendencies contribute to the propensity to engage in prosocial behavior. The oxytocin receptor gene (OXTR) has also been associated with prosocial tendencies and behaviors. There has been little research, however, investigating whether the relationship between OXTR and prosocial behaviors is mediated by prosocial tendencies. This relationship may also vary among different types of prosocial behavior. The current study examines the relationship between OXTR, gender, prosocial tendencies, and both altruistic and public prosocial behavior endorsement. Students at a midwestern university (N = 398; 89.2% Caucasian; Mage  = 20.76; 26.6% male) provided self-report measures of prosocial tendencies and behaviors and buccal cells for genotyping OXTR polymorphisms. Results indicated that OXTR single nucleotide polymorphism (SNP) rs2268498 genotype significantly predicted empathic concern, whereas gender moderated the association between several other OXTR SNPs and prosocial tendencies. Increased prosocial tendencies predicted increased altruistic prosocial behavior endorsement and decreased public prosocial behavior endorsement. Our findings suggest an association between genetic variation in OXTR and endorsement of prosocial behavior indirectly through prosocial tendencies, and that the pathway is dependent on the type of prosocial behavior and gender. © 2014 Wiley Periodicals, Inc.

Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices: Concept, Basic Techniques, and Outcomes

PubMed Central

Saad, Wael E. A.

2012-01-01

Patients with gastric variceal bleeding require a multidisciplinary team approach including hepatologists, endoscopists, diagnostic radiologists, and interventional radiologists. Upper gastrointestinal endoscopy is the first-line diagnostic and management tool for bleeding gastric varices, as it is in all upper gastrointestinal bleeding scenarios. In the United States when endoscopy fails to control gastric variceal bleeding, a transjugular intrahepatic portosystemic shunt (TIPS) traditionally is performed along the classic teachings of decompressing the portal circulation. However, TIPS has not shown the same effectiveness in controlling gastric variceal bleeding that it has with esophageal variceal bleeding. For the past 2 decades, the balloon-occluded retrograde transvenous obliteration (BRTO) procedure has become common practice in Asia for the management of gastric varices. BRTO is gaining popularity in the United States. It has been shown to be effective in controlling gastric variceal bleeding with low rebleed rates. BRTO has many advantages over TIPS in that it is less invasive and can be performed on patients with poor hepatic reserve and those with encephalopathy (and may even improve both). However, its by-product is occlusion of a spontaneous hepatofugal (TIPS equivalent) shunt, and thus it is contradictory to the traditional American doctrine of portal decompression. Indeed, BRTO causes an increase in portal hypertension, with potential aggravation of esophageal varices and ascites. This article discusses the concept, technique, and outcomes of BRTO within the broader management of gastric varices. PMID:23729982

Process improvement in cardiac surgery: development and implementation of a reoperation for bleeding checklist.

PubMed

Loor, Gabriel; Vivacqua, Alessandro; Sabik, Joseph F; Li, Liang; Hixson, Eric D; Blackstone, Eugene H; Koch, Colleen G

2013-11-01

High-performing health care organizations differentiate themselves by focusing on continuous process improvement initiatives aimed at enhancing patient outcomes. Reoperation for bleeding is an event associated with considerable morbidity risk. Hence, our primary objective was to develop and implement a formal operative checklist to reduce technical reasons for postoperative bleeding. From January 1, 2011, through June 30, 2012, 5812 cardiac surgical procedures were performed at Cleveland Clinic (Cleveland, OH). A multidisciplinary team developed a simple, easy-to-perform hemostasis checklist based on the most common sites of bleeding. An extensive educational in-service was performed before limited, then universal, checklist implementation. Geometric charts were used to track the number of cases between consecutive reoperations for bleeding. We compared these before (phase 0) and after the first limited implementation phase (phase 1) and the universal implementation phase (phase 2) of the checklist. The average number of cases between consecutive reoperations for bleeding increased from 32 in phase 0 to 53 in both phase 1 (P = .002) and phase 2 (P = .01). A substantial reduction in reoperation for bleeding cases followed implementation of a formalized hemostasis checklist. Our findings underscore the important influence of memory aids that focus attention on surgical techniques to improve patient outcomes in a complex, operative work environment. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Costs of major intracranial, gastrointestinal and other bleeding events in patients with atrial fibrillation - a nationwide cohort study.

PubMed

Jakobsen, Marie; Kolodziejczyk, Christophe; Klausen Fredslund, Eskild; Poulsen, Peter Bo; Dybro, Lars; Paaske Johnsen, Søren

2017-06-12

Use of oral anticoagulation therapy in patients with atrial fibrillation (AF) involves a trade-off between a reduced risk of ischemic stroke and an increased risk of bleeding events. Different anticoagulation therapies have different safety profiles and data on the societal costs of both ischemic stroke and bleeding events are necessary for assessing the cost-effectiveness and budgetary impact of different treatment options. To our knowledge, no previous studies have estimated the societal costs of bleeding events in patients with AF. The objective of this study was to estimate the 3-years societal costs of first-incident intracranial, gastrointestinal and other major bleeding events in Danish patients with AF. The study was an incidence-based cost-of-illness study carried out from a societal perspective and based on data from national Danish registries covering the period 2002-2012. Costs were estimated using a propensity score matching and multivariable regression analysis (first difference OLS) in a cohort design. Average 3-years societal costs attributable to intracranial, gastrointestinal and other major bleeding events were 27,627, 17,868, and 12,384 EUR per patient, respectively (2015 prices). Existing evidence shows that the corresponding costs of ischemic stroke were 24,084 EUR per patient (2012 prices). The average costs of bleeding events did not differ between patients with AF who were on oral anticoagulation therapy prior to the event and patients who were not. The societal costs attributable to major bleeding events in patients with AF are significant. Intracranial haemorrhages are most costly to society with average costs of similar magnitude as the costs of ischemic stroke. The average costs of gastrointestinal and other major bleeding events are lower than the costs of intracranial haemorrhages, but still substantial. Knowledge about the relative size of the costs of bleeding events compared to ischemic stroke in patients with AF constitutes valuable evidence for decisions-makers in Denmark as well as in other countries.

Risk of Hemorrhage Attributed to Underlying Chronic Diseases and Uninterrupted Aspirin Therapy of Patients Undergoing Minor Oral Surgical Procedures: A Retrospective Cohort Study.

PubMed

Rojanaworarit, Chanapong; Limsawan, Soontaree

2017-01-01

This study aimed to estimate the risk of bleeding following minor oral surgical procedures and uninterrupted aspirin therapy in high-risk patients or patients with existing chronic diseases compared to patients who did not use aspirin during minor oral surgery at a public hospital. This retrospective cohort study analyzed the data of 2912 patients, aged 20 years or older, who underwent 5251 minor oral surgical procedures at a district hospital in Thailand. The aspirin group was comprised of patients continuing aspirin therapy during oral surgery. The non-aspirin group (reference) included all those who did not use aspirin during surgery. Immediate and late-onset bleeding was evaluated in each procedure. The risk ratio of bleeding was estimated using a multilevel Poisson regression. The overall cumulative incidence of immediate bleeding was 1.3% of total procedures. No late-onset bleeding was found. A significantly greater incidence of bleeding was found in the aspirin group (5.8% of procedures, p<0.001). After adjusting for covariates, a multilevel Poisson regression model estimated that the bleeding risk in the aspirin group was 4.5 times higher than that of the non-aspirin group (95% confidence interval, 2.0 to 10.0; p<0.001). However, all bleeding events were controlled by simple hemostatic measures. High-risk patients or patients with existing chronic diseases who continued aspirin therapy following minor oral surgery were at a higher risk of hemorrhage than general patients who had not used aspirin. Nonetheless, bleeding complications were not life-threatening and could be promptly managed by simple hemostatic measures. The procedures could therefore be provided with an awareness of increased bleeding risk, prepared hemostatic measures, and postoperative monitoring, without the need for discontinuing aspirin, which could lead to more serious complications.

Risks of Bleeding Recurrence and Cardiovascular Events With Continued Aspirin Use After Lower Gastrointestinal Hemorrhage.

PubMed

Chan, Francis K L; Leung Ki, En-Ling; Wong, Grace L H; Ching, Jessica Y L; Tse, Yee Kit; Au, Kim W L; Wu, Justin C Y; Ng, Siew C

2016-08-01

It is not clear whether use of low-dose aspirin should be resumed after an episode of lower gastrointestinal (GI) bleeding. We assessed the long-term risks of recurrent lower GI bleeding and serious cardiovascular outcomes after aspirin-associated lower GI bleeding. We performed a retrospective study of patients diagnosed with lower GI bleeding (documented melena or hematochezia and absence of upper GI bleeding) from January 1, 2000 through December 31, 2007 at the Prince of Wales Hospital in Hong Kong. Using the hospital registry, we analyzed data from 295 patients on aspirin and determined their outcomes during a 5-year period. Outcomes included recurrent lower GI bleeding, serious cardiovascular events, and death from other causes, as determined by an independent, blinded adjudication committee. Outcomes were compared between patients assigned to the following groups based on cumulative duration of aspirin use: <20% of the follow-up period (121 nonusers) vs ≥50% of the observation period (174 aspirin users). Within 5 years, lower GI bleeding recurred in 18.9% of aspirin users (95% confidence interval [CI], 13.3%-25.3%) vs 6.9% of nonusers (95% CI, 3.2%-12.5%; P = .007). However, serious cardiovascular events occurred in 22.8% of aspirin users (95% CI, 16.6%-29.6%) vs 36.5% of nonusers (95% CI, 27.4%-45.6%; P = .017), and 8.2% of aspirin users died from other causes (95% CI, 4.6%-13.2%) vs 26.7% of nonusers (95% CI, 18.7%-35.4%; P = .001). Multivariable analysis showed that aspirin use was an independent predictor of rebleeding, but protected against cardiovascular events and death. Among aspirin users with a history of lower GI bleeding, continuation of aspirin is associated with an increased risk of recurrent lower GI bleeding, but reduced risk of serious cardiovascular events and death. Copyright © 2016. Published by Elsevier Inc.

Prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy: a systematic review and external validation study.

PubMed

Hilkens, N A; Algra, A; Greving, J P

2016-01-01

ESSENTIALS: Prediction models may help to identify patients at high risk of bleeding on antiplatelet therapy. We identified existing prediction models for bleeding and validated them in patients with cerebral ischemia. Five prediction models were identified, all of which had some methodological shortcomings. Performance in patients with cerebral ischemia was poor. Background Antiplatelet therapy is widely used in secondary prevention after a transient ischemic attack (TIA) or ischemic stroke. Bleeding is the main adverse effect of antiplatelet therapy and is potentially life threatening. Identification of patients at increased risk of bleeding may help target antiplatelet therapy. This study sought to identify existing prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy and evaluate their performance in patients with cerebral ischemia. We systematically searched PubMed and Embase for existing prediction models up to December 2014. The methodological quality of the included studies was assessed with the CHARMS checklist. Prediction models were externally validated in the European Stroke Prevention Study 2, comprising 6602 patients with a TIA or ischemic stroke. We assessed discrimination and calibration of included prediction models. Five prediction models were identified, of which two were developed in patients with previous cerebral ischemia. Three studies assessed major bleeding, one studied intracerebral hemorrhage and one gastrointestinal bleeding. None of the studies met all criteria of good quality. External validation showed poor discriminative performance, with c-statistics ranging from 0.53 to 0.64 and poor calibration. A limited number of prediction models is available that predict intracranial hemorrhage or major bleeding in patients on antiplatelet therapy. The methodological quality of the models varied, but was generally low. Predictive performance in patients with cerebral ischemia was poor. In order to reliably predict the risk of bleeding in patients with cerebral ischemia, development of a prediction model according to current methodological standards is needed. © 2015 International Society on Thrombosis and Haemostasis.

Bleeding frequency and characteristics among hematologic malignancy inpatient rehabilitation patients with severe thrombocytopenia.

PubMed

Fu, Jack B; Tennison, Jegy M; Rutzen-Lopez, Isabel M; Silver, Julie K; Morishita, Shinichiro; Dibaj, Seyedeh S; Bruera, Eduardo

2018-03-28

To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia. Retrospective descriptive analysis. Comprehensive cancer center acute inpatient rehabilitation unit. Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (μL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016. Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients. Bleeding events noted in the medical record. Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/μL on the day of admission and 22,000/μL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/μL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/μL mean platelet counts respectively (p = .003). Forty-four percent of patients were transferred back to the primary acute care service with infection being the most common reason for transfer. This study is the first to examine exercise-related bleeding complications during acute inpatient rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.

Initial evaluation of rectal bleeding in young persons: a cost-effectiveness analysis.

PubMed

Lewis, James D; Brown, Alphonso; Localio, A Russell; Schwartz, J Sanford

2002-01-15

Evaluation of rectal bleeding in young patients is a frequent diagnostic challenge. To determine the relative cost-effectiveness of alternative diagnostic strategies for young patients with rectal bleeding. Cost-effectiveness analysis using a Markov model. Probability estimates were based on published medical literature. Cost estimates were based on Medicare reimbursement rates and published medical literature. Persons 25 to 45 years of age with otherwise asymptomatic rectal bleeding. The patient's lifetime. Modified societal perspective. Diagnostic strategies included no evaluation, colonoscopy, flexible sigmoidoscopy, barium enema, anoscopy, or any feasible combination of these procedures. Life expectancy and costs. For 35-year-old patients, the no-evaluation strategy yielded the least life expectancy. The incremental cost-effectiveness of flexible sigmoidoscopy compared with no evaluation or with any strategy incorporating anoscopy (followed by further evaluation if no anal disease was found on anoscopy) was less than $5300 per year of life gained. A strategy of flexible sigmoidoscopy plus barium enema yielded the greatest life expectancy, with an incremental cost of $23 918 per additional life-year gained compared with flexible sigmoidoscopy alone. As patient age at presentation of rectal bleeding increased, evaluation of the entire colon became more cost-effective. The incremental cost-effectiveness of flexible sigmoidoscopy plus barium enema compared with colonoscopy was sensitive to estimates of the sensitivity of the tests. In a probabilistic sensitivity analysis comparing flexible sigmoidoscopy with anoscopy followed by flexible sigmoidoscopy if needed, the middle 95th percentile of the distribution of the incremental cost-effectiveness ratios ranged from flexible sigmoidoscopy yielding an increased life expectancy at reduced cost to $52 158 per year of life gained (mean, $11 461 per year of life saved). Evaluation of the colon of persons 25 to 45 years of age with otherwise asymptomatic rectal bleeding increases the life expectancy at a cost comparable to that of colon cancer screening.

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

PubMed

Tamez, Hector; Généreux, Philip; Yeh, Robert W; Amin, Amit P; Fan, Weihong; White, Harvey D; Kirtane, Ajay J; Stone, Gregg W; Gibson, C Michael; Harrington, Robert A; Bhatt, Deepak L; Pinto, Duane S

2018-05-04

Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI. © 2018 Wiley Periodicals, Inc.

Previous hypertensive hemorrhage increases the risk for bleeding and ischemia for PCI patients on dual antiplatelet therapy.

PubMed

Qiao, Manli; Bi, Qi; Fu, Paul; Wang, Yixin; Song, Zhe; Guo, Fang

2017-06-01

The use of antiplatelet therapy after intracerebral hemorrhage remains controversial, while the use of dual antiplatelet therapy (DAPT) is required after cardiac stenting. In this study, we examine the risk of bleeding and ischemic events for PCI patients with a history of hypertensive hemorrhage on DAPT. A total of 128 cases and 153 controls were selected from Chinese patients with cardiac stenting on dual anti-platelet therapy for a single-center retrospective case-control study. Patients with a history of hypertensive hemorrhage were selected for the case group, while patients with a history of hypertension were chosen as control. All patients were on aspirin 100 mg and clopidogrel 75 mg after cardiac stenting, and were followed for a duration of 12-48 months. The primary outcomes were intracerebral hemorrhage, major bleeding, and major adverse cardiovascular and cerebrovascular events. A history of previous hypertensive hemorrhage was not found to be a risk factor for intracerebral hemorrhage and major bleeding while on dual anti-platelet therapy. However, a history of either hypertensive hemorrhage or coronary artery disease was independently found to be risk factors for major adverse cardiovascular and cerebrovascular events. On sub-group analysis, patients with a history of hypertensive hemorrhage within 12 months were found to be at higher risk for bleeding on dual anti-platelet therapy, while patients with history of hypertensive hemorrhage outside of 12 months on dual anti-platelet therapy did not have the same increased risk. A history of hypertensive hemorrhage and coronary heart disease were two independent risk factors for major adverse cardiovascular and cerebrovascular events in PCI patients taking DAPT. A history of hypertensive hemorrhage less than 12 months had an increased risk for recurrent intracerebral hemorrhage and major bleeding in PCI patients taking DAPT.

Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial).

PubMed

Washam, Jeffrey B; Hellkamp, Anne S; Lokhnygina, Yuliya; Piccini, Jonathan P; Berkowitz, Scott D; Nessel, Christopher C; Becker, Richard C; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Singer, Daniel E; Patel, Manesh R

2017-08-15

Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS 2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effects of the Contact Activation System on Hemorrhage

PubMed Central

Simão, Fabrício; Feener, Edward P.

2017-01-01

The contact activation system (CAS) exerts effects on coagulation via multiple mechanisms, which modulate both the intrinsic and extrinsic coagulation cascades as well as fibrinolysis and platelet activation. While the effects of the CAS on blood coagulation measured as activated partial thromboplastin time shortening are well documented, genetic mutations that result in deficiencies in the expression of either plasma prekallikrein (PPK) or factor XII (FXII) are not associated with spontaneous bleeding or increased bleeding risk during surgery. Deficiencies in these proteins are often undiagnosed for decades and detected later in life during routine coagulation assays without an apparent clinical phenotype. Increased interest in the CAS as a potentially safe target for antithrombotic therapies has emerged, in large part, from studies on animal models with provoked thrombosis, which have shown that deficiencies in PPK or FXII can reduce thrombus formation without increasing bleeding. Gene targeting and pharmacological studies in healthy animals have confirmed that PPK and FXII blockade does not cause coagulopathies. These findings support the conclusion that CAS is not required for hemostasis. However, while deficiencies in FXII and PPK do not significantly affect bleeding associated with peripheral wounds, recent reports have demonstrated that these proteins can promote hemorrhage in the retina and brain. Intravitreal injection of plasma kallikrein (PKal) induces retinal hemorrhage and intracerebral injection of PKal increases intracranial bleeding. PPK deficiency and PKal inhibition ameliorates hematoma formation following cerebrovascular injury in diabetic animals. Moreover, both PPK and FXII deficiency are protective against intracerebral hemorrhage caused by tissue plasminogen activator-mediated thrombolytic therapy in mice with thrombotic middle cerebral artery occlusion. Thus, while the CAS is not required for hemostasis, its inhibition may provide an opportunity to reduce hemorrhage in the retina and brain. Characterization of the mechanisms and potential clinical implications associated with the effects of the CAS on hemorrhage requires further consideration of the effects of PPK and FXII on hemorrhage beyond their putative effects on coagulation cascades. Here, we review the experimental and clinical evidence on the effects of the CAS on bleeding and hemostatic mechanisms. PMID:28824910

Diffuse gastrointestinal bleeding and BK polyomavirus replication in a pediatric allogeneic haematopoietic stem cell transplant patient.

PubMed

Koskenvuo, M; Lautenschlager, I; Kardas, P; Auvinen, E; Mannonen, L; Huttunen, P; Taskinen, M; Vettenranta, K; Hirsch, H H

2015-01-01

Patients undergoing haematopoietic stem cell transplantation (HSCT) are at high risk of severe gastrointestinal bleeding caused by infections, graft versus host disease, and disturbances in haemostasis. BK polyomavirus (BKPyV) is known to cause hemorrhagic cystitis, but there is also evidence of BKV shedding in stool and its association with gastrointestinal disease. We report putative association of BKPyV replication with high plasma viral loads in a pediatric HSCT patient developing hemorrhagic cystitis and severe gastrointestinal bleeding necessitating intensive care. The observation was based on chart review and analysis of BKPyV DNA loads in plasma and urine as well as retrospective BKPyV-specific IgM and IgG measurements in weekly samples until three months post-transplant. The gastrointestinal bleeding was observed after a >100-fold increase in the plasma BKPyV loads and the start of hemorrhagic cystitis. The BKPyV-specific antibody response indicated past infection prior to transplantation, but increasing IgG titers were seen following BKPyV replication. The gastrointestinal biopsies were taken at a late stage of the episode and were no longer informative of BK polyomavirus involvement. In conclusion, gastrointestinal complications with bleeding are a significant problem after allogeneic HSCT to which viral infections including BKPyV may contribute. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparative analysis of bleeding risk by the location and shape of arachnoid cysts: a finite element model analysis.

PubMed

Lee, Chang-Hyun; Han, In Seok; Lee, Ji Yeoun; Phi, Ji Hoon; Kim, Seung-Ki; Kim, Young-Eun; Wang, Kyu-Chang

2017-01-01

Although arachnoid cysts (ACs) are observed in various locations, only sylvian ACs are mainly regarded to be associated with bleeding. The reason for this selective association of sylvian ACs with bleeding is not understood well. This study is to investigate the effect of the location and shape of ACs on the risk of bleeding. A developed finite element model of the head/brain was modified for models of sylvian, suprasellar, and posterior fossa ACs. A spherical AC was placed at each location to compare the effect of AC location. Bowl-shaped and oval-shaped AC models were developed to compare the effect by shape. The shear force on the spot-weld elements (SFSW) was measured between the dura and the outer wall of the ACs or the comparable arachnoid membrane in the normal model. All AC models revealed higher SFSW than comparable normal models. By location, sylvian AC displayed the highest SFSW for frontal and lateral impacts. By shape, small outer wall AC models showed higher SFSW than large wall models in sylvian area and lower SFSW than large ones in posterior fossa. In regression analysis, the presence of AC was the only independent risk of bleeding. The bleeding mechanism of ACs is very complex, and the risk quantification failed to show a significant role of location and shape of ACs. The presence of AC increases shear force on impact condition and may be a risk factor of bleeding, and sylvian location of AC may not have additive risks of AC bleeding.

Successful Endoscopic Hemostasis Is a Protective Factor for Rebleeding and Mortality in Patients with Nonvariceal Upper Gastrointestinal Bleeding.

PubMed

Han, Yong Jae; Cha, Jae Myung; Park, Jae Hyun; Jeon, Jung Won; Shin, Hyun Phil; Joo, Kwang Ro; Lee, Joung Il

2016-07-01

Rebleeding and mortality rates remain high in patients with nonvariceal upper gastrointestinal bleeding. To identify clinical and endoscopic risk factors for rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding. This study was performed in patients with nonvariceal upper gastrointestinal bleeding who underwent upper endoscopic procedures between July 2006 and February 2013. Clinical and endoscopic characteristics were compared among patients with and without rebleeding and mortality. Logistic regression analysis was performed to determine independent risk factors for rebleeding and mortality. After excluding 64 patients, data for 689 patients with nonvariceal upper gastrointestinal bleeding were analyzed. Peptic ulcer (62.6 %) was by far the most common source of bleeding. Endoscopic intervention was performed within 24 h in 99.0 % of patients, and successful endoscopic hemostasis was possible in 80.7 % of patients. The 30-day rebleeding rate was 13.1 % (n = 93). Unsuccessful endoscopic hemostasis was found to be the only independent risk factor for rebleeding (odds ratio 79.6; 95 % confidence interval 37.8-167.6; p = 0.000). The overall 30-day mortality rate was 3.2 % (n = 23). Unsuccessful endoscopic hemostasis (odds ratio 4.9; 95 % confidence interval 1.7-13.9; p = 0.003) was also associated with increased 30-day mortality in patients with nonvariceal upper gastrointestinal bleeding. Successful endoscopic hemostasis is an independent protective factor for both rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding.

The use of a co-design model in improving timely bleed reporting by adults with haemophilia living in the Auckland region of New Zealand.

PubMed

d'Young, A I; Young, L; Ockelford, P A; Brasser, M; Slavin, K; Manson, L; Preston, S

2014-05-01

Many adult patients diagnosed with phenotypically moderate and severe haemophilia living in the Auckland region of New Zealand do not report bleeding episodes within a timeframe that allows for optimal assessment and management. This can result in poor clinical outcomes for patients and poor oversight of the use of expensive clotting factor concentrates. Our goal was to improve both the number and speed at which bleeding episodes were reported to our centre, improving access to care and clinical oversight of the use of expensive factor concentrates and aiding the development of a care partnership with patients. We worked with 70 adult PWH living in the Auckland region of New Zealand with moderate and severe haemophilia A and B. Over a 5-month period between March and July 2013 we used a co-design model to develop and implement a range of strategies to improve the timing and frequency of bleed reporting. Mean bleed reporting time was reduced threefold, with a threefold increase in the number of bleeds reported per month. We reduced the number of bleeding episodes reported outside of a prespecified 48-h time limit by 68%. We significantly improved bleed reporting and time to report, indicating improved access to our services, improved clinical oversight and improved accountability to our national funder. We have achieved a care partnership and a reduction in factor consumption for the study population without compromising the quality of care they receive. © 2013 John Wiley & Sons Ltd.

Factors Associated with Bleeding and Thrombosis in Children Receiving Extracorporeal Membrane Oxygenation.

PubMed

Dalton, Heidi J; Reeder, Ron; Garcia-Filion, Pamela; Holubkov, Richard; Berg, Robert A; Zuppa, Athena; Moler, Frank W; Shanley, Thomas; Pollack, Murray M; Newth, Christopher; Berger, John; Wessel, David; Carcillo, Joseph; Bell, Michael; Heidemann, Sabrina; Meert, Kathleen L; Harrison, Richard; Doctor, Allan; Tamburro, Robert F; Dean, J Michael; Jenkins, Tammara; Nicholson, Carol

2017-09-15

Extracorporeal membrane oxygenation (ECMO) is used for respiratory and cardiac failure in children but is complicated by bleeding and thrombosis. (1) To measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support; (2) to identify factors associated with these complications; and (3) to determine the impact of these complications on patient outcome. This was a prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals, carried out from December 2012 to September 2014. ECMO was used on 514 consecutive patients under age 19 years. Demographics, anticoagulation practices, severity of illness, circuitry components, bleeding, thrombotic events, and outcome were recorded. Survival was 54.9%. Bleeding occurred in 70.2%, including intracranial hemorrhage in 16%, and was independently associated with higher daily risk of mortality. Circuit component changes were required in 31.1%, and patient-related clots occurred in 12.8%. Laboratory sampling contributed to transfusion requirement in 56.6%, and was the sole reason for at least one transfusion in 42.2% of patients. Pump type was not associated with bleeding, thrombosis, hemolysis, or mortality. Hemolysis was predictive of subsequent thrombotic events. Neither hemolysis nor thrombotic events increased the risk of mortality. The incidences of bleeding and thrombosis are high during ECMO support. Laboratory sampling is a major contributor to transfusion during ECMO. Strategies to reduce the daily risk of bleeding and thrombosis, and different thresholds for transfusion, may be appropriate subjects of future trials to improve outcomes of children requiring this supportive therapy.

Costs of treating bleeding and perforated peptic ulcers in The Netherlands.

PubMed

de Leest, Helena; van Dieten, Hiske; van Tulder, Maurits; Lems, Willem F; Dijkmans, Ben A C; Boers, Maarten

2004-04-01

Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs includes perforations and bleeds. Several preventive strategies are being tested for cost-effectiveness, but little is known about the costs of the complications they are trying to prevent. We estimated the direct costs of hospital treatment of bleeding and perforated ulcers in a university hospital, from data in discharge letters and the hospital management information system. Eligible patients had been treated in the VU University Medical Center between January 1997 and August 2000 for an ulcer bleed or perforation (International Classification of Diseases code 531-4). Resource use comprised hospitalization days and diagnostic and therapeutic interventions. Insurance claim prices determined the costs from the payers' perspective. In a secondary analysis we excluded resource use that was clearly related to the treatment of comorbid illness. Fifty-three patients with a bleeding (n = 35) or perforated ulcer (n = 15) or both (n = 3) were studied, including 14 with comorbidity; 22 complications occurred in the stomach, 29 in the duodenum, one in both stomach and duodenum, and one after partial gastrectomy. A simultaneous bleed and perforation was most expensive (26,000 euro), followed by perforation (19,000 euro) and bleeding (12,000 euro). A bleed in the duodenum was more expensive than in the stomach (13,000 euro vs 10,000 euro), while the opposite was seen for perforations (13,000 euro vs 21,000 euro). Comorbidity increased costs substantially: even after correction for procedures unrelated to the ulcer complication, comorbidity more than doubled the costs of treatment. Treatment of complicated ulcers is expensive, especially in patients with comorbid conditions.

Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial.

PubMed

James, Stefan; Budaj, Andrzej; Aylward, Philip; Buck, Kristen K; Cannon, Christopher P; Cornel, Jan H; Harrington, Robert A; Horrow, Jay; Katus, Hugo; Keltai, Matyas; Lewis, Basil S; Parikh, Keyur; Storey, Robert F; Szummer, Karolina; Wojdyla, Daniel; Wallentin, Lars

2010-09-14

Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant. In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding. URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Association of aspirin use with major bleeding in patients with and without diabetes.

PubMed

De Berardis, Giorgia; Lucisano, Giuseppe; D'Ettorre, Antonio; Pellegrini, Fabio; Lepore, Vito; Tognoni, Gianni; Nicolucci, Antonio

2012-06-06

The benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage. To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin. A population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensity-matched on a 1-to-1 basis with individuals who did not take aspirin during this period. Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy. There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39-5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44). In a population-based cohort, aspirin use was significantly associated with an increased risk of major gastrointestinal or cerebral bleeding episodes. Patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.

Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH).

PubMed

Appelmann, Iris; Kreher, Stephan; Parmentier, Stefani; Wolf, Hans-Heinrich; Bisping, Guido; Kirschner, Martin; Bergmann, Frauke; Schilling, Kristina; Brümmendorf, Tim H; Petrides, Petro E; Tiede, Andreas; Matzdorff, Axel; Griesshammer, Martin; Riess, Hanno; Koschmieder, Steffen

2016-04-01

Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients. This review discusses the causes, differential diagnoses, prevention, and management of bleeding episodes in patients with MPN, aiming at defining updated standards of care in these often challenging situations.

Rare case-series of electrocautery burn following off-pump coronary artery bypass grafting

PubMed Central

Sabzi, Feridoun; Niazi, Mojtaba; Ahmadi, Alireza

2014-01-01

Abstract: With an increasing number of off-pump coronary artery surgery procedures in high-risk patients with coagulopathy, including renal failure, hepatic failure and anticoagulant drug-using patients, the frequency of related complications such as repeated exploration for bleeding is also increasing. The associated co-morbidity and repeated use of electrocautery in postoperative bleeding leaves patients susceptible to electrocautery ulcers. In this case series, rare cases of cautery burn with unique causative mechanisms are described. PMID:23669602

Playing prosocial video games increases the accessibility of prosocial thoughts.

PubMed

Greitemeyer, Tobias; Osswald, Silvia

2011-01-01

Past research has provided abundant evidence that playing violent video games increases aggressive tendencies. In contrast, evidence on possible positive effects of video game exposure on prosocial tendencies has been relatively sparse. The present research tested and found support for the hypothesis that exposure to prosocial video games increases the accessibility of prosocial thoughts. These results provide support to the predictive validity of the General Learning Model (Buckley & Anderson, 2006) for the effects of exposure to prosocial media on social tendencies. Thus, depending on the content of the video game, playing video games can harm but may also benefit social relations.

Primary Macroglobulinemia

PubMed Central

Edwards, A. M.; Costopoulous, L. B.; Bell, H. E.

1964-01-01

Clinical features presented by a patient with primary macroglobulinemia over a four-year period included cachexia, weight loss, bleeding tendency, anemia, lymphadenopathy, hepatosplenomegaly and recurrent pulmonary bacterial infections. Immunoelectrophoresis demonstrated the presence of a β2 macroglobulin which, on ultracentrifugation, was found to have a sedimentation constant of 14.9 S20, w; this macroglobulin constituted over 40% of the total serum protein. Postmortem findings included the typical “naked” lymphocyte infiltration of the reticuloendothelial system, with septic embolization from a terminal Gram-negative bacteremia, associated with a mesenteric vascular occlusion. A feature of particular interest was the antemortem appearance of gas in the portal venous system, shown on two abdominal scout radiographs taken one and two hours before death. The diagnostic significance of this rare radiologic sign is discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15 PMID:14226112

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use

PubMed Central

Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.

2016-01-01

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an “unacceptable health risk” during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

PubMed

Martinelli, Ida; Lensing, Anthonie W A; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S; Prins, Martin H

2016-03-17

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. © 2016 by The American Society of Hematology.

Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2006-10-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).

Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2005-07-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).

No evidence of purported lunar effect on hospital admission rates or birth rates.

PubMed

Margot, Jean-Luc

2015-01-01

Studies indicate that a fraction of nursing professionals believe in a "lunar effect"-a purported correlation between the phases of the Earth's moon and human affairs, such as birth rates, blood loss, or fertility. This article addresses some of the methodological errors and cognitive biases that can explain the human tendency of perceiving a lunar effect where there is none. This article reviews basic standards of evidence and, using an example from the published literature, illustrates how disregarding these standards can lead to erroneous conclusions. Román, Soriano, Fuentes, Gálvez, and Fernández (2004) suggested that the number of hospital admissions related to gastrointestinal bleeding was somehow influenced by the phases of the Earth's moon. Specifically, the authors claimed that the rate of hospital admissions to their bleeding unit is higher during the full moon than at other times. Their report contains a number of methodological and statistical flaws that invalidate their conclusions. Reanalysis of their data with proper procedures shows no evidence that the full moon influences the rate of hospital admissions, a result that is consistent with numerous peer-reviewed studies and meta-analyses. A review of the literature shows that birth rates are also uncorrelated to lunar phases. Data collection and analysis shortcomings, as well as powerful cognitive biases, can lead to erroneous conclusions about the purported lunar effect on human affairs. Adherence to basic standards of evidence can help assess the validity of questionable beliefs.

Knee arthroplasty and bleeding: when to remove drainages.

PubMed

Ares, Oscar; Seijas, Roberto; Hernandez, Alberto; Castellet, Enric; Sallent, Andrea

2013-02-01

The aim of this study is an attempt to clarify the productive time of drainages as we find that the use of drains in knee arthroplasty is controversial, and there is no consensus regarding their length-time maintenance. We analysed the survival curve of bleeding within three surgical techniques for knee arthroplasty and the effect of two variables on survival curve. One hundred and eighty-eight out of 234 knees were included in the study, and patients were divided into three groups according to the surgical technique: conventional total knee arthroplasty (TKA), subvastus TKA and unicompartmental knee arthroplasty. Variables of study were type of surgery, number and placement of drains. Mean of survival curve for postoperative bleeding time was 16 h (95 % CI: 15.4; 16.6). The risk for longer bleeding increased 1.38-fold with each additional drain used (95 % CI 1.1; 1.8). According to the present study, drains can be safely removed at around 17 h postoperative. Bleeding time reduces as less drains are applied. Therapeutic study, Level III.

Combined hormonal contraceptive trials: variable data collection and bleeding assessment methodologies influence study outcomes and physician perception.

PubMed

Mishell, Daniel R; Guillebaud, John; Westhoff, Carolyn; Nelson, Anita L; Kaunitz, Andrew M; Trussell, James; Davis, Ann Jeanette

2007-01-01

Initially approved for use in the United States nearly 50 years ago, oral hormonal contraceptives containing both estrogen and progestin have undergone steady improvements in safety and convenience. Concurrent with improvements in safety associated with decreasing doses of both steroids, there has been an increased incidence of unscheduled bleeding and spotting. There exist no standards regarding data collection techniques and methods, and reporting and analysis of bleeding and spotting events during combined hormonal contraceptive (CHC) trials. For the regulatory review of hormonal contraceptives, data regarding the incidence of bleeding and spotting events are not included in either of the traditional categories of efficacy and safety. Standardization of methods for collecting and analyzing data about cycle control in all clinical trials of CHCs is long overdue. Until such standards are developed and implemented, clinicians need to familiarize themselves with the techniques used in each study in order to provide correct information to their patients about the frequency of bleeding and spotting associated with different formulations and delivery systems.

Acceleration of high-pressure-ratio single-spool turbojet engine as determined from component performance characteristics I : effect of air bleed at compressor outlet

NASA Technical Reports Server (NTRS)

Rebeske, John J , Jr; Rohlik, Harold E

1953-01-01

An analytical investigation was made to determine from component performance characteristics the effect of air bleed at the compressor outlet on the acceleration characteristics of a typical high-pressure-ratio single-spool turbojet engine. Consideration of several operating lines on the compressor performance map with two turbine-inlet temperatures showed that for a minimum acceleration time the turbine-inlet temperature should be the maximum allowable, and the operating line on the compressor map should be as close to the surge region as possible throughout the speed range. Operation along such a line would require a continuously varying bleed area. A relatively simple two-step area bleed gives only a small increase in acceleration time over a corresponding variable-area bleed. For the modes of operation considered, over 84 percent of the total acceleration time was required to accelerate through the low-speed range ; therefore, better low-speed compressor performance (higher pressure ratios and efficiencies) would give a significant reduction in acceleration time.

Evaluation and management of abnormal uterine bleeding in premenopausal women.

PubMed

Sweet, Mary Gayle; Schmidt-Dalton, Tarin A; Weiss, Patrice M; Madsen, Keith P

2012-01-01

Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal uterine bleeding generally can be divided into anovulatory and ovulatory patterns. Chronic anovulation can lead to irregular bleeding, prolonged unopposed estrogen stimulation of the endometrium, and increased risk of endometrial cancer. Causes include polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of antipsychotics or antiepileptics. Women 35 years or older with recurrent anovulation, women younger than 35 years with risk factors for endometrial cancer, and women with excessive bleeding unresponsive to medical therapy should undergo endometrial biopsy. Treatment with combination oral contraceptives or progestins may regulate menstrual cycles. Histologic findings of hyperplasia without atypia may be treated with cyclic or continuous progestin. Women who have hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia. The levonorgestrel-releasing intrauterine system is an effective treatment for menorrhagia. Oral progesterone for 21 days per month and nonsteroidal anti-inflammatory drugs are also effective. Tranexamic acid is approved by the U.S. Food and Drug Administration for the treatment of ovulatory bleeding, but is expensive. When clear structural causes are identified or medical management is ineffective, polypectomy, fibroidectomy, uterine artery embolization, and endometrial ablation may be considered. Hysterectomy is the most definitive treatment.

Effects of platelet concentrate storage time reduction in patients after blood stem cell transplantation.

PubMed

Heuft, H-G; Goudeva, L; Krauter, J; Peest, D; Buchholz, S; Tiede, A

2013-07-01

To evaluate the clinical effect of platelet concentrate (PC) transfusions after PC storage time reduction to 4 days. This was a single-centre cohort study comparing two 3-month periods of time, before and after the reduction of PC storage time from 5 to 4 days. Seventy-seven consecutive patients with PC transfusions were enrolled after blood stem cell transplantation. Corrected platelet count increment (CCI) on the morning after transfusion, time to next platelet transfusion, need for red blood cell (RBC) transfusion and clinical bleeding symptoms were compared. Platelet concentrate storage time was reduced between period 1 (storage for up to 5 days, median storage time 78 h, range 11-136 h) and period 2 (storage for up to 4 days, median storage time 53 h, range 11-112 h). Patients were comparable for age, weight, body surface area, underlying disorder, type of transplantation and transfused platelet dose. The CCI increased from a median of 4 (range 0-20) to 8 (0-68) × 10(9) /l per 10(11) platelets/m(2) (P < 0·0001). Time to next PC transfusion increased from 1·1 to 2·0 days (P < 0·0001). Any bleeding symptom was noted in 20 of 36 patients (56%) vs. 9/41 patients (22%, P < 0·01). Nose bleeds, haematuria and bleeding at more than one site were significantly reduced. Frequency of RBC transfusion within 5 days after PC transfusion was reduced from 74 to 58% (P < 0·0001). Platelet concentrate storage time shortening was associated with highly significant CCI increase, reduced RC needs and lower patient numbers with bleeding events. © 2013 International Society of Blood Transfusion.

Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients.

PubMed

Rahe-Meyer, Niels; Fennema, Hein; Schulman, Sam; Klimscha, Walter; Przemeck, Michael; Blobner, Manfred; Wulf, Hinnerk; Speek, Marcel; McCrary Sisk, Christine; Williams-Herman, Debora; Woo, Tiffany; Szegedi, Armin

2014-11-01

Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables. This randomized, double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery. Patients received sugammadex 4 mg/kg or usual care (neostigmine or spontaneous recovery) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. The Cochran-Mantel-Haenszel method, stratified by thromboprophylaxis and renal status, was used to estimate relative risk and 95% confidence interval (CI) of bleeding events with sugammadex versus usual care. Safety was further evaluated by prespecified endpoints and adverse event reporting. Of 1,198 patients randomized, 1,184 were treated (sugammadex n = 596, usual care n = 588). Bleeding events within 24 h (classified by an independent, blinded Adjudication Committee) were reported in 17 (2.9%) sugammadex and 24 (4.1%) usual care patients (relative risk [95% CI], 0.70 [0.38 to 1.29]). Compared with usual care, increases of 5.5% in activated partial thromboplastin time (P < 0.001) and 3.0% in prothrombin time (P < 0.001) from baseline with sugammadex occurred 10 min after administration and resolved within 60 min. There were no significant differences between sugammadex and usual care for other blood loss measures (transfusion, 24-h drain volume, drop in hemoglobin, and anemia), or risk of venous thromboembolism, and no cases of anaphylaxis. Sugammadex produced limited, transient (<1 h) increases in activated partial thromboplastin time and prothrombin time but was not associated with increased risk of bleeding versus usual care.

An institutional pilot study to investigate physical activity patterns in boys with haemophilia.

PubMed

Bouskill, V; Hilliard, P; Stephens, S; Zhang, C; Whitney, K; Carcao, M

2016-09-01

Haemophilia is a bleeding disorder characterized by musculoskeletal bleeding. Trauma-induced bleeding into joints and muscles may be associated with participation in physical activities. Recognizing this, persons with haemophilia may limit physical activities to avoid bleeding. The characterization of physical activity profiles (type, intensity, frequency and duration) in children with differing severities of haemophilia has not been well documented. This is required to better understand the relationship between physical activity and bleeding in children with haemophilia. This study was a prospective, cross-sectional, observational study to compare the quantity, type and intensity of physical activity as measured by accelerometry in boys with different haemophilia severities. Subjects wore an accelerometer daily for 1 week and completed validated self-report PedHAL and 3DPAR questionnaires. Accelerometer activity levels were classified as sedentary, light, moderate or vigorous. A total of 66 males were enrolled, 24 had mild/moderate and 42 had severe haemophilia. Subjects average age was 11.52 years (±3.99) and their average BMI was 20.74 kg m(2) (±5.68). Boys with severe haemophilia reported significantly more time per day spent in sedentary activities compared to those with mild/moderate haemophilia. Furthermore, the amount of time engaged in sedentary activities increased with age in those boys with severe haemophilia, whereas the opposite was true in those with mild/moderate haemophilia. We speculate that prophylaxis in children with severe haemophilia permitted them to engage in similar amounts of moderate to vigorous physical activity (MVPA) as children with mild/moderate haemophilia. Increasing sedentary time in the severe cohort with age may be attributed to increasing arthropathy among other psychosocial factors. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Use of Contraindicated Antiplatelet Medications in the Setting of Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

PubMed

Barnes, Geoffrey D; Stanislawski, Maggie A; Liu, Wenhui; Barón, Anna E; Armstrong, Ehrin J; Ho, P Michael; Klein, Andrew; Maddox, Thomas M; Nallamothu, Brahmajee K; Rumsfeld, John S; Tsai, Thomas T; Bradley, Steven M

2016-07-01

Several antiplatelet medications used during and after percutaneous coronary intervention (PCI) are contraindicated for specific patient groups. A broad assessment of contraindicated medication use and associated clinical outcomes is not well described. Using national Veterans Affairs Clinical Assessment, Reporting, and Tracking Program data for all PCI between 2007 and 2013, we evaluated patients with contraindications to commonly used antiplatelet medications during and after PCI, defined in accordance with package inserts. Adjusted association between contraindicated medication use and outcomes of periprocedural bleeding and 30-day mortality were assessed using Cox proportional hazards with inverse probability weighting. Among 64 294 patients undergoing PCI, 11 315(17.6%) had a contraindication to a common antiplatelet medication and 737 (6.5%) of these patients received a contraindicated medication. In unadjusted analyses, any contraindicated medication use was associated with both increased bleeding and 30-day mortality. In adjusted models, contraindicated abciximab use in patients with thrombocytopenia (hazard ratio, 2.23; 95% confidence interval, 1.58-3.16) and in patients with a previous stroke (hazard ratio, 1.93; 95% confidence interval, 1.37-2.71) remained significantly associated with increased bleeding. Contraindicated abciximab use was not significantly associated with 30-day mortality in adjusted models. Use of eptifibatide in dialysis patients was not significantly associated with an increased risk of bleeding or mortality. In this national cohort, ≈18% of patients undergoing PCI had contraindications to common antiplatelet medications. Approximately 6% of those patients received a contraindicated medication with attendant bleeding risk, although this did not translate into significantly higher risk of 30-day mortality. Continued efforts to reduce contraindicated medication use may help avoid periprocedural complications. © 2016 American Heart Association, Inc.

[Gastrointestinal bleeding and potentially inappropriate medication by NSAIDs].

PubMed

Pastor Cano, Josep; Aranda García, Ana; Sánchez Ruiz, José Francisco; Rausell Rausell, Víctor José; Tobaruela Soto, Mariana; Gascón Cánovas, Juan José

2018-05-28

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are widely used but they increase the risk of gastrointestinal haemorrage among other adverse effects. The objective of this study was to compare potentially inappropriate medications (PIM) by NSAIDs using the original Beers Criteria, a global reference for evaluating elderly people's prescriptions, and the Spanish adaptation of the same; and the relation between PIM of NSAIDs and gastrointestinal bleeding. The study was a retrospective observational study carried out located in a primary care district in the province of de Murcia, south-eastern Spain. The study population (n=7.856) were citizens aged 65 and above, with at least one drug prescribed in a Spanish health district during the study period . We analized illnesses and treatments registered in the primary care's electronic medical history of patients and hospital admissions, during the 12 month study period (2012). The original Beers Criteria and their Spanish adaptation were used to evaluate PIM of NSAIDs in patients considering the medication globally and also each active substance. Gastrointestinal bleeding events recorded in the data bases studied were evaluated. Detection of PIM of NSAIDs was 5,6% with the original version and 7,0% (Δ=25,5%; p less than 0,001) with the adapted one. PIM of NSAIDs was related with an increased incidence of gastrointestinal bleeding without significant differences between PIM exposed and NSAID exposed patients AINE (RR=1,6; IC:0,2-14,5). The Spanish adaptation of the Beers criteria identified a greater degree of PIM of NSAIDs than the original version, and in both versions the detection of PIM was not related with a significant increase of gastrointestinal bleeding compared to patients exposed to NSAIDs.

Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study.

PubMed

Sundström, Johan; Hedberg, Jakob; Thuresson, Marcus; Aarskog, Pernilla; Johannesen, Kasper Munk; Oldgren, Jonas

2017-09-26

There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events. We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had ≥80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time. In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal. © 2017 American Heart Association, Inc.

Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study

PubMed Central

Søgaard, Mette; Skjøth, Flemming; Kjældgaard, Jette Nordstrøm; Larsen, Torben Bjerregaard; Hjortshøj, Søren Pihlkjær; Riahi, Sam

2017-01-01

Objectives Outcomes of atrial fibrillation (AF) in patients with severe mental disorders are largely unknown. We compared rates of stroke, fatal thromboembolic events and bleeding in patients with AF with and without mental disorders. Design Nationwide registry-based cohort study. Setting Denmark (population 5.6 million), 2000–2015. Participants Patients with AF with schizophrenia (n=534), severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and calendar time to patients with AF without mental disorders. Exposure Inpatient or hospital-based outpatient diagnosis of schizophrenia, severe depression or bipolar disease. Primary and secondary outcome measures HRs for stroke, fatal thromboembolic events and major bleeding comparing patients with and without mental disorders estimated by Cox regression with sequential adjustment for risk factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant therapy (OAT). Results Compared with matched comparisons, crude 5-year HRs of ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI 0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease. After adjusting for risk factors, comorbidity and OAT, these HRs declined towards the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to 5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95% CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95% CI 0.58 to 1.15). Conclusion Patients with AF with schizophrenia or severe depression experienced increased rates of stroke and major bleeding compared with matched comparisons. This increase was largely explained by differences in the prevalence of risk factors for stroke and bleeding, comorbidity and initiation of OAT during follow-up. Patients with AF with schizophrenia further experienced higher mortality following thromboembolic events than matched comparisons without mental disorders. PMID:29217725

Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

PubMed

Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

2015-08-01

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Intrauterine contraception].

PubMed

Tauber, P F

1984-09-01

Approximately 60 million women worldwide use IUDs. Despite worldwide distribution, the total number of IUD carriers has barely increased since 1970. Due to its risks and side effects there is a retrograding tendency both in West Germany and the US. To generate positive development, 3 basic trends have emerged: 1) Restrictive usage of the pharmacologically inactive, 1st generation IUDs such as the Lippes Loop or the Saf-T-Coil, 2) the increasing usage of small plastic IUDs with bioactive alloys to decrease failure rates such as the copper (2nd generation) or hormone-releasing IUDs, and 3) improvements made by changing its design to reduce side effects without loss of contraceptive effectiveness. Almost all IUDs increase monthly blood loss by 50-100%. The risk of illness for women with IUDs is 2-3 times higher than for a woman without or with other contraceptive methods. About 20% of all expulsions occur unnoticed. There are 2 kinds of perforations: primary (iatrogenic), at time of insertion, and secondary, some time after insertion. The IUD failure rate is about 1-3 pregnancies/100 woman years. In case of pregnancy, the IUD must be removed immediately. IUD insertion requires consent of the woman and can be made to women from 16 years on, presupposing moral maturity. IUD insertion after a miscarriage or abortion does not lead to risks or complications. Due to its corrosive quality, the copper IUD can only remain inside the uterus for a limited time. IUDs could become an excellent contraceptive method if it were possible to decrease bleeding, design easily-removeable IUDs, and prolong their potential for duration in the body.

Interleukin-1 and IL-1 receptor antagonist in gingival crevicular fluid.

PubMed

Rawlinson, A; Dalati, M H; Rahman, S; Walsh, T F; Fairclough, A L

2000-10-01

This study aimed to investigate the cytokine IL-1beta and its receptor antagonist IL-1ra in gingival crevicular fluid (GCF), in patients with adult periodontitis. A total of 40 GCF samples were harvested from 10 subjects with moderate to severe adult periodontitis and 10 healthy controls. Subjects were selected from both genders, with all the upper anterior teeth present, and with no relevant systemic illness, pregnancy or recent medication. All subjects were non-smokers and had not received any periodontal therapy within the preceding 3 months. Deep bleeding sites, deep non-bleeding sites and healthy sites were investigated in relation to upper anterior teeth. Clinical measurements were recorded for each site, after obtaining a GCF sample. IL-1beta and IL-1ra were quantified using new commercially available ELISA kits (Quantikine), and could be detected in all samples. The mean concentration for IL-1beta was 0.11 (SD 0.14) pg/microl for bleeding periodontitis sites, 0.04 (0.05) pg/microl for non-bleeding periodontitis sites, and 0.01 (0.03) pg/microl for healthy sites (p<0.001). In contrast, the mean concentration for IL-1ra was 6.99 (9.78) pg/microl for healthy sites, 0.59 (0.44) pg/microl for non-bleeding periodontitis sites, and 0.44 (0.36) pg/microl for bleeding periodontitis sites (p<0.001, except for comparisons between bleeding and non-bleeding periodontitis sites, p>0.05). For healthy sites, a strong inverse relationship was found between IL-1beta and IL-1ra levels in GCE. The results suggest a strong relationship between the severity of adult periodontitis and the increasing GCF levels of IL-1beta and decreasing levels of IL-1ra.

Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.

PubMed

Napolitano, M; Di Minno, M N D; Batorova, A; Dolce, A; Giansily-Blaizot, M; Ingerslev, J; Schved, J-F; Auerswald, G; Kenet, G; Karimi, M; Shamsi, T; Ruiz de Sáez, A; Dolatkhah, R; Chuansumrit, A; Bertrand, M A; Mariani, G

2016-09-01

A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 μg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 μg kg(-1) (divided as three doses). Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies. © 2016 John Wiley & Sons Ltd.

Effect of anticoagulation on endothermal ablation of the great saphenous vein.

PubMed

Sharifi, Mohsen; Mehdipour, Mahshid; Bay, Curt; Emrani, Farnaz; Sharifi, Jalaladdin

2011-01-01

A growing number of patients who are on systemic anticoagulation with warfarin require endovenous thermal ablation for reflux disease in the great saphenous vein (GSV). Little is known about the effects of anticoagulation on periprocedural bleeding and long-term closure rates of the treated veins. This study evaluated the effects of uninterrupted anticoagulation in patients undergoing endovenous thermal ablation. In this prospective observational study, 88 limbs of patients on warfarin (anticoagulation group [AG]) who underwent endovenous thermal ablation for GSV reflux disease were compared with 92 limbs in patients receiving no anticoagulation or antiplatelet agents (control group [CG]). Forty percent of AG patients were also receiving antiplatelet therapy. Periprocedural bleeding and closure rate at 1 year were evaluated. No major bleeding occurred in either group. Minor bleeding was noted in 8 of 88 procedures in the AG vs 4 of 92 in the CG (P = 0.24); all in patients receiving radiofrequency ablation. Four of the eight minor bleeds in the AG were noted in patients receiving "triple therapy" with warfarin, aspirin, and clopidogrel or ticlopidine. Triple therapy in the AG was associated with a higher risk of minor bleeding compared with the CG (relative risk, 13.0; 95% confidence interval, 4.10-41.19, P < .001). All treated venous segments remained closed at the 1-year follow-up in both groups. In this relatively small, nonrandomized study comparing endovenous thermal ablation in patients with and without warfarin, no differences were found in periprocedural risk of major bleeding or closure rate of the treated venous segments. Minor bleeding was increased in patients receiving triple therapy with warfarin, aspirin, and a thienopyridine who underwent radiofrequency ablation. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Long Term Use of Aspirin and the Risk of Gastrointestinal Bleeding

PubMed Central

Huang, Edward S.; Strate, Lisa L.; Ho, Wendy W.; Lee, Salina S.; Chan, Andrew T.

2011-01-01

Background In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear. Methods We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion. Results Over a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (≥2 standard [325-mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) compared with non-regular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for 6-14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for >14 tablets/week (Ptrend<.001). Similar dose-response relationships were observed among short-terms users (≤ 5 years; Ptrend<.001) and long-term users (>5 years; Ptrend<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer greater risk of bleeding (Ptrend=0.28). Conclusions Regular aspirin use is associated with gastrointestinal bleeding. Risk appears more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short-term and long-term users. PMID:21531232

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE.

PubMed

Lassen, M R; Fisher, W; Mouret, P; Agnelli, G; George, D; Kakkar, A; Mismetti, P; Turpie, A G G

2012-05-01

Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2). All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10 days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles. © 2012 International Society on Thrombosis and Haemostasis.

Etiology and Outcome of Acute Gastrointestinal Bleeding in Iran:A Review Article

PubMed Central

Masoodi, Mohsen; Saberifiroozi, Mehdi

2012-01-01

Upper gastrointestinal bleeding (UGIB) is defined as bleeding that results from lesions located above the ligament of Treitz and is a common cause for emergency hospital admissions in patients with gastrointestinal disorders. UGIB also increases the risk of morbidity and mortality in patients already hospitalized for other reasons. According to epidemiological surveys of acute UGIB in Iran, peptic ulcer is the most common endoscopic diagnosis. Gastric and duodenal erosion accounts for 16.4%-25% of etiologies. Other relatively common causes of UGIB are variceal hemorrhage, Mallory-Weiss tears, and arterial and venous malformations. However, in 9%-13.3% of patients, the endoscopy is normal. PMID:24829656

Never giving up: outcomes and presentation of emergency general surgery in geriatric octogenarian and nonagenarian patients.

PubMed

Shah, Adil A; Zafar, Syed Nabeel; Kodadek, Lisa M; Zogg, Cheryl K; Chapital, Alyssa B; Iqbal, Aftab; Greene, Wendy R; Cornwell, Edward E; Havens, Joaquim; Nitzschke, Stephanie; Cooper, Zara; Salim, Ali; Haider, Adil H

2016-08-01

Aging of the population necessitates consideration of the increasing number of older adults requiring emergency care. The objective of this study was to compare outcomes and presentation of octogenarian and/or nonagenarian emergency general surgery (EGS) patients with younger adults. Based on a standardized definition of EGS, patients in the 2007 to 2011 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample were queried for primary EGS diagnoses. Included patients were categorized into older (≥80 years) vs younger (<80 years) adults based on a marked increase in mortality around aged 80 years. Using propensity scores, risk-adjusted differences in major morbidity, mortality, length of stay (LOS), and cost were compared. Of 3,707,465 included patients, 17.2% (n = 637,588) were ≥80 years. Relative to younger adults, older patients most frequently presented for gastrointestinal-bleeding (odds ratio [95% confidence intervals]: 2.81 [2.79 to 2.82]) and gastrostomy care (2.46 [2.39 to 2.53]). Despite higher odds of mortality (1.67 [1.63 to 1.69]), older adults exhibited lower risk-adjusted odds of morbidity (.87 [.86 to .88]), shorter LOS (4.50 vs 5.14 days), and lower total hospital costs ($10,700 vs $12,500). Octogenarian and/or nonagenarian patients present differently than younger adults. Reductions in complications, LOS, and cost among surviving older adults allude to a "survivorship tendency" to never give up, despite collectively higher mortality risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Bleeding pattern and user satisfaction in second consecutive levonorgestrel-releasing intrauterine system users: results of a prospective 5-year study.

PubMed

Heikinheimo, O; Inki, P; Schmelter, T; Gemzell-Danielsson, K

2014-06-01

What is the bleeding pattern during second consecutive levonorgestrel-releasing intrauterine system (LNG-IUS) use? Consecutive use of LNG-IUS is associated with a predictable bleeding pattern, characterized by the absence of the initial period of irregular bleeding seen after interval insertion of an LNG-IUS and a non-bleeding pattern in the vast majority of women. With increased popularity of the LNG-IUS for long-term birth control and treatment of heavy menstrual bleeding (HMB), consecutive use of the system is becoming more frequent. One previous study showed 60% amenorrhea rate in consecutive IUS users; however, the sample size was small. A prospective multicenter study in four European countries recruited women who wished to continue with LNG-IUS use immediately after the first 5-year period. A total of 204 women were followed up until the end of the first year of the second IUS. Thereafter 170 women continued into the extension phase of the study up to the full 5 years of use of the second IUS and 144 women continued to the end of the study. A total of 170 women (mean age 39 years) who had been using their first LNG-IUS for between 4 years 3 months and 4 years 9 months, either for contraception or for treatment of HMB, and who planned to replace the device with a new LNG-IUS, were recruited and followed up to 5 years of the second IUS use. A total of 17 centers in four European countries were involved in the study. Bleeding patterns were analyzed using daily bleeding diaries using 90-day reference periods (RP) for the first year of the second IUS use and for the last RP of each year during Years 2-5 of use. Approximately 70% of women were free of bleeding during Years 2-5 and up to 49% were amenorrheic. There was a slight increase in the number of bleeding/spotting days of ∼3 days during the first RP immediately after the placement of the second IUS, whereafter the number of bleeding/spotting days returned to the level preceding the second IUS insertion or below that. Absence of bleeding was associated with high overall satisfaction and continuation rates. No serious adverse events assessed as related to the LNG-IUS use occurred during the 5-year period. The cumulative expulsion rate during the 5-year study period was 1.2%. The sample size was large enough to study bleeding patterns, and subjects are likely to represent typical consecutive IUS users, and therefore, the role of chance is small. The women represent a selected group as they had already successfully used their first IUS for almost 5 years and were willing to continue its use-however, this is currently a common clinical situation. The results may therefore not be extrapolated to first-time users of the LNG-IUS. These data are of importance when counseling women who are making decisions concerning long-term contraception. This study was funded by Bayer Pharma AG. P.I. and T.S. are full-time employees of Bayer Pharma AG. O.H. and K. G-D. have received consultancy fees from Bayer Pharma AG. The publication was developed jointly by all authors without third-party involvement and no honoraria were paid for any authors for their contribution to this manuscript. NCT00393198.

What's Your Position? Strategies for Safely Reaching Patient Comfort Goals After Cardiac Catheterization via Femoral Approach.

PubMed

Suggs, Patricia M; Lewis, Rebecca; Hart, Ann C; Troutman-Jordan, Meredith; Hardin, Sonya R

Patients frequently complain of back pain after cardiac catheterization, and there is a lack of evidence to guide practice regarding patient comfort while maintaining hemostasis at femoral access site after cardiac catheterization. The aim of this study was to examine if frequent position changes affect a patient's pain level or increase incidents of bleeding in the recovery period after cardiac catheterization. A quasi-experimental pretest/posttest design was used to evaluate a patient's reported pain levels and positioning changes during bed rest period postprocedure. Twenty charts were reviewed to note documentation of patient position, self-reported pain rating related to pain relief goals, and occurrence of bleeding at the procedure site. A survey was conducted to reveal nurse attitudes, knowledge, and beliefs regarding positioning and pain management for patients in the post-cardiac catheterization period. Results from this survey were used to develop education and data collection tools. Education regarding perceived barriers and importance of maximizing activity orders for patient comfort was provided to nursing staff. After nurse education, an additional 20 charts were reviewed to note if increasing frequency of position change affects pain levels reported by patients or if any increased incidence of bleeding was noted with greater frequency of position change. Data were analyzed using correlation analyses. Greater levels of pain were associated with higher pain ratings (r = 0.796, P < .000). Use of position change only as a comfort measure was negatively associated with pain ratings; in other words, lower patient pain ratings were associated with use of positioning only without addition of medications to address complaint (r = -0.493, P < .023). There was a significant increase in number of pain management goals met from before to after education intervention (P < .046). Nurse concern for increased bleeding was found to be the most common barrier for use of position changes for comfort after cardiac catheterization. This initial analysis suggests position changes in conjunction with pain medication are beneficial in managing pain after cardiac catheterization. There was no increase in bleeding or complications reported; however this study had a small sample size, and caution should be used regarding generalization of findings.

The predictive value of multiple electrode platelet aggregometry for postoperative bleeding complications in patients undergoing coronary artery bypass graft surgery

PubMed Central

Woźniak, Karolina; Hryniewiecki, Tomasz; Kruk, Mariusz; Różański, Jacek; Kuśmierczyk, Mariusz

2016-01-01

Introduction Postoperative bleeding is one of the most serious complications of cardiac surgery and requires transfusion of blood or blood products. Acetylsalicylic acid (ASA) and clopidogrel (CLO) are the two most commonly used antiplatelet agents; when used in combination (i.e., as dual antiplatelet therapy [DAPT]), they exert a synergistic effect. Dual antiplatelet therapy, however, significantly increases the risk of postoperative bleeding. The effect of antiplatelet therapy can be monitored by platelet aggregation testing. One of the most commonly methods used for assessing platelet reactivity is multiple electrode aggregometry (MEA) which can be performed with the use of Multiplate analyzer. Although the method has long been used in interventional cardiology to assess the effect of antiplatelet therapy, it is not available at cardiac surgery departments as a standard diagnostic procedure. The aim of the study was to establish the frequency of bleeding complications following coronary artery bypass graft (CABG) surgery in patients on single antiplatelet therapy (SAPT) and patients on DAPT and to determine the usefulness of routine measurement of platelet responsiveness before CABG surgery in patients receiving antiplatelet therapy. Material and methods A consecutive cohort of 200 patients referred for elective surgical treatment of stable coronary artery disease was enrolled (100 consecutive patients on SAPT [ASA 75 mg/day] and 100 consecutive patients on DAPT [ASA 75 mg/day + CLO 75 mg/day]). All subjects continued their antiplatelet therapy until the day before surgery. For each subject, platelet aggregation testing in the form of an ASPI test and an ADP test was performed on the Multiplate analyzer. Each subject underwent coronary artery bypass grafting surgery. For the primary and secondary endpoints in our study we adopted the definition provided in ‘Standardised Bleeding Definitions for Cardiovascular Clinical Trials: A Consensus Report from the Bleeding Academic Research Consortium’ (‘Circulation’, 2011) for BARC type 4 bleeding (i.e. CABG-related bleeding). Results An ROC curve was constructed for the ASPI test and ADP test for a total of 200 patients. No significant correlations were demonstrated between the ASPI test results and either the primary endpoint or the secondary endpoints. A correlation was found between the ADP test results and the composite primary endpoint and each of the secondary endpoints. The primary endpoint of major postoperative bleeding occurred in 16 subjects. From the ROC curve, we established the optimal cut-off value for the ADP test of 26 U at sensitivity of 72%, specificity of 69%, positive predictive value of 69.90%, and negative predictive value of 71.13%. Conclusions In patients on antiplatelet therapy, an ADP test result of < 26 U is strongly predictive of serious bleeding complications after CABG surgery. The MEA ADP test allows to identify the group of patients at an increased risk of postoperative bleeding. PMID:27212971

Labor and delivery in a patient with hemophilia B.

PubMed

Przkora, R; Euliano, T Y; Roussos-Ross, K; Zumberg, M; Robicsek, S A

2011-07-01

Hemophilia B is a rare X-linked disorder that may cause dramatic bleeding. Women account for only 3.2% of those clinically affected. The X-linked inheritance frequently delays the diagnosis in women and may expose the patient to an increased risk of adverse events. There is limited experience with these patients during labor and delivery. A 28-year-old primiparous woman with hemophilia B (bleeding phenotype) delivered a male infant by an unplanned cesarean delivery under general anesthesia following treatment with factor IX and normalization of her coagulation parameters, guided by thromboelastography. Postpartum vaginal bleeding required transfusion of two units of packed red blood cells. Factor IX supplementation continued for one week. Once diagnosed with hemophilia B, a multidisciplinary approach and advanced antenatal planning can increase the likelihood of a safe delivery. Neuraxial approaches and cesarean delivery are recommended only after normalization of the coagulation profile. The male fetus of a hemophilia A or B patient requires special attention. Operative vaginal delivery and invasive fetal monitoring should be avoided. Thromboelastography is an excellent technique to assess parturients with bleeding disorders or peripartum hemorrhage and may be underused. Copyright © 2011 Elsevier Ltd. All rights reserved.

Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel.

PubMed

Funk, Sidney; Miller, Michael M; Mishell, Daniel R; Archer, David F; Poindexter, Alfred; Schmidt, Juergen; Zampaglione, Edio

2005-05-01

The safety and efficacy of a single-rod implantable contraceptive containing etonogestrel (Implanontrade mark) were investigated in a multicenter clinical trial. Sexually active American women (N=330) with apparently normal menstrual cycles used the implant for up to 2 years. All subjects recorded bleeding and/or spotting daily in a diary. Safety was assessed through adverse experiences (AEs), laboratory tests and physical and gynecologic examinations. Total exposure was 474 woman-years (6186 cycles), and 68% of subjects had at least 1 year of exposure. No pregnancies occurred. The most common bleeding pattern observed throughout the study was infrequent bleeding, defined as less than three episodes of bleeding in a reference period (excluding amenorrhea). The least common pattern was frequent bleeding, defined as more than five episodes of bleeding in a reference period. Infrequent, prolonged and frequent bleeding patterns were most common early in the study and declined thereafter. During the 3-month Reference Periods 2-8 (Months 4-24), the incidence of amenorrhea ranged from 14% to 20%. Forty-three subjects (13%) withdrew from the study because of bleeding pattern changes and 76 subjects (23%) discontinued because of other AEs. Other common AEs leading to discontinuation, besides bleeding irregularities, were emotional lability (6.1%), weight increase (3.3%), depression (2.4%) and acne (1.5%). Use of Implanon (etonogestrel subdermal implant, referred to herein as ENG implant) for up to 2 years had no clinically significant effects on laboratory parameters, physical and pelvic examinations, vital signs or body mass index. The average length of time required for ENG implant insertion and that for removal were 0.5 and 3.5 min, respectively, and all the procedures were uncomplicated. The return to normal menstrual cycles and fertility was rapid after removal. Implanon is a safe, highly effective and rapidly reversible new method of contraception.

Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice.

PubMed

Sostres, Carlos; Carrera-Lasfuentes, Patrica; Lanas, Angel

2017-10-01

The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied. To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case-control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0. Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (<30 days) of NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32-5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms. The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users.

Bleeding prevalence and transfusion requirement in patients with thrombocytopenia in the emergency department.

PubMed

Turvani, Fabrizio; Pigozzi, Luca; Barutta, Letizia; Pivetta, Emanuele; Pizzolato, Elisa; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

2014-10-01

Thrombocytopenia is the most common coagulation disorder in critically ill patients. No studies have investigated the epidemiology and clinical impact of this condition in emergency department (ED) patients. We aimed to investigate epidemiological features, incidence of bleeding, and diagnostic and therapeutic requirements of patients with thrombocytopenia admitted to the ED. We performed a retrospective observational study enrolling all patients admitted to the medical-surgical ED of the "Città della Salute e della Scienza di Torino" Hospital with a platelet count <150×10(9) PLTs/L, during four non-consecutive months. There were no exclusion criteria. The study included 1218 patients. The percentage of patients with severe (<50×10(9) PLTs/L) or very severe (<20×10(9) PLTs/L) thrombocytopenia was about 12%. Thrombocytopenia associated with liver cirrhosis was the most represented etiology. On the contrary, the most frequent cause in patients with newly recognized low platelet count was disseminated intravascular coagulation/sepsis. The incidence of bleeding and hypovolemia, as well as the need of transfusional support and mechanical, surgical or endoscopic hemostasis progressively increased with the severity of thrombocytopenia. Our results suggest that the detection of a platelet count lower than 50×10(9) PLTs/L may help to identify patients with higher bleeding risk in the ED setting. Additional studies are required to evaluate whether, in this setting, thrombocytopenia may represent an independent risk factor for bleeding episodes and increased mortality.

Hawthorn Herb Increases the Risk of Bleeding after Cardiac Surgery: An Evidence-Based Approach.

PubMed

Rababa'h, Abeer M; Altarabsheh, Salah E; Haddad, Osama; Deo, Salil V; Obeidat, Yagthan; Al-Azzam, Sayer

2016-08-22

Hawthorn extract consumption is becoming more widespread among the Jordanian population with cardiovascular disorders. We conducted this prospective observational longitudinal study to determine the impact of hawthorn extract on bleeding risk in patients who undergo cardiac surgery. A prospective observational study was performed on 116 patients who underwent cardiac surgery in the period between June 2014 and May 2015. Patients were divided into two groups: Group I (patients recently consumed hawthorn extract) and Group II (patients never consumed hawthorn extract). Endpoint measures included the rates of reopening to control bleeding, early mortality, duration of intensive care unit stay, total in-hospital stay period, and duration and amount of chest tube drainage. Hawthorn patients had a significantly higher rate of postoperative bleeding necessitating take back to the operating room compared to the control group (10% versus 1%; P = .03) respectively. The overall mortality rate for group I and II was 4% and 0% respectively; P = .17. Chest tubes were kept in for longer times in group I compared to group II (54 ± 14.6 versus 49 ± 14.7 hours respectively; P = .01). Group I stayed longer in the intensive care unit compared to group II (24 versus 22 hours respectively; P = .01). The total in-hospital stay period was comparable between the two groups. Hawthorn extract consumption does increase the potential for bleeding and the amount of chest tube output after cardiac surgery.

Dose Constraint for Minimizing Grade 2 Rectal Bleeding Following Brachytherapy Combined With External Beam Radiotherapy for Localized Prostate Cancer: Rectal Dose-Volume Histogram Analysis of 457 Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiraishi, Yutaka; Yorozu, Atsunori; Ohashi, Toshio, E-mail: ohashi@rad.med.keio.ac.jp

2011-11-01

Purpose: To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. Methods and Materials: A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and formore » rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. Results: Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 {<=}35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 {<=}0.5 ml and a V30 {<=}35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. Conclusion: The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of Grade 2 rectal bleeding.« less

Epsilon aminocaproic acid for the prevention of delayed postoperative bleeding in retired racing greyhounds undergoing gonadectomy.

PubMed

Marín, Liliana M; Iazbik, M Cristina; Zaldivar-Lopez, Sara; Guillaumin, Julien; McLoughlin, Mary A; Couto, C Guillermo

2012-07-01

To evaluate the effects of epsilon aminocaproic acid (EACA) on the prevalence of postoperative bleeding in retired racing Greyhounds (RRG), and to assess its effects on selected thrombelastography (TEG) and fibrinolysis variables. Double-blinded, prospective, randomized study. 100 RRG had elective ovariohysterectomy or orchiectomy and were administered EACA or placebo for 3 days after surgery. TEG variables were analyzed preoperatively and 24, 48, and 72 hours after surgery. Thirty percent (15/50) of RRG in the placebo group had delayed postoperative bleeding starting 36-48 hours after surgery compared with 10% (5/50) in the EACA group (P = .012). On the TEG variables, the slopes for R and K time were significantly different between treatment groups (P <.05); the R and K time decreased over time in the EACA group after surgery whereas they increased in the placebo group. The angle, maximal amplitude (MA), and G slopes were also significantly different between treatment groups (P = .001, .001, and .006, respectively). The angle, MA, and G increased postoperatively over time in the EACA group and decreased in the placebo group. All these changes are supportive of hypercoagulability associated with EACA administration. Postoperative administration of EACA significantly decreased the prevalence of postoperative bleeding in RRG undergoing surgery by increasing the clot strength. © Copyright 2012 by The American College of Veterinary Surgeons.

Management of antithrombotic therapy in patients with coronary artery disease or atrial fibrillation who underwent abdominal surgical operations.

PubMed

Schizas, Dimitrios; Kariori, Maria; Boudoulas, Konstantinos Dean; Siasos, Gerasimos; Patelis, Nikolaos; Kalantzis, Charalampos; Carmen-Maria, Moldovan; Vavuranakis, Manolis

2018-04-02

Patients treated with antithrombotic therapy that require abdominal surgical procedures has progressively increased overtime. The management of antithrombotics during both the peri- and post- operative period is of crucial importance. The goal of this review is to present current data concerning the management of antiplatelets in patients with coronary artery disease and of anticoagulants in patients with atrial fibrillation who had to undergo abdominal surgical operations. For this purpose, incidence of major adverse cardiovascular events (MACE) and risk of antithrombotic use during surgical procedures, as well as the recommendations based on recent guidelines were reported. A thorough search of PubMed, Scopus and the Cochrane Databases was conducted to identify randomized controlled trials, observational studies, novel current reviews, and ESC and ACC/AHA guidelines on the subject. Antithrombotic use in daily clinical practice results to two different pathways: reduction of thromboembolic risk, but a simultaneous increase of bleeding risk. This may cause a therapeutic dilemma during the perioperative period. Nevertheless, careless cessation of antithrombotics can increase MACE and thromboembolic events, however, maintenance of antithrombotic therapy may increase bleeding complications. Studies and current guidelines can assist clinicians in making decisions for the treatment of patients that undergo abdominal surgical operations while on antithrombotic therapy. Aspirin should not be stopped perioperatively in the majority of surgical operations. Determining whether to discontinue the use of anticoagulants before surgery depends on the surgical procedure. In surgical operations with a low risk for bleeding, oral anticoagulants should not be discontinued. Bridging therapy should only be considered in patients with a high risk of thromboembolism. Finally, patients with an intermediate risk for thromboembolism, management should be individualized according to patient's thrombotic and bleeding risk. Management of antithrombotics therapy during the perioperative period in patients undergoing abdominal surgery should follow a patient-centered approach according to a patient's medical history and thrombotic risk weighted for bleeding risk. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials?

PubMed

Duerschmied, D; Brachmann, J; Darius, H; Frey, N; Katus, H A; Rottbauer, W; Schäfer, A; Thiele, H; Bode, C; Zeymer, Uwe

2018-04-20

The number of patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is increasing. Since these patients have a CHA 2 DS 2 -VASc score of 1 or higher, they should be treated with oral anticoagulation to prevent stroke. However, combination therapy with oral anticoagulation for prevention of embolic stroke and dual platelet inhibition for prevention of coronary thrombosis significantly increases bleeding complications. The optimal combination, intensity and duration of antithrombotic combination therapy is still not known. In the rather small randomized WOEST trial, the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to the conventional triple therapy with VKA, clopidogrel and aspirin. In the PIONEER AF-PCI trial, two rivaroxaban-based treatment regimens significantly reduced bleeding complications compared to conventional triple therapy without increasing embolic or ischemic complications following PCI. Dual therapy with rivaroxaban and clopidogrel appeared to provide an optimal risk-benefit ratio. In the RE-DUAL PCI trial, dual therapy with dabigatran also reduced bleeding complications compared to conventional triple therapy. With respect to the composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization dabigatran-based dual therapy was non-inferior to VKA-based triple therapy. The upcoming trials AUGUSTUS with apixaban and ENTRUST-PCI with edoxaban will further examine the use of NOACs in this setting. While recent guidelines recommend NOAC-based dual therapy in only a subset of patients (those who are at increased risk of bleeding), the available data now suggest that this should be the preferred choice for the majority of patients. Adding aspirin to this primary choice for up to 4 weeks in patients at especially high ischemic risk would likely prevent atherothrombotic events, but this needs further investigation. Taken together, it is time to adjust our practice and move to dual therapy consisting of a NOAC plus clopidogrel in most patients.

Comparison of scoring systems and outcome of patients admitted to a liver intensive care unit of a tertiary referral centre with severe variceal bleeding.

PubMed

Al-Freah, M A B; Gera, A; Martini, S; McPhail, M J W; Devlin, J; Harrison, P M; Shawcross, D; Abeles, R D; Taylor, N J; Auzinger, G; Bernal, W; Heneghan, M A; Wendon, J A

2014-06-01

Acute variceal haemorrhage (AVH) is associated with significant mortality. To determine outcome and factors associated with hospital mortality (HM) in patients with AVH admitted to intensive care unit (ICU) and to compare outcomes of patients requiring transfer to a tertiary ICU (transfer group, TG) to a local in-patient group (LG). A retrospective study of all adult patients (N = 177) admitted to ICU with AVH from 2000-2008 was performed. Median age was 48 years (16-80). Male represented 58%. Median MELD score was 16 (6-39), SOFA score was 8 (6-11). HM was higher in patients who had severe liver disease or critical illness measured by MELD, SOFA, APACHE II scores and number of failed organs (NFO), P < 0.05. Patients with day-1 lactate ≥ 2 mmol/L had increased HM (P < 0.001). MELD score performed as well as APACHE II, SOFA and NFO (P < 0.001) in predicting HM (AUROC = 0.84, 0.81, 0.79 and 0.82, respectively P > 0.05 for pair wise comparisons). Re-bleeding was associated with increased HM (56.9% vs. 31.6%, P = 0.002). The TG (n = 124) had less severe liver disease and critical illness and consequently had lower HM than local patients (32% vs. 57%, P = 0.002). TG patients with ≥2 endoscopies prior to transfer had increased 6-week mortality (P = 0.03). Time from bleeding to transfer ≥3 days was associated with re-bleeding (OR = 2.290, P = 0.043). MELD score was comparable to ICU prognostic models in predicting mortality. Blood lactate was also predictive of hospital mortality. Delays in referrals and repeated endoscopy were associated with increased re-bleeding and mortality in this group. © 2014 John Wiley & Sons Ltd.

Antiplatelet therapy in PCI

PubMed Central

Fanaroff, Alexander; Rao, Sunil

2018-01-01

Platelets play a key role in mediating stent thrombosis, the major cause of ischemic events in the immediate period following percutaneous coronary intervention (PCI). For this reason, antiplatelet therapy, started at the time of PCI and continued for at least 30 days afterwards, is the cornerstone of antithrombotic therapy after PCI. However, the use of antiplatelet agents increase bleeding risk, with more potent antiplatelet agents further increasing bleeding risk. For this reason, balancing prevention of ischemic events with risk of bleeding is fundamental to the effective use of antiplatelet agents. In the past 5 years, potent and fast-acting P2Y12 inhibitors have been introduced, and have augmented the antiplatelet armamentarium available to interventional cardiologists. In this review, we review the preclinical and clinical data surrounding these new agents, and discuss the significant questions and controversies that still exist regarding the optimal antiplatelet strategy. PMID:28582206

Aspirin Use Prior to Coronary Artery Bypass Grafting Surgery: a Systematic Review.

PubMed

Elbadawi, Ayman; Saad, Marwan; Nairooz, Ramez

2017-02-01

Aspirin use before coronary artery bypass graft (CABG) surgery has been a puzzling question for years. Controversy existed regarding the overall benefits vs. risk of pre-operative aspirin use and was translated to conflicting guidelines from major societies. Observational studies have suggested a reduced mortality with pre-operative aspirin use. A meta-analysis of randomized controlled trials showed increased risk of post-operative bleeding with aspirin, with no associated increased mortality risk. A recent large randomized controlled trial did not find a significant difference in bleeding risk or post-operative mortality with pre-CABG aspirin use. The results of available studies showed a beneficial effect with pre-CABG aspirin use by decreasing thrombotic complications and perioperative myocardial infarction, with an associated adverse risk of bleeding that did not affect mortality rates. Given overall benefit-risk assessment, we are in favor of pre-operative aspirin use in CABG patients.

Risk of gastrointestinal bleeding during anticoagulant treatment.

PubMed

Lanas-Gimeno, Aitor; Lanas, Angel

2017-06-01

Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

Association of Proton Pump Inhibitors with Reduced Risk of Warfarin-related Serious Upper Gastrointestinal Bleeding

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Smalley, Walter E.; Daugherty, James R.; Dupont, William D.; Stein, C. Michael

2016-01-01

Background & Aims Proton-pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective non-steroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. Methods This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow up. The study endpoints were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Results Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% CI, 0.63–0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94–1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84–1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39–0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. Conclusions In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the greatest reduction occurred in patients also taking antiplatelet drugs or NSAIDs. PMID:27639805

Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.

PubMed

Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Smalley, Walter E; Daugherty, James R; Dupont, William D; Stein, C Michael

2016-12-01

Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up. The study end points were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94-1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84-1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39-0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the greatest reduction occurred in patients also taking antiplatelet drugs or NSAIDs. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Clinical epidemiological characteristics and change trend of upper gastrointestinal bleeding over the past 15 years].

PubMed

Wang, Jinping; Cui, Yi; Wang, Jinhui; Chen, Baili; He, Yao; Chen, Minhu

2017-04-25

To investigate the clinical epidemiology change trend of upper gastrointestinal bleeding (UGIB) over the past 15 years. Consecutive patients who was diagnosed as continuous UGIB in the endoscopy center of The First Affiliated Hospital of Sun-Yat University during the period from 1 January 1997 to 31 December 1998 and the period from 1 January 2012 to 31 December 2013 were enrolled in this study. Their gender, age, etiology, ulcer classification, endoscopic treatment and hospitalization mortality were compared between two periods. In periods from 1997 to 1998 and 2012 to 2013, the detection rate of UGIB was 9.99%(928/9 287) and 4.49%(1 092/24 318)(χ 2 =360.089, P=0.000); the percentage of male patients was 73.28%(680/928) and 72.44% (791/1 092) (χ 2 =0.179, P=0.672), and the onset age was (47.3±16.4) years and (51.4±18.2) years (t=9.214, P=0.002) respectively. From 1997 to 1998, the first etiology of UGIB was peptic ulcer bleeding, accounting for 65.2%(605/928)[duodenal ulcer 47.8%(444/928), gastric ulcer 8.3%(77/928), stomal ulcer 2.3%(21/928), compound ulcer 6.8%(63/928)],the second was cancer bleeding(7.0%,65/928), and the third was esophageal and gastric varices bleeding (6.4%,59/928). From 2012 to 2013, peptic ulcer still was the first cause of UGIB, but the ratio obviously decreased to 52.7%(575/1092)(χ 2 =32.467, P=0.000)[duodenal ulcer 31.9%(348/1092), gastric ulcer 9.4%(103/1092), stomal ulcer 2.8%(30/1092), compound ulcer 8.6%(94/1092)]. The decreased ratio of duodenal ulcer bleeding was the main reason (χ 2 =53.724, P=0.000). Esophageal and gastric varices bleeding became the second cause (15.1%,165/1 092, χ 2 =38.976, P=0.000), and cancer was the third cause (9.2%,101/1 092, χ 2 =3.352, P=0.067). The largest increasing amplitude of the onset age was peptic ulcer bleeding [(46.2±16.7) years vs. (51.9±18.9) years, t=-5.548, P=0.000), and the greatest contribution to the amplitude was duodenal ulcer bleeding [(43.4±15.9) years vs. (48.4±19.4) years, t=-3.935, P=0.000], while the onset age of esophageal and gastric varices bleeding [(49.8±14.1) years vs. (48.8±13.9) years, t=0.458, P=0.648] and cancer [(58.4±13.4) years vs. (58.9±16.7) years, t=-0.196, P=0.845] did not change significantly. Compared with the period from 1997 to 1998, the detection rate of high risk peptic ulcer rebleeding (Forrest stage I(a, I(b, II(a and II(b) increased (χ 2 =39.958, P=0.000) in the period from 2012 to 2013. From 1997 to 1998, 54 patients underwent endoscopic treatment, and the achievement ratio of hemostasis was 79.6% (43/54). From 2012 to 2013, 261 patients underwent endoscopic treatment and the achievement ratio of hemostasis was 96.9%(253/261), which was significantly higher (χ 2 =23.287, P=0.000). Compared to the period from 1997 to 1998, more patients with variceal bleeding or non-variceal bleeding received endoscopic treatment in time (39.0% vs. 70.3%, χ 2 =51.930, P=0.000; 3.6% vs. 15.6%, χ 2 =62.292, P=0.000, respectively), and higher ratio of patients staging Forrest stage I(a to II(b also received endoscopic treatment in the period from 2012 to 2013 [27.4%(26/95) vs. 68.5%(111/162), χ 2 =40.739, P=0.000]. More qualified endoscopic hemostatic techniques were used, containing thermocoagulation (0 vs. 15.2%, χ 2 =79.518, P=0.000), hemostatic clip (0 vs. 55.9%, χ 2 =20.879, P=0.000), hemostatic clip combined with thermocoagulation (4.3% vs. 16.4%, χ 2 =5.154, P=0.023), while less single injection was used (87.1% vs. 6.2%, χ 2 =10.420, P=0.001), and single spraying for hemostasis was completely abandoned in the period from 2012 to 2013. The ratio of inpatients undergoing reoperation decreased obviously in the period from 2012 to 2013 [9.3%(86/928) vs. 6.0%(65/1092), χ 2 =7.970, P=0.005], while no significant difference was found in mortality during hospitalization between two periods. Compared with the period from 1997 to1998, the mean onset age of UGIB increased, and the ratio of peptic ulcer bleeding decreased due to the reduction of duodenal ulcer bleeding, the detection rate of high risk peptic ulcer rebleeding increased, the cure rate of endoscopic treatment for UGIB increased, more reasonable and immediate hemostatic methods were used, but overall mortality did not change obviously in the period from 2012 to 2013.

A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study.

PubMed

Hoffmann, Till; Assmann, Alexander; Dierksen, Angelika; Roussel, Elisabeth; Ullrich, Sebastian; Lichtenberg, Artur; Albert, Alexander; Sixt, Stephan

2018-04-18

Although off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. This prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan-Meier estimates. There was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P < .001). The key results were confirmed after adjustment by propensity score-based analyses. When combined with early and specific restoration of hemostatic reserves after cardiac surgery, very low-dose recombinant activated factor VII treatment of refractory bleeding is effective and not associated with any apparent increase in adverse events. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Peptic ulcer bleeding patients with Rockall scores ≥6 are at risk of long-term ulcer rebleeding: A 3.5-year prospective longitudinal study.

PubMed

Yang, Er-Hsiang; Cheng, Hsiu-Chi; Wu, Chung-Tai; Chen, Wei-Ying; Lin, Meng-Ying; Sheu, Bor-Shyang

2018-01-01

Patients with high Rockall scores have increased risk of rebleeding and mortality within 30 days after peptic ulcer bleeding, but long-term outcomes deserve follow-up after cessation of proton pump inhibitors. The paper aimed to validate whether patients with high Rockall scores have more recurrent ulcer bleeding in a 3.5-year longitudinal cohort. Between August 2011 and July 2014, 368 patients with peptic ulcer bleeding were prospectively enrolled after endoscopic hemostasis to receive proton pump inhibitors for at least 8 to 16 weeks. These subjects were categorized into either a Rockall scores ≥6 group (n = 257) or a Rockall scores <6 group (n = 111) and followed up until July of 2015 to assess recurrent ulcer bleeding. The proportion of patients with rebleeding during the 3.5-year follow-up was higher in patients with Rockall scores ≥6 than in those with scores <6 (10.51 vs. 3.63 per 100 person-year, P = 0.004, log-rank test). Among patients with Rockall scores ≥6, activated partial thromboplastin time prolonged ≥1.5-fold (P = 0.045), American Society of Anesthesiologists physical status class ≥III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent factors found to increase rebleeding risk. The cumulative rebleeding rate was higher in patients with Rockall scores ≥6 with more than or equal to any two additional factors than in those with fewer than two additional factors (15.69 vs. 7.63 per 100 person-year, P = 0.012, log-rank test). Patients with Rockall scores ≥6 are at risk of long-term recurrent peptic ulcer bleeding. The risk can be independently increased by the presence of activated partial thromboplastin time prolonged ≥1.5-fold, American Society of Anesthesiologists class ≥III, and gastric ulcer in patients with Rockall scores ≥6. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Independent risk factors of 30-day outcomes in 1264 patients with peptic ulcer bleeding in the USA - large ulcers do worse

PubMed Central

Camus, Marine; Jensen, Dennis M.; Kovacs, Thomas O.; Jensen, Mary Ellen; Markovic, Daniela; Gornbein, Jeffrey

2016-01-01

Background Predictors of worse outcomes (rebleeding, surgery and death) of peptic ulcer bleeding (PUB’s) are essential indicators because of significant morbidity and mortality. rates of PUB’s. However those have been rarely infrequently reported since changes in medical therapy (proton poump inhibitors-PPI) and application of newer endoscopic hemostasis. Aim Our purposes were to determine: 1) independent risk factors of 30-day rebleeding, surgery, and death and 2) whether ulcer size is an independent predictor of major outcomes in patients with severe PUB’s after successful endoscopic hemostasis and treatment with optimal medical (high dose IV PPI) vs. prior treatment (high dose IV histamine 2 antagonists – H2RA’s). Methods A large prospectively followed population of patients hospitalized with severe PUB’s between 1993 and 2011 at two US tertiary care academic medical centers, stratified by stigmata of recent hemorrhage (SRH) was studied. Using multivariable logistic regression analyses, independent risk factors of each outcome (rebleeding, surgery, and death) up to 30 days were analyzed. Effects of medical treatment (H2RA patients 1993–2005 vs. PPI’s 2006–2011) were also analysed. Results 1264 patients were included. For ulcers ≥10mm, the odds of 30-day rebleeding increased 6% per each 10% increase in ulcer size (OR 1.06, 95%CI 1.02–1.10, p=0.0053). Other risk factors of 30-day rebleeding were major SRH, inpatient start of bleeding, and prior GI bleeding. Major SRH and ulcer size ≥10 mm were predictors of 30-day surgery. Risk factors of 30-day death were major SRH, inpatient bleeding, any initial platelet transfusion or fresh frozen plasma transfusion ≥2 units. Among patients with major SRH and outpatient start of bleeding, larger ulcer size was also a risk factor for death (OR 1.08 per 10% increase in ulcer size, 95%CI 1.02–1.14, p=0.0095). Ulcer size was a significant independent variable for both time periods. Conclusions Ulcer size is a risk factor and should be carefully recorded at initial endoscopy to improve patient triage and management. PMID:27000531

Detection of bleeding disorders in Lebanon: outcomes of a pilot programme.

PubMed

Djambas Khayat, C; Samaha, H; Noun, P; Bakhos Asmar, J D; Taher, A; Adib, S; Inati, A; Sakr, S

2014-03-01

To promote management and awareness of bleeding disorders in Lebanon, a pilot programme was launched in 2009 by the Lebanese Hemophilia Association assisted by World Federation of Hemophilia. The aim of this study was to diagnose patients with bleeding disorders and to assess the potential challenges in implementing a screening programme. The pilot project was launched in 26 social health centres in the Bekaa valley. The study tools included the evaluation of the Tossetto Bleeding Score and the Pictorial Bleeding Assessment Chart (PBAC) for menstruation. Persons with a bleeding score higher than 2 and PBAC higher than 185 were eligible for further blood tests including the prothrombin time, partial thromboplastin time, complete blood count, bleeding time and von Willebrand ristocetin cofactor activity. 643 patients were enrolled, of whom 60.6% were women. Overall, 91 persons had an abnormal score. 50 eligible patients were tested: 32 had normal tests, nine new patients with severe Von Willebrand were discovered, 4 had VW:RiCo of 40, 3 prolonged APTT and 2 thrombocytopaenia. There was a clear correlation between the severity of the score and the willingness to perform the tests (P = 0.02). Women were reluctant to participate fully when investigators were men. The probability of adherence to the screening protocol is significantly increased when directed by women health care professional. For patients with milder forms, global screening programmes were neither feasible nor acceptable but those more severely affected have to be identified. Providers are crucial in preselecting patients with blood problems who are not coping well. © 2013 John Wiley & Sons Ltd.

Unplanned Reoperations in Neurosurgical Patients Due to Postoperative Bleeding

PubMed Central

Zheng, Xin-Rui; Chen, Tao; Yang, Yue-Fan; Rao, Wei; Wang, Guan-Ying; Zhang, Shan-Hong; Fei, Zhou

2015-01-01

Abstract The aim of this study is to investigate the incidence of unplanned reoperations from all causes due to bleeding in neurosurgical patients. The medical records of patients who received neurosurgical procedures at our hospital were retrospectively reviewed and data of patients who received reoperations were extracted and summarized. A literature review was conducted of the Medline, Cochrane, EMBASE, and Google Scholar databases up to November 2013. The main outcome measure was the rate of unplanned reoperations due to bleeding. At our hospital, 68 patients with a mean age of 41.5 ± 21.5 years (range, 7 months to 76 years) received an unplanned reoperation. More than 70% of the patients were older than 18 years, 64.7% were males, and 94.1% had cranial surgery. Almost 60% of the patients received >1 blood transfusion (58.8%) after the first surgery. Of the 68 patients, 35 (51.5%) received a second operation due to bleeding. Univariate logistic regression analysis only showed that an increasing time interval between the first and second surgery was associated with a decreased chance of the reoperation being performed due to bleeding (odds ratio [OR] = 0.843, 95% confidence interval [CI]: 0.720–0.987; P = .033). Of 229 studies identified, 5 retrospective reports with a total of 1375 patients were included in the analysis. The rate of reoperations for bleeding in the 5 studies ranged from 4.2% to 31.5%. Employing measures to reduce postoperative bleeding may help reduce the rate of unplanned neurosurgical reoperations. PMID:26061301

Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures.

PubMed

Deutsch, David; Boustière, Christian; Ferrari, Emile; Albaladejo, Pierre; Morange, Pierre-Emmanuel; Benamouzig, Robert

2017-06-01

The use of direct oral anticoagulants (DOACs) was an important step forward in the management of atrial fibrillation and venous thromboembolism (VTE). The DOACs, anti-IIa for dabigatran and anti-Xa for rivaroxaban, apixaban and edoxaban, all have a rapid onset of action and a short half life. There is no need for routine hemostasis testing for treatment monitoring of a DOAC. Compared with vitamin K antagonists (VKAs), DOACs may increase the risk of gastrointestinal bleeding (relative risk 1.25). Withholding the DOAC treatment, evaluating the time of the last intake and estimating the patient's renal function are the first steps in the management of gastrointestinal bleeding. For patients without impaired renal function, achieving low coagulation takes around 24 h after the last intake of a DOAC. The use of DOAC antagonists will be helpful in controlling bleeding in the most severe and urgent situations. Idarucizumab is available for clinical use for dabigatran and andexanet is currently being reviewed by drug agencies for rivaroxaban, apixaban and edoxaban. It is important to assess the bleeding risk associated with the planned procedure, and the patient's renal function before withholding DOAC therapy for a scheduled intervention. It is mandatory to strengthen the local hemostasis strategies in DOAC-treated patients undergoing a therapeutic endoscopic procedure. Resuming or not resuming anticoagulation with a DOAC after bleeding or a risky procedure depends on the thrombotic and bleeding risk as well as the procedure involved. This discussion should always involve the cardiologist and decisions should be taken by a pluridisciplinary team.

Time Trends of Aspirin and Warfarin Use on Stroke and Bleeding Events in Chinese Patients With New-Onset Atrial Fibrillation

PubMed Central

Guo, Yutao; Wang, Hao; Tian, Yingchun; Wang, Yutang

2015-01-01

BACKGROUND: Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population. METHODS: We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF. RESULTS: Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61.9% in 2012 in the latter (P for trend for both, < .005). In the overall cohort, the annual stroke rate was approximately 6% and the annual major bleeding rate was about 1%. Compared with nonantithrombotic therapy, the hazard ratio for ischemic stroke was 0.68 (95% CI, 0.39-1.18) for aspirin and 1.39 (0.54-3.59) for warfarin. CONCLUSIONS: Aspirin use increased among Chinese patients newly diagnosed with AF, with no relationship to the patient’s stroke or bleeding risk. Warfarin use was very low. Given the health-care burden of AF and its complications, our study has major implications for health-care systems in non-Western countries, given the global burden of this common arrhythmia. PMID:25501045

Prediction and Reduction of Noise in Pneumatic Bleed Valves

NASA Astrophysics Data System (ADS)

Taghavi Nezhad, Shervin

This study investigates numerically the fluid mechanics and acoustics of pneumatic bleed valves used in turbofan engines. The goal is to characterized the fundamental processes of noise generation and devise strategies for noise reduction. Three different methods are employed for both analysis and redesign of the bleed valve to reduce noise. The bleed valve noise problem is carefully divided into multiple smaller problems. For large separations and tonal noises, the unsteady Reynolds-Averaged Navier-Stokes (URANS) method is utilized. This method is also applied in the re-designing of the bleed valve geometry. For the bleed valve muffler, which is comprised of perforated plates and a honeycomb, a Reynolds-Averaged Navier-Stokes (RANS) method combined with a simplified acoustic analogy is used. The original muffler design is modified to improve noise attenuation. Finally, for sound scattering through perforated plates, a fully implicit linearized Euler solver is developed. The problem of sound interaction with perforated plates is studied from two perspectives. In the first study the effect of high--speed mean flow is considered and it is shown that at Strouhal numbers of around 0.2-0.25 there is an increase in transmitted incident sound. In the second part, the interaction of holes in two--dimensional perforated plates is investigated using three different configurations. The study demonstrates that the hole interaction has a significant impact on sound attenuation, especially at high frequencies.

Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis.

PubMed

Olde Damink, S W M; Dejong, C H C; Jalan, R

2009-04-15

Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life-threatening complications. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and contains high amounts of leucine and valine. UGI bleed therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce net catabolism. To describe the hyperammonaemic and catabolic consequences of UGI bleeding in cirrhosis. A semi-structured literature search was performed using PubMed and article references. It has recently been proven that ('simulation of ') a UGI bleed in patients with cirrhosis leads to impaired protein synthesis that can be restored by intravenous infusion of isoleucine. This may have therapeutic implications for the function of rapidly dividing cells and short half-life proteins such as clotting factors. Renal and small bowel ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia that resulted from a UGI bleed. This provides an explanation for the therapeutic failure of the current clinical therapies that are aimed at large bowel-derived ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis. New pharmacological therapies to diminish postbleeding hyperammonaemia should target the altered inter-organ ammonia metabolism and promote ammonia excretion and/or increase the excretion of precursors of ammoniagenesis, e.g. l-ornithine-phenylacetate.

Playing prosocial video games increases empathy and decreases schadenfreude.

PubMed

Greitemeyer, Tobias; Osswald, Silvia; Brauer, Markus

2010-12-01

Past research provided abundant evidence that exposure to violent video games increases aggressive tendencies and decreases prosocial tendencies. In contrast, research on the effects of exposure to prosocial video games has been relatively sparse. The present research found support for the hypothesis that exposure to prosocial video games is positively related to prosocial affect and negatively related to antisocial affect. More specifically, two studies revealed that playing a prosocial (relative to a neutral) video game increased interpersonal empathy and decreased reported pleasure at another's misfortune (i.e., schadenfreude). These results lend further credence to the predictive validity of the General Learning Model (Buckley & Anderson, 2006) for the effects of media exposure on social tendencies.

Increased recombinant activated factor VII use and need for surgical reexploration following a switch from aprotinin to epsilon-aminocaproic acid in infant cardiac surgery.

PubMed

Scott, John P; Costigan, Daniel J; Hoffman, George M; Simpson, Pippa M; Dasgupta, Mahua; Punzalan, Rowena; Berens, Richard J; Tweddell, James S; Stuth, Eckehard A E

2014-05-01

To evaluate whether conversion from aprotinin to epsilon-aminocaproic acid (EACA) during infant cardiac surgery was associated with increased perioperative bleeding. Structured retrospective chart review. University-affiliated large congenital cardiac surgery program. Records from 145 infants (age < 1 yr) receiving aprotinin as antifibrinolytic therapy for cardiac surgery between 6/1/2006 and 12/31/2006 were compared with a cohort of infants receiving EACA for cardiac surgery between 6/1/2008 and 12/31/2008. Sixty-eight infants received aprotinin and 77 infants received EACA. Measured indicators of perioperative bleeding included transfusion volumes, recombinant activated clotting factor VIIa (rFVIIa) administration, need for reexploration, and perioperative chest tube output. EACA treated patients received significantly more rFVIIa for uncontrolled bleeding (19/77 [25%] vs 3/68 [4%]; P < 0.001) and required surgical reexploration more frequently (21/77 [27%] vs 7/68 [10%]; P = 0.01]. Median (25th-75th percentiles) intraoperative platelet transfusion requirements were also increased after the switch to EACA (28 mL [0-58 mL] vs 0 mL [0 mL - 34.5 mL]), but this difference did not reach statistical significance (P = 0.06). Bleeding in infant cardiac surgery increased following the change in antifibrinolytic therapy from aprotinin to EACA. Given the potential for major harm, especially thrombotic complications, from rFVIIa use, prospective studies examining the safety of postcardiopulmonary bypass rFVIIa administration in infants are necessary before the routine off-label use may be recommended. Copyright © 2014 Elsevier Inc. All rights reserved.

[Endovascular interventions for multiple trauma].

PubMed

Kinstner, C; Funovics, M

2014-09-01

In recent years interventional radiology has significantly changed the management of injured patients with multiple trauma. Currently nearly all vessels can be reached within a reasonably short time with the help of specially preshaped catheters and guide wires to achieve bleeding control of arterial und venous bleeding. Whereas bleeding control formerly required extensive open surgery, current interventional methods allow temporary vessel occlusion (occlusion balloons), permanent embolization and stenting. In injured patients with multiple trauma preinterventional procedural planning is performed with the help of multidetector computed tomography whenever possible. Interventional radiology not only allows minimization of therapeutic trauma but also a considerably shorter treatment time. Interventional bleeding control has developed into a standard method in the management of vascular trauma of the chest and abdomen as well as in vascular injuries of the upper and lower extremities when open surgical access is associated with increased risk. Additionally, pelvic trauma, vascular trauma of the superior thoracic aperture and parenchymal arterial lacerations of organs that can be at least partially preserved are primarily managed by interventional methods. In an interdisciplinary setting interventional radiology provides a safe and efficient means of rapid bleeding control in nearly all vascular territories in addition to open surgical access.

Quality-by-design (QbD): effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powder measured by the ASTM D 6940-04 segregation tester.

PubMed

Xie, Lin; Wu, Huiquan; Shen, Meiyu; Augsburger, Larry L; Lyon, Robbe C; Khan, Mansoor A; Hussain, Ajaz S; Hoag, Stephen W

2008-10-01

The objective of this study was to examine the effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powders measured by the ASTM D 6940-04 segregation tester using design of experiments (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The segregation tendency of a blend was determined by measuring the last/first (L/F) ratio, the ratio of aspirin concentrations between the first and last samples discharged from the tester. A 2(2) factorial design was used to determine the effects of measurement parameters [amount of material loaded (W), number of segregation cycles] with number of replicates 6. ANOVA showed that W was a critical parameter for segregation testing. The L/F value deviated further from 1 (greater segregation tendency) with increasing W. A 2(3) full factorial design was used to assess the effects of formulation variables: grade of ASP (unmilled, milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that the grade of ASP was the main effect contributing to segregation tendency. Principal Component Regression Analysis established a correlation between L/F and the physical properties of the blend related to ASP and MCC, the ASP/MCC particle size ratio (PSR) and powder cohesion. The physical properties of the blend related to density and flow were not influenced by the grade of ASP and were not related to the segregation tendency of the blend. The direct relationship between L/F and PSR was determined by univariate analysis. Segregation tendency increased as the ASP to MCC particle size increased. This study highlighted critical test parameters for segregation testing and identified critical physical properties of the blends that influence segregation tendency. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries.

PubMed

Mo, Chen; Sun, Gang; Lu, Ming-Liang; Zhang, Li; Wang, Yan-Zhi; Sun, Xi; Yang, Yun-Sheng

2015-05-07

To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and bleeding. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to December 2013, and checked conference abstracts of randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI events (hemorrhage, ulcer, perforation, or obstruction) in patients taking LDA. The preventive effects of PPIs were compared with the control group [taking placebo, a cytoprotective agent, or an H2 receptor antagonist (H2RA)] in LDA-associated upper GI injuries. The meta-analysis was performed using RevMan 5.1 software. We evaluated 8780 participants in 10 RCTs. The meta-analysis showed that PPIs decreased the risk of LDA-associated upper GI ulcers (OR = 0.16; 95%CI: 0.12-0.23) and bleeding (OR = 0.27; 95%CI: 0.16-0.43) compared with control. For patients treated with dual anti-platelet therapy of LDA and clopidogrel, PPIs were able to prevent the LDA-associated GI bleeding (OR = 0.36; 95%CI: 0.15-0.87) without increasing the risk of major adverse cardiovascular events (MACE) (OR = 1.00; 95%CI: 0.76-1.31). PPIs were superior to H2RA in prevention of LDA-associated GI ulcers (OR = 0.12; 95%CI: 0.02-0.65) and bleeding (OR = 0.32; 95%CI: 0.13-0.79). PPIs are effective in preventing LDA-associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and clopidogrel did not increase the risk of MACE.

Haemophilia A carriers experience reduced health-related quality of life.

PubMed

Gilbert, L; Paroskie, A; Gailani, D; Debaun, M R; Sidonio, R F

2015-11-01

Haemophilia A is an X-linked recessive bleeding disorder that primarily affects males. Emerging data support evidence for increased bleeding in female haemophilia A carriers despite factor VIII activity within the normal range. Data regarding the effect of increased bleeding on health-related quality of life (HR-QOL) in haemophilia A carriers is sparse. We tested the hypothesis that haemophilia A carriers have reduced HR-QOL related to bleeding symptoms. We conducted a cross-sectional study at Vanderbilt University. Case subjects were obligate or genetically verified haemophilia A carriers age 18-60 years. Control subjects were mothers of children with cancer who receive care at the Vanderbilt paediatric haematology-oncology clinic. Trained interviewers administered the Rand 36-Item Health Survey 1.0, a validated questionnaire evaluating eight health concepts that may affect HR-QOL, to each study participant. Mann-Whitney U-tests were used to compare median scores for the eight health domains between the case and control groups. Forty-two haemophilia A carriers and 36 control subjects were included in analyses. Haemophilia A carriers had significantly lower median scores for the domains of 'Pain' (73.75 vs. 90; P = 0.02) and 'General health' (75 vs. 85; P = 0.01) compared to control subjects. Haemophilia A carriers in our study demonstrated significantly lower median scores on the Rand 36-item Health Survey 1.0 in the domains of 'Pain' and 'General Health' compared to women in the control group. Our findings highlight the need for further investigation of the effect of bleeding on HR-QOL in this population. © 2015 John Wiley & Sons Ltd.

Impaired thrombin generation and fibrin clot formation in patients with dilutional coagulopathy during major surgery.

PubMed

Schols, S E M; Lancé, M D; Feijge, M A H; Damoiseaux, J; Marcus, M A; Hamulyák, K; Ten Cate, H; Heemskerk, J W M; van Pampus, E C M

2010-02-01

Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.

Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project

PubMed Central

Soucie, J. Michael; Gill, Joan Cox

2017-01-01

This analysis of the US Hemophilia Treatment Center Network and the Centers for Disease Control and Prevention surveillance registry assessed trends in prophylaxis use and its impact on key indicators of arthropathy across the life-span among participants with severe hemophilia A. Data on demographics, clinical characteristics, and outcomes were collected prospectively between 1999 and 2010 at annual clinical visits to 134 hemophilia treatment centers. Trends in treatment and outcomes were evaluated using cross-sectional and longitudinal analyses. Data analyzed included 26 614 visits for 6196 males; mean age at first registry visit was 17.7 years; and median was 14 (range, 2 to 69). During this time, prophylaxis use increased from 31% to 59% overall, and by 2010, 75% of children and youths <20 years were on prophylaxis. On cross-sectional analysis, bleeding rates decreased dramatically for the entire population (P < .001) in parallel with increased prophylaxis usage, possibly because frequent bleeders adopted prophylaxis. Joint bleeding decreased proportionately with prophylaxis (22%) and nonprophylaxis (23%), and target joints decreased more with prophylaxis (80% vs 61%). Joint, total, and target joint bleeding on prophylaxis were 33%, 41%, and 27%, respectively, compared with nonprophylaxis. On longitudinal analysis of individuals over time, prophylaxis predicted decreased bleeding at any age (P < .001), but only prophylaxis initiation prior to age 4 years and nonobesity predicted preservation of joint motion (P < .001 for each). Using a national registry, care providers in a specialized health care network for a rare disorder were able to detect and track trends in outcomes over time. PMID:28183693

Abnormal uterine bleeding in VTE patients treated with rivaroxaban compared to vitamin K antagonists.

PubMed

De Crem, Nico; Peerlinck, Kathelijne; Vanassche, Thomas; Vanheule, Kristine; Debaveye, Barbara; Middeldorp, Saskia; Verhamme, Peter; Peetermans, Marijke

2015-10-01

Rivaroxaban is a convenient oral anticoagulant for patients with venous thromboembolism (VTE). The impact of rivaroxaban and vitamin K antagonists (VKAs) on abnormal uterine bleeding (AUB) in real life has not been previously explored. We performed a single-center retrospective study on AUB in female VTE patients of reproductive age who were treated with either rivaroxaban or VKAs. Questionnaire results were available for 52 patients in each treatment group. Approximately two thirds of all women reported AUB after initiation of anticoagulant therapy. Patients using rivaroxaban were more likely to experience prolonged (>8days) menstrual bleeding (27 % vs. 8.3%, P=0.017). Rivaroxaban treatment increased the duration of menstrual bleeding from median 5 (IQR 3.5-6.0) days before start of treatment to 6 (IQR 4.1-8.9) days (P<0.001). VKA treatment did not lead to significant prolongation of the menstrual period. Patients on rivaroxaban more frequently reported an unscheduled contact with a physician for AUB than women using VKAs (41% vs. 25%, P=0.096). They also reported increased need for menorrhagia-related medical or surgical intervention (25% vs. 7.7%, P=0.032) and had more adaptations of anticoagulant therapy (15% vs. 1.9%, P=0.031). AUB is frequent after initiation of anticoagulant therapy for acute symptomatic VTE. Compared to VKAs, rivaroxaban was associated with prolonged menstrual bleeding and more medical interventions and adaptation of anticoagulant treatment for AUB. These data can guide proactive discussion with patients starting anticoagulant therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduced hemoglobin and increased C-reactive protein are associated with upper gastrointestinal bleeding.

PubMed

Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Togawa, Akira; Shirai, Yoshinori; Ichiki, Noboru; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Sueishi, Makoto

2014-02-07

To investigate the early upper gastrointestinal endoscopy (endoscopy) significantly reduces mortality resulting from upper gastrointestinal (GI) bleeding. Upper GI bleeding was defined as 1a, 1b, 2a, and 2b according to the Forrest classification. The hemoglobin (Hb), and C-reactive protein (CRP) were examined at around the day of endoscopy and 3 mo prior to endoscopy. The rate of change was calculated as follows: (the result of blood examination on the day of endoscopy - the results of blood examination 3 mo prior to endoscopy)/(results of blood examination 3 mo prior to endoscopy). Receiver operating characteristic curves were created to determine threshold values. Seventy-nine men and 77 women were enrolled. There were 17 patients with upper GI bleeding: 12 with a gastric ulcer, 3 with a duodenal ulcer, 1 with an acute gastric mucosal lesion, and 1 with gastric cancer. The area under the curve (AUC), threshold, sensitivity, and specificity of Hb around the day of endoscopy were 0.902, 11.7 g/dL, 94.1%, and 77.1%, respectively, while those of CRP were 0.722, 0.5 mg/dL, 70.5%, and 73%, respectively. The AUC, threshold, sensitivity, and specificity of the rate of change of Hb were 0.851, -21.3%, 76.4%, and 82.6%, respectively, while those of CRP were 0.901, 100%, 100%, and 82.5%, respectively. Predictors for upper GI bleeding were Hb < 11.7 g/dL, reduction rate in the Hb > 21.3% and an increase in the CRP > 100%, 3 mo before endoscopy.

Mechanisms of Normal and Abnormal Endometrial Bleeding

PubMed Central

Lockwood, Charles J.

2011-01-01

Expression of tissue factor (TF), the primary initiator of coagulation, is enhanced in decidualized human endometrial stromal cells (HESC) during the progesterone-dominated luteal phase. Progesterone also augments a second HESC hemostatic factor, plasminogen activator inhibitor-1 (PAI-1). In contrast, progestins inhibit HESC matrix metalloproteinase (MMP)-1, 3 and 9 expression to stabilize endometrial stromal and vascular extracellular matrix. Through these mechanisms decidualized endometrium is rendered both hemostatic and resistant to excess trophoblast invasion in the mid-luteal phase and throughout gestation to prevent hemorrhage and accreta. In non-fertile cycles, progesterone withdrawal results in decreased HESC TF and PAI-expression and increased MMP activity and inflammatory cytokine production promoting the controlled hemorrhage of menstruation and related tissue sloughing. In contrast to these well ordered biochemical processes, unpredictable endometrial bleeding associated with anovulation reflects absence of progestational effects on TF, PAI-1 and MMP activity as well as unrestrained angiogenesis rendering the endometrium non-hemostatic, proteolytic and highly vascular. Abnormal bleeding associated with long-term progestin-only contraceptives results not from impaired hemostasis but from unrestrained angiogenesis leading to large fragile endometrial vessels. This abnormal angiogenesis reflects progestational inhibition of endometrial blood flow promoting local hypoxia and generation of reactive oxygen species that increase production of angiogenic factors such as vascular endothelial growth factor (VEGF) in HESCs and Angiopoietin-2 (Ang-2) in endometrial endothelial cells while decreasing HESC expression of angiostatic, Ang-1. The resulting vessel fragility promotes bleeding. Aberrant angiogenesis also underlies abnormal bleeding associated with myomas and endometrial polyps however there are gaps in our understanding of this pathology. PMID:21499503

Effect of kaolin addition on the performance of controlled low-strength material using industrial waste incineration bottom ash.

PubMed

Naganathan, Sivakumar; Razak, Hashim Abdul; Hamid, Siti Nadzriah Abdul

2010-09-01

Incineration of industrial waste produces large quantities of bottom ash which are normally sent to secured landfill, but is not a sustainable solution. Use of bottom ash in engineering applications will contribute to sustainability and generate revenue. One way of using the industrial waste incineration bottom ash is in controlled low-strength material (CLSM). Use of bottom ash in CLSM has problems related to bleeding and excessive strength development and so an additive has to be used to control bleeding and strength development. The main objective of this research is to study the effect of kaolin addition on the performance of CLSM made using industrial waste incineration bottom ash. CLSM mixes were made with bottom ash, cement, and refined kaolin. Various tests were performed on the CLSM in fresh and hardened states including compressive strength, water absorption, California bearing ratio (CBR) and the tests for concentration of leachable substances on the bleed and leachate. The compressive strength of CLSM tested ranged from 0.11 to 9.86 MPa. CBR values ranged from 6 to 46, and water absorption values from 12 to 36%. It was shown that the addition of kaolin delayed the initial setting time of CLSM mixtures, reduced bleeding, lowered the compressive strength, and increased the values of water absorption, sorption, and initial surface absorption. The CLSM tested did not have corrosivity. It was shown that the hardened CLSM was non hazardous, and the addition of kaolin increased the concentration of heavy metals and salts in the bleed and leachate.

Abnormal Uterine Bleeding

MedlinePlus

... abnormal uterine bleeding? Abnormal uterine bleeding is any heavy or unusual bleeding from the uterus (through your ... one symptom of abnormal uterine bleeding. Having extremely heavy bleeding during your period can also be considered ...

Perioperative Care of a Patient with Refractory Idiopathic Thrombocytopenic Purpura Undergoing Total Knee Arthroplasty

PubMed Central

Gudimetla, Veera; Stewart, Andrew; Luscombe, Karen L; Charalambous, Charalambos P

2012-01-01

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement. PMID:23269964

Flow in a planar convergent-divergent nozzle

NASA Astrophysics Data System (ADS)

Kotteda, V. M. K.; Mittal, S.

2017-05-01

Flow in a convergent-divergent nozzle is studied for pressure ratios (NPR) of 1-11 and exit-to-throat area ratios of 1.2 to 2.0. The unsteady compressible Navier-Stokes equations along with the Spalart-Allmaras turbulence model are solved using a stabilized finite element method in two dimensions. Asymmetric flow is observed at moderate NPR. The side loads due to the flow asymmetry increase with increases in NPR and area ratio. Various flow regimes that are possible in the entire parameter space are identified. The introduction of boundary layer bleed results in steady and symmetric flow conditions at all NPR. Consequently, the nozzle does not experience a lateral force for any NPR. Application of bleed leads to a significant downstream shift in the shock location at low to moderate NPR. Compared to no-bleed, the nozzle experiences a loss of thrust in this regime. The thrust performance for {NPR} > 6 is, however, unaffected by bleed. The effect of nozzle geometry on the flow at various NPR is studied. Four different geometries with the same area ratio and nozzle length are considered. These geometries differ from each other in terms of the nozzle surface profile, including the discontinuity in slope of the surface. Barring some minor differences at low to moderate NPR, the flow is similar for all the geometries considered.

Pharmacological interventions for stress ulcer prophylaxis in critically ill patients: a mixed treatment comparison network meta-analysis and a recursive cumulative meta-analysis.

PubMed

Sridharan, Kannan; Sivaramakrishnan, Gowri; Gnanaraj, Jerome

2018-02-01

Proton pump inhibitors (PPI), histamine-2 receptor antagonists (H2RA), sucralfate and antacids are the commonly administered agents for stress ulcer prophylaxis (SUP) in critically ill patients. The authors of this paper have conducted a network meta-analysis to compare the efficacy of these agents in SUP. Electronic databases were searched for randomized controlled trials, cohort studies and conference abstracts for studies comparing a SUP agent in critically ill patients to another active SUP agent or placebo. Overt, occult and clinically significant upper gastro-intestinal (UGI) bleeding, all-cause mortality, pneumonia, gastric colonization and ICU length of stay were considered as the outcome measures. A random effects model was used to generate pooled estimates. A total of 53 studies (4258 participants) were included. The pooled estimates were in favor of PPI and sucralfate for the overt UGI bleeding. PPI and H2RA bolus were associated with increased risk of gastric colonization and pneumonia. SUP in critically ill patients was not associated with any benefit with regard to clinically significant bleeding episodes. However, PPI and sucralfate significantly reduces overt UGI bleeding. On the contrary, PPI and H2RA bolus are associated with an increased risk of gastric colonization and pneumonia.

Effects of dietary fish oil on serum lipids and blood coagulation in peritoneal dialysis patients.

PubMed

Lempert, K D; Rogers, J S; Albrink, M J

1988-02-01

The effects of a daily fish oil supplement rich in eicosapentaenoic acid were studied in 11 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Serum lipids, platelet aggregation studies, and template bleeding times were determined before and after 4 weeks of fish oil treatment. The lipid studies were repeated approximately 20 weeks after stopping fish oil supplement. At the end of the treatment period, serum triglycerides (mean +/- SEM) decreased from 297 +/- 42 to 211 +/- 29 mg/dL (P less than .01), high density lipoprotein (HDL) cholesterol fell from 45 +/- 3 to 41 +/- 3 mg/dL (P less than .05), and low density lipoprotein (LDL) cholesterol increased from 172 +/- 16 to 208 +/- 19 mg/dL (P less than .05). After discontinuing the fish oil supplement, the triglycerides increased to 278 +/- 39 mg/dL, which was no different than the value before fish oil treatment. No significant changes occurred in template bleeding time (TBT), platelet count, hematocrit, or platelet aggregation response. Clinically important uremic bleeding was not apparent. We conclude that in CAPD patients a fish oil supplement favorably effects hypertriglyceridemia and can be ingested without promoting uremic bleeding. The likely beneficial impact on atherogenesis resulting from the lowering of the triglycerides may, however, be counteracted by concomitant changes in HDL- and LDL-cholesterol.

Development of a shared decision-making tool to assist patients and clinicians with decisions on oral anticoagulant treatment for atrial fibrillation.

PubMed

Kaiser, Karen; Cheng, Wendy Y; Jensen, Sally; Clayman, Marla L; Thappa, Andrew; Schwiep, Frances; Chawla, Anita; Goldberger, Jeffrey J; Col, Nananda; Schein, Jeff

2015-12-01

Decision aids (DAs) are increasingly used to operationalize shared decision-making (SDM) but their development is not often described. Decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) involve a trade-off between lowering stroke risk and increasing OAC-associated bleeding risk, and consideration of how treatment affects lifestyle. The benefits and risks of OACs hinge upon a patient's risk factors for stroke and bleeding and how they value these outcomes. We present the development of a DA about AF that estimates patients' risks for stroke and bleeding and assesses their preferences for outcomes. Based on a literature review and expert discussions, we identified stroke and major bleeding risk prediction models and embedded them into risk assessment modules. We identified the most important factors in choosing OAC treatment (warfarin used as the default reference OAC) through focus group discussions with AF patients who had used warfarin and clinician interviews. We then designed preference assessment and introductory modules accordingly. We integrated these modules into a prototype AF SDM tool and evaluated its usability through interviews. Our tool included four modules: (1) introduction to AF and OAC treatment risks and benefits; (2) stroke risk assessment; (3) bleeding risk assessment; and (4) preference assessment. Interactive risk calculators estimated patient-specific stroke and bleeding risks; graphics were developed to communicate these risks. After cognitive interviews, the content was improved. The final AF tool calculates patient-specific risks and benefits of OAC treatment and couples these estimates with patient preferences to improve clinical decision-making. The AF SDM tool may help patients choose whether OAC treatment is best for them and represents a patient-centered, integrative approach to educate patients on the benefits and risks of OAC treatment. Future research is needed to evaluate this tool in a real-world setting. The development process presented can be applied to similar SDM tools.

Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial.

PubMed

Kato, Eri Toda; Giugliano, Robert P; Ruff, Christian T; Koretsune, Yukihiro; Yamashita, Takeshi; Kiss, Robert Gabor; Nordio, Francesco; Murphy, Sabina A; Kimura, Tetsuya; Jin, James; Lanz, Hans; Mercuri, Michele; Braunwald, Eugene; Antman, Elliott M

2016-05-20

Elderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF-TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age. Twenty-one thousand one-hundred and five patients enrolled in the ENGAGE AF-TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P<0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups (Ptrend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66-1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70-0.99]). The absolute risk difference in major bleeding (-82 events/10 000 pt-yrs) and in intracranial hemorrhage (-73 events/10 000 pt-yrs) both favored edoxaban over warfarin in older patients. Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

PubMed

Breivik, H; Bang, U; Jalonen, J; Vigfússon, G; Alahuhta, S; Lagerkranser, M

2010-01-01

Central neuraxial blocks (CNBs) for surgery and analgesia are an important part of anaesthesia practice in the Nordic countries. More active thromboprophylaxis with potent antihaemostatic drugs has increased the risk of bleeding into the spinal canal. National guidelines for minimizing this risk in patients who benefit from such blocks vary in their recommendations for safe practice. The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) appointed a task force of experts to establish a Nordic consensus on recommendations for best clinical practice in providing effective and safe CNBs in patients with an increased risk of bleeding. We performed a literature search and expert evaluation of evidence for (1) the possible benefits of CNBs on the outcome of anaesthesia and surgery, for (2) risks of spinal bleeding from hereditary and acquired bleeding disorders and antihaemostatic drugs used in surgical patients for thromboprophylaxis, for (3) risk evaluation in published case reports, and for (4) recommendations in published national guidelines. Proposals from the taskforce were available for feedback on the SSAI web-page during the summer of 2008. Neuraxial blocks can improve comfort and reduce morbidity (strong evidence) and mortality (moderate evidence) after surgical procedures. Haemostatic disorders, antihaemostatic drugs, anatomical abnormalities of the spine and spinal blood vessels, elderly patients, and renal and hepatic impairment are risk factors for spinal bleeding (strong evidence). Published national guidelines are mainly based on experts' opinions (weak evidence). The task force reached a consensus on Nordic guidelines, mainly based on our experts' opinions, but we acknowledge different practices in heparinization during vascular surgery and peri-operative administration of non-steroidal anti-inflammatory drugs during neuraxial blocks. Experts from the five Nordic countries offer consensus recommendations for safe clinical practice of neuraxial blocks and how to minimize the risks of serious complications from spinal bleeding. A brief version of the recommendations is available on http://www.ssai.info.

Normal tissue complication probability (NTCP) models for late rectal bleeding, stool frequency and fecal incontinence after radiotherapy in prostate cancer patients.

PubMed

Schaake, Wouter; van der Schaaf, Arjen; van Dijk, Lisanne V; Bongaerts, Alfons H H; van den Bergh, Alfons C M; Langendijk, Johannes A

2016-06-01

Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects. The study sample was composed of 262 patients with localized or locally advanced prostate cancer (stage T1-3). Anorectal toxicity was prospectively assessed using a standardized follow-up program. Different anatomical subregions within and around the anorectum were delineated. A LASSO logistic regression analysis was used to analyze dose volume effects on toxicity. In the univariable analysis, rectal bleeding, increase in stool frequency and fecal incontinence were significantly associated with a large number of dosimetric parameters. The collinearity between these predictors was high (VIF>5). In the multivariable model, rectal bleeding was associated with the anorectum (V70) and anticoagulant use, fecal incontinence was associated with the external sphincter (V15) and the iliococcygeal muscle (V55). Finally, increase in stool frequency was associated with the iliococcygeal muscle (V45) and the levator ani (V40). No significant associations were found for rectal pain. Different anorectal side effects are associated with different anatomical substructures within and around the anorectum. The dosimetric variables associated with these side effects can be used to optimize radiotherapy treatment planning aiming at prevention of specific side effects and to estimate the benefit of new radiation technologies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acute on chronic gastrointestinal bleeding: a unique clinical entity.

PubMed

Rockey, Don C; Hafemeister, Adam C; Reisch, Joan S

2017-06-01

Gastrointestinal bleeding is defined in temporal-spatial terms-as acute or chronic, and/or by its location in the gastrointestinal tract. Here, we define a distinct type of bleeding, which we have coined 'acute on chronic' gastrointestinal bleeding. We prospectively identified all patients who underwent endoscopic evaluation for any form of gastrointestinal bleeding at a University Hospital. Acute on chronic bleeding was defined as the presence of new symptoms or signs of acute bleeding in the setting of chronic bleeding, documented as iron deficiency anemia. Bleeding lesions were categorized using previously established criteria. We identified a total of 776, 254, and 430 patients with acute, chronic, or acute on chronic bleeding, respectively. In patients with acute on chronic gastrointestinal bleeding, lesions were most commonly identified in esophagus (28%), colon and rectum (27%), and stomach (21%) (p<0.0001 vs locations for acute or chronic bleeding). In those specifically with acute on chronic upper gastrointestinal bleeding (n=260), bleeding was most commonly due to portal hypertensive lesions, identified in 47% of subjects compared with 29% of acute and 25% of chronic bleeders, (p<0.001). In all patients with acute on chronic bleeding, 30-day mortality was less than that after acute bleeding alone (2% (10/430) vs 7% (54/776), respectively, p<0.001). Acute on chronic gastrointestinal bleeding is common, and in patients with upper gastrointestinal bleeding was most often a result of portal hypertensive upper gastrointestinal tract pathology. Reduced mortality in patients with acute on chronic gastrointestinal bleeding compared with those with acute bleeding raises the possibility of an adaptive response. Copyright © 2017 American Federation for Medical Research.

Cooling system with compressor bleed and ambient air for gas turbine engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marsh, Jan H.; Marra, John J.

A cooling system for a turbine engine for directing cooling fluids from a compressor to a turbine blade cooling fluid supply and from an ambient air source to the turbine blade cooling fluid supply to supply cooling fluids to one or more airfoils of a rotor assembly is disclosed. The cooling system may include a compressor bleed conduit extending from a compressor to the turbine blade cooling fluid supply that provides cooling fluid to at least one turbine blade. The compressor bleed conduit may include an upstream section and a downstream section whereby the upstream section exhausts compressed bleed airmore » through an outlet into the downstream section through which ambient air passes. The outlet of the upstream section may be generally aligned with a flow of ambient air flowing in the downstream section. As such, the compressed air increases the flow of ambient air to the turbine blade cooling fluid supply.« less

Upper gastrointestinal bleeding: an ammoniagenic and catabolic event due to the total absence of isoleucine in the haemoglobin molecule.

PubMed

Olde Damink, S W; Dejong, C H; Deutz, N E; van Berlo, C L; Soeters, P B

1999-06-01

Upper gastrointestinal bleeding causes increased urea concentrations in patients with normal liver function and high ammonia concentrations in patients with impaired liver function. This ammoniagenesis may precipitate encephalopathy. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and has high amounts of leucine and valine. Upper gastrointestinal bleeding therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce a cascade of events culminating in net catabolism. This may influence the function of rapidly dividing cells and short half-life proteins. We hypothesize that, following a variceal bleed in a cirrhotic patient, the lack of isoleucine in blood protein is the cause of the exaggerated ammoniagenesis and catabolism. We propose that intravenous administration of isoleucine may serve as a simple therapeutic that transforms blood protein in a balanced protein, resulting in only a short-lived rise in ammonia and urea production, and preventing interference with protein synthesis.

Association Between Use of Non–Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation

PubMed Central

Chang, Shang-Hung; Chou, I-Jun; Yeh, Yung-Hsin; Chiou, Meng-Jiun; Wen, Ming-Shien; Kuo, Chi-Tai; See, Lai-Chu

2017-01-01

Importance Non–vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016. Exposures NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin. Main Outcomes and Measures Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. Results Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P < .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone. Conclusions and Relevance Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs. PMID:28973247

Geographic information system and multilevel analysis: gingival status among 12-year-old schoolchildren in São Paulo, Brazil.

PubMed

Pereira, Stela Márcia; Pardi, Vanessa; Cortellazzi, Karine L; Ambrosano, Glaucia Maria Bovi; Vettorazzi, Carlos Alberto; Ferraz, Sílvio F B; Meneghim, Marcelo de Castro; Pereira, Antonio Carlos

2014-02-01

To evaluate gingival and calculus status among schoolchildren 12 years of age using a geographic information system and multilevel analysis. A total of 1 002 schoolchildren were selected from 18 municipal districts by means of cluster sampling, from among 25 public and private schools in Piracicaba, São Paulo, Brazil, in 2005. Examinations were carried out by a single calibrated examiner utilizing the criteria of the World Health Organization, as well as the Community Periodontal Index. Social, economic, and behavioral variables were recorded with the use of a questionnaire and were used in the individual analysis (first level). The variables "percentage of heads of families without income" and "percentage of illiterate heads of families" were used in the contextual analysis (second level). A geographic information system was constructed for mapping the distribution of gingival bleeding. The variables were visually distinguished in the maps and demonstrated a tendency toward better gingival health in the central areas of the city, which are recognized as more privileged. On the contextual level, only the "percentage of illiterate heads of families" was significantly associated to gingival bleeding. The study confirms better oral health status among schoolchildren from privileged families, but does not confirm the data regarding "income." The individuals from areas in which the heads of family did not have income were not associated to a higher prevalence of gingival problems. This suggests that these individuals are reasonably protected from the impact of social privation due to the actions of public health care services in the municipality.

No Evidence of Purported Lunar Effect on Hospital Admission Rates or Birth Rates

PubMed Central

Margot, Jean-Luc

2015-01-01

Background Studies indicate that a fraction of nursing professionals believe in a “lunar effect”—a purported correlation between the phases of the Earth’s moon and human affairs, such as birth rates, blood loss, or fertility. Purpose This article addresses some of the methodological errors and cognitive biases that can explain the human tendency of perceiving a lunar effect where there is none. Approach This article reviews basic standards of evidence and, using an example from the published literature, illustrates how disregarding these standards can lead to erroneous conclusions. Findings Román, Soriano, Fuentes, Gálvez, and Fernández (2004) suggested that the number of hospital admissions related to gastrointestinal bleeding was somehow influenced by the phases of the Earth’s moon. Specifically, the authors claimed that the rate of hospital admissions to their bleeding unit is higher during the full moon than at other times. Their report contains a number of methodological and statistical flaws that invalidate their conclusions. Reanalysis of their data with proper procedures shows no evidence that the full moon influences the rate of hospital admissions, a result that is consistent with numerous peer-reviewed studies and meta-analyses. A review of the literature shows that birth rates are also uncorrelated to lunar phases. Conclusions Data collection and analysis shortcomings, as well as powerful cognitive biases, can lead to erroneous conclusions about the purported lunar effect on human affairs. Adherence to basic standards of evidence can help assess the validity of questionable beliefs. PMID:25756232

Cost-Effectiveness Analysis of Biogeneric Recombinant Activated Factor VII (AryoSeven™) and Activated Prothrombin Complex Concentrates (FEIBA™) to Treat Hemophilia A Patients with Inhibitors in Iran.

PubMed

Golestani, Mina; Eshghi, Peyman; Rasekh, Hamid Reza; Cheraghali, Abdoll Majid; Salamzadeh, Jamshid; Naderi, Majid; Managhchi, Mohammad Reza; Hoorfar, Hamid; Toogeh, Gholam Reza; Imani, Ali; Khodayari, Mohammad Taghi; Habibpanah, Behnaz; Hantooshzadeh, Razieh

2016-01-01

Nowadays, bypassing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCC) are used to treat bleeding episodes in the Hemophilia patients with inhibitors. AryoSeven® is an Iranian biogeneric rFVIIa with homogeneity of efficacy and the nature to NovoSeven in a comparative trial. The current clinical trial aimed to evaluate the cost-effectiveness of FEIBA and AryoSeven® by Decision Analytic Model according to the Iranian healthcare system. An open label, multi-center, cross-over clinical trial was designed. Patients were categorized into 3 groups based on their prior tendency to one or none of the products. To determine the premium therapeutic strategy, the Incremental cost-effectiveness ratio (ICER) was calculated. Protocol F led to more treatment success in group F than the other groups (P= 0.03). Also, there was a significant statistical difference between the mean of effectiveness scores in the groups using protocol F (P = 0.01). The effectiveness of protocol F and A were 89% and 72%, respectively. ICER cost US$ to manage an episode of bleeding to get one more unit of effectiveness using FEIBA VS. AryoSeven. Although the results showed that AryoSeven was more cost-effective compared to FEIBA, the two strategies were undominated. In other words, both medicines can be applied in the first line of the treatment if the cost of FEIBA was reduced. The present clinical trial was registered at IRCT website, under ID No.2013020612380N1.

The use of navigation (BrainLAB Vector vision(2)) and intraoperative 3D imaging system (Siemens Arcadis Orbic 3D) in the treatment of gunshot wounds of the maxillofacial region.

PubMed

Gröbe, Alexander; Weber, Christoph; Schmelzle, Rainer; Heiland, Max; Klatt, Jan; Pohlenz, Philipp

2009-09-01

Gunshot wounds are a rare occurrence during times of peace. The removal of projectiles is recommended; in some cases, however, this is a controversy. The reproduction of a projectile image can be difficult if it is not adjacent to an anatomical landmark. Therefore, navigation systems give the surgeon continuous real-time orientation intraoperatively. The aim of this study was to report our experiences for image-guided removal of projectiles and the resulting intra- and postoperative complications. We investigated 50 patients retrospectively; 32 had image-guided surgical removal of projectiles in the oral and maxillofacial region. Eighteen had surgical removal of projectiles without navigation assistance. There was a significant correlation (p = 0.0136) between the navigated surgery vs. not-navigated surgery and complication rate, including major bleeding (n = 4 vs. n = 1, 8% vs. 2%), soft tissue infections (n = 7 vs. n = 2, 14% vs. 4%), and nerval damage (n = 2 vs. n = 0, 4% vs. 0%; p = 0.038) and between the operating time and postoperative complications. A high tendency between operating time and navigated surgery (p = 0.1103) was shown. When using navigation system, we could reduce operating time. In conclusion, there is a significant correlation between reduced intra- and postoperative complications, including wound infections, nerval damage, and major bleeding, and the appropriate use of a navigation system. In all these cases, we could present reduced operating time. Cone-beam computed tomography plays an important role in detecting projectiles or metallic foreign bodies intraoperatively.

Customization of laparoscopic gastric devascularization and splenectomy for gastric varices based on CT vascular anatomy.

PubMed

Kawanaka, Hirofumi; Akahoshi, Tomohiko; Nagao, Yoshihiro; Kinjo, Nao; Yoshida, Daisuke; Matsumoto, Yoshihiro; Harimoto, Norifumi; Itoh, Shinji; Yoshizumi, Tomoharu; Maehara, Yoshihiko

2018-01-01

Laparoscopic gastric devascularization(Lap GDS) and splenectomy (SPL) for gastric varices is technically challenging because of highly developed collateral vessels and bleeding tendency. We investigated the feasibility of customization of Lap GDS and SPL based on CT vascular anatomy. We analyzed 61 cirrhotic patients with gastric varices who underwent Lap GDS and SPL between 2006 and 2014. Lap GDS was customized according to the afferent feeding veins (left gastric vein (LGV) and/or posterior gastric vein (PGV)/short gastric vein (SGV)) and efferent drainage veins (gastrorenal shunt and/or gastrophrenic shunt, or numerous retroperitoneal veins) based on CT imaging. Thirty-four patients with efferent drainage veins suitable for balloon-occluded retrograde transvenous obliteration (B-RTO) underwent B-RTO instead of surgical GDS, with subsequent Lap SPL. Among 27 patients with gastric varices unsuitable for B-RTO, 15 patients with PGV/SGV underwent Lap GDS of the greater curvature and SPL, and 12 patients with LGV or LGV/PGV/SGV underwent Lap GDS of the greater and lesser curvature and SPL. The mean operation time was 294 min and mean blood loss was 198 g. There was no mortality or severe morbidity. Gastric varices were eradicated in all 61 patients, with no bleeding or recurrence during a mean follow-up of 55.9 months. The cumulative 3-, 5-, and 7-year survival rates were 92, 82, and 64%, respectively. Lap GDS and SPL customized based on CT vascular anatomy is a safe and effective procedure for treating gastric varices.

Is there a difference in bleeding after left ventricular assist device implant: centrifugal versus axial?

PubMed

Gaffey, Ann C; Chen, Carol W; Chung, Jennifer J; Han, Jason; Bermudez, Christian A; Wald, Joyce; Atluri, Pavan

2018-02-13

Continuous-flow left ventricular assist devices (CF-LVAD) have become the standard of care for patients with end stage heart failure. Device reliability has increased, bringing the potential for VAD, compared to transplant, into debate. However, complications continue to limit VADs as first line therapy. Bleeding is a major morbidity. A debate exists as to the difference in bleeding profile between the major centrifugal and axial flow devices. We hypothesized that there would be similar adverse bleeding event profiles between the 2 major CF-LVADs. We retrospectively investigated isolated CF LVADs performed at our institution between July 2010 and July 2015: HeartMateII (HMII, n = 105) and HeartWare (HVAD, n = 34). We reviewed demographic, perioperative and short- and long-term outcomes. There was no significant difference in demographics or comorbidities. There was a low incidence of gastrointestinal (GI) bleed 3.9% in HMII and 2.9% in HVAD (p = 0.78). Preoperatively, the cohorts did not differ in coagulation measures (p = 0.95). Within the post-operative period, there was no difference in product transfusion: red blood cells (p = 0.10), fresh frozen plasma (p = 0.19), and platelets (p = 0.89). Post-operatively, a higher but not significantly different number of HMII patients returned to the operating room for bleeding (n = 27) compared to HVAD (n = 6, p = 0.35). There was no difference in rates of stroke (p = 0.65), re-intubation (p = 0.60), driveline infection (p = 0.05), and GI bleeding (p = 0.31). The patients had equivalent ICU LOS (p = 0.86) and index hospitalization LOS (p = 0.59). We found no difference in the rate of bleeding complications between the current commercially available axial and centrifugal flow devices.

Mentha longifolia syrup in secondary amenorrhea: a double-blind, placebo-controlled, randomized trials

PubMed Central

2012-01-01

Background Amenorrhea is defined as the cessation of menses. Hormone therapy is the most common treatment. Due to the contraindications and side effects of it and the increasing demand for alternative medicine substitutes, Mentha longifolia L. was used in this study. Mentha longifolia L. is a known medication in Iranian traditional medicine to induce menstrual bleeding in women with secondary amenorrhea and oligomenorrhea. Methods A double-blind, randomized, placebo-controlled, multicenter study was conducted in 120 women with secondary amenorrhea and oligomenorrhea. Treatment consisted of sequential oral syrup, 45 ml (15 ml three times a day) for 2 weeks. If the patients did not have menstruation after 2 weeks of taking the medication, we would wait for two more weeks. If the patients had menstruation at each stage of using the drug, we started it one week after the end of menstruation. But if the patients had not menstruate after four weeks (two-week using of drug and waiting for two more weeks), the previous steps were repeated. The drug and placebo were repeated in three cycles of menstruation. Bleeding was documented by the patient on diary cards. The primary outcome variable was the occurrence (yes/no) of bleeding during the first treatment cycle. The secondary efficacy outcome was the regularity of bleeding pattern during the three cycles of the study. Results The number of women with bleeding during the first cycle were higher in the drug group as in the placebo group (68.3% vs. 13.6%; p < 0.001). The regularity of bleeding throughout the study was markedly better in the drug group compared with those given placebo (33.3% vs. 3.3%; p < 0.001). No notable complication or side effect was reported in relation to Mentha longifolia L. syrup. Conclusion In conclusion, Mentha longifolia L. syrup is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with secondary amenorrhea and oligomenorrhea. PMID:23351184

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U; Herman, Sarah E M; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M; Lozier, Jay N; Wiestner, Adrian

2015-12-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733. Copyright© Ferrata Storti Foundation.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID:26430171

Risk of Atrial Fibrillation and Bleeding Diathesis Associated With Ibrutinib Treatment: A Systematic Review and Pooled Analysis of Four Randomized Controlled Trials.

PubMed

Yun, Seongseok; Vincelette, Nicole D; Acharya, Utkarsh; Abraham, Ivo

2017-01-01

Clinical trials raised concern that ibrutinib may increase the risk of atrial fibrillation/flutter (Afib/Aflutter) and major bleeding. However, the association has not been statistically validated, and there is no consensus regarding optimal management of anticoagulation among patients receiving ibrutinib who develop Afib/Aflutter. We performed a systematic review and pooled analysis to precisely assess the risk of Afib/Aflutter and bleeding associated with ibrutinib treatment in patients with hematologic malignancies. We searched PubMed, EMBASE, Cochrane Database, and meeting abstracts up to May 15, 2016, for randomized controlled trials comparing ibrutinib to chemotherapy, monoclonal antibody, or a combination. Primary outcomes were serious Afib/Aflutter and major bleeding. Secondary outcomes were all-grade Afib/Aflutter and bleeding. We calculated the Mantel-Haenszel risk ratio (RR) and estimated the effect of the treatments using a fixed-effects model. Ibrutinib treatment was associated with a significantly higher incidence of serious Afib/Aflutter (3.03% vs. 0.80%, RR = 3.80, 95% confidence interval [CI] = 1.56-9.29, P = .003), all-grade Afib/Aflutter (8.18% vs. 0.93%, RR = 8.81, 95% CI = 2.70-28.75, P = .0003), and all-grade bleeding (4.85% vs. 1.55%, RR = 2.93, 95% CI = 1.14-7.52, P = .03) compared to control treatments. The observed between-treatment difference in major bleeding rates was not statistically significant (3.69% vs. 2.13%, RR = 1.72, 95% CI = 0.95-3.11, P = .07). The risk of these adverse events was not different between subgroups on the basis of pathology, treatment setting, dose, and duration of ibrutinib exposure. The risks of Afib/Aflutter and all-grade bleeding were significantly higher in the ibrutinib group. These results indicate the need for vigilant monitoring while the patient is receiving ibrutinib therapy, and careful assessment of the risks and benefits of anticoagulation is required. Copyright © 2016 Elsevier Inc. All rights reserved.

Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE.

PubMed

Pan, Yuesong; Jing, Jing; Chen, Weiqi; Meng, Xia; Li, Hao; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2017-05-16

To investigate the short-term time course risks and benefits of clopidogrel with aspirin in minor ischemic stroke or TIA. Data were derived from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. The primary outcome was a new ischemic stroke. Safety outcomes included any bleeding and moderate to severe bleeding. Time course analyses were performed for the outcomes of both stroke and bleeding. A total of 145 (71.1%), 13 (6.4%), and 12 (5.9%) of 204 new ischemic strokes in the clopidogrel-aspirin group vs 223 (75.6%), 19 (6.4%), and 8 (2.7%) of 295 in the aspirin alone group occurred at the first, second, and third week, respectively. A total of 23 (38.3%), 15 (25.0%), and 9 (15.0%) of 60 bleeding cases in the clopidogrel-aspirin group vs 15 (36.6%), 8 (19.5%), and 3 (7.3%) of 41 in the aspirin alone group occurred at the first, second, and third week, respectively. Clopidogrel-aspirin treatment numerically reduced the risk of ischemic stroke within the first 2 weeks. From the 10th day, the number of any bleeding cases caused by dual antiplatelets outweighed that of new stroke reduced by dual antiplatelets. Clopidogrel-aspirin treatment may have a benefit of reducing stroke risk outweighing the potential risk of increased bleeding especially within the first 2 weeks compared with aspirin alone in patients with minor stroke or TIA. NCT00979589. This study provides Class II evidence that for patients with minor stroke or TIA, the reduction of stroke risk from clopidogrel plus aspirin within the first 2 weeks outweighs the risk of bleeding compared with aspirin alone. © 2017 American Academy of Neurology.

Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Westenbrink, B Daan; Alings, Marco; Granger, Christopher B; Alexander, John H; Lopes, Renato D; Hylek, Elaine M; Thomas, Laine; Wojdyla, Daniel M; Hanna, Michael; Keltai, Matyas; Steg, P Gabriel; De Caterina, Raffaele; Wallentin, Lars; van Gilst, Wiek H

2017-03-01

Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS 2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P<.0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P<.0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk.

PubMed

Seeger, Julia; Bothner, Carlo; Dahme, Tillman; Gonska, Birgid; Scharnbeck, Dominik; Markovic, Sinisa; Rottbauer, Wolfgang; Wöhrle, Jochen

2016-03-01

The randomized PROTECT AF trial demonstrated non-inferiority of left atrial appendage (LAA) closure to oral anticoagulation with warfarin. Current guidelines give a class IIb recommendation for LAA closure. We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk. 101 consecutive non-valvular atrial fibrillation patients (age 74.7 ± 7.5 years) at high risk for stroke (CHA2DS2-VASc Score 4.4 ± 1.6) and high bleeding risk (HAS-BLED Score 4.2 ± 1.3) received LAA closure with either the Watchman closure device (n = 38) or the Amplatzer cardiac plug (n = 63). Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3-6 months after device implantation, followed by long-term antiplatelet therapy with aspirin. No anticoagulation was given after device implantation. Mean follow-up was 400 days. One patient (1 %) experienced a transient ischemic attack, and two patients (2 %) suffered from ischemic stroke. While on recommended antiplatelet therapy, bleeding occurred in 12/101 patients (12 %). Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy (3.0 vs. 16.2 %, p < 0.05) while ischemic or thrombotic events were similar. Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score. Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events.

Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score.

PubMed

Smith, J Gustav; Wieloch, Mattias; Koul, Sasha; Braun, Oscar Ö; Lumsden, Jonathan; Rydell, Emil; Ohman, Jenny; Scherstén, Fredrik; Svensson, Peter J; van der Pals, Jesper

2012-10-01

The aim of this study was to evaluate the prevalence of triple antithrombotic therapy (TT) (warfarin, aspirin and clopidogrel) in patients following an acute coronary syndrome (ACS), the bleeding risk compared to double antiplatelet therapy (DAPT) (aspirin and clopidogrel) and evaluate the accuracy of the HAS-BLED risk score in predicting serious bleeding events in TT patients. We retrospectively identified all ACS patients on TT upon discharge from the Coronary Care Unit at Skane University Hospital between 2005 and 2010. TT patients were compared to age- and sex-matched control patients discharged with DAPT. Major bleeding was defined in accordance with the HAS-BLED derivation study. A total of 2,423 patients were screened, of whom 159 (6.6%) were on TT. The mean age was 67.2 (±0.9) years. The most common indication for TT was atrial fibrillation (n=63, 39.6%) followed by apical akinesia (n=60, 37.8%), and the mean duration of TT was 3.7 (±0.3) months. Upon termination of TT, warfarin was discontinued in 82 (52.2%) patients and clopidogrel in 57 (36.3%) patients. The cumulative incidence of spontaneous bleeding events was significantly higher with TT compared to DAPT at one year (10.2% vs. 3.2%; p=0.01). The HAS-BLED score significantly predicted spontaneous bleeding events in TT patients (area under the receiver operating characteristic [ROC] curve 0.67; 95% CI=0.54-0.79; p=0.048). TT was relatively common following acute coronary syndrome and was associated with a threefold increase in major bleeding compared to DAPT at one year. The HAS-BLED risk score predicted bleeding events with moderate accuracy.