Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol for contraception and control of menstrual symptoms.

PubMed

Jensen, Jeffrey T; Archer, David F

2008-02-01

Considerable recent interest has focused on new methods of delivery of oral contraceptives that reduce or eliminate the hormone-free interval in order to improve convenience and acceptability, but maintain contraceptive efficacy, minimize side effects and reduce or eliminate the frequency of withdrawal bleeding episodes. Studies in several countries, including the US, have documented that many women would prefer to have no episodes of withdrawal bleeding when using oral contraceptives. This review focuses on a unique oral contraceptive formulation containing levonogestrel 90 microg and ethinyl estradiol 20 microg, approved for use in a continuous dosing regimen designed to eliminate withdrawal bleeding throughout the entire year.

Thrombopoietin receptor agonists for prevention and treatment of chemotherapy-induced thrombocytopenia in patients with solid tumours.

PubMed

Zhang, Xia; Chuai, Yunhai; Nie, Wei; Wang, Aiming; Dai, Guanghai

2017-11-27

Chemotherapy-induced thrombocytopenia (CIT) is defined as a peripheral platelet count less than 100×10 9 /L, with or without bleeding in cancer patients receiving myelosuppressive chemotherapy. CIT is a significant medical problem during chemotherapy, and it carries the risk of sub-optimal overall survival and bleeding. Alternative interventions to platelet transfusion are limited. Different stages of preclinical and clinical studies have examined the thrombopoietin receptor agonists (TPO-RAs) for CIT in patients with solid tumours. To assess the effects of TPO-RAs to prevent and treat CIT in patients with solid tumours:(1) to prevent CIT in patients without thrombocytopenia before chemotherapy, (2) to prevent recurrence of CIT, and (3) to treat CIT in patients with thrombocytopenia during chemotherapy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, to 28 September 2017), MEDLINE (from 1950 to 28 September 2017), as well as online registers of ongoing trials (Clinical Trials, Chinese Clinical Trial Register, Australian New Zealand Clinical Trial Registry, WHO ICTRP Search Portal, International Standard Randomised Controlled Trial Number registry, GlaxoSmithKline Clinical Study Register, and Amgen Clinical Trials) and conference proceedings (American Society of Hematology, American Society of Clinical Oncology, European Hematology Association, European Society of Medical Oncology, and Conference Proceedings Citation Index-Science, from 2002 up to September 2017) for studies. Randomised controlled trials (RCTs) comparing TPO-RAs alone, or in combination with other drugs, to placebo, no treatment, other drugs, or another TPO-RAs for CIT in patients with solid tumours. Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard methodological methods expected by Cochrane. We identified six trials eligible for inclusion, of which two are ongoing, and one awaiting classification study. The three included trials were conducted at many different sites in Europe, America, and Asia. All of the three studies recruited adult and elder participants (no children were included) with solid tumours, and compared TPO-RAs with placebo. No studies compared TPO-RAs alone, or in combination with other drugs, to no treatment, or other drugs, or another TPO-RAs.We judged the overall risk of bias as high as we found a high risk for detection bias. We assessed the risk of bias arising from inadequate blinding of outcome assessors as high for number and severity of bleeding episodes (one of the primary outcomes).To prevent CIT: We included two trials (206 participants) comparing TPO-RAs (eltrombopag, multiple-dose oral administration with chemotherapy) with placebo. The use of TPO-RAs may make little or no difference to the all-cause mortality at 33 weeks of follow-up (RR 1.35, 95% CI 0.53 to 3.45; one trial, 26 participants; low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 0.62, 95% CI 0.22 to 1.78; two trials, 206 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (RR 0.36, 95% CI 0.06 to 2.06; two trials, 206 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life.To prevent recurrence of CIT: We included one trial (62 participants) comparing TPO-RAs (romiplostim, single-dose subcutaneous administration with chemotherapy) with placebo. There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 2.80, 95% CI 0.17 to 47.53; one trial, 62 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (no severe/life-threatening bleeding episodes; one trial, 62 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), it is planned to give TPO-RAs (romiplostim, subcutaneous administration with chemotherapy) to participants, but to date this trial has not reported any outcomes.To treat CIT: We found one ongoing study (expected recruitment 83 participants), which is planned to give TPO-RAs (eltrombopag, seven days orally) to participants when their platelet counts are less than 75×10 9 /L during chemotherapy. This trial was originally planned to complete in March 2017, however, the completion date has passed and no results are reported.The one awaiting classification study included patients without thrombocytopenia before chemotherapy (to prevent CIT), patients with thrombocytopenia during chemotherapy (to prevent recurrence of CIT), and other patients during chemotherapy (uncertain whether CIT had happened). There was no evidence for a difference in the number of patients with at least one bleeding episode of any severity (RR 0.27, 95% CI 0.07 to 1.02; one trial, 75 participants). There was no evidence for a difference in the number of patients with at least one severe/life-threatening bleeding episode (RR 0.44, 95% CI 0.03 to 6.77; one trial, 75 participants). This study did not address overall survival or quality of life. No certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. There was no evidence to support the use of TPO-RAs for treating CIT in patients with solid tumours.

A devastating outcome after adenoidectomy and tonsillectomy: ideas for improved prevention and management.

PubMed

Windfuhr, Jochen P; Schloendorff, Georg; Sesterhenn, Andreas M; Prescher, Andreas; Kremer, Bernd

2009-02-01

To develop strategies that may assist the surgeon to prevent and manage severe bleeding complications after adenoidectomy and tonsillectomy. Retrospective. Expert reports for malpractice lawsuits or professional boards were reviewed. The review was restricted to "deaths" and "permanent generalized neurological deficiencies." Forty-three cases matched our search criteria, including 32 deaths. Adenoidectomy cases (2) were associated with immediate bleeding because of direct vascular injury resulting in one death. Tonsillectomy cases were associated with delayed and repeated episodes of bleeding resulting in 31 deaths, including 19 children. Autopsy verified predominantly aspiration and vascular injuries. An apallic syndrome prevailed in surviving patients. Careful inspection of the nasopharynx immediately before adenoidectomy and curettage in a piecemeal fashion under visual control is helpful to prevent direct injury to aberrant arteries. Tonsillectomy cases are associated with delayed and episodic bleeding with spontaneous cessation and young age. Inpatient observation should be strongly considered in cases with repeated bleeding episodes to provide immediate treatment. The follow-up should be focused on disturbed wound healing. Outcome appears to be dependent on adequate airway management. Rigid instruments and tracheotomy in case of intubation failure are highly recommended to facilitate airway protection and ventilation.

A splenic artery aneurysm presenting with multiple episodes of upper gastrointestinal bleeding: a case report.

PubMed

De Silva, W S L; Gamlaksha, D S; Jayasekara, D P; Rajamanthri, S D

2017-05-03

Splenic artery aneurysm is rare and its diagnosis is challenging due to the nonspecific nature of the clinical presentation. We report a case of a splenic artery aneurysm in which the patient presented with chronic dyspepsia and multiple episodes of minor intragastric bleeding. A 60-year-old, previously healthy Sri Lankan man presented with four episodes of hematemesis and severe dyspeptic symptoms over a period of 6 months. The results of two initial upper gastrointestinal endoscopies and an abdominal ultrasound scan were unremarkable. A third upper gastrointestinal endoscopy detected a pulsatile bulge at the posterior wall of the gastric antrum. A contrast-enhanced computed tomogram of his abdomen detected a splenic artery aneurysm measuring 3 × 3 × 2.5 cm. While awaiting routine surgery, he developed a torrential upper gastrointestinal bleeding and shock, leading to emergency laparotomy. Splenectomy and en bloc resection of the aneurysm with the posterior stomach wall were performed. Histology revealed evidence for a true aneurysm without overt, acute, or chronic inflammation of the surrounding gastric mucosa. He became completely asymptomatic 2 weeks after the surgery. Splenic artery aneurysms can result in recurrent upper gastrointestinal bleeding. The possibility of impending catastrophic bleeding should be remembered when managing patients with splenic artery aneurysms after a minor bleeding. Negative endoscopy and ultrasonography should require contrast-enhanced computed tomography to look for the cause of recurrent upper gastrointestinal bleeding.

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.

Late-onset severe biliary bleeding after endoscopic pigtail plastic stent insertion.

PubMed

Yasuda, Muneji; Sato, Hideki; Koyama, Yuki; Sakakida, Tomoki; Kawakami, Takumi; Nishimura, Takeshi; Fujii, Hideki; Nakatsugawa, Yoshikazu; Yamada, Shinya; Tomatsuri, Naoya; Okuyama, Yusuke; Kimura, Hiroyuki; Ito, Takaaki; Morishita, Hiroyuki; Yoshida, Norimasa

2017-01-28

Here, we report our experience with a case of severe biliary bleeding due to a hepatic arterial pseudoaneurysm that had developed 1 year after endoscopic biliary plastic stent insertion. The patient, a 78-year-old woman, presented with hematemesis and obstructive jaundice. Ruptured hepatic arterial pseudoaneurysm was diagnosed, which was suspected to have been caused by long-term placement of an endoscopic retrograde biliary drainage (ERBD) stent. This episode of biliary bleeding was successfully treated by transarterial embolization (TAE). Pseudoaneurysm leading to hemobilia is a rare but potentially fatal complication in patients with long-term placement of ERBD. TAE is a minimally invasive procedure that offers effective treatment for biliary bleeding.

Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome.

PubMed

Salva, Inês; Batalha, Sara; Maia, Raquel; Kjollerstrom, Paula

2016-06-01

Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

Patterns and predictors of vaginal bleeding in the first trimester of pregnancy

PubMed Central

Hasan, Reem; Baird, Donna D.; Herring, Amy H.; Olshan, Andrew F.; Jonsson Funk, Michele L.; Hartmann, Katherine E.

2010-01-01

Purpose Although first-trimester vaginal bleeding is an alarming symptom, few studies have investigated the prevalence and predictors of early bleeding. This study characterizes first trimester bleeding, setting aside bleeding that occurs at time of miscarriage. Methods Participants (n=4539) were women ages 18–45 enrolled in Right From the Start, a community-based pregnancy study (2000–2008). Bleeding information included timing, heaviness, duration, color, and associated pain, as well as recurrence risk in subsequent pregnancies. Life table analyses were used to describe gestational timing of bleeding. Factors associated with bleeding were investigated using multiple logistic regression, with multiple imputation for missing data. Results Approximately one-fourth of participants (n=1207) reported bleeding (n=1656 episodes), but only 8% of women with bleeding reported heavy bleeding. Of the spotting and light bleeding episodes (n=1555), 28% were associated with pain. Among heavy episodes (n=100), 54% were associated with pain. Most episodes lasted less than 3 days, and most occurred between gestational weeks 5–8. Twelve percent of women with bleeding and 13% of those without experienced miscarriage. Maternal characteristics associated with bleeding included fibroids and prior miscarriage. Conclusions Consistent with the hypothesis that bleeding is a marker for placental dysfunction, bleeding is most likely to be seen around the time of the luteal-placental shift. PMID:20538195

Defining upper gastrointestinal bleeding from linked primary and secondary care data and the effect on occurrence and 28 day mortality.

PubMed

Crooks, Colin John; Card, Timothy Richard; West, Joe

2012-11-13

Primary care records from the UK have frequently been used to identify episodes of upper gastrointestinal bleeding in studies of drug toxicity because of their comprehensive population coverage and longitudinal recording of prescriptions and diagnoses. Recent linkage within England of primary and secondary care data has augmented this data but the timing and coding of concurrent events, and how the definition of events in linked data effects occurrence and 28 day mortality is not known. We used the recently linked English Hospital Episodes Statistics and General Practice Research Database, 1997-2010, to define events by; a specific upper gastrointestinal bleed code in either dataset, a specific bleed code in both datasets, or a less specific but plausible code from the linked dataset. This approach resulted in 81% of secondary care defined bleeds having a corresponding plausible code within 2 months in primary care. However only 62% of primary care defined bleeds had a corresponding plausible HES admission within 2 months. The more restrictive and specific case definitions excluded severe events and almost halved the 28 day case fatality when compared to broader and more sensitive definitions. Restrictive definitions of gastrointestinal bleeding in linked datasets fail to capture the full heterogeneity in coding possible following complex clinical events. Conversely too broad a definition in primary care introduces events not severe enough to warrant hospital admission. Ignoring these issues may unwittingly introduce selection bias into a study's results.

Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation.

PubMed

Mariani, Guglielmo; Napolitano, Mariasanta; Dolce, Alberto; Pérez Garrido, Rosario; Batorova, Angelika; Karimi, Mehran; Platokouki, Helen; Auerswald, Günter; Bertrand, Anne-Marie; Di Minno, Giovanni; Schved, Jean F; Bjerre, Jens; Ingerslev, Jorgen; Sørensen, Benny; Ruiz-Saez, Arlette

2013-02-01

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

Determining the in-hospital cost of bleeding in patients undergoing percutaneous coronary intervention.

PubMed

Ewen, Edward F; Zhao, Liping; Kolm, Paul; Jurkovitz, Claudine; Fidan, Dogan; White, Harvey D; Gallo, Richard; Weintraub, William S

2009-06-01

The economic impact of bleeding in the setting of nonemergent percutaneous coronary intervention (PCI) is poorly understood and complicated by the variety of bleeding definitions currently employed. This retrospective analysis examines and contrasts the in-hospital cost of bleeding associated with this procedure using six bleeding definitions employed in recent clinical trials. All nonemergent PCI cases at Christiana Care Health System not requiring a subsequent coronary artery bypass were identified between January 2003 and March 2006. Bleeding events were identified by chart review, registry, laboratory, and administrative data. A microcosting strategy was applied utilizing hospital charges converted to costs using departmental level direct cost-to-charge ratios. The independent contributions of bleeding, both major and minor, to cost were determined by multiple regression. Bootstrap methods were employed to obtain estimates of regression parameters and their standard errors. A total of 6,008 cases were evaluated. By GUSTO definitions there were 65 (1.1%) severe, 52 (0.9%) moderate, and 321 (5.3%) mild bleeding episodes with estimated bleeding costs of $14,006; $6,980; and $4,037, respectively. When applying TIMI definitions there were 91 (1.5%) major and 178 (3.0%) minor bleeding episodes with estimated costs of $8,794 and $4,310, respectively. In general, the four additional trial-specific definitions identified more bleeding events, provided lower estimates of major bleeding cost, and similar estimates of minor bleeding costs. Bleeding is associated with considerable cost over and above interventional procedures; however, the choice of bleeding definition impacts significantly on both the incidence and economic consequences of these events.

Impact of acute bleeding on daily activities of patients with congenital hemophilia with inhibitors and their caregivers and families: observations from the Dosing Observational Study in Hemophilia (DOSE).

PubMed

Recht, Michael; Neufeld, Ellis J; Sharma, Vivek R; Solem, Caitlyn T; Pickard, A Simon; Gut, Robert Z; Cooper, David L

2014-09-01

There is limited understanding of the effects of bleeding episodes on the daily lives of patients with congenital hemophilia with inhibitors and their caregivers. This analysis of the Dosing Observational Study in Hemophilia examined the impact of acute bleeding episodes on work, school, and family activities. Patients and caregivers participated in a diary study for 90 or more days or until patients experienced four bleeding episodes. All bleed treatments, interference with daily activities, and quality-of-life assessments were captured in daily records. Patients and caregivers reported planned workdays or school days eligible to be "lost" so as to differentiate from days lost because of disability or nonworking status, weekends, and vacations. Diaries were completed for 39 patients (18 adults and 21 children). Bleeding episodes that continued for 3 or more days (16.4%) accounted for most of the major changes to family plans. For the 38 patients with bleeding episodes, 47% of 491 bleed days fell on planned workdays or school days; the remainder fell on weekends, holidays, or nonworkdays or non-school days and therefore did not count as "lost days." Patients reported a loss of productivity on a greater percentage of eligible bleed days than did caregivers (3.9% vs. 0.8%, respectively). Patients and caregivers reported 13.5%/9.3% fully missed and 3.5%/7.6% partially missed days. This study demonstrated that in hemophilia with inhibitors, bleeding episodes interfere with the daily activities of patients and their caregivers. Furthermore, documenting only lost days underestimated the impact of bleeding episodes because of the high percentage of days without planned work or school. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Efficacy, safety and tolerability of recombinant factor VIII (REFACTO) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria.

PubMed

Pollmann, H; Externest, D; Ganser, A; Eifrig, B; Kreuz, W; Lenk, H; Pabinger, I; Schramm, W; Schwarz, T F; Zimmermann, R; Zavazava, N; Oldenburg, J; Klamroth, R

2007-03-01

An open-label, multicentre, postmarketing surveillance study conducted in Germany and Austria with recombinant factor VIII (REFACTO) has enrolled 217 patients (mean age 26.3 years) from 38 haemophilia centres during the first 4.8 years. Most patients (188/217; 86.6%) had severe to moderately severe haemophilia A, of whom 153 completed sufficient diary information for the main efficacy analysis. These 153 patients experienced a median of 6.6 (interquartile range 1.4-18.6) bleeding episodes per year. Patients treated with prophylaxis experienced a median of 4.4 (1.1-9.3) bleeds per year, while patients treated on-demand experienced a median of 22.8 (11.3-29.0) bleeds per year. Overall, most physicians (41/43 [95.3%]) were 'very satisfied' or 'satisfied' with the efficacy of REFACTO in the treatment of bleeding episodes. A total of 137 non-serious adverse events have been reported in 52/217 patients (24.0%) to date. In addition, 129 serious adverse events in 87 patients (40%) were reported, including 41 cases of 'less than expected therapeutic effect' (LETE). Of these, 39 LETE cases were reported in one centre; however, patients in this centre experienced considerably fewer bleeding episodes per year than patients outside this centre. Overall, six patients (2.8%) have developed de novo inhibitors, three of which were considered high titre. Four of these patients were at high risk (0-50 exposure days [ED]) of inhibitor formation, one was at intermediate risk (51-100 ED) and one was at low risk (>100 ED). These results emphasize the benefit of postmarketing surveillance and, overall, this study confirms the efficacy, safety and tolerability of REFACTO in the treatment of patients with haemophilia A.

Defining upper gastrointestinal bleeding from linked primary and secondary care data and the effect on occurrence and 28 day mortality

PubMed Central

2012-01-01

Background Primary care records from the UK have frequently been used to identify episodes of upper gastrointestinal bleeding in studies of drug toxicity because of their comprehensive population coverage and longitudinal recording of prescriptions and diagnoses. Recent linkage within England of primary and secondary care data has augmented this data but the timing and coding of concurrent events, and how the definition of events in linked data effects occurrence and 28 day mortality is not known. Methods We used the recently linked English Hospital Episodes Statistics and General Practice Research Database, 1997–2010, to define events by; a specific upper gastrointestinal bleed code in either dataset, a specific bleed code in both datasets, or a less specific but plausible code from the linked dataset. Results This approach resulted in 81% of secondary care defined bleeds having a corresponding plausible code within 2 months in primary care. However only 62% of primary care defined bleeds had a corresponding plausible HES admission within 2 months. The more restrictive and specific case definitions excluded severe events and almost halved the 28 day case fatality when compared to broader and more sensitive definitions. Conclusions Restrictive definitions of gastrointestinal bleeding in linked datasets fail to capture the full heterogeneity in coding possible following complex clinical events. Conversely too broad a definition in primary care introduces events not severe enough to warrant hospital admission. Ignoring these issues may unwittingly introduce selection bias into a study’s results. PMID:23148590

Association Between First-Trimester Vaginal Bleeding and Miscarriage

PubMed Central

Hasan, Reem; Baird, Donna D.; Herring, Amy H.; Olshan, Andrew F.; Jonsson Funk, Michele L.; Hartmann, Katherine E.

2009-01-01

Objective To estimate the strength of association between first-trimester bleeding and miscarriage, setting aside the bleeding at time of loss. Methods Women enrolled in a community-based pregnancy cohort study before or during early pregnancy. Detailed, first-trimester bleeding data were collected by telephone interview. Bleeding episodes proximal to miscarriage (within 4 days) were excluded. We used discrete-time hazard models to evaluate the association between bleeding and miscarriage. Models were adjusted for maternal age, prior miscarriage, and smoking. Exploratory regression tree analysis was used to evaluate the relative importance of other bleeding characteristics (duration, associated pain, color, timing). Results Of the 4510 participants, 1204 (27%) reported some first-trimester vaginal bleeding or spotting, and 517 miscarriages were observed. Eight percent of those with bleeding reported heavy bleeding episodes. When we evaluated any bleeding, including episodes of only spotting, the unadjusted relative odds (OR) of miscarriage for women with bleeding (n=1204) was 1.1 (95% confidence interval [CI] 0.9–1.3). However, women who reported heavy bleeding (n=97)had nearly three times the risk of miscarriage compared to women without bleeding during the first trimester (OR 3.0, 95% CI 1.9–4.6). Adjustment for covariates had little effect on estimates. Further analyses suggested that women with heavy bleeding accompanied by pain were the group accounting for most of the elevated risk. Conclusion Heavy bleeding in the first trimester, particularly when accompanied by pain, is associated with higher risk of miscarriage. Spotting and light episodes are not, especially if only lasting 1–2 days.. PMID:19888046

Association between first-trimester vaginal bleeding and miscarriage.

PubMed

Hasan, Reem; Baird, Donna D; Herring, Amy H; Olshan, Andrew F; Jonsson Funk, Michele L; Hartmann, Katherine E

2009-10-01

To estimate the strength of association between first-trimester bleeding and miscarriage, setting aside bleeding at time of loss. Women enrolled in a community-based pregnancy cohort study before or during early pregnancy. Detailed first-trimester bleeding data were collected by telephone interview. Bleeding episodes proximal to miscarriage (within 4 days) were excluded. We used discrete-time hazard models to evaluate the association between bleeding and miscarriage. Models were adjusted for maternal age, prior miscarriage, and smoking. Exploratory regression tree analysis was used to evaluate the relative importance of other bleeding characteristics (duration, associated pain, color, timing). Of the 4,510 participants, 1,204 (27%) reported some first-trimester vaginal bleeding or spotting, and 517 miscarriages were observed. Eight percent of those with bleeding reported heavy bleeding episodes. When we evaluated any bleeding, including episodes of only spotting, the unadjusted relative odds ratio (OR) of miscarriage for women with bleeding (n=1,204) was 1.1 (95% confidence interval [CI] 0.9-1.3). However, women who reported heavy bleeding (n=97) had nearly three times the risk of miscarriage compared with women without bleeding during the first trimester (OR 3.0, 95% CI 1.9-4.6). Adjustment for covariates had little effect on estimates. Further analyses suggested that women with heavy bleeding accompanied by pain were the group accounting for most of the elevated risk. Heavy bleeding in the first trimester, particularly when accompanied by pain, is associated with higher risk of miscarriage. Spotting and light episodes are not, especially if lasting only 1-2 days. II.

Circadian occurrence of variceal bleeding in patients with liver cirrhosis.

PubMed

Siringo, S; Bolondi, L; Sofia, S; Hermida, R C; Gramantieri, L; Gaiani, S; Piscaglia, F; Carbone, C; Misitano, B; Corinaldesi, R

1996-12-01

Several clinical events have a rhythmicity over the 24 h period. We assessed the presence of periodic rhythm in the occurrence of haematemesis in patients with liver cirrhosis under different daylight regimens, namely during standard time and during daylight savings. Over a 48 month period there were 212 consecutive admissions of 118 cirrhotics with variceal bleeding. Complete data were available for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60 (33.1%) started with melaena. One hundred and two (56%) episodes occurred during daylight savings and 79 (44%) occurred during standard time. The cosinor test showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45 h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple component rhythmometry. The time peaks of onset of variceal haemorrhage did not change significantly during standard time and daylight savings. Patients with more than one haematemesis episode significantly bled over the same time interval. The present study confirms that over the 24 h period variceal bleeding in cirrhotic patients occurs with a predictable rhythmicity that does not seem to be under the control of the light-dark cycle. The finding of a chronorisk for variceal haemorrhage addresses specific questions for pathophysiological studies as well as for new treatment strategies.

Epsilon aminocaproic acid prevents bleeding in severely thrombocytopenic patients with hematological malignancies.

PubMed

Antun, Ana G; Gleason, Shannon; Arellano, Martha; Langston, Amelia A; McLemore, Morgan L; Gaddh, Manila; el Rassi, Fuad; Bernal-Mizrachi, Leon; Galipeau, Jacques; Heffner, Leonard T; Winton, Elliott F; Khoury, Hanna J

2013-11-01

Despite prophylactic platelet transfusions, bleeding remains a significant problem in thrombocytopenic patients. The antifibrinolytic agent epsilon aminocaproic acid (EACA) was administered to 44 chronically (median duration, 273 days) and severely (platelet count, 8 × 10(9)/L; range, 1 × 10(9)/L-19 × 10(9)/L) thrombocytopenic patients with hematological malignancies. Prophylactic EACA at a dose of 1 g twice daily was orally administered for a median duration of 47 days (range, 7 days-209 days) until the platelet count recovered to > 30; × 10(9) /L. Platelets were only transfused if bleeding occurred. While receiving EACA, 59% of the patients did not bleed, 25% had 19 episodes of spontaneously resolving minor bleeding that did not require platelet transfusion, and 16% received a median of 4 platelet transfusions (range, 1 transfusion-8 transfusions) for 1 major traumatic and 9 spontaneous grade 2 to grade 3 bleeding (based on the World Health Organization classification of idiopathic thrombocytopenic purpura). No EACA toxicities were noted, and venous thromboses were not observed. EACA is well tolerated and is associated with a low risk of major bleeding in patients with hematological malignancies who are experiencing chronic severe thrombocytopenia. © 2013 American Cancer Society.

Lonoctocog Alfa: A Review in Haemophilia A.

PubMed

Al-Salama, Zaina T; Scott, Lesley J

2017-10-01

Lonoctocog alfa (rVIII-SingleChain; Afstyla ® ) is a novel single-chain recombinant factor VIII (FVIII) molecule, with a truncated B-domain and the heavy and light chains covalently linked to form a stable and homogenous drug that binds with high affinity to von Willebrand factor (VWF). Intravenous lonoctocog alfa is approved for the prophylaxis and treatment of bleeding in patients with haemophilia A in several countries worldwide. In two pivotal, multicentre trials, lonoctocog alfa was effective in the treatment of bleeding episodes and as prophylaxis, including for perioperative management in adults, adolescents and children. In terms of haemostatic efficacy in controlling bleeding episodes, overall treatment and investigator-assessed success rates were high across all age groups, with the majority of these bleeds controlled with a single injection of lonoctocog alfa. Low median spontaneous, overall and traumatic annualized bleeding rates were evident with prophylactic lonoctocog alfa regimens in both trials. Lonoctocog alfa was generally well-tolerated, with very low rates of injection-site reactions. No previously treated patient experienced an anaphylactic reaction or developed an inhibitor. In conclusion, lonoctocog alfa is an effective and generally well-tolerated alternative to conventional FVIII products for the treatment and prophylaxis of bleeding, including in the surgical setting, in adults, adolescents and children with haemophilia A.

Platelet transfusions in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit.

PubMed

Habr, Bassem; Charpentier, Julien; Champigneulle, Benoît; Dechartres, Agnès; Daviaud, Fabrice; Geri, Guillaume; Cariou, Alain; Chiche, Jean-Daniel; Mira, Jean-Paul; Pène, Frédéric

2015-12-01

Thrombocytopenia is a frequent finding in critically ill cancer patients for whom indications of platelet transfusions are unclear. We herein addressed the current practices in platelet transfusion and the risk of bleeding in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit (ICU). A retrospective monocenter study over a 7-year period was conducted in a medical ICU. Adult patients with malignancies and hypoproliferative thrombocytopenia, and who received at least one platelet concentrate during their ICU stay, were included. 296 patients were included and received a total of 904 platelet transfusions, for prophylactic indications in 300 (33.2 %) episodes, for securing an invasive procedure in 257 (28.4 %), and for treatment of minor to major bleeding manifestations in 347 (38.4 %). Most prophylactic transfusions (80 %) were performed at platelet count thresholds below 10-20 × 10(9)/L. Platelet increments were generally low in all three indications, 10 (interquartile range 2-25), 11 (2-25), and 8 (0-21) × 10(9)/L, respectively. A total of 97 major ICU-acquired bleeding events occurred in 40 patients. About half of those bleeding episodes (54.7 %) occurred at platelet counts below 20 × 10(9)/L. However, neither low admission platelet count nor low nadir platelet counts were predictive of ICU-acquired bleeding. The in-ICU mortality rate tended to be higher in patients with severe ICU-acquired bleeding events (50 vs. 36 %). Most prophylactic platelet transfusions were given using thresholds of 10-20 × 10(9)/L in critically ill thrombocytopenic cancer patients. The individual risk of ICU-acquired severe bleeding appears hardly predictable with the depth of thrombocytopenia.

Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A.

PubMed

Young, G; Mahlangu, J; Kulkarni, R; Nolan, B; Liesner, R; Pasi, J; Barnes, C; Neelakantan, S; Gambino, G; Cristiano, L M; Pierce, G F; Allen, G

2015-06-01

Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly). Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of < 1 IU dL(-1) [< 1%]). The study enrolled 71 subjects. The starting rFVIIIFc regimen was twice-weekly prophylaxis (Day 1, 25 IU kg(-1) ; Day 4, 50 IU kg(-1) ); dose (≤ 80 IU kg(-1) ) and dosing interval (≥ 2 days) were adjusted as needed. A subset of subjects had sequential pharmacokinetic evaluations of FVIII and rFVIIIFc. The primary endpoint was development of inhibitors (neutralizing antibodies). Secondary endpoints included pharmacokinetics, annualized bleeding rate (ABR), and number of infusions required to control a bleed. No subject developed an inhibitor to rFVIIIFc. Adverse events were typical of a pediatric hemophilic population. The rFVIIIFc half-life was prolonged relative to that of FVIII, consistent with observations in adults and adolescents. The median ABR was 1.96 overall, and 0.00 for spontaneous bleeds; 46.4% of subjects reported no bleeding episodes on study. Ninety-three per cent of bleeding episodes were controlled with one to two infusions. The median average weekly rFVIIIFc prophylactic dose was 88.11 IU kg(-1) . At study end, 62 of 69 subjects (90%) were infusing twice weekly. Among subjects who had been previously receiving FVIII prophylaxis, 74% reduced their dosing frequency with rFVIIIFc. Twice-weekly infusions with rFVIIIFc were well tolerated and yielded low bleeding rates in children with severe hemophilia A. © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Signs and Symptoms of a Bleeding Disorder in Women

MedlinePlus

... heavy bleeding after dental surgery, other surgery, or childbirth. I have experienced prolonged bleeding episodes that might ... a result of: Dental surgery, other surgery, or childbirth; Frequent nose bleeds (longer than 10 minutes); Bleeding ...

Stroke and Bleeding Risk Associated With Antithrombotic Therapy for Patients With Nonvalvular Atrial Fibrillation in Clinical Practice

PubMed Central

An, JaeJin; Niu, Fang; Lang, Daniel T; Jazdzewski, Kristin P; Le, Paul T; Rashid, Nazia; Meissner, Brian; Mendes, Robert; Dills, Diana G; Aranda, Gustavus; Bruno, Amanda

2015-01-01

Background The quality of antithrombotic therapy for patients with nonvalvular atrial fibrillation during routine medical care is often suboptimal. Evidence linking stroke and bleeding risk with antithrombotic treatment is limited. The purpose of this study was to evaluate the associations between antithrombotic treatment episodes and outcomes. Methods and Results A retrospective longitudinal observational cohort study was conducted using patients newly diagnosed with nonvalvular atrial fibrillation with 1 or more stroke risk factors (CHADS2 ≥1) in Kaiser Permanente Southern California between January 1, 2006 and December 31, 2011. A total of 1782 stroke and systemic embolism (SE) and 3528 major bleed events were identified from 23 297 patients during the 60 021 person-years of follow-up. The lowest stroke/SE rates and major bleed rates were observed in warfarin time in therapeutic range (TTR) ≥55% episodes (stroke/SE: 0.87 [0.71 to 1.04]; major bleed: 4.91 [4.53 to 5.28] per 100 person-years), which was similar to the bleed rate in aspirin episodes (4.95 [4.58 to 5.32] per 100 person-years). The warfarin TTR ≥55% episodes were associated with a 77% lower risk of stroke/SE (relative risk=0.23 [0.18 to 0.28]) compared to never on therapy; and the warfarin TTR <55% and on-aspirin episodes were associated with a 20% lower and with a 26% lower risk of stroke/SE compared to never on therapy, respectively. The warfarin TTR <55% episodes were associated with nearly double the risk of a major bleed compared to never on therapy (relative risk=1.93 [1.74 to 2.14]). Conclusions Continuation of antithrombotic therapy as well as maintaining an adequate level of TTR is beneficial to prevent strokes while minimizing bleeding events. PMID:26187996

Vedolizumab Treatment for Ulcerative Colitis in an Elderly Multimorbid Patient with Hemophilia A.

PubMed

Schäffler, Holger; Huth, Astrid; Lamprecht, Georg; Anders, Olaf

2017-01-01

The treatment of inflammatory bowel diseases (IBD) can be challenging, especially in elderly multimorbid patients. Since incidence and prevalence rates of IBD are rising steadily, treatment of older patients with relevant and also rare comorbidities will be of increasing relevancy for caregivers. Here we report on a 74-year-old multimorbid patient with severe ulcerative colitis (UC) and hemophilia A. Because of the chronic active disease, therapy with a tumor necrosis factor-α inhibitor was started. He suffered from a severe infectious complication (pneumonia) under therapy with infliximab. The therapy was changed to vedolizumab, with which the patient stayed in long-term clinical and endoscopic remission. Because the patient had a non-ST-segment elevation myocardial infarction in April 2016, he received dual platelet inhibitor therapy with aspirin and clopidogrel. Because of consecutive aspirin intolerance, the therapy was changed to clopidogrel monotherapy. Although the UC was treated appropriately with vedolizumab and the patient was in endoscopic mucosal remission, recurrent bleeding episodes from multiple inflammatory pseudopolyps occurred. The bleeding episodes resolved quickly after immediate treatment with factor VIII (Kogenate®). In conclusion, we describe the first patient in the literature with UC and hemophilia A who stayed in long-term remission under therapy with vedolizumab. From our point of view, vedolizumab can be safely administered in the setting of UC and hemophilia A. Antiplatelet drugs which inhibit primary hemostasis must be used with caution in this setting. Bleeding episodes can be treated safely and effectively with factor VIII (Kogenate®).

Use of Ulipristal Acetate for the Management of Fibroid-Related Acute Abnormal Uterine Bleeding.

PubMed

Arendas, Kristina; Leyland, Nicholas A

2016-01-01

Episodes of acute abnormal uterine bleeding related to uterine fibroids can cause significant morbidity. Traditional management with high-dose hormonal regimens may not be as effective when used in women with fibroids. A 32-year-old woman with a 12 cm uterine fibroid presented with an episode of acute abnormal uterine bleeding requiring blood transfusion. In lieu of using a hormonal maintenance regimen after the bleeding had stabilized, the patient was treated with ulipristal acetate 5 mg daily for three months. Amenorrhea was induced rapidly and the patient had no further episodes of acute excessive uterine bleeding. She subsequently underwent a laparoscopic myomectomy with a satisfactory outcome. Ulipristal acetate has been shown to induce amenorrhea rapidly in women with uterine fibroids, and it can be a useful treatment in the emergency management of fibroid-related acute abnormal uterine bleeding. Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Treatment of unscheduled bleeding in continuous oral contraceptive users with doxycycline: a randomized controlled trial.

PubMed

Kaneshiro, Bliss; Edelman, Alison; Carlson, Nichole; Morgan, Kristin; Nichols, Mark; Jensen, Jeffrey

2010-06-01

To estimate whether doxycycline, a matrix metalloproteinase inhibitor, would decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive pill. Participants initiating a continuous oral contraceptive pill (20 micrograms of ethinyl estradiol/90 micrograms of levonorgestrel) were randomly assigned to receive either doxycycline (100 mg orally twice daily) or placebo taken for 5 days at the onset of each bleeding or spotting episode during the first 84 days of the study period. For the final 28 days of the study, participants were observed on the oral contraceptive pill alone. The primary outcome was the number of bleeding and spotting days. A sample size of 66 (33 in each arm) was calculated to detect a 50% reduction in bleeding (beta=0.80, alpha=0.05) and accounted for a 30% dropout rate. Sixty-six women were randomly assinged (33 in each study group). There were no significant differences during the 84-day treatment in bleeding or spotting days (doxycycline [mean {standard error}, placebo, P=.32) or the length of the longest bleeding or spotting episode (doxycycline, placebo, P=.70) between study groups. Similarly, no significant differences in bleeding patterns existed between groups during the final 28 days. Doxycycline, administered once bleeding has started, does not decrease unscheduled bleeding or shorten episodes of unscheduled bleeding in continuous oral contraceptive pill users. I.

Liver transplantation for severe hepatic trauma: Experience from a single center

PubMed Central

Delis, Spiros G; Bakoyiannis, Andreas; Selvaggi, Gennaro; Weppler, Debbie; Levi, David; Tzakis, Andreas G

2009-01-01

Liver transplantation has been reported in the literature as an extreme intervention in cases of severe and complicated hepatic trauma. The main indications for liver transplant in such cases were uncontrollable bleeding and postoperative hepatic insufficiency. We here describe four cases of orthotopic liver transplantation after penetrating or blunt liver trauma. The indications were liver failure, extended liver necrosis, liver gangrene and multiple episodes of gastrointestinal bleeding related to portal hypertension, respectively. One patient died due to postoperative cerebral edema. The other three patients recovered well and remain on immunosuppression. Liver transplantation should be considered as a saving procedure in severe hepatic trauma, when all other treatment modalities fail. PMID:19340909

Von Willebrand factor, a versatile player in gastrointestinal bleeding in left ventricular assist device recipients?

PubMed

Fischer, Quentin; Huisse, Marie-Geneviève; Voiriot, Guillaume; Caron, Claudine; Lepage, Laurent; Dilly, Marie-Pierre; Nataf, Patrick; Ajzenberg, Nadine; Kirsch, Matthias

2015-01-01

Bleeding originating in the gastrointestinal (GI) tract is one of the most common adverse events after left ventricular assist device (LVAD) implantation. In these patients, GI bleeding appears to be the consequence of altered hemostasis on the one hand and alterations of the GI microvasculature on the other. We report the case of a patient who suffered repeated, severe GI bleeding early after implantation of a HeartMate II continuous-flow LVAD. After failure of conventional treatment strategies, GI bleeding was controlled using repeated transfusions of a purified von Willebrand factor (VWF) concentrate, almost devoid of Factor VIII (Wilfactin, LFB). No episodes of pump thrombosis were noted. Subsequent to VWF transfusions, we observed a progressive normalization of circulating vascular endothelial growth factor levels. Our data raise the possibility that, in addition to its hemostatic properties, transfusions of VWF might have acted as an antiangiogenic factor. © 2014 AABB.

[Rupture of splenic artery pseudoaneurysm: an unusual cause of upper gastrointetinal bleeding].

PubMed

Herrera-Fernández, Francisco Antonio; Palomeque-Jiménez, Antonio; Serrano-Puche, Félix; Calzado-Baeza, Salvador Francisco; Reyes-Moreno, Montserrat

2014-01-01

Bleeding from a pancreatic pseudocyst is a severe complication after pancreatitis that can lead to a massive gastrointestinal blood loss. Pseudocyst rupture into the stomach is an unusual complication. We report the case of a 34-year-old woman with a history of alcoholism and a pancreatic pseudocyst. One year after follow-up of her pseudocyst, she arrived at the emergency room with an episode of upper gastrointestinal bleeding. An upper digestive endoscopy showed active bleeding in the subcardial fundus, which could not be endoscopically controlled. Abdominal angio-CT confirmed the diagnosis of a splenic artery pseudoaneurysm in close contact with the back wall of the stomach, as well as a likely fistulization of it. The patient was urgently operated and a distal splenopancreatectomy and fistulorrhaphy was performed. The rupture of a splenic artery pseudoaneurysm may rarely present as upper gastrointestinal bleeding. This may be lethal if not urgently treated.

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.

Hemophilic Chronic Synovitis: Therapy of Hemarthrosis using Endovascular Embolization of Knee and Elbow Arteries

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

Galli, E., E-mail: emgalli1@yahoo.com.ar; Baques, A.; Moretti, N.

2013-08-01

PurposeCongenital hemophilia is a hereditary bleeding disorder that affects 1 in 5,000 males and is characterized by repetitive musculoskeletal bleeding episodes. Selective embolization of the knee and elbow arteries can prevent bleeding episodes. To evaluate the long-term efficacy of these procedures, we assessed the outcomes of 30 procedures performed in our center.MethodsWe performed 30 procedures in 27 hemophilic patients, including 23 knee, and 7 elbow procedures. To evaluate the efficacy of selective embolization of knee and elbow arteries in people with hemophilia, we analyzed the number of bleeding episodes during 12 months before the procedure compared with the amount ofmore » episodes that occurred 3, 6, and 12 months after embolization.ResultsTwenty-nine of 30 procedures were classified as successful. The median of 1.25 episodes per month (range 0-3) observed before the procedure was reduced to 0 (range 0-1.67; p < 0.001) at 3 months, 0.17 (range 0-1.67; p < 0.001) at 6 months, and 0.33 (range 0-1.67; p = 0.024) at 12 months. Three patients remained free of bleeding events for more than 6 months. Additionally, after the procedure there was a significant reduction in factor FVIII usage that sustained up to 12 months after the procedures. No serious adverse events were observed.ConclusionsSelective angiographic embolization of knee and elbow arteries is a feasible procedure that can prevent repetitive bleedings, which would translate in better joint outcomes for these patients.« less

A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.

PubMed

Mehta, Darshan A; Oladapo, Abiola O; Epstein, Joshua D; Novack, Aaron R; Neufeld, Ellis J; Hay, Joel W

2016-02-01

Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to determine the number of bleeding episodes avoided. Based on the median on-demand dose of 695 mcg per kg per bleed, reported by the DOSE registry, the annual rFVIIa on-demand cost was $34,009 per kg of body weight. The annual rFVIIa on-demand cost was $22,020 per kg of body weight when the median dose of 450 mcg per kg per bleed reported by the HTRS registry was considered. The annual cost rose to $38,461 per kg of body weight when the rFVIIa on-demand dose of 786 mcg per kg per bleed among patients infusing an initial dose ≥ 250 mcg per kg was considered. The aPCC (85 units per kg per every other day) and rFVIIa (90 mcg per kg per every day) annual prophylaxis costs were $26,536 and $60,700, respectively. Also, aPCC and rFVIIa prophyaxis treatments were estimated to prevent a total of 20.8 and 12.9 annual bleeding episodes, respectively. When compared with the on-demand dose of 695 mcg per kg per bleed (DOSE registry), the annual aPCC and rFVIIa prophylaxis costs were 21.9% lower and 78.4% higher, respectively. Additionally, aPCC prophylaxis saved $360 per kg for each bleeding episode avoided. rFVIIa prophylaxis cost $2,066 per kg for each bleeding episode avoided. Compared with the on-demand dose of 450 mcg per kg per bleed (HTRS registry), aPCC and rFVIIa prophylaxis costs were 20.5% and 174.9% higher, respectively. In this case, aPCC and rFVIIa prophylaxis treatment costs were $217 per kg and $2,995 per kg, respectively, for each bleeding episode avoided. aPCC and rFVIIa prophylaxis costs were 31.0% lower and 57.8% higher, respectively, when compared with the rFVIIa on-demand dose of 786 mcg per kg per bleed, among patients infusing an initial dose ≥ 250 mcg per kg (HTRS registry). In this case, aPCC prophylaxis saved $573 per kg for each bleeding episode avoided, while rFVIIa prophylaxis costs $1,724 per kg for each bleeding episode avoided. Results of the 2-way sensitivity analyses were robust in the majority of the scenarios considered. aPCC prophylaxis may be cost saving for managing hemophilia patients with inhibitors who bleed frequently and infuse significant quantities of rFVIIa on-demand.

Endovascular Management of Acute Bleeding Arterioenteric Fistulas

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

Leonhardt, Henrik; Mellander, Stefan; Snygg, Johan

2008-05-15

The objective of this study was to review the outcome of endovascular transcatheter repair of emergent arterioenteric fistulas. Cases of abdominal arterioenteric fistulas (defined as a fistula between a major artery and the small intestine or colon, thus not the esophagus or stomach), diagnosed over the 3-year period between December 2002 and December 2005 at our institution, were retrospectively reviewed. Five patients with severe enteric bleeding underwent angiography and endovascular repair. Four presented primary arterioenteric fistulas, and one presented a secondary aortoenteric fistula. All had massive persistent bleeding with hypotension despite volume substitution and transfusion by the time of endovascularmore » management. Outcome after treatment of these patients was investigated for major procedure-related complications, recurrence, reintervention, morbidity, and mortality. Mean follow-up time was 3 months (range, 1-6 months). All massive bleeding was controlled by occlusive balloon catheters. Four fistulas were successfully sealed with stent-grafts, resulting in a technical success rate of 80%. One patient was circulatory stabilized by endovascular management but needed immediate further open surgery. There were no procedure-related major complications. Mean hospital stay after the initial endovascular intervention was 19 days. Rebleeding occurred in four patients (80%) after a free interval of 2 weeks or longer. During the follow-up period three patients needed reintervention. The in-hospital mortality was 20% and the 30-day mortality was 40%. The midterm outcome was poor, due to comorbidities or rebleeding, with a mortality of 80% within 6 months. In conclusion, endovascular repair is an efficient and safe method to stabilize patients with life-threatening bleeding arterioenteric fistulas in the emergent episode. However, in this group of patients with severe comorbidities, the risk of rebleeding is high and further intervention must be considered. Patients with cancer may only need treatment for the acute bleeding episode, and an endovascular approach has the advantage of low morbidity.« less

A comparison of bleeding patterns and cycle control using two transdermal contraceptive systems: a multicenter, open-label, randomized study.

PubMed

Gruber, D; Skřivánek, A; Serrani, M; Lanius, V; Merz, M

2015-02-01

To investigate the bleeding pattern and cycle control parameters of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a patch containing 0.6 mg EE and 6 mg norelgestromin (NGMN). In this phase III, open-label, randomized, parallel-group trial, healthy women aged 18-35 years (smokers aged 18-30 years) received either the EE/GSD patch (n=200) or the EE/NGMN patch (n=198). Treatment consisted of one patch per week for 3 weeks followed by a 7-day, patch-free interval for seven cycles. Bleeding control was assessed in two 90-day reference periods. In reference period 1, mean number of bleeding/spotting days was comparable across treatment groups (p>0.05). However, in reference period 2, there were fewer bleeding/spotting days in the EE/GSD patch group (15.7 versus 18.4; p<0.0001). Mean number of bleeding/spotting episodes was comparable across groups for both reference periods, but bleeding/spotting episodes were shorter for the EE/GSD patch than the EE/NGMN patch during reference period 1 (5.13 days versus 5.53 days, respectively; p<0.05) and reference period 2 (5.07 versus 5.66; p=0.0001). Both treatment groups showed a similar frequency of withdrawal bleeding episodes; however, across all seven cycles, the length of these episodes was consistently shorter with the EE/GSD patch (p<0.01). There were no notable treatment differences in intracyclic bleeding. Bleeding pattern and cycle control achieved with the EE/GSD patch was similar to that of the EE/NGMN patch. The paper presents data on the bleeding pattern and cycle control parameters of an investigational transdermal contraceptive patch containing EE and GSD compared with an approved contraceptive patch containing EE and NGMN. This descriptive study found that bleeding patterns associated with the EE/GSD patch were similar to those of an EE/NGMN patch providing higher EE exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Economic evaluation of major knee surgery with recombinant activated factor VII in hemophilia patients with high titer inhibitors and advanced knee arthropathy: exploratory results via literature-based modeling.

PubMed

Ballal, Rahul D; Botteman, Marc F; Foley, Isaac; Stephens, Jennifer M; Wilke, Caitlyn T; Joshi, Ashish V

2008-03-01

People with severe hemophilia suffer from frequent intra-articular hemorrhages, leading to pain, swelling, reduced flexion, and arthropathy. Elective orthopedic surgery using factor VIII (FVIII) replacement to prevent uncontrolled bleeding has been endorsed as an effective treatment option for patients with severe or advanced hemophilic arthropathy. These surgeries reduce pain, restore mobility and function, and reduce the frequency of recurrent joint bleeds. Unfortunately, some patients with hemophilia develop inhibitors to FVIII, which neutralize FVIII activity and render the use of even massive amounts of FVIII replacement ineffective and surgery very risky. For this reason, elective surgical procedures in high-titer inhibitor patients had largely been abandoned until the introduction of new agents, such as recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Denmark). rFVIIa has been shown effective for prophylaxis during elective surgery and has therefore improved the feasibility of orthopedic surgery in hemophilia patients with high-titer inhibitors. The present research explored, from a modified US payer perspective, the direct economic and quality of life benefits of four different elective knee surgeries (total knee replacement [TKR], knee arthrodesis [KA], proximal tibial osteotomy, and distal femoral osteotomy) with rFVIIa coverage in hemophilia patients with high-titer inhibitors. An exploratory literature-based life-table model was developed to compare the direct medical costs and quality of life of two hypothetical cohorts of high-titer inhibitor patients with frequent bleeding episodes: one undergoing and the other not undergoing elective knee surgery. Knee surgery costs included perioperative rFVIIa costs, inpatient and rehabilitation care, and repeat procedures due to surgery failure, prosthesis loosening or deep infection. Based on efficacy studies, knee surgery was assumed to reduce mean annual bleeding episodes at the affected joint from 9.13 to 1.64. The cost of managing each bleeding episode was estimated at $15 298. Thus, by reducing bleeding episodes, surgery was expected to result in related cost offsets. All costs were expressed in 2006 US dollars. Surgery was also assumed to result in gains in quality of life by reducing pain and reducing bleeding episodes. The impact of pain reduction on quality of life and utility was estimated by simulating EQ-5D scores for a typical patient with and without knee surgery. Based on the model, average knee surgery costs are predicted to range from a low of $694 000 (for KA) to a high of $855 000 (for TKR). However, knee surgery is also expected to reduce the subsequent number of bleeding episodes and resultant costs, leading to long-term costs savings. Due to improvement in pain levels, surgical patients are expected to experience improvements in quality-adjusted life-years (QALYs). Thus, surgery appears to be the preferred strategy (i.e., saves costs and increases QALYs). Based on the assumptions used in the model, the initial cost of knee surgery was offset during the 8th and 10th years for KA and TKR, respectively, with intermediate break-even time for the other surgeries. As expected, cost savings and gains in QALYs increased over time, as well as the cost effective ness of knee surgery. Specifically, the cost per QALY with KA and TKR fell under $50 000/QALY during the 6th and 8th years, respectively, with intermediate time for the other surgeries. The present exploratory analysis is based on the long-term extrapolation of data from a small number of patients without inhibitors and short-term studies. It suggests that major knee surgery utilizing rFVIIa in hemophilia patients with inhibitors may be cost-effective on average, with expected cost savings apparent within a decade of knee surgery. The present exploratory results should be validated with real-world, longitudinal patient data.

Brief psychotic disorder mimicking the symptoms of cerebrovascular attack evoked by symptoms that symbolized death in a patient with terminal stage stomach cancer: case report and review of the literature.

PubMed

Onishi, Hideki; Okuno, Shigeko; Yae, Suzu; Sairenji, Motonori; Onose, Masanari; Mizuno, Yasuhiro; Kawanishi, Chiaki

2006-03-01

We report here a terminally ill patient with stomach cancer who developed a brief psychotic disorder mimicking cerebrovascular attack after a short episode of nasal bleeding. Close examination of the patient revealed that nasal bleeding was an event that symbolized deterioration of the general condition leading to death for the patient. A 77-year-old male, who was diagnosed as having stomach cancer and was receiving palliative care, presented with tremor and insomnia just after a short episode of nasal bleeding and showed reduced response to stimuli mimicking cerebrovascular attack. Laboratory data were unremarkable. The next day, catatonic behavior developed. He had no history of psychiatric illness or drug or alcohol abuse. After receiving haloperidol, psychiatric symptoms disappeared and he returned to the previous level of functioning within 3 days. The patient explained that he had seen a patient whose general condition deteriorated after nasal bleeding and regarded nasal bleeding as a symptom of deteriorating general condition leading to death and thereafter became afraid of the nasal bleeding. Although, nasal bleeding is common and usually not severe in medical settings, for the patient, it was an event that symbolized deterioration of the general condition leading to death. Brief psychotic disorder in cancer patients is rare in the literature, although patients receiving terminal care share various kinds of psychological burden. Medical staff in the palliative care unit should be aware of the psychological distress experienced by each patient and consider brief psychotic disorder as part of the differential diagnosis when patients show unexplained neurological-like and/or psychiatric symptoms.

Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin.

PubMed

Brekelmans, Marjolein P A; Scheres, Luuk J J; Bleker, Suzanne M; Hutten, Barbara A; Timmermans, Anne; Büller, Harry R; Middeldorp, Saskia

2017-04-03

Abnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared the incidence of abnormal vaginal bleeding between patients in both treatment arms and collected information on clinical presentation, diagnostic procedures, management and outcomes. In the AMPLIFY trial, 1122 women were treated with apixaban and 1106 received enoxaparin/warfarin. A clinically relevant non-major (CRNM) vaginal bleeding occurred in 28 (2.5 %) apixaban and 24 (2.1 %) enoxaparin/warfarin recipients (odds ratio [OR] 1.2, 95 % confidence interval [CI] 0.7-2.0). Of all CRNM bleeds, 28 of 62 (45 %) and 24 of 120 (20 %) were of vaginal origin in the apixaban and enoxaparin/warfarin group, respectively (OR 3.4; 95 % CI 1.8-6.7). Premenopausal vaginal bleeds on apixaban were characterised by more prolonged bleeding (OR 2.3; 95 %CI 0.5-11). In both pre- and postmenopausal vaginal bleeds, diagnostic tests were performed in six (21 %) and in seven (29 %) apixaban and enoxaparin/warfarin treated patients, respectively. Medical treatment was deemed not necessary in 16 (57 %) apixaban and 16 (67 %) enoxaparin/warfarin recipients. The severity of clinical presentation and course of the bleeds was mild in 75 % of the cases in both groups. In conclusion, although the absolute number of vaginal bleeding events is comparable between apixaban and enoxaparin/warfarin recipients, the relative occurrence of vaginal bleeds is higher in apixaban-treated women. The characteristics and severity of bleeding episodes were comparable in both treatment arms.

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy.

PubMed

Matarraz, Sergio; Leoz, Pilar; Fernández, Carlos; Colado, Enrique; Chillón, María Carmen; Vidriales, María Belén; González, Marcos; Rivera, Daniel; Osuna, Carlos Salvador; Caballero-Velázquez, Teresa; Van Der Velden, Vincent; Jongen-Lavrencic, Mojca; Gutiérrez, Oliver; Bermejo, Ana Yeguas; Alonso, Luis García; García, Monique Bourgeois; De Ramón Sánchez, Cristina; García-Donas, Gloria; Mateo, Aránzazu García; Recio, Isabel; Sánchez-Real, Javier; Mayado, Andrea; Gutiérrez, María Laura; Bárcena, Paloma; Barrena, Susana; López, Antonio; Van Dongen, Jacques; Orfao, Alberto

2018-03-23

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34 + /CD7 + and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival.In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study.

PubMed

Merz, M; Kroll, R; Lynen, R; Bangerter, K

2015-02-01

The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). In this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18-45 years (smokers aged 18-35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. Mean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. The findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

A pilot, randomised controlled trial of a rotational thromboelastometry-based algorithm to treat bleeding episodes in extracorporeal life support: the TEM Protocol in ECLS Study (TEMPEST).

PubMed

Buscher, Hergen; Zhang, David; Nair, Priya

2017-10-01

Minimal evidence to guide haemostatic therapy for bleeding in extracorporeal life support (ECLS) has resulted in wide variability in practice. We aimed to show that a goal-directed algorithm incorporating results from thromboelastometry (TEM) is feasible and safe for the timely management of bleeding episodes in adult patients receiving ECLS. A pilot randomised controlled trial involving 16 adult patients who underwent ECLS, randomised over 10 months. The intervention group was treated according to a goal-directed algorithm based on TEM results during bleeding episodes. Apart from the intervention, both groups received standard care including conventional laboratory coagulation tests. Need for blood product transfusion, haemorrhagic and thromboembolic complications and survival. There was a statistically non-significant trend towards reduction in the amount of blood products transfused, occurrence of bleeding, and thrombotic complications, when comparing the intervention arm with the control arm. Survival to hospital discharge was 69%. A significant correlation was found between fibrinogen levels and FIBTEM clot firmness at 10 minutes (R = 0.812; P < 0.001); activated partial thromboplastin time and clotting time HEPTEM/INTEM ratio (R = -0.719; P < 0.001); and platelet count and EXTEM clot firmness at 10 minutes (R = 0.783; P < 0.001). TEM allows assessment for coagulation status in a timely manner and its use for the treatment of bleeding episodes in adult patients receiving ECLS appears feasible and safe. Clinical benefit should be investigated in larger multicentre randomised trials.

Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Blanco, Patricia; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews; this review compares different platelet transfusion doses. Objectives To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 × 1011/m2 ± 25%, standard dose 2.2 × 1011/m2 ± 25%, high dose 4.4 × 1011/m2 ± 25%). Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Main results We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT). Overall the methodological quality of studies was low to moderate across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence). Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference −0.17, 95% CI −0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants). Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.20, 95% CI 0.82 to 1.77; low-quality evidence); or high-dose and standard-dose groups (one study; 855 participants; RR 1.11, 95% CI 0.73 to 1.68; low-quality evidence). Two studies reported the time to first bleeding episodes; we were unable to perform a meta-analysis. Both studies (959 participants) individually found that the time to first bleeding episode was either the same, or longer, in the low-dose group compared to the standard-dose group. One study (855 participants) found that the time to the first bleeding episode was the same in the high-dose group compared to the standard-dose group. Three studies reported all-cause mortality within 30 days from the start of the study. There was no difference in all-cause mortality between treatment arms (low-dose versus standard-dose: three studies; 1070 participants; RR 2.04, 95% CI 0.70 to 5.93; low-quality evidence; low-dose versus high-dose: one study; 849 participants; RR 1.33, 95% CI 0.50 to 3.54; low-quality evidence; and high-dose versus standard-dose: one study; 855 participants; RR 1.71, 95% CI 0.51 to 5.81; low-quality evidence). Six studies reported the number of platelet transfusions; we were unable to perform a meta-analysis. Two studies (959 participants) out of three (1070 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a standard-dose. One study (849 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a high-dose strategy. One study (855 participants) out of three (1007 participants) found no difference in the number of platelet transfusions between the high-dose and standard-dose groups. One study reported on transfusion reactions. This study’s authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events. None of the studies reported quality-of-life. Authors’ conclusions In haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found no evidence to suggest that a low-dose platelet transfusion policy is associated with an increased bleeding risk compared to a standard-dose or high-dose policy, or that a high-dose platelet transfusion policy is associated with a decreased risk of bleeding when compared to a standard-dose policy. A low-dose platelet transfusion strategy leads to an increased number of transfusion episodes compared to a standard-dose strategy. A high-dose platelet transfusion strategy does not decrease the number of transfusion episodes per participant compared to a standard-dose regimen, and it may increase the number of transfusion-related adverse events. Findings from this review would suggest a change from current practice, with low-dose platelet transfusions used for people receiving in-patient treatment for their haematological disorder and high-dose platelet transfusion strategies not being used routinely. PMID:26505729

Cost-effectiveness analysis of late prophylaxis vs. on-demand treatment for severe haemophilia A in Italy.

PubMed

Coppola, A; D'Ausilio, A; Aiello, A; Amoresano, S; Toumi, M; Mathew, P; Tagliaferri, A

2017-05-01

Long-term regular administrations of factor VIII (FVIII) concentrate (prophylaxis) initiated at an early age prevents bleeding in patients with severe haemophilia A (HA). The 5-year prospective Italian POTTER study provided evidence of benefits in adolescents and adults of late prophylaxis (LP) vs. on-demand therapy (OD) in reducing bleeding episodes and joint morbidity and improving quality of life; however, costs were increased. The aim of this study was to determine the cost-effectiveness of LP vs. OD with sucrose-formulated recombinant FVIII in adolescents and adults with severe HA in Italy. A Markov model evaluated lifetime cost-effectiveness of LP vs. OD in patients with severe HA in Italy, from both the healthcare and societal perspectives. Clinical input parameters were taken from the POTTER study and published literature. Health utility values were assigned to each health state as measured by the joint disease severity Pettersson score. Costs were expressed in Euro (€) 2014, including drug and other medical costs. Sensitivity analyses were performed considering societal perspective (including productivity lost) and varying relative risk of bleeding episodes between regimens. Clinical outcomes and costs were discounted at 6% according to previous studies. Lifetime incremental discounted quality-adjusted life-years (QALYs) were +4.26, whereas incremental discounted costs were +€229,694 from a healthcare perspective, with estimated incremental cost-effectiveness ratios (ICERs) equal to €53,978/QALY. Sensitivity analyses confirmed the base-case results showing lower ICERs with the societal perspective. Late prophylaxis vs. on-demand therapy results in a cost-effective approach with ICERs falling below the threshold considered acceptable in Italy. © 2017 John Wiley & Sons Ltd.

Preventing bleeds by treatment: new era for haemophilia changing the paradigm.

PubMed

Marijke van den Berg, H

2016-07-01

Coagulation products have allowed patients with severe haemophilia to lead a normal life. This is, however, only true for patients who received an early diagnosis and could start with primary prophylaxis. The absence of a positive family history for haemophilia, in the majority of children with severe haemophilia, postpones the age that treatment can be started. This makes general awareness of the clinical presentation important and a proper diagnosis a prerequisite for progress. The long delay between joint bleeding and overt arthropathy has been an important factor in the delay of implementation of primary prophylaxis. After the development of guidelines on 'how to treat', implementation of the advised practice is needed. Data collection of current treatment regimens in haemophilia centres will support the further optimization of the care for persons with haemophilia and further optimize treatment guidelines. Episodic ('on demand') therapy as a treatment strategy for severe haemophilia needs reconsideration. In an era where clotting factor concentrates are abundant and gene therapy a reality, all patients with severe haemophilia should be offered a strategy of bleeding prevention. © 2016 John Wiley & Sons Ltd.

Novel Application of Percutaneous Cryotherapy for the Treatment of Recurrent Oral Bleeding From a Noninvoluting Congenital Hemangioma Involving the Right Buccal Space and Maxillary Tuberosity

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

Salehian, Sepand, E-mail: sepand@med.umich.edu; Gemmete, Joseph J., E-mail: gemmete@med.umich.edu; Kasten, Steven, E-mail: skasten@med.umich.edu

2011-02-15

Cryotherapy is the application of varying extremes of cold temperatures to destroy abnormal tissue. The intent of this article is to describe a novel technique using percutaneous cryotherapy for treating a noninvoluting congenital craniofacial hemangioma (NICH). An 18-year-old woman with type 1 von Willebrand's disease, as well as a qualitative platelet aggregation disorder, presented with multiple recurrent episodes of oral bleeding from a NICH involving the right buccal space and maxillary tuberosity. The patient was initially treated with a combination of endovascular particulate embolization, percutaneous sclerotherapy, tissue cauterization, and laser therapy between the ages of 4 and 8 years ofmore » age. At 18 years of age, the patient presented with recurrent episodes of oral bleeding related to the NICH. Endovascular embolization was performed using particulate and a liquid embolic agent with limited success. Due to the refractory nature of this bleeding, the patient underwent successful lesion ablation using percutaneous cryotherapy. At 9-month follow-up, the patient is asymptomatic with no episodes of recurrent bleeding.« less

Budget Impact Analysis of Prolonged Half-Life Recombinant FVIII Therapy for Hemophilia in the United States.

PubMed

McMullen, Suzanne; Buckley, Brieana; Hall, Eric; Kendter, Jon; Johnston, Karissa

2017-01-01

Hemophilia A is a factor VIII deficiency, associated with spontaneous, recurrent bleeding episodes. This may lead to comorbidities such as arthropathy and joint replacement, which contribute to morbidity and increased health care expenditure. Recombinant factor VIII Fc fusion protein (rFVIIIFc), a prolonged half-life factor therapy, requires fewer infusions, resulting in reduced treatment burden. Use a budget impact analysis to assess the potential economic impact of introducing rFVIIIFc to a formulary from the perspective of a private payer in the United States. The budget impact model was developed to estimate the potential economic impact of adding rFVIIIFc to a private payer formulary across a 2-year time period. The eligible patient population consisted of inhibitor-free adults with severe hemophilia A, receiving recombinant-based episodic or prophylaxis treatment regimens. Patients were assumed to switch from conventional recombinant factor treatment to rFVIIIFc. Only medication costs were included in the model. The introduction of rFVIIIFc is estimated to have a budget impact of 1.4% ($0.12 per member per month) across 2 years for a private payer population of 1,000,000 (estimated 19.7 individuals receiving treatment for hemophilia A). The introduction of rFVIIIFc is estimated to prevent 124 bleeds across 2 years at a cost of $1891 per bleed avoided. Hemophilia A is a rare disease with a low prevalence; therefore, the overall cost to society of introducing rFVIIIFc is small. Considerations for comprehensively assessing the budget impact of introducing rFVIIIFc should include episodic and prophylaxis regimens, bleed avoidance, and annual factor consumption required under alternative scenarios. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

Complications of Uterine Fibroids and Their Management, Surgical Management of Fibroids, Laparoscopy and Hysteroscopy versus Hysterectomy, Haemorrhage, Adhesions, and Complications

PubMed Central

Mettler, Liselotte; Schollmeyer, Thoralf; Tinelli, Andrea; Malvasi, Antonio; Alkatout, Ibrahim

2012-01-01

A critical analysis of the surgical treatment of fibroids compares all available techniques of myomectomy. Different statistical analyses reveal the advantages of the laparoscopic and hysteroscopic approach. Complications can arise from the location of the fibroids. They range from intermittent bleedings to continuous bleedings over several weeks, from single pain episodes to severe pain, from dysuria and constipation to chronic bladder and bowel spasms. Very seldom does peritonitis occur. Infertility may result from continuous metro and menorrhagia. The difficulty of the laparoscopic and hysteroscopic myomectomy lies in achieving satisfactory haemostasis using the appropriate sutures. The hysteroscopic myomectomy requires an operative hysteroscope and a well-experienced gynaecologic surgeon. PMID:22619681

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

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.

Management of initial bleeding or spotting after levonorgestrel-releasing intrauterine system placement: a randomized controlled trial.

PubMed

Sørdal, Terje; Inki, Pirjo; Draeby, John; O'Flynn, Mary; Schmelter, Thomas

2013-05-01

To assess the efficacy of tranexamic acid or mefenamic acid in the management of the initial "nuisance" bleeding or spotting in the period immediately after placement of the levonorgestrel-releasing intrauterine system. Women were randomized after levonorgestrel-releasing intrauterine system placement to oral tranexamic acid (500 mg), mefenamic acid (500 mg), or placebo three times daily during bleeding or spotting episodes over a 90-day treatment period. Treatment was initiated from onset of a bleeding or spotting episode and continued until the first day after bleeding or spotting stopped and restarted with a new bleeding or spotting episode. The primary efficacy variable was reduction in the number of bleeding or spotting days. Tranexamic acid and mefenamic acid were compared with placebo using a one-sided Wilcoxon rank-sum test. Bonferroni-Holm adjustment was used to account for multiple testing. A total of 204 women were screened; 187 were randomized to tranexamic acid (n=63), mefenamic acid (n=63), or placebo (n=61). The median number of bleeding or spotting days experienced during treatment was 25, 29, and 33 days in the three groups, respectively. The median number of bleeding or spotting days was reduced by 6 days (95% confidence interval [CI] -14.0 to 1.0, P=.049) with tranexamic acid and by 3 days (95% CI -11.0 to 5.0, P=.229) with mefenamic acid compared with placebo. The relative risk of bleeding or spotting compared with placebo with tranexamic acid and mefenamic acid was 0.82 (95% CI 0.65-1.03) and 0.89 (95% CI 0.71-1.11), respectively. Most women (85% or more) were satisfied with the levonorgestrel-releasing intrauterine system across the groups. Tranexamic acid and mefenamic acid during the first 90 days after levonorgestrel-releasing intrauterine system placement do not alleviate "nuisance" bleeding or spotting. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01295294. I.

Effects of a 6-week, individualized, supervised exercise program for people with bleeding disorders and hemophilic arthritis.

PubMed

Mulvany, Ruth; Zucker-Levin, Audrey R; Jeng, Michael; Joyce, Catherine; Tuller, Janet; Rose, Jonathan M; Dugdale, Marion

2010-04-01

People with bleeding disorders may develop severe arthritis due to joint hemorrhages. Exercise is recommended for people with bleeding disorders, but guidelines are vague and few studies document efficacy. In this study, 65% of people with bleeding disorders surveyed reported participating in minimal exercise, and 50% indicated a fear of exercise-induced bleeding, pain, or physical impairment. The purpose of this study was to examine the feasibility, safety, and efficacy of a professionally designed, individualized, supervised exercise program for people with bleeding disorders. A single-group, pretest-posttest clinical design was used. Thirty-three patients (3 female, 30 male; 7-57 years of age) with mild to severe bleeding disorders were enrolled in the study. Twelve patients had co-existing illnesses, including HIV/AIDS, hepatitis, diabetes, fibromyalgia, neurofibromatosis, osteopenia, osteogenesis imperfecta, or cancer. Pre- and post-program measures included upper- and lower-extremity strength (force-generating capacity), joint range of motion, joint and extremity circumference, and distance walked in 6 minutes. Each patient was prescribed a 6-week, twice-weekly, individualized, supervised exercise program. Twenty participants (61%) completed the program. Pre- and post-program data were analyzed by paired t tests for all participants who completed the program. No exercise-induced injuries, pain, edema, or bleeding episodes were reported. Significant improvements occurred in joint motion, strength, and distance walked in 6 minutes, with no change in joint circumference. The greatest gains were among the individuals with the most severe joint damage and coexisting illness. Limitations included a small sample size with concomitant disease, which is common to the population, and a nonblinded examiner. A professionally designed and supervised, individualized exercise program is feasible, safe, and beneficial for people with bleeding disorders, even in the presence of concomitant disease. A longitudinal study with a larger sample size, a blinded examiner, and a control group is needed to confirm the results.

Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A

PubMed Central

Mahlangu, Johnny; Powell, Jerry S.; Ragni, Margaret V.; Chowdary, Pratima; Josephson, Neil C.; Pabinger, Ingrid; Hanabusa, Hideji; Gupta, Naresh; Kulkarni, Roshni; Fogarty, Patrick; Perry, David; Shapiro, Amy; Pasi, K. John; Apte, Shashikant; Nestorov, Ivan; Jiang, Haiyan; Li, Shuanglian; Neelakantan, Srividya; Cristiano, Lynda M.; Goyal, Jaya; Sommer, Jurg M.; Dumont, Jennifer A.; Dodd, Nigel; Nugent, Karen; Vigliani, Gloria; Luk, Alvin; Brennan, Aoife

2014-01-01

This phase 3 pivotal study evaluated the safety, efficacy, and pharmacokinetics of a recombinant FVIII Fc fusion protein (rFVIIIFc) for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in 165 previously treated males aged ≥12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2, weekly prophylaxis (65 IU/kg, n = 24); and arm 3, episodic treatment (10-50 IU/kg, n = 23). A subgroup compared recombinant FVIII (rFVIII) and rFVIIIFc pharmacokinetics. End points included annualized bleeding rate (ABR), inhibitor development, and adverse events. The terminal half-life of rFVIIIFc (19.0 hours) was extended 1.5-fold vs rFVIII (12.4 hours; P < .001). Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. In arm 1, the median weekly dose was 77.9 IU/kg; approximately 30% of subjects achieved a 5-day dosing interval (last 3 months on study). Across arms, 87.3% of bleeding episodes resolved with 1 injection. Adverse events were consistent with those expected in this population; no subjects developed inhibitors. rFVIIIFc was well-tolerated, had a prolonged half-life compared with rFVIII, and resulted in low ABRs when dosed prophylactically 1 to 2 times per week. This trial was registered at www.clinicaltrials.gov as #NCT01181128. PMID:24227821

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.

Vaginal bleeding

MedlinePlus

... who are approaching menopause. Women who take oral contraceptives may experience episodes of abnormal vaginal bleeding. Often ... Practice Bulletin No. 110: noncontraceptive uses of hormonal contraceptives. Obstet Gynecol . 2010;115(1):206-218. PMID: ...

Is on-demand treatment effective in patients with severe haemophilia?

PubMed

Aznar, J A; Marco, A; Jiménez-Yuste, V; Fernández-Fontecha, E; Pérez, R; Soto, I; Parra, R; Moreno, M; Mingot, M E; Moret, A

2012-09-01

On-demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on-demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on-demand and short-term prophylaxis regimen; the rest was under on-demand treatment. One hundred and forty-five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy-one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty-three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty-six patients underwent orthopaedic surgery at least once. These data show that on-demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary. © 2012 Blackwell Publishing Ltd.

Poland's syndrome: report of a variant.

PubMed

Legbo, Jacob Ndas

2006-01-01

Poland's syndrome is a rare congenital anomaly consisting of unilateral partial or total absence of a breast and/or pectoralis major muscle, and ipsilateral symbrachydactyly. Many structural and functional abnormalities have been described in association with the syndrome. However, only a few hemostatic disorders have been reported. The case of a 12-year-old secondary school girl with unilateral hypoplasia of the breast, absence of anterior axillary fold and absence of the pectoralis major muscle is hereby presented. She also had thrombocytopenia and several episodes of spontaneous bleeding from the ipsilateral anterior chest wall. She did well on medical treatment, with no recurrence of bleeding 10 months after treatment. The author is not aware of any previously reported case of Poland's syndrome associated with bleeding disorder in Africa. This case is presented to alert clinicians of its existence and possible association with hematological disorders.

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.

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.

Endoscopic variceal ligation for primary prophylaxis of esophageal variceal hemorrhage in pre-liver transplant patients.

PubMed

Lim, Eu Jin; Gow, Paul J; Angus, Peter W

2009-11-01

Endoscopic variceal ligation (EVL) is widely used to prevent esophageal variceal bleeding in patients with advanced cirrhosis. However, the safety and efficacy of EVL in this setting have not been clearly established. This study included 300 adult patients with cirrhosis on our liver transplant waitlist who underwent upper gastrointestinal endoscopy. Esophageal varices deemed to be at high risk of bleeding were banded until eradication or transplantation. A retrospective review of patient notes and endoscopy databases was undertaken, and the number of banding episodes, complications, and patient outcomes were recorded. Forty-two of 300 patients presented with or had previous variceal bleeding prior to referral and were excluded from the analysis. Of the remaining 258 patients, 101 underwent a total of 259 banding episodes (2.6 per patient) with a median follow-up post-banding of 18.4 months per patient (a total of 150 patient years). Failed prophylaxis occurred in 2 patients (2%), and there were 3 episodes (1.2%) of acute hematemesis from band-induced ulceration. One patient (1%) had mild esophageal stricturing post-banding without dysphagia. Four of 36 patients (11%) previously found to have moderately sized or larger varices that were not banded presented with hematemesis due to variceal bleeding and were subsequently banded. None of the patients that received banding died because of bleeding or failed to receive a transplant as a result of banding complications. This study shows that in liver transplant candidates, EVL is highly effective in preventing first variceal bleed. Although banding carries a small risk of band-induced bleeding, this rate is low in comparison with the predicted rate of variceal bleeding in this population.

A randomized controlled trial of treatment options for troublesome uterine bleeding in Implanon users

PubMed Central

Weisberg, E.; Hickey, M.; Palmer, D.; O'Connor, V.; Salamonsen, L.A.; Findlay, J.K.; Fraser, I.S.

2009-01-01

BACKGROUND Pilot data have indicated that both doxycycline alone and mifepristone combined with ethinyl estradiol (EE) are effective in stopping episodes of bleeding in Implanon users with troublesome bleeding. We compared four treatments against a placebo in Implanon users and tested whether repeated treatment improved subsequent bleeding patterns. METHOD Implanon users aged 18–45 years were randomized to treatment with (i) mifepristone 25 mg given twice on day 1 followed by 4 days of EE 20 µg; (ii) doxycycline 100 mg twice daily for 5 days; (iii) mifepristone 25 mg given twice on day 1 plus doxycycline 100 mg twice daily for 5 days; (iv) doxycycline 100 mg twice daily with EE 20 µg daily; and (v) placebo twice daily for 5 days. The primary end-point was the number of days of bleeding/spotting immediately following initiation of the first 5-day course of each therapy, compared with placebo. RESULTS There were 204 women assigned to treatment. Mifepristone in combination with either EE or doxycycline was significantly more effective in stopping an episode of bleeding (mean 4.0 days (CI 3.5–4.6) and 4.4 days (CI 3.8–5.2), respectively) than doxycycline alone or in combination with EE, or placebo (6.4 days (CI 4.4–9.2), 6.4 days (CI 4.8–8.6) and 6.4 days (CL 5.1–8.0), respectively). CONCLUSION Mifepristone combined with either EE or doxycycline was significantly more effective than placebo in terminating an episode of bleeding in Implanon users. However there was no improvement in subsequent bleeding patterns. Trial registration number: ACTR # 012605000206628. PMID:19369294

Susoctocog Alfa: A Review in Acquired Haemophilia A.

PubMed

Burness, Celeste B; Scott, Lesley J

2016-05-01

Intravenous susoctocog alfa (Obizur(®)) is a recombinant, B-domain deleted, porcine sequence antihaemophilic factor VIII (FVIII) product that has recently been approved for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA). Intravenous susoctocog alfa was an effective and generally well tolerated treatment for serious bleeding episodes in adult patients with AHA in a multinational, phase II/III trial (n = 28 evaluable). Patients received an initial dose of susoctocog alfa 200 U/kg, with subsequent dosages based on target FVIII trough levels and clinical assessments. All patients had a positive haemostatic response (based on predefined criteria) of the primary bleed 24 h after the first infusion of susoctocog alfa, with the bleed successfully controlled at the time of final dosing in 86 % of patients. The most frequently reported adverse reaction (incidence >5 %) was the development of inhibitory antibodies against susoctocog alfa (porcine FVIII). Overall, 25 % of antibody naive patients developed anti-susoctocog alfa antibodies during the study. No serious treatment-related adverse events, thrombotic events or allergic reactions were reported during the trial. In conclusion, intravenous susoctocog alfa is a useful addition to the limited treatment options available for the management of acute bleeding episodes in adults with AHA.

Clinical utility and patient perspectives on the use of extended half-life rFIXFc in the management of hemophilia B

PubMed Central

Miguelino, Maricel G; Powell, Jerry S

2014-01-01

Hemophilia B is an X-linked genetic disease caused by mutation of the gene for coagulation protein factor IX (FIX), with an incidence of approximately once every 30,000 male births in all populations and ethnic groups. When severe, the disease leads to spontaneous life threatening bleeding episodes. When untreated, most patients die from bleeding complications before 25 years of age. Current therapy requires frequent intravenous infusions of therapeutic recombinant or plasma-derived protein concentrates containing FIX. Most patients administer the infusions at home every few days, and must limit their physical activities to avoid abnormal bleeding when the FIX activity levels are below normal. After completing the pivotal Phase III clinical trial, a new therapeutic FIX preparation that has been engineered for an extended half-life in circulation, received regulatory approval in March 2014 in Canada and the US. This new FIX represents a major therapeutic advance for patients with hemophilia B. The half-life is prolonged due to fusion of the native FIX molecule with the normal constant region of immunoglobulin G. This fusion molecule then follows the normal immunoglobulin recirculation pathways through endothelial cells, resulting in prolonged times in circulation. In the clinical trials, over 150 patients successfully used eftrenonacog alfa regularly for more than 1 year to prevent spontaneous bleeding, to successfully treat any bleeding episodes, and to provide effective coagulation for major surgery. All infusions were well tolerated and effective, with no inhibitors detected and no safety concerns. This promising therapy should allow patients to use fewer infusions to maintain appropriate FIX activity levels in all clinical settings. PMID:25143713

Interventions for treating acute bleeding episodes in people with acquired hemophilia A.

PubMed

Zeng, Yan; Zhou, Ruiqing; Duan, Xin; Long, Dan; Yang, Songtao

2014-08-28

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). In most cases, bleeding episodes are spontaneous and severe at presentation. The optimal hemostatic therapy is controversial. To determine the efficacy of hemostatic therapies for acute bleeds in people with acquired hemophilia A; and to compare different forms of therapy for these bleeds. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 4) and MEDLINE (Ovid) (1948 to 30 April 2014). We searched the conference proceedings of the: American Society of Hematology; European Hematology Association; International Society on Thrombosis and Haemostasis (ISTH); and the European Association for Haemophilia and Allied Disorders (EAHAD) (from 2000 to 30 April 2014). In addition to this we searched clinical trials registers. All randomised controlled trials and quasi-randomised trials of hemostatic therapies for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. No randomised clinical trials of hemostatic therapies for acquired hemophilia A were found. Thus, we are not able to draw any conclusions or make any recommendations on the optimal hemostatic therapies for acquired hemophilia A based on the highest quality of evidence. GIven that carrying out randomized controlled trials in this field is a complex task, the authors suggest that, while planning randomised controlled trials in which patients can be enrolled, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence, which hopefully, in the future, will also be appraised and incorporated in a Cochrane Review.

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.

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.

First bleeding episode from oesophageal varices in cirrhotic patients: a prospective study of endoscopic predictive factors.

PubMed

Colombo, E; Casiraghi, M A; Minoli, G; Prada, A; Terruzzi, V; Bortoli, A; Carnovali, M; Gullotta, R; Imperiali, G; Comin, U

1995-09-01

Two hundred patients affected by liver cirrhosis and oesophageal varices were studied in 9 Gastrointestinal Units in Lombardy (Northern Italy) in order to assess factors possibly related to variceal bleeding. Only patients without any previous episode of gastrointestinal bleeding were included in the prospective evaluation. For each patient demographic data, aetiology of cirrhosis, various clinical and biochemical parameters able to group patients into the three Child-Pugh Classes, endoscopic items for calculation of Beppu's and of NIEC prognostic scores were recorded on computerized cards. Patients were regularly interviewed every three months for one year and underwent an upper gastrointestinal endoscopy at enrollment, after six months and in case of bleeding. Within the twelve-month follow-up period, 29 out of the 200 patients (14%) bled and 52 out of 200 died (26%). In 16 of the 52 patients who died (59% of bleeding patients) death was directly related to gastrointestinal bleeding. Bleeding from oesophageal varices was endoscopically proven in 19/29 patients, in another 9 bleeding was classified as from unknown source and in one patient a bleeding gastric ulcer was diagnosed. Univariate analysis of all the recorded clinical, biochemical and endoscopic parameters, performed by Chi-square method and Fisher exact test showed that the presence of RWM (p < 0.001) was the only factor significantly associated to variceal bleeding within one year. Relationship between size of varices and bleeding was very close to the statistical significance but did not achieve it (p = 0.058).

Overall mortality among patients surviving an episode of peptic ulcer bleeding

PubMed Central

Ruigomez, A.; Rodriguez, L. A.; Hasselgren, G.; Johansson, S.; Wallander, M.

2000-01-01

STUDY OBJECTIVE—The authors investigated whether patients who have survived an acute episode of peptic ulcer bleeding (PUB) have an excess long term all cause mortality compared with the general population free of PUB.
DESIGN—Follow up study of previously identified cohort of patients with a PUB episode and a general population cohort.
SETTING—The source population included all people aged 30 to 89 years, registered with general practitioners in the United Kingdom.
PATIENTS—All patients alive one month after the PUB episode constituted the cohort of PUB patients (n=978). A control group of 5000 people was randomly sampled from the source population. The same eligibility criteria as for patients with PUB were applied to the control series. Also, controls had to be free of PUB before start date.
MAIN RESULTS—Relative risk of mortality among PUB patients was 2.1, 95%CI: 1.7, 2.6) compared with the general population. This increased mortality risk occurred mainly in the patients less than 60 years old. No difference was observed between men and women. The excess mortality was not only circumscribed to deaths attributable to recurrent gastrointestinal bleed, but also cardiovascular, cancer and other causes.
CONCLUSIONS—People who have survived an acute episode of PUB have a reduced long term survival compared with the general population.This reduction was stronger among middle age patients than in the elderly.


Keywords: cohort study; mortality; peptic ulcer; bleeding; population-based study PMID:10715746

Factor VII deficiency: a single-center experience.

PubMed

Salcioglu, Zafer; Akcay, Arzu; Sen, Hulya Sayilan; Aydogan, Gonul; Akici, Ferhan; Tugcu, Deniz; Ayaz, Nuray Aktay; Baslar, Zafer

2012-11-01

Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.

Poland's syndrome: report of a variant.

PubMed Central

Legbo, Jacob Ndas

2006-01-01

Poland's syndrome is a rare congenital anomaly consisting of unilateral partial or total absence of a breast and/or pectoralis major muscle, and ipsilateral symbrachydactyly. Many structural and functional abnormalities have been described in association with the syndrome. However, only a few hemostatic disorders have been reported. The case of a 12-year-old secondary school girl with unilateral hypoplasia of the breast, absence of anterior axillary fold and absence of the pectoralis major muscle is hereby presented. She also had thrombocytopenia and several episodes of spontaneous bleeding from the ipsilateral anterior chest wall. She did well on medical treatment, with no recurrence of bleeding 10 months after treatment. The author is not aware of any previously reported case of Poland's syndrome associated with bleeding disorder in Africa. This case is presented to alert clinicians of its existence and possible association with hematological disorders. Images Figure 1 PMID:16532987

Extended-Cycle Levonorgestrel/Ethinylestradiol and Low-Dose Ethinylestradiol (Seasonique(®)): A Review of Its Use as an Oral Contraceptive.

PubMed

Burness, Celeste B

2015-06-01

A 91-day extended-cycle oral contraceptive (OC) consisting of levonorgestrel/ethinylestradiol 150/30 µg for 84 days and ethinylestradiol 10 µg for 7 days (Seasonique(®)) has recently been approved for the prevention of pregnancy in adult women in the EU. This regimen allows for a reduction in the number of withdrawal bleeding episodes to four per year, compared with 13 episodes per year with conventional 28-day regimens. Seasonique(®) was effective in preventing pregnancy in a large (n = 1006), noncomparative trial of healthy, sexually active women. In this trial, the overall Pearl index (pregnancies per 100 woman-years of use) in women aged 18-35 years (n = 621) was 0.76 and the Pearl index for method-failure (compliant use) was 0.26. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with a mean of 2 days of bleeding and 1 day of spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting was highest during the first few cycles of use and decreased thereafter. Seasonique(®) was generally well tolerated, with a tolerability profile in line with that expected for OCs. Seasonique(®) extends the contraceptive options currently available to women, particularly in those who desire fewer withdrawal bleeding episodes.

Challenges and successes in the treatment of hemophilia: the story of a patient with severe hemophilia A and high-titer inhibitors

PubMed Central

Saba, Hussain I; Tran, Duc Quang

2012-01-01

In the past, patients with severe hemophilia have suffered a substantially reduced quality of life with frequent bleeding episodes, disabling arthropathy, and shorter life expectancy. In addition, methods of treatment and management have been costly and time-consuming, and have placed a considerable burden on patients’ physical and psychological well-being. With the advent of the on-demand therapy and prophylactic treatment paradigm, patients have been able to receive care with less interruption of daily activities. Treatments may be more challenging for hemophiliacs with inhibitors to replacement factor; however, recent advances in the use of bypassing agents and immune tolerance therapy have enabled them to aggressively manage their disease while maintaining their independence. This review focuses on the challenges of treating such a severe hemophiliac through examination of the lifetime experience of a young adult male with a severe form of congenital hemophilia A. At this stage of his life, the patient has minimal disabilities and is inhibitor-free through optimal care and strong family support. His aspiration to pursue a productive life has led him to a career in medicine. After receiving his medical degree, he pursued a specialty in the treatment of hemophilia. By assisting other hemophilia patients, he exemplifies both the rewards of persevering through episodes of bleeding and other complications and the fact that disabilities can be minimized when managed meticulously and in a timely fashion to enable a productive and dignified life. PMID:22715320

Women's bleeding patterns: ability to recall and predict menstrual events. World Health Organization Task Force on Psychosocial Research in Family, Planning, Special Programme of Research, Development and Research Training in Human Reproduction.

PubMed

1981-01-01

Objective records of the occurrence of menstrual bleeding were compared with women's subjective assessments of the timing and duration of these events. The number of days a woman experienced bleeding during each episode was relatively constant; however, the length of the bleeding episode varied greatly among the 13 cultures studies. A greater understanding of menstrual patterns is possible if the pattern is seen as a succession of discrete events rather than as a whole. A more careful use of terminology relating to these discrete events would provide greater understanding of menstruation for the woman concerned and those advising her. The methodology employed in the collection of data about menstrual events among illiterate women is described and suggestions given as to how such information can be most efficiently obtained.

Congenital afibrinogenemia: from etiopathogenesis to challenging clinical management.

PubMed

Stanciakova, Lucia; Kubisz, Peter; Dobrotova, Miroslava; Stasko, Jan

2016-07-01

Congenital afibrinogenemia belongs to the group of autosomal recessive bleeding disorders and represents the absolute deficiency of fibrinogen detected by an antigenic test. This can lead to severe clinical manifestations of the disorder. Therefore, it is very important to take afibrinogenemia into account in the process of the differential diagnostics of the patients. The authors provide a summary of currently available literature about afibrinogenemia. They collected the information from the scientific journals dedicated to thrombosis and hemostasis and searched world-wide databases. Expert commentary: The most frequent clinical manifestation of this disorder is mucosal bleeding, but musculoskeletal bleeding pattern, gynecologic and obstetric issues, spontaneous bleeding, episodes provoked by minor injury or any other intervention, and even paradoxical thromboembolic events have been published. Afibrinogenemia is the consequence of mutations of the homozygous or compound heterozygous type in gene FGA, FGB or FGG encoding fibrinogen. Pregnant women with a family history, or with a history of consanguinity ought to be properly counselled. However, primary prophylaxis of bleeding events is not suggested. The article deals with actual information about afibrinogenemia contributing to its early diagnosis and effective treatment, which in many cases requires multidisciplinary approach.

Haemophilia and joint disease: pathophysiology, evaluation, and management

PubMed Central

Knobe, Karin; Berntorp, Erik

2011-01-01

In patients with haemophilia, regular replacement therapy with clotting factor concentrates (prophylaxis) is effective in preventing recurrent bleeding episodes into joints and muscles. However, despite this success, intra-articular and intramuscular bleeding is still a major clinical manifestation of the disease. Bleeding most commonly occurs in the knees, elbows, and ankles, and is often evident from early childhood. The pathogenesis of haemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage, and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (haemophilic synovitis) that contribute to end-stage degeneration (haemophilic arthropathy); with pain and limitation of motion severely affecting patients’ quality of life. If joint bleeding is not treated adequately, it tends to recur, resulting in a vicious cycle that must be broken to prevent the development of chronic synovitis and degenerative arthritis. Effective prevention and management of haemophilic arthropathy includes the use of early, aggressive prophylaxis with factor replacement therapies, as well as elective procedures, including restorative physical therapy, analgesia, aspiration, synovectomy, and orthopaedic surgery. Optimal treatment of patients with haemophilia requires a multidisciplinary team comprising a haematologist, physiotherapist, orthopaedic practitioner, rehabilitation physician, occupational therapist, psychologist, social workers, and nurses. Journal of Comorbidity 2011;1:51–59 PMID:29090136

A randomized controlled trial of electrocoagulation-enabled biopsy versus conventional biopsy in the diagnosis of endobronchial lesions.

PubMed

Khan, Ajmal; Aggarwal, Ashutosh N; Agarwal, Ritesh; Bal, Amanjit; Gupta, Dheeraj

2011-01-01

Although electrocoagulation at time of endobronchial biopsy can potentially reduce procedure-related bleeding during fiberoptic bronchoscopy (FOB), it can also impair quality of tissue specimen; credible data for either are lacking. To evaluate the impact of hot biopsy on the quality of tissue samples and to quantify the amount of procedure-related bleeding during endobronchial biopsy. In this single-center, prospective, single-blind, randomized controlled study we included adult patients referred for FOB and having endobronchial lesions. Patients were randomized to bronchial biopsy using an electrocoagulation-enabled biopsy forceps, with (EC+ group) or without (EC- group) application of electrocoagulation current (40 W for 10 s in a monopolar mode). Procedure-related bleeding was semi-quantified by observer description, as well as through a visual analogue scale. Overall quality of biopsy specimen and tissue damage were assessed and graded by a pulmonary pathologist blinded to FOB details. 160 patients were randomized to endobronchial biopsy with (n = 81) or without (n = 79) the application of electrocoagulation. There were no severe bleeding episodes in either group, and severity of bleeding in the EC+ and EC- groups was similar (median visual analogue scale scores of 14 and 16, respectively). Histopathological diagnosis was similar in the EC+ and EC- groups (77.8% and 82.3%, respectively). There was no significant difference in tissue quality between the two groups. Use of electrocoagulation-enabled endobronchial biopsy does not alter specimen quality and does not result in any significant reduction in procedure-related bleeding. Copyright © 2010 S. Karger AG, Basel.

Clinical manifestations and outcomes of antithrombotic treatment of the Tan Tock Seng Hospital Singapore antiphospholipid syndrome cohort.

PubMed

Tan, B E; Thong, B Y H; Shivananda, S; Han, W W; Chng, H H

2009-07-01

To examine the clinical manifestations, intensity of oral anticoagulation and outcomes in the prevention of recurrent thromboses in patients with antiphospholipid syndrome (APS) in a tertiary rheumatology centre in Singapore. Retrospective case review of consecutive patients with APS attending a rheumatology clinic from 1st January 2004 to 31st December 2005. There were 59 (44%) patients with definite APS and 75 (56%) with probable APS. Systemic lupus erythematosus (SLE) was the most common cause of secondary APS. Hypertension and hyperlipidaemia were the most common cardiovascular comorbidities. The most common manifestations were haematological (thrombocytopaenia and haemolytic anaemia), neurological (seizure, headache) and pulmonary hypertension. Among those with definite APS, there were similar proportions with arterial and venous thromboses. Recurrent thromboses occurred in 14 (23.7%) patient with definite APS receiving warfarin, comprising 14 (73.7%) episodes of arterial and 5 (26.3%) episodes of venous thromboses. Recurrent arterial thromboses occurred at international normalized ratio (INR) of <2 in 5 (35.7%), INR 2-3 in 6 (42.9%), INR > 3 in 3 (21.4%) episodes, respectively. Recurrent venous thromboses occurred at INR < 2 in 4 (80.0%) and INR > 3 in 1 (20.0%) episode, respectively. Twenty-eight episodes of bleeding occurred in 21 (35.6%) patients, the majority (78.6%) being minor bleeding. Two-thirds of all major bleeds occurred at INR >/= 3. Venous and arterial thromboses were equally common in our patients with definite APS, although recurrent thromboses were more common in the arterial circulation. Target INR > 3 was associated with lower rates of recurrent arterial thromboses but higher rates of major and recurrent bleeding. Target INR >/= 2 appeared to be sufficient to prevent recurrent venous thromboses.

Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage

PubMed Central

Chun, Stephen G; Pedro, Patrick; Yu, Mihae; Takanishi, Danny M

2011-01-01

Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency. PMID:21966332

Bleeding from duodenal ulcer in a patient with bilio-pancreatic diversion.

PubMed

Garancini, Mattia; Luperto, Margherita; Delitala, Alberto; Maternini, Matteo; Uggeri, Franco

2011-12-01

Scopinaro's bilio-pancreatic diversion is considered as an acceptable malabsorptive surgical approach for the treatment of morbid obesity. We describe a case of acute recurrent gastro-intestinal bleeding in a patient with a previous Scopinaro's bilio-pancreatic diversion. At the first admission in our department, gastroscopy, colonoscopy, contrast-enhanced computerized tomography and angiography resulted negative for active bleeding. Hypovolemic shock indicated laparotomy and an intraoperative enteroscopy performed through a small enterotomy showed an ulcerative perforation sourced in an ischemic portion of a distended duodenal stump, with a bleeding branch of gastro-duodenal artery at the bottom. Hemorrhage was stopped with stitches. Two years later a new episode of duodenal bleeding associated with severe malnutrition occurred. A covered chronic ischemic perforation sustained by duodenal distension due to biliopancreatic limb sub-obstruction appeared to be the most probable etiology of the recurrent duodenal bleeding. The patient underwent again to laparotomy and adhesiolysis; hemorrhage was stopped by means of ligation of gastroduodenal artery and bilio-pancreatic diversion was converted into a standard Roux-en-Y gastroenterostomy with an entero-entero anastomosis 40 cm from the Treitz ligament in order to restore an anatomo-functional condition guaranteeing normal absorption and intestinal transit. After Scopinaro's bilio-pancreatic diversion duodenal bleeding can represent a rare serious presentation of biliopancreatic limb obstruction; because of the complex anatomical reconstruction performed during this intervention, the duodenum results unavailable during upper gastro-intestinal endoscopy, and if a duodenal bleeding is suspected laparotomy followed by enteroscopy represents an effective diagnostic approach.

Anal carcinoma and HIV infection: is it time for screening?

PubMed

Herranz-Pinto, P; Sendagorta-Cudós, E; Bernardino-de la Serna, J I; Peña-Sánchez de Rivera, J M

2014-03-01

A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5cm sized tumor, with infiltration at the base was detected on digital exam, located at 15mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have been prevented? Copyright © 2013 Elsevier España, S.L. All rights reserved.

Chromogenic Factor VIII Assays for Improved Diagnosis of Hemophilia A.

PubMed

Rodgers, Susan; Duncan, Elizabeth

2017-01-01

Hemophilia A is an inherited bleeding disorder caused by a reduced level of factor VIII coagulant activity (FVIII:C) in blood. Bleeding episodes may occur spontaneously in the severe form of hemophilia or after trauma in the milder forms. It is important that patients are diagnosed correctly, which includes placing them into the correct severity category of the disorder so that appropriate treatment can be given. Diagnosis is made by determination of the amount of FVIII:C in the blood, usually using a one-stage factor VIII:C assay. However, approximately one third of patients with mild or moderate hemophilia will have much lower results by the chromogenic assay, with some of them having normal results by the one-stage assay. The chromogenic factor VIII assay is used in some specialized hemophilia reference centers and is recommended for the diagnosis of mild hemophilia A, as this assay is considered to better reflect the severity status of hemophilia patients than the one-stage assay.

Oral Surgical Treatment of Patients With Chronic Liver Disease: Assessments of Bleeding and Its Relationship With Thrombocytopenia and Blood Coagulation Parameters.

PubMed

Cocero, Nadia; Bezzi, Marta; Martini, Silvia; Carossa, Stefano

2017-01-01

Cirrhotic patients awaiting liver transplantation require eradication of infectious oral foci to prevent septic episodes after transplantation; however, cirrhosis can hinder hemostasis and can result in severe bleeding. The present study assessed the bleeding risk factors connected with the clinical history of these patients and the characteristics of the extractions. We retrospectively analyzed 1183 extractions in 318 patients, including 47 with severe end-stage liver disease who were outside of our intention-to-treat bracket (ie, platelet count [PLT] >40 × 10 3 /μL and international normalized ratio [INR] <2.5). Follow-up examinations included inspection of the oral cavity on the first, third, and seventh days, with reparatory surgery in the case of severe bleeding. Continuous variables were compared using the Mann-Whitney U and Kruskal-Wallis tests, and categorical variables were compared using Fisher's exact test. Binary logistic regression analysis was also performed. Within the intention-to-treat bracket, 1 of the 271 patients (0.4%) required surgical repair. The bleeding rate for an INR of 2.5 or more was significantly greater than that for a PLT of 40 × 10 3 /μL or less (4 of 10 [40%] versus 2 of 34 [6%]; P = .02]. All 3 patients with both an INR of 2.5 or more and a PLT of 40 × 10 3 /μL or less exhibited severe bleeding. No significant association between the occurrence of bleeding with either liver disease etiology or the number of molars extracted was found. No patient required hospitalization. Patients with a PLT greater than 40 × 10 3 /μL and an INR of less than 2.5 can be considered relatively low-risk patients. However, an INR of 2.5 or more and, to a minor degree, a PLT of 40 × 10 3 /μL or less represent significant risk factors. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

A case of multiple recurrence of Clostridium difficile infection with severe hematochezia in an immunocompromised host.

PubMed

Zhang, Xuewu; Chen, Yunbo; Gu, Silan; Zheng, Beiwen; Lv, Tao; Lou, Yinjun; Jin, Jie

2016-12-01

Clostridium difficile infection (CDI) is increasing in incidence and severity. Clinically, diarrhea frequently occurs, but severe hematochezia is rarely seen with CDI. We describe here a hematopoietic stem cell transplantation (HSCT) recipient who experienced life-threatening gastrointestinal bleeding due to severe CDI. Subsequent stool surveillance and molecular typing observed the patient who had two episodes of recurrence with a new strain of C. difficile distinct from the initial infection. We analyze C. difficile strains obtained from the patient, and also discuss the diagnosis and treatment of this case. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigation of Women with Postmenopausal Uterine Bleeding: Clinical Practice Recommendations

PubMed Central

Munro, Malcolm G

2014-01-01

Postmenopausal uterine bleeding is defined as uterine bleeding after permanent cessation of menstruation resulting from loss of ovarian follicular activity. Bleeding can be spontaneous or related to ovarian hormone replacement therapy or to use of selective estrogen receptor modulators (eg, tamoxifen adjuvant therapy for breast carcinoma). Because anovulatory “cycles” with episodes of multimonth amenorrhea frequently precede menopause, no consensus exists regarding the appropriate interval of amenorrhea before an episode of bleeding that allows for the definition of postmenopausal bleeding. The clinician faces the possibility that an underlying malignancy exists, knowing that most often the bleeding comes from a benign source. Formerly, the gold-standard clinical investigation of postmenopausal uterine bleeding was institution-based dilation and curettage, but there now exist office-based methods for the evaluation of women with this complaint. Strategies designed to implement these diagnostic methods must be applied in a balanced way considering the resource utilization issues of overinvestigation and the risk of missing a malignancy with underinvestigation. Consequently, guidelines and recommendations were developed to consider these issues and the diverse spectrum of practitioners who evaluate women with postmenopausal bleeding. The guideline development group determined that, for initial management of spontaneous postmenopausal bleeding, primary assessment may be with either endometrial sampling or transvaginal ultrasonography, allowing patients with an endometrial echo complex thickness of 4 mm or less to be managed expectantly. Guidelines are also provided for patients receiving selective estrogen receptor modulators or hormone replacement therapy, and for an endometrial echo complex with findings consistent with fluid in the endometrial cavity. PMID:24377427

Recombinant factor VIIa (eptacog alfa): a pharmacoeconomic review of its use in haemophilia in patients with inhibitors to clotting factors VIII or IX.

PubMed

Lyseng-Williamson, Katherine A; Plosker, Greg L

2007-01-01

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment. Prophylactic treatment with recombinant factor VIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery. Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia. In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters. Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients undergoing or not undergoing surgery was predicted to decline over time, as savings were realised from the decrease in the number of bleeding episodes requiring treatment in patients who underwent surgery. In haemophilia patients with inhibitors, recombinant factor VIIa is clinically effective in controlling mild to moderate bleeds, and in maintaining haemostasis in patients undergoing orthopaedic surgery. Available pharmacoeconomic data from several countries, despite inherent limitations, support the use of recombinant factor VIIa as a treatment option that is at least cost neutral relative to aPCC in treating mild to moderate bleeds in this patient population. In addition, orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors is generally cost saving relative to not having surgery over the medium to long term, as the acquisition costs of recombinant factor VIIa are offset by cost savings resulting from the decrease in the number of joint-related bleeds.

Health economics in haemophilia: a review from the clinician's perspective.

PubMed

Escobar, M A

2010-05-01

Health economic evaluations provide valuable information for healthcare providers, facilitating the treatment decision-making process in a climate where demand for healthcare exceeds the supply. Although an uncommon disease, haemophilia is a life-long condition that places a considerable burden on patients, healthcare systems and society. This burden is particularly large for patients with haemophilia with inhibitors, who can develop serious bleeding complications unresponsive to standard factor replacement therapies. Hence, bleeding episodes in these patients are treated with bypassing agents such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrates (pd-APCC). With the efficacy of these agents now well established, a number of health economic studies have been conducted to compare their cost-effectiveness for the on-demand treatment of bleeding episodes in haemophiliacs with inhibitors. In a cost-utility analysis, which assesses the effects of treatment on quality of life (QoL) and quantity of life, the incremental cost per quality-adjusted life-year (QALY) gained (US $44,834) indicated that rFVIIa was cost-effective. Similarly, eight of 11 other economic modelling evaluations found that rFVIIa was more cost-effective than pd-APCC in the on-demand treatment of bleeding episodes. These findings indicate that treating patients with haemophilia promptly and with the most effective therapy available may result in cost savings.

Establishment of a prenatal diagnosis schedule as part of a prophylaxis program of factor XIII deficiency in the southeast of Iran.

PubMed

Naderi, Majid; Reykande, Samira Esmaeili; Dorgalaleh, Akbar; Alizadeh, Shaban; Tabibian, Shadi; Einollahi, Nahid; Moghaddam, Ebrahim Miri

2016-01-01

Factor XIII deficiency (FXIIID) is an extremely rare bleeding disorder with a prevalence of 1 in 3 million in the general population. Compared to its global incidence, it has the greatest prevalence in Sistan and Baluchistan Province in the southeast of Iran. The high incidence of FXIIID in this region causes a high rate of morbidity and mortality among the affected individuals because of life-threatening episodes such as central nervous system (CNS) bleeding, umbilical cord bleeding, as well as miscarriage. CNS bleeding leads to a considerable number of neurological and behavioral complications. Therefore, we have designed an established prenatal diagnosis (PND) program to prevent the increasing incidence of life-threatening bleeding episodes and related complications among neonates with congenital FXIIID. This study was conducted from September 2013 to August 2014. A consent form was signed by the parents. Fetal sampling was done via abdominal chorionic villus sampling passage under local anesthesia and ultrasonic guidance within the first trimester of pregnancy. Fetal DNA was extracted, and PCR-restriction fragment length polymorphism was performed for the only reported mutation of FXIII (Trp187Arg) in the southeast of Iran. During the period of study, PND was performed on eight fetuses. Six fetuses were offspring of parental consanguineous marriages, and all of them had a positive family history of FXIIID. Seven out of the eight fetuses had a family member with CNS bleeding due to FXIIID. Four fetuses had a FXIIID-related death. One of the fetuses bore homozygous Trp187Arg mutation, whereas six were heterozygous, and one of the mothers gave birth to an unaffected fetus. To the best of our knowledge, PND is a possible solution to control high incidence of life-threatening episodes of FXIIID in southeast Iran.

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.

Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.

PubMed

Callan, Mary Beth; Haskins, Mark E; Wang, Ping; Zhou, Shangzhen; High, Katherine A; Arruda, Valder R

2016-01-01

Severe hemophilia A (HA) is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII) clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV) vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency) and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs.

Intra-alveolar epsilon-aminocaproic acid for the control of post-extraction bleeding in anticoagulated patients: randomized clinical trial.

PubMed

da Silva, R V; Gadelha, T B; Luiz, R R; Torres, S R

2018-03-27

The aim of this study was to compare the effectiveness of the intra-alveolar administration of epsilon-aminocaproic acid (EACA) and daily gentle rinsing with EACA mouthwash with that of routine postoperative procedures for the control of bleeding after tooth extraction in anticoagulated patients. A randomized clinical trial was conducted involving 52 patients submitted to 140 tooth extractions, assigned randomly to two groups. The intervention group was treated with intra-alveolar administration of EACA immediately after surgery and gentle rinsing with EACA mouthwash during the postoperative period. The control group received routine postoperative recommendations. A single episode of immediate bleeding occurred in the intervention group. Late bleeding episodes occurred in 23 procedures (16.4%): 11 (15.7%) in the intervention group and 12 (17.1%) in the control group. Among the patients with late bleeding, 18 (78.3%) events were classified as moderate and were controlled by the patient applying pressure to a gauze pack placed over the extraction socket. The remaining five cases (21.7%) required re-intervention. No statistically significant difference in the frequency of postoperative bleeding was observed between the groups. Thus, routine measures were as effective for the control of bleeding after simple tooth extractions in anticoagulated patients as the topical administration of EACA. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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.

Adequate dietary fiber supplement and TONE can help avoid surgery in most patients with advanced hemorrhoids.

PubMed

Garg, Pankaj; Singh, Pratiksha

2017-06-01

The root cause of hemorrhoids resides in three deranged defecation habits (DDH), namely increased straining, prolonged defecation-time, and frequent bowel-motions. These DDH are responsible for the development of new hemorrhoids, progression of existing one and hemorrhoidal rupture (bleeding). DDH can be corrected with the help of the "TONE" mnemonic. TONE entails specifying exact treatment goals: T, three minutes at defecation; O, once-a-day defecation frequency; N, no straining during passing motions; E, enough fiber. TONE can be implemented by proper counseling and by prescribing fiber supplement appropriately (5-6 teaspoonfuls of psyllium husk with 600 mL of water daily. Corrected DDH would prevent the progression of hemorrhoids and bleeding episodes. An office procedure may be done to further downgrade the hemorrhoids. Patients with advanced hemorrhoids (grades III and IV) who were referred for surgery were prescribed fiber supplement and were counseled to follow TONE. The outcome parameters evaluated were improvement in prolapse, bleeding episodes, satisfaction levels. A total of 102 patients (75 males and 10 females, mean age 46.0±13.5 years, 17 lost to follow-up) with advanced hemorrhoids (41 with early grade III, 38 with late grade III, and 6 with grade IV) were included in the study. All patients had symptoms of prolapsed hemorrhoids and bleeding episodes were present in 71.8% (61/85) of patients. After the follow-up of 40 (12-96) months, 68.2% (58/85) patients were highly satisfied, 12.9% (11/85) were moderately satisfied and 18.9% (16/85) were not satisfied with treatment. Prolapse improved in 56.5% (48/85), did not progress over time in 25.9 (22/85) and continued to progress in 4.7% (4/85) patients. 12.9% (11/85) underwent operation for hemorrhoids. Bleeding episodes decreased from 71.8% (61/85) to 29.4% (25/85) (P<0.0001). Adequate fiber supplement combined with the TONE method can correct DDH, thus stopping the progression of hemorrhoids and bleeding, and preventing surgery in most patients with advanced hemorrhoids.

A historical cycle control comparison of two drospirenone-containing combined oral contraceptives: ethinylestradiol 30 μg/drospirenone 3 mg administered in a 21/7 regimen versus ethinylestradiol 20 μg/drospirenone 3 mg administered in a 24/4 regimen.

PubMed

Marr, Joachim; Gerlinger, Christoph; Kunz, Michael

2012-05-01

To compare the bleeding patterns and cycle control of an oral contraceptive (OC) containing ethinylestradiol (EE) 30 μg/drospirenone (drsp) 3mg administered in a 21/7 regimen versus a lower-dose OC containing EE 20 μg/drsp 3mg administered in a 24/4 regimen, using data from two identically designed studies. In the first study, 326 healthy women (18-35 years) received EE 30 μg/drsp 3mg in a 21/7 regimen. In the second study, 1027 healthy women (17-36 years) received EE 20 μg/drsp 3mg in a 24/4 regimen. Participants recorded bleeding using daily completed diaries over 13 treatment cycles. During cycles 1-12, the prevalence of scheduled withdrawal bleeding was lower with EE 20 μg/drsp 3mg 24/4 than with EE 30 μg/drsp 3mg 21/7 (82.0-91.7% versus 94.8-100.0% of women, respectively); moreover, a higher proportion of women reported a maximum intensity of light scheduled withdrawal bleeding with EE 20 μg/drsp 3mg 24/4 than with EE 30 μg/drsp 3mg 21/7 (30.9-39.0% versus 13.8-20.5% of women, respectively). In cycles 2-13, unscheduled intracyclic bleeding was reported by 7.7-13.8% of EE 20 μg/drsp 3mg 24/4 recipients and 3.8-7.9% of EE 30 μg/drsp 3mg 21/7 recipients; these were mainly single bleeding days. During reference periods 1-4, the mean number of bleeding episodes was similar between groups (3.1-3.3 episodes with EE 20 μg/drsp 3mg 24/4 versus 3.2 episodes with EE 30 μg/drsp 3mg 21/7). A low-dose 24/4 regimen OC containing EE 20 μg/drsp 3mg is generally comparable in terms of bleeding to a higher-dose 21/7 regimen OC containing EE30 μg/drsp 3mg. Between-treatment differences in bleeding intensity and unscheduled intracyclic bleeding rates were observed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ad hoc cost analysis of the new gastrointestinal bleeding algorithm in patients with ventricular assist device.

PubMed

Hirose, Hitoshi; Sarosiek, Konrad; Cavarocchi, Nicholas C

2014-01-01

Gastrointestinal bleed (GIB) is a known complication in patients receiving nonpulsatile ventricular assist devices (VAD). Previously, we reported a new algorithm for the workup of GIB in VAD patients using deep bowel enteroscopy. In this new algorithm, patients underwent fewer procedures, received less transfusions, and took less time to make the diagnosis than the traditional GIB algorithm group. Concurrently, we reviewed the cost-effectiveness of this new algorithm compared with the traditional workup. The procedure charges for the diagnosis and treatment of each episode of GIB was ~ $2,902 in the new algorithm group versus ~ $9,013 in the traditional algorithm group (p < 0.0001). Following the new algorithm in VAD patients with GIB resulted in fewer transfusions and diagnostic tests while attaining a substantial cost savings per episode of bleeding.

Factors associated with the effect of open splenectomy for immune thrombocytopenic purpura.

PubMed

Li, Ying; Zhang, Dawei; Hua, Fanli; Gao, Song; Wu, Yangjiong; Xu, Jianmin

2017-01-01

To assess the effect and complications of open splenectomy (OS) for immune thrombocytopenic purpura (ITP) and determine preoperative factors associated with surgical effect. This was a retrospective analysis of ITP patients who failed medical therapy and were treated with OS between 1997 and 2014 at the Jinshan Hospital, China. Follow-up was 60 months. Surgical effect was determined from platelet counts and bleeding episodes. Complications were assessed including bleeding episodes. Preoperative factors were identified by logistic regression analysis. Fifty-six patients (48.2 ± 16.2 yr old; 39 females) were included. Disease course was 31.2 ± 48.2 months; 91.1% patients had preoperative platelet count <20 × 10 9 /L. OS effect at 1 wk, 1 month, 1 yr, and 5 yrs was in 91.1%, 92.9%, 91.1%, and 89.3% patients, respectively. Pneumonia or lower extremity thrombosis occurred in 7.1% patients. Postoperative mild, moderate, and severe bleeding occurred in 33.9%, 50.0%, and 16.1% patients, respectively. No patients required blood transfusion. Mortality was zero. Larger spleen size associated with surgical effect at 1 wk, 1 month, and 1 yr, and lower preoperative minimum platelet count associated with effect at 5 yrs (P < 0.05). Open splenectomy is an effective treatment with less complications for the management of ITP. Lower preoperative minimum platelet count associated with successful OS at 5 yrs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Experience in the treatment of some complications of portal hypertension in alcoholic liver cirrhosis].

PubMed

Savić, Zeljka; Vracarić, Vladimir; Hadnadjev, Ljiljana; Petrović, Zora; Damjanov, Dragomir

2011-11-01

Portal hypertension (PH) is hemodynamical abnormality associated with the most serious complications of alcoholic liver cirrhosis (ALC): ascites, varices and variceal bleeding. The aim of this study was to determine characteristics of portal hypertension, especially of upper gastrointestinal bleedings in patients with alcoholic liver cirrhosis (ALC). A total of 237 patients with ALC were observed in a 3-year period. A total of 161 patients (68%) were hospitalized because of PH elements: 86 (36.3%) had upper gastrointestinal bleeding, 75 (31.7%) were decompensated. Only 76 (32%) of the patients had icterus. General mortality was 85 (36%). According to the source of bleeding, 61 (71%) patients bled from varices, and 25 (29%) from other sources with existing varices but non-incriminated for bleeding in 16 (64%) of those patients. Active bleeding or stigmata of recent bleeding were found in 63 (73%) cases. Endoscopic treatment of variceal bleeding along with octreotide applied in 20 (32.78%) patients, just octreotide in 32 (52.46%), and octreotid plus balloon tamponade in 9 (14.75%). According to Child-Pugh classification, 25 (29%) of the bleeding patients were in class A, score 5.4; 43 (50%) in class B, score 7.8; and 18 (21%) in class C, score 10.9. Average hemoglobin level was 93 g/L, hematocrit 0.27, AST 71.52 U/L (normal to 37 U/L), ALT 37.74 U/L (normal to 40 U/L). Until this bleeding episode, 41 (47%) of the patients already bled. In the decompensated patients 3 (4%) were in Child Pugh class A, score 6; 42 (56%) in class B, score 8.3; and 30 (40%) in class C, score 10.6. Until this decompensation episode, 7 (9.3%) patients already bled. Patients with ALC need early detection of varices, primary and secondary profilaxis of variceal bleeding and adequate therapy of ascites. When bleeding occurs, patients need urgent upper endoscopy and intensive treatment.

Case report and systematic literature review of a novel etiology of sinistral portal hypertension presenting with UGI bleeding: Left gastric artery pseudoaneurysm compressing the splenic vein treated by embolization of the pseudoaneurysm.

PubMed

Hakim, Seifeldin; Bortman, Jared; Orosey, Molly; Cappell, Mitchell S

2017-03-01

A novel case is reported of upper gastrointestinal (UGI) bleeding from sinistral portal hypertension, caused by a left gastric artery (LGA) pseudoaneurysm (PA) compressing the splenic vein (SV) that was successfully treated with PA embolization. A 41-year-old man with previous medical history of recurrent, alcoholic pancreatitis presented with several episodes of hematemesis and abdominal pain for 48 hours. Physical examination revealed a soft abdomen, with no abdominal bruit, no pulsatile abdominal mass, and no stigmata of chronic liver disease. The hemoglobin declined acutely from 12.3 to 9.3 g/dL. Biochemical parameters of liver function and routine coagulation profile were entirely within normal limits. Abdominal CT revealed a 5-cm-wide peripancreatic mass compressing the stomach and constricting the SV. Esophagogastroduodenoscopy showed blood oozing from portal hypertensive gastropathy, small nonbleeding gastric cardial and fundal varices, gastric compression from the extrinsic mass, and no esophageal varices. MRCP and angiography showed that the mass was vascular, arose from the LGA, compressed the mid SV without SV thrombosis, and caused sinistral portal hypertension. At angiography, the PA was angioembolized and occluded. The patient has been asymptomatic with no further bleeding and a stable hemoglobin level during 8 weeks of follow-up. Literature review of the 14 reported cases of LGA PA revealed that this report of acute UGI bleeding from sinistral portal hypertension from a LGA PA constricting the SV is novel; one previously reported patient had severe anemia without acute UGI bleeding associated with sinistral portal hypertension from a LGA PA. A patient presented with UGI bleeding from sinistral portal hypertension from a LGA PA compressing the SV that was treated by angiographic obliteration of the PA which relieved the SV compression and arrested the UGI bleeding. Primary therapy for this syndrome should be addressed to obliterate the PA and not the secondarily constricted SV.

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.

An innovative outcome-based care and procurement model of hemophilia management.

PubMed

Gringeri, Alessandro; Doralt, Jennifer; Valentino, Leonard A; Crea, Roberto; Reininger, Armin J

2016-06-01

Hemophilia is a rare bleeding disorder associated with spontaneous and post-traumatic bleeding. Each hemophilia patient requires a personalized approach to episodic or prophylactic treatment, but self-management can be challenging for patients, and avoidable bleeding may occur. Patient-tailored care may provide more effective prevention of bleeding, which in turn, may decrease the likelihood of arthropathy and associated chronic pain, missed time from school or work, and progressive loss of mobility. A strategy is presented here aiming to reduce or eliminate bleeding altogether through a holistic approach based on individual patient characteristics. In an environment of budget constraints, this approach would link procurement to patient outcome, adding incentives for all stakeholders to strive for optimal care and, ultimately, a bleed-free world.

Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor.

PubMed

Gopalakrishnan, Natarajan; Usha, Thiruvengadam; Thopalan, Balasubramaniyan; Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Thirumalvalavan, Kaliaperumal; Sakthirajan, Ramanathan

2016-10-01

Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far. © 2016 International Society for Hemodialysis.

Duodenal plexiform fibromyxoma as a cause of obscure upper gastrointestinal bleeding: A case report.

PubMed

Moris, Demetrios; Spanou, Evangelia; Sougioultzis, Stavros; Dimitrokallis, Nikolaos; Kalisperati, Polyxeni; Delladetsima, Ioanna; Felekouras, Evangelos

2017-01-01

We are reporting the first-to our knowledge-case of duodenal Plexiform Fibromyxoma causing obscure upper gastrointestinal bleeding. Plexiform fibromyxoma triggered recurrent upper gastrointestinal bleeding episodes in a 63-year-old man who remained undiagnosed, despite multiple hospitalizations, extensive diagnostic workups and surgical interventions (including gastrectomies), for almost 17 years. During hospitalization for the last bleeding episode, an upper gastrointestinal endoscopy revealed an intestinal hemorrhagic nodule. The lesion was deemed unresectable by endoscopic means. An abdominal computerized tomography disclosed no further lesions and surgery was decided. The lesion at operation was found near the edge of the duodenal stump and treated with pancreas-preserving duodenectomy (1st and 2nd portion). Postoperative recovery was mainly uneventful and a 20-month follow-up finds the patient in good health with no need for blood transfusions.Plexiform fibromyxomas stand for a rare and widely unknown mesenchymal entity. Despite the fact that they closely resemble other gastrointestinal tumors, they distinctly vary in clinical management as well as the histopathology. Clinical awareness and further research are compulsory to elucidate its clinical course and prognosis.

Clinical significance of neonatal menstruation.

PubMed

Brosens, Ivo; Benagiano, Giuseppe

2016-01-01

Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Angiographic embolization in the treatment of intrahepatic arterial bleeding in patients with blunt abdominal trauma.

PubMed

Kong, Ya-Lin; Zhang, Hong-Yi; He, Xiao-Jun; Zhao, Gang; Liu, Cheng-Li; Xiao, Mei; Zhen, Yu-Ying

2014-04-01

Angiographic embolization (AE) as an adjunct non-operative treatment of intrahepatic arterial bleeding has been widely used. The present study aimed to evaluate the efficacy of selective AE in patients with hepatic trauma. Seventy patients with intrahepatic arterial bleeding after blunt abdominal trauma who had undergone selective AE in 10 years at this institution were retrospectively reviewed. The criteria for selective AE included active extravasation on contrast-enhanced CT, an episode of hypotension or a decrease in hemoglobin level during the non-operative treatment. The data of the patients included demographics, grade of liver injuries, mechanism of blunt abdominal trauma, associated intra-abdominal injuries, indications for AE, angiographic findings, type of AE, and AE-related hepatobiliary complications. In the 70 patients, 32 (45.71%) had high-grade liver injuries. Extravazation during the early arterial phase mainly involved the right hepatic segments. Thirteen (18.57%) patients underwent embolization of intrahepatic branches and the extrahepatic trunk and these patients all developed AE-related hepatobiliary complications. In 19 patients with AE-related complications, 14 received minimally invasive treatment and recovered without severe sequelae. AE is an adjunct treatment for liver injuries. Selective and/or super-selective AE should be advocated to decrease the incidence and severity of AE-related hepatobiliary complications.

Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs

PubMed Central

Callan, Mary Beth; Haskins, Mark E.; Wang, Ping; Zhou, Shangzhen; High, Katherine A.; Arruda, Valder R.

2016-01-01

Severe hemophilia A (HA) is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII) clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV) vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency) and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1–2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs. PMID:27011017

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

PubMed Central

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

2016-01-01

Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

Hemophilia in Sports: A Case Report and Prophylactic Protocol

PubMed Central

Maffet, Mark; Roton, Jimmy

2017-01-01

Objective: To describe a successful prophylactic protocol for managing an athlete with hemophilia playing at a high level of contact sports. Background: Published data show that team physicians are not comfortable either treating athletes with bleeding disorders or allowing them to participate in contact sports. Much of the literature historically has recommended against allowing athletes with bleeding disorders to play sports at all and certainly against playing contact sports. Hemophilia treatment can now include prophylactic injections of recombinant factor VIII to prevent bleeding episodes. Modern treatments hold the promise of allowing athletes with hemophilia to participate in contact sports. Differential Diagnosis: Mild, moderate, or severe hemophilia; von Willebrand disease; other factor deficiencies. Treatment: A treatment protocol was developed that included prophylactic factor VIII injections on a regular basis and when the athlete was injured. Uniqueness: This is the first published case report of an athlete with known hemophilia being successfully treated and participating in National Collegiate Athletic Association collegiate basketball for 2 full seasons. Conclusions: Sports medicine teams can successfully manage an athlete with hemophilia playing a contact sport. PMID:27863189

Congenital Factor VII Deficiency in Children at Tertiary Health Care Facility in Pakistan.

PubMed

Alam, Muhammad Matloob; Moiz, Bushra; Rehman, Karim Abdur; Jethwani, Priyanka; Fadoo, Zehra

2015-10-01

This study presents the demographics, clinical spectrum, and outcome of patients with congenital factor VII (FVII) deficiency at a tertiary care center over a period of 12 years. Of the 49 patients, 27 (55%) patients were males. Consanguinity was found in 92% of the patients. The median age of symptom onset was 2.4 (interquartile range [IQR]: 1.1-6.5) years with a median age of 5.8 (IQR: 3.1-10) years at diagnosis. Life-threatening complications like intracranial bleeding (ICB) and intra-abdominal bleeding (IAB) were observed in 8 (16.4%) patients. We found that 11 (55%) of the 20 patients with FVII coagulant activity (FVIIc) <1% were either asymptomatic or showed mild phenotype. In contrast, 9 (53%) of the 17 patients with FVIIc >5% were affected by severe symptoms. Age <1 year was the only identified risk factor associated with development of life-threatening bleeding episodes (P = .042; odds ratio 6.46). Overall, 4 (8.2%) died as a consequence of ICB (3 patients) and IAB (1 patient). © The Author(s) 2013.

Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A.

PubMed

Du, Lily M; Nurden, Paquita; Nurden, Alan T; Nichols, Timothy C; Bellinger, Dwight A; Jensen, Eric S; Haberichter, Sandra L; Merricks, Elizabeth; Raymer, Robin A; Fang, Juan; Koukouritaki, Sevasti B; Jacobi, Paula M; Hawkins, Troy B; Cornetta, Kenneth; Shi, Qizhen; Wilcox, David A

2013-01-01

It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response to vascular injury, we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally inducible treatment to maintain haemostasis for haemophilia A. Here we show that haematopoietic stem cell gene therapy can prevent the occurrence of severe bleeding episodes in dogs with haemophilia A for at least 2.5 years after transplantation. We employ a clinically relevant strategy based on a lentiviral vector encoding the ITGA2B gene promoter, which drives platelet-specific expression of human FVIII permitting storage and release of FVIII from activated platelets. One animal receives a hybrid molecule of FVIII fused to the von Willebrand Factor propeptide-D2 domain that traffics FVIII more effectively into α-granules. The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus, platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A.

Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A

PubMed Central

Du, Lily M.; Nurden, Paquita; Nurden, Alan T.; Nichols, Timothy C.; Bellinger, Dwight A.; Jensen, Eric S.; Haberichter, Sandra L.; Merricks, Elizabeth; Raymer, Robin A.; Fang, Juan; Koukouritaki, Sevasti B.; Jacobi, Paula M.; Hawkins, Troy B.; Cornetta, Kenneth; Shi, Qizhen; Wilcox, David A.

2013-01-01

It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response to vascular injury, we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally inducible treatment to maintain haemostasis for haemophilia A. Here we show that haematopoietic stem cell gene therapy can prevent the occurrence of severe bleeding episodes in dogs with haemophilia A for at least 2.5 years after transplantation. We employ a clinically relevant strategy based on a lentiviral vector encoding the ITGA2B gene promoter, which drives platelet-specific expression of human FVIII permitting storage and release of FVIII from activated platelets. One animal receives a hybrid molecule of FVIII fused to the von Willebrand Factor propeptide-D2 domain that traffics FVIII more effectively into α-granules. The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus, platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A. PMID:24253479

Portal hypertension and gastrointestinal bleeding: Diagnosis, prevention and management

PubMed Central

Biecker, Erwin

2013-01-01

Bleeding from esophageal varices is a life threatening complication of portal hypertension. Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal. Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol. Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method. Therapy of acute bleeding is based on three strategies: vasopressor drugs like terlipressin, antibiotics and endoscopic therapy. In refractory bleeding, self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt (TIPS). Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate. Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking. Therapy of refractory bleeding relies on shunt-procedures like TIPS. Bleeding from ectopic varices, portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common. Possible medical and endoscopic treatment options are discussed. PMID:23964137

Safety and effectiveness of rivaroxaban and warfarin in moderate-to-advanced CKD: real world data.

PubMed

Di Lullo, Luca; Tripepi, Giovanni; Ronco, Claudio; De Pascalis, Antonio; Barbera, Vincenzo; Granata, Antonio; Russo, Domenico; Di Iorio, Biagio Raffaele; Paoletti, Ernesto; Ravera, Maura; Fusaro, Maria; Bellasi, Antonio

2018-06-07

In recent years, novel anticoagulant drugs have been introduced in the clinical armamentarium and have progressively gained momentum. Although their use is increasing among CKD patients, some skepticism about their risk-benefit ratio still persists. We sought to investigate the safety and effectiveness of rivaroxaban in a cohort of moderate-to-advanced CKD patients. This observational, retrospective, longitudinal study involved 347 consecutive CKD stage 3b-4 (according to NKF-KDOQI guidelines) patients enrolled from 8 cardiac outpatient clinics between March 2015 and October 2017. All patients received anticoagulation (100 warfarin vs. 247 rivaroxaban) as part of their non-valvular atrial fibrillation management at the attending physician's discretion. Clinical effectiveness (defined as the occurrence of ischemic stroke, venous thromboembolism, or transient ischemic attack) and safety (intracranial hemorrhage, gastrointestinal or other bleeding) were assessed separately. Over a mean follow-up period of 16 ± 0.3 months, 25 stroke episodes (15 hemorrhagic, and 10 ischemic) occurred in 24 warfarin treated patients vs. none in the rivaroxaban arm. There were 5 vs. 0 episodes of deep venous thrombosis and 8 vs. 2 major episodes of bleeding in the warfarin and rivaroxaban groups, respectively. In contrast, the proportion of minor episodes of bleeding was similar between groups. Rivaroxaban seems a safe and effective therapeutic option in CKD stage 3b-4 patients. However, future randomized controlled trials are needed to definitively establish the role of rivaroxaban in CKD patients.

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. Objectives To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 × 109/L); standard trigger (10 × 109/L); higher trigger (20 × 109/L, 30 × 109/L, 50 × 109/L); or alternative platelet trigger (for example platelet mass)). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 × 109/L) versus a higher trigger (20 × 109/L or 30 × 109/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations. The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review. Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence). One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors’ own results; low-quality evidence). Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence). Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence). Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence). Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference −2.09, 95% CI −3.20 to −0.99; low-quality evidence). One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09). None of the studies reported on quality of life. Authors’ conclusions In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 × 109/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 × 109/L or 30 × 109/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 × 109/L or 30 × 109/L). Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 × 109/L) in the absence of other risk factors for bleeding. PMID:26576687

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation.

PubMed

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-11-18

Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 x 10(9)/L); standard trigger (10 x 10(9)/L); higher trigger (20 x 10(9)/L, 30 x 10(9)/L, 50 x 10(9)/L); or alternative platelet trigger (for example platelet mass)). We used the standard methodological procedures expected by Cochrane. Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 x 10(9)/L) versus a higher trigger (20 x 10(9)/L or 30 x 10(9)/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations.The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review.Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity.Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence).One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors' own results; low-quality evidence).Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence).Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence).Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence).Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference -2.09, 95% CI -3.20 to -0.99; low-quality evidence).One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09).None of the studies reported on quality of life. In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 x 10(9)/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L).Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 x 10(9)/L) in the absence of other risk factors for bleeding.

Dermal arteritis of the nasal philtrum in a Giant Schnauzer and three Saint Bernard dogs.

PubMed

Torres, Sheila M F; Brien, Timothy O; Scott, Danny W

2002-10-01

Arteritis of the nasal philtrum is described in four dogs. Two of the Saint Bernards were related. The lesions were solitary, well-circumscribed, linear ulcers that were neither pruritic nor painful. The age of the dogs at the time the owners first noticed the lesion ranged from 3 to 6 years. The ulcers had been present for 0.5-5 years before diagnosis was pursued. Three of the dogs experienced repeated, mild episodes of arterial bleeding from the ulcers. Two dogs also experienced a severe episode of bleeding that required surgical intervention. Histopathological findings included a V-shaped ulcer, neutrophilic dermal inflammation subjacent to the ulcer and lymphoplasmacytic dermatitis bordering the ulcer. The most remarkable pathological findings were present in the deep dermal arteries and arterioles subjacent to the ulcer. The changes were characterized by subendothelial spindle cell proliferation with marked extracellular matrix deposition that stained blue with Alcian Blue (mucin) and Masson's trichrome (collagen) and resulted in intimal thickening, and stenosis of dermal arteries and arterioles. Immunohistochemical studies suggested that the proliferating spindle cells were of either myofibroblast or smooth muscle origin (actin and vimentin positive). Anti-inflammatory therapy (glucocorticoids; tetracycline and niacinamide; fish oil) may be beneficial for long-term control of this condition, however, long-term maintenance treatment appears to be necessary.

Pure versus mixed electrosurgical current for endoscopic biliary sphincterotomy: a meta-analysis of adverse outcomes.

PubMed

Verma, Dharmendra; Kapadia, Asha; Adler, Douglas G

2007-08-01

Endoscopic biliary sphincterotomy (ES) can cause bleeding, pancreatitis, and perforation. This has, in part, been attributed to the type of electrosurgical current used for ES. No consensus exists on the optimal type of electrosurgical current for ES to maximize safety. To compare the rates of complications in patients undergoing ES via pure current versus mixed current. A systematic review of published, prospective, randomized trials that compared pure current with mixed current for ES. Patients undergoing ES, with random assignment to either current group. Data were standardized for pancreatitis and postsphincterotomy bleeding. There were insufficient data to analyze perforation risk. A random-effects model was used. Bleeding, pancreatitis, and perforation. A total of 804 patients from 4 trials that compared pure current to mixed current were analyzed. The aggregated rate of pancreatitis was 3.8%, 95% confidence interval (CI) 1.0%-6.6%, for the pure-current group versus 7.9%, 95% CI 3.1%-12.7%, for the mixed-current group; the difference was not statistically significant. The rate of bleeding (all severity groups) for the pure-current group was 37.3% (95% CI 27.3%, 47.3%), which was significantly higher than that of the mixed-current group (12.2% [95% CI 4.1%, 20.3%]). Mild bleeding was significantly more frequent with pure current (28.9% [95% CI 16.3, 41.4]) compared with mixed current (9.4% [95% CI 2.1%, 16.8%]). Variables, including endoscopist skill and cannulation difficulty, were difficult to measure. The rate of pancreatitis in patients who underwent ES when using pure current was not significantly different from those when using mixed current. Pure current was associated with more episodes of bleeding, primarily mild bleeding. Data were insufficient to analyze the perforation risk.

Sudden oronasal bleeding in a young child.

PubMed

Hey, Edmund

2008-10-01

Sudden severe upper-airway obstruction occurring in a hospital setting can sometimes precipitate an episode of acute haemorrhagic pulmonary oedema. A review of 197 published case reports shows that the presenting feature is almost always the sudden appearance of blood stained fluid coming up through the larynx or out through the mouth and nose of an adult or child in obvious respiratory distress. Such overt features are seen in 10-15% of cases of sudden severe, but sub-lethal, upper-airway obstruction. Signs normally appear within minutes once the obstruction is relieved but are occasionally only recognized after 1-4 h. All signs and symptoms usually resolve within 12-24 h. Other causes of acute pulmonary haemorrhage are rare in young children. If what looks like blood is seen in, or coming from, the mouth or nose of a previously healthy young child who has suddenly become distressed and started to struggle for breath, that child has most probably suffered an episode of acute pulmonary oedema, and the commonest precipitating cause is sudden upper-airway obstruction.

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.

Recombinant activated factor VII in the treatment of bleeds and for the prevention of surgery-related bleeding in congenital haemophilia with inhibitors.

PubMed

Santagostino, Elena; Escobar, Miguel; Ozelo, Margareth; Solimeno, Luigi; Arkhammar, Per; Lee, Hye Youn; Rosu, Gabriela; Giangrande, Paul

2015-06-01

The availability of recombinant activated factor VII (rFVIIa, eptacog alfa activated) has greatly advanced the care of patients with haemophilia A or B who have developed inhibitors against the infused replacement factor. Recombinant FVIIa is licensed for the on-demand treatment of bleeding episodes and the prevention of bleeding in surgery or invasive procedures in patients with congenital haemophilia with inhibitors. This article attempts to review in detail the extensive evidence of rFVIIa in congenital haemophilia patients with inhibitors. Patients with acute bleeding episodes are best treated on demand at home, to achieve the short- and long-term benefits of rapid bleed control. Key prospective studies have shown that rFVIIa achieves consistently high efficacy rates in the management of acute (including joint) bleeds in inhibitor patients in the home treatment setting. Substantial post-approval data from key registries also support the on-demand efficacy profile of rFVIIa established by the prospective clinical trials. The availability of rFVIIa has allowed major surgery to become a reality for inhibitor patients. Studies in key surgery, including orthopaedic procedures, have found that rFVIIa provides consistently high efficacy rates. Importantly, the wealth of data does not raise any unexpected safety concerns surrounding rFVIIa use; this is likely because rFVIIa is a recombinant product with a localised mechanism of action at the site of vascular injury. In summary, rFVIIa is established as an effective and well-tolerated first-line treatment for on-demand bleeding control and bleed prevention during minor and major (including elective orthopaedic) surgery in inhibitor patients. Use of rFVIIa has been a major step towards narrowing the gap in outcomes between inhibitor patients and non-inhibitor patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recurrent haematomas of the thigh: a case of von Willebrand's disease presenting to a sports clinic

PubMed Central

Owens, S.; Baglin, T.

2000-01-01

Von Willebrand's disease is a relatively common mild form of haemophilia. It should be suspected in assessing sports injuries when excessive bleeding occurs in response to relatively mild trauma. Those with the disease should remain active but avoid contact sports. They should not take aspirin or non-steroidal anti-inflammatory drugs, which may exacerbate bleeding, and should be given supportive treatment to cover dental extraction, surgery, or significant bleeding episodes. Key Words: von Willebrand's disease; haemophilia; haematoma; sports clinic PMID:10786868

[Biochemical characteristics of compensation of posthemorrhagic anemia in patients presenting with nasal bleeding].

PubMed

Boĭko, N V; Kolmakova, T S; Bykova, V V

2010-01-01

This work was designed to study the development of compensatory processes during posthemorrhagic anemia in 82 patients presenting with nasal bleeding (NB). The patients were allocated to three groups. Group 1 included patients with isolated episodes of NB, group 2 was comprised of patients in a moderately severe condition with recurring NB, group 3 was composed of patients in a severe condition with recurring NB. The general medical examination was supplemented by the evaluation of factors maintaining the oxygen-transporting function of the blood (hemoglobin affinity for oxygen, erythrocyte content of 2.3-diphosphoglyceric (2.3-DPG) acid as the principal modulator of hemoglobin affinity for oxygen) and indicators of energy (carbohydrate) metabolism in plasma and erythrocytes (glucose-6-phosphate dehydrogenase (G-6-PDH) activity, pyruvic acid (PA), lactate and lactate dehydrogenase (LDH) levels). Changes of biochemical parameters in patients presenting with incidental episodes of NB (group 1) suggested a compensatory increase in functional potential of the blood oxygen-transporting system. Patients of group 2 showed evidence of development of the modulation-type adaptive and compensatory mechanisms. Those of group 3 experienced a decrease of the 2.3-DPH level in erythrocytes and enhancement of hemoglobin affinity for oxygen which slowed down its uptake by the tissues. Tissue hypoxia and accompanying acidosis aggravated the impairment of gas-transporting function of the blood. In is concluded that patients of group 3 are at risk of uncompensated hypoxic hypoxia associated with the unfavourable changes in the oxygen-transporting function and the impairment of the functional potential of erythrocytes. Taken together, these untoward factors may be responsible for the severe clinical conditions of these patients.

Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A

PubMed Central

PORADA, C. D.; SANADA, C.; LONG, C. R.; WOOD, J. A.; DESAI, J.; FREDERICK, N.; MILLSAP, L.; BORMANN, C.; MENGES, S. L.; HANNA, C.; FLORES-FOXWORTH, G.; SHIN, T.; WESTHUSIN, M. E.; LIU, W.; GLIMP, H.; ZANJANI, E. D.; LOZIER, J. N.; PLISKA, V.; STRANZINGER, G.; JOERG, H.; KRAEMER, D. C.; ALMEIDA-PORADA, G.

2010-01-01

Summary Background Large animal models that accurately mimic human hemophilia A (HA) are in great demand for developing and testing novel therapies to treat HA. Objectives To re-establish a line of sheep exhibiting a spontaneous bleeding disorder closely mimicking severe human HA, fully characterize their clinical presentation, and define the molecular basis for disease. Patients/methods Sequential reproductive manipulations were performed with cryopreserved semen from a deceased affected ram. The resultant animals were examined for hematologic parameters, clinical symptoms, and responsiveness to human FVIII (hFVIII). The full coding region of sheep FVIII mRNA was sequenced to identify the genetic lesion. Results and conclusions The combined reproductive technologies yielded 36 carriers and 8 affected animals. The latter had almost non-existent levels of FVIII:C and extremely prolonged aPTT, with otherwise normal hematologic parameters. These animals exhibited bleeding from the umbilical cord, prolonged tail and nail cuticle bleeding time, and multiple episodes of severe spontaneous bleeding, including hemarthroses, muscle hematomas and hematuria, all of which responded to hFVIII. Inhibitors of hFVIII were detected in four treated animals, further establishing the preclinical value of this model. Sequencing identified a premature stop codon and frame-shift in exon 14, providing a molecular explanation for HA. Given the decades of experience using sheep to study both normal physiology and a wide array of diseases and the high homology between human and sheep FVIII, this new model will enable a better understanding of HA and facilitate the development and testing of novel treatments that can directly translate to HA patients. PMID:19943872

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

PubMed

Sempere, L; Palazón, J M; Sánchez-Payá, J; Pascual, S; de Madaria, E; Poveda, M J; Carnicer, F; Zapater, P; Pérez-Mateo, M

2009-04-01

to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

Orthopaedic management of haemophilia arthropathy of the ankle.

PubMed

Pasta, G; Forsyth, A; Merchan, C R; Mortazavi, S M J; Silva, M; Mulder, K; Mancuso, E; Perfetto, O; Heim, M; Caviglia, H; Solimeno, L

2008-07-01

Joint bleeding, or haemarthrosis, is the most common type of bleeding episode experienced by individuals with haemophilia A and B. This leads to changes within the joints, including synovial proliferation, which results in further bleeding and chronic synovitis. Blood in the joint can also directly damage the cartilage, and with repeated bleeding, there is progressive destruction of both cartilage and bone. The end result is known as haemophilic arthropathy. The joints most commonly affected are the knees, elbows and ankles, although any synovial joint may be involved. In the ankle, both the tibiotalar and subtalar joints may be affected and joint bleeding and arthropathy can lead to a number of deformities. Haemophilic arthropathy can be prevented through regular factor replacement prophylaxis and implementing physiotherapy. However, when necessary, there are multiple surgical and non-surgical options available. In early ankle arthropathy with absent or minimal joint changes, both radioisotopic and chemical synoviorthesis can be used to reduce the hypertrophied synovium. These procedures can decrease the frequency of bleeding episodes, minimizing the risk of articular cartilage damage. Achilles tendon lengthening can be performed, in isolation or in combination with other surgical measures, to correct Achilles tendon contractures. Both arthroscopic and open synovectomies are available as a means to remove the friable villous layer of the synovium and are often indicated when bleeding episodes cannot be properly controlled by factor replacement therapy or synoviorthesis. In the later stages of ankle arthropathy, other surgical options may be considered. Debridement may be indicated when there are loose pieces of cartilage or anterior osteophytes, and can help to improve the joint function, even in the presence of articular cartilage damage. Supramalleolar tibial osteotomy may be indicated in patients with a valgus deformity of the hindfoot without degenerative radiographic findings. Joint fusion, or arthrodesis, is the treatment of choice in the advanced stages of ankle arthropathy although total ankle replacement is currently available. Early ankle replacement components were associated with a poor outcome, but as implant designs have improved, there have been successful outcomes achieved. As the ankle is a commonly affected joint in many individuals with haemophilia, it is important to add to the knowledge base to validate indications and timing of surgical and non-surgical interventions in ankle arthropathy.

Increased levels of Porphyromonas gingivalis are associated with ischemic and hemorrhagic cerebrovascular disease in humans: an in vivo study

PubMed Central

GHIZONI, Janaina Salomon; TAVEIRA, Luís Antônio de Assis; GARLET, Gustavo Pompermaier; GHIZONI, Marcos Flávio; PEREIRA, Jefferson Ricardo; DIONÍSIO, Thiago José; BROZOSKI, Daniel Thomas; SANTOS, Carlos Ferreira; SANT'ANA, Adriana Campos Passanezi

2012-01-01

Objective: This study investigated the role of periodontal disease in the development of stroke or cerebral infarction in patients by evaluating the clinical periodontal conditions and the subgingival levels of periodontopathogens. Material and Methods: Twenty patients with ischemic (I-CVA) or hemorrhagic (H-CVA) cerebrovascular episodes (test group) and 60 systemically healthy patients (control group) were evaluated for: probing depth, clinical attachment level, bleeding on probing and plaque index. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were both identified and quantified in subgingival plaque samples by conventional and real-time PCR, respectively. Results: The test group showed a significant increase in each of the following parameters: pocket depth, clinical attachment loss, bleeding on probing, plaque index and number of missing teeth when compared to control values (p<0.05, unpaired t-test). Likewise, the test group had increased numbers of sites that were contaminated with P. gingivalis (60%x10%; p<0.001; chi-squared test) and displayed greater prevalence of periodontal disease, with an odds ratio of 48.06 (95% CI: 5.96-387.72; p<0.001). Notably, a positive correlation between probing depth and the levels of P. gingivalis in ischemic stroke was found (r=0.60; p=0.03; Spearman's rank correlation coefficient test). A. actinomycetemcomitans DNA was not detected in any of the groups by conventional or real-time PCR. Conclusions: Stroke patients had deeper pockets, more severe attachment loss, increased bleeding on probing, increased plaque indexes, and in their pockets harbored increased levels of P. gingivalis. These findings suggest that periodontal disease is a risk factor for the development of cerebral hemorrhage or infarction. Early treatment of periodontitis may counteract the development of cerebrovascular episodes. PMID:22437687

[Comparison of predictive factors related to the mortality and rebleeding caused by variceal bleeding: Child-Pugh score, MELD score, and Rockall score].

PubMed

Lee, Ja Young; Lee, Jin Heon; Kim, Soo Jin; Choi, Dae Rho; Kim, Kyung Ho; Kim, Yong Bum; Kim, Hak Yang; Yoo, Jae Young

2002-12-01

The first episode of variceal bleeding is one of the most frequent causes of death in patients with liver cirrhosis. The Child-Pugh(CP) scoring system has been widely accepted for prognostic assessment. Recently, MELD has been known to be better than the CP scoring system for predicting mortality in patients with end-stage liver diseases. The Rockall risk scoring system was developed to predict the outcome of upper GI bleeding including variceal bleeding. The aim of this study was to investigate the mortality rate of first variceal bleeding and the predictability of each scoring system. We evaluated the 6-week mortality rate, rebleeding rate, and 1-year mortality rate of all the 136 patients with acute variceal bleeding without previous episode of hemorrhage between January 1, 1998 and December 31, 2000. The CP score, MELD score, and Rockall score were estimated and analyzed. Among 136 patients, 35 patients with hepatoma and 8 patients with follow-up loss were excluded. Six-week mortality rate, 1-year mortality rate, and rebleeding rate of first variceal bleeding were 24.7%, 35.5%, and 12.9%, respectively. The c-statistics of CP, MELD, and Rockall score for predicting 6-week mortality rate were 0.809 (p<0.001, 95% CI, 0.720-0.898), 0.804 (p<0.001, 95% CI, 0.696-0.911), 0.787 (p<0.001, 95% CI, 0.683-0.890), respectively. For 1-year mortality rate, c-statistics were 0.765 (p<0.005, 95% CI, 0.665-0.865), 0.780 (p<0.005, 95% CI, 0.676-0.883), 0.730 (p<0.01, 95% CI, 0.627-0.834), respectively. The CP, MELD, and Rockall scores were reliable measures of mortality risk in patients with first variceal bleeding. The CP classification is useful in its easy applicability.

Leopold: the "bleeder prince" and public knowledge about hemophilia in Victorian Britain.

PubMed

Rushton, Alan R

2012-07-01

Hemophilia is a rare bleeding disorder inherited by males born of unaffected female carriers of the trait. British physicians became knowledgeable about this hereditary disease early in the nineteenth century as they investigated families transmitting the character through several generations. Prince Leopold (b. 1853), the fourth son of Queen Victoria, experienced recurrent bleeding episodes and was diagnosed with hemophilia during childhood. His hemorrhagic attacks were first described in the medical journals during 1868, and subsequently in the London and provincial newspapers. The royal family carefully managed news about health matters, and many newspapers reported widespread public sympathy for the travails of the queen and her children. But the republican press argued that the disaffected working classes resented the hyperbole connecting the health of royal individuals with the political future of the entire nation. Public discussion of hemophilia transformed it from a rare medical phenomenon to a matter of national news. Practicing physicians, the royal family, and the general public all came to understand the clinical features and the hereditary nature of the problem. Members of the royal family subsequently utilized this information to guide the marriages of their own children to prevent the spread of this dreaded bleeding disorder.

[Portal hypertension. Evidence-based guide].

PubMed

Mercado, Miguel Angel; Orozco Zepeda, Héctor; Plata-Muñoz, Juan José

2004-01-01

Treatment of portal hypertension has evolved widely during the last decades. Advances in physiopathology have allowed better application of therapeutic options and also have permitted to know the natural history of varices and variceal bleeding, predicting which patients have a higher risk of bleeding. It also permits probability of designing patient treatment. According to liver function and subadjacent liver disease, it is possible to offer different alternatives within the three possible scenarios (primary prophylaxis, acute bleeding episode, and secondary prophylaxis). For primary prophylaxis, pharmacotherapy offers the best choice. Endoscopic banding is also growing in these scenarios and probably will be accepted in the near future. For the acute bleeding episode, endoscopic therapy (sclerosis and/or bands) and/or pharmacologic therapy (octreotide, terlipresin) represent best choice, considering TIPS as a rescue option. Surgery is not used routinely in this scenario in most centers. For secondary prophylaxis, pharmaco- and endoscopic therapy are first-line treatments, while TIPS and surgery as second-line treatments. TIPS is mainly used in patients on a waiting list for liver transplantation. Surgery offers good results for low-risk patients, with good liver function and with portal blood-flow preserving procedures (selective shunts, extensive devascularizations). Liver transplantation is recommended for patients with poor liver function because together with portal hypertension, it treats subadjacent liver disease.

Dysfunctional uterine bleeding as an early sign of polycystic ovary syndrome during adolescence.

PubMed

Deligeoroglou, E K; Creatsas, G K

2015-08-01

Excessive uterine bleeding during the early years after menarche can be worrisome to the girl and her parents. The most prevalent diagnosis set is Dysfunctional uterine bleeding (DUB), after thorough examination and exclusion of other causes of abnormal uterine bleeding. The aim of this article was to review our knowledge and share our experience as tertiary reference center of pediatric-adolescent gynecology in Greece. We conducted a review of current literature using Pubmed and MedLine as our primary databases, as well as providing commentary considering work up, treatment and follow-up of our DUB patients. Insufficient progesterone production and subsequent abnormal shedding of the endometrium appears to orchestrate the pathophysiology of DUB in adolescence. Hypothalamic-pituitary-ovarian (HPO) axis immaturity right after menarche, is usually the most plausible cause. Nevertheless, it is necessary to exclude other, possibly even life-threatening causes. Complete work up including physical examination, laboratory and imaging studies (complete blood count, b-HCG, hormonal levels and ultrasonography) is needed, and appropriate treatment with combined oral contraceptives is administered accordingly. Although menstrual disorders are very common in early adolescence, a severe episode of DUB should always be thoroughly attended by any physician. Follow-up should be offered in all young patients due to high incidence of recurrence or subsequent development of endocrine disorders such as Polycystic Ovary Syndrome (PCOS).

Safety and effectiveness of room temperature stable recombinant factor VIIa in patients with haemophilia A or B and inhibitors: Results of a multinational, prospective, observational study.

PubMed

Kavakli, K; Demartis, F; Karimi, M; Eshghi, P; Neme, D; Chambost, H; Sommer, L; Zak, M; Benson, G

2017-07-01

A room temperature stable formulation of recombinant activated factor VII (NovoSeven ® ), allowing convenient storage and therefore improved treatment access, has been developed. Bioequivalence to the previous NovoSeven ® was demonstrated in healthy humans, leading to European approval (2008). Although no confirmed cases of neutralising antibodies to rFVIIa in patients with haemophilia A or B have been observed with the original formulation, changes in formulation or storage condition may alter immunogenicity. SMART-7™ was designed to investigate the safety of NovoSeven ® in a real-world setting in patients with haemophilia A or B with inhibitors. Study medication was not provided by the sponsor, and treatment was at the discretion of the treating physician, in accordance with the local label. Patient baseline information was collected at enrolment. Information on safety, drug exposure and bleeding episodes was collected and FVII antibody screening was encouraged at baseline and performed at the investigator's discretion. Fifty-one patients were enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were observed. Although four cases of reduced therapeutic response were reported, FVII antibody screening was negative. Forty-eight patients experienced 618 bleeding episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538 bleeding episodes treated with NovoSeven ® monotherapy, 94.2% stopped by end of treatment. Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven ® under real-world conditions. © 2017 John Wiley & Sons Ltd.

Mallory-Weiss tear

MedlinePlus

... the liver and problems with blood clotting make future bleeding episodes more likely to occur. ... Jensen DM. Gastrointestinal hemorrhage. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.

PubMed

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I; Fischer, Kathelijn; Gill, Joan C; P'Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St Ledger, Katie; Pabinger, Ingrid

2016-08-04

Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. © 2016 by The American Society of Hematology.

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.

Colorado tick fever

MedlinePlus

... cord ( meningitis ) Irritation and swelling of the brain ( encephalitis ) Repeated bleeding episodes for no apparent cause Call ... Beckham JD, Tyler KL. Encephalitis. In: Bennett JE, Dolin R, ... Principles and Practice of Infectious Disease, Updated Edition . ...

Effect of home testing of international normalized ratio on clinical events.

PubMed

Matchar, David B; Jacobson, Alan; Dolor, Rowena; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Vertrees, Julia E; Shih, Mei-Chiung; Holodniy, Mark; Lavori, Philip

2010-10-21

Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes. We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death). The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001). As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.).

An automated database case definition for serious bleeding related to oral anticoagulant use.

PubMed

Cunningham, Andrew; Stein, C Michael; Chung, Cecilia P; Daugherty, James R; Smalley, Walter E; Ray, Wayne A

2011-06-01

Bleeding complications are a serious adverse effect of medications that prevent abnormal blood clotting. To facilitate epidemiologic investigations of bleeding complications, we developed and validated an automated database case definition for bleeding-related hospitalizations. The case definition utilized information from an in-progress retrospective cohort study of warfarin-related bleeding in Tennessee Medicaid enrollees 30 years of age or older. It identified inpatient stays during the study period of January 1990 to December 2005 with diagnoses and/or procedures that indicated a current episode of bleeding. The definition was validated by medical record review for a sample of 236 hospitalizations. We reviewed 186 hospitalizations that had medical records with sufficient information for adjudication. Of these, 165 (89%, 95%CI: 83-92%) were clinically confirmed bleeding-related hospitalizations. An additional 19 hospitalizations (10%, 7-15%) were adjudicated as possibly bleeding-related. Of the 165 clinically confirmed bleeding-related hospitalizations, the automated database and clinical definitions had concordant anatomical sites (gastrointestinal, cerebral, genitourinary, other) for 163 (99%, 96-100%). For those hospitalizations with sufficient information to distinguish between upper/lower gastrointestinal bleeding, the concordance was 89% (76-96%) for upper gastrointestinal sites and 91% (77-97%) for lower gastrointestinal sites. A case definition for bleeding-related hospitalizations suitable for automated databases had a positive predictive value of between 89% and 99% and could distinguish specific bleeding sites. Copyright © 2011 John Wiley & Sons, Ltd.

A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.

PubMed

Koninckx, P R; Spielmann, D

2005-08-01

To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen. This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28. Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium. The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.

Creatinine-modified Child-Turcotte-Pugh score is a good predictor of a short-term survival in patients with bleeding from esophageal varices.

PubMed

Radisavljević, Mirjana; Bjelaković, Goran; Jović, Jasna; Radovanović-Dinić, Biljana; Benedoto-Stojanov, Danijela; Brzački, Vesna; Marković-Živković, Bojana

2017-01-01

Bleeding from esophageal varices is a significant factor in mortality of patients with terminal liver cirrhosis. This complication is a major health problem for recipients on the list for liver transplant. In that regard, studying predictors of variceal bleeding episode is very important. Also, it is important to find the best survival predictor among prognostic scores. The aim of the study was to compare validity of prognostic scores in assessment of survival in hospital-treated patients after bleeding from esophageal varices, and to compare validity of baseline Child-Turcotte-Pugh (CTP) and Modul for End-stage Liver Disease (MELD) scores with CTP creatinine modified (CTP-crea) I and II scores in assessment of survival in patients within a long-term follow-up period after the episode of bleeding from esophageal varices. The study included a total of 126 patients suffering from terminal liver cirrhosis submited to testing CTP score score I and II, MELD score, MELD Na score, integrated MELD score, MELD sodium (MESO) index, United Kingdom Model for End-Stage Liver Disease (UKELD) score and updated MELD score. Patients with bleeding from esophageal varices most often had CTP score rank C (46,9%). CTP score rank B had 37.5% patients, while the smallest percentage of patients had CTP rank A, 15.6% of them. Patients who have values of CTP score higher than 10.50 and bleeding from esophagus, have 3.2 times higher chance for death outcome compared to other patients. Patients who have values of CTP-crea I score higher than 10.50 and bleeding from esophagus, have 3.1 times higher chance for death out-come than other patients. Patients who have values of CTP-crea II score higher than 11.50 and bleeding from esophagus, have 3,7 times higher chance for death outcome compared to other patients. Survival of patients with bleeding from esophageal varices in the short-term follow up can be predicted by following CTP score and creatinine modified CTP scores. Patients with bleeding from esophageal varices who have CTP score and CTP-crea I score higher than 10.5 and CTP-crea II score higher than 11.5, have statistically significantly higher risk from mortality within one-month follow-up compared to patients with bleeding from esophageal varices who have lower numerical values of scores of the CTP group.

Video-assisted minithoracotomy for blunt diaphragmatic rupture presenting as a delayed hemothorax.

PubMed

Ota, Hideki; Kawai, Hideki; Matsuo, Tsubasa

2014-01-01

Diaphragmatic ruptures after blunt trauma are rare life-threatening conditions. Most of them occur on the left-sided hemidiaphragm with herniation or associated organ injuries after a motor vehicle accident. We present an unusual case of blunt diaphragmatic rupture resulting in a delayed hemothorax. A 62-year-old man presented with acute dyspnea that initiated while straining to pass stool. He had a bruise on the lower back region of his right thorax after a slip-and-fall accident 7 days previously. Chest computed tomographic scans revealed a right-sided hemothorax without any evidence of herniation or associated organ injuries. Emergency surgery was performed through a video-assisted minithoracotomy. During surgery, we identified a diaphragmatic laceration with a severed blood vessel originating from the right superior phrenic artery. The lesion was repaired with interrupted horizontal mattress sutures. The total amount of bleeding was approximately 2000 mL. The patient had an uneventful recovery with no further bleeding episodes.

Drug-induced Epistaxis: An Often-Neglected Adverse Effect.

PubMed

Meirinho, Sara; Relvas, Ricardo; Alves, Gilberto

2018-02-12

Epistaxis is an active nose bleeding with a population occurrence of approximately 60%. Although epistaxis is a common clinical complaint, the majority of the cases are benign and caused by local induced factors (e.g., trauma and local inflammation). Nevertheless, it is also recognised that epistaxis can be induced after some drugs intake. Due to the increasing use of drugs or drug combinations that potentially may induce epistaxis, this review aims to alert healthcare professionals for this often neglected adverse drug effect and its possible complications. A comprehensive literature search was performed on PubMed and Google Scholar databases, considering the literature published from January 1985 to December 2015, using medical terms related to the scope of drug-induced epistaxis, nosebleeds and nasal blood supply. As expected, anticoagulant and antiplatelet drugs are the main pharmacotherapeutic agents associated with epistaxis, particularly warfarin, dabigatran, rivaroxaban and aspirin. However, it was reported that some selective serotonin reuptake inhibitors, intranasal corticosteroids, certain antibiotics and other drugs or drug associations can also be responsible by nosebleeds. Although most of these epistaxis episodes are mild to moderate, being spontaneously reversed or requiring only minor medical approaches to control it, there are also several case reports, as well as retrospective and prospective studies, documenting severe epistaxis episodes after specific medicines intake. In these cases some invasive medical interventions are demanded to manage the bleeding and avoid life-threatening consequences. This work provides an integrated and comprehensive review on drug-induced epistaxis bridging the gap in the current scientific literature addressing this topic. Therefore, the scientific information gathered and discussed will be valuable to raise awareness of doctors and pharmacists for this drug-related problem, as well as to promote their active pharmacovigilance and reinforce patient education. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

PubMed

Knoebl, P; Marco, P; Baudo, F; Collins, P; Huth-Kühne, A; Nemes, L; Pellegrini, F; Tengborn, L; Lévesque, H

2012-04-01

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large-scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty-seven per cent of the non-pregnancy-related cases were male. Four hundred and seventy-four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy-seven patients underwent immunosuppression, and 72.6% achieved complete remission. Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA. © 2012 International Society on Thrombosis and Haemostasis.

Disorders of Platelet Function

PubMed Central

Huebsch, Lothar B.; Harker, Laurence A.

1981-01-01

Platelets play an important role in hemostasis, and alterations in platelet function may be the cause of abnormal bleeding in a wide variety of congenital and acquired clinical disorders. Platelet dysfunction may be classified as disorders of (1) substrate connective tissue, (2) adhesion, (3) aggregation and (4) platelet-release reaction. The congenital defects of platelet function, although uncommon, have provided important insights into platelet physiology and pathophysiology and, as a group, are less common, better characterized and more readily classified than the acquired defects. The severity of bleeding resulting from platelet dysfunction varies greatly and is substantially increased when another defect of hemostasis coexists. A disorder of platelet function is suspected on the basis of the history and physical examination and is confirmed by the finding of a prolonged bleeding time in the presence of an adequate number of platelets. A specific diagnosis often requires measurements of the factor VIII and von Willebrand factor complex and other tests of platelet function. Some of these tests may be available only in specialized laboratories. Therapy for bleeding episodes resulting from platelet dysfunction is directed at (1) removing or treating the underlying cause of the platelet disorder; (2) replacing the missing plasma cofactors needed to support normal platelet function (such as by the transfusion of cryoprecipitate in patients with von Willebrand disease, and (3) transfusing functional platelets in the form of platelet concentrates in patients with disorders of intrinsic platelet dysfunction. ImagesFigure 1.Figure 2.Figure 3. PMID:7013276

Formation of obstructing blood clot in the ureter in a patient with Glanzmann's thrombasthenia.

PubMed

Kilincaslan, Huseyin; Leblebisatan, Goksel; Tepeler, Abdulkadir; Karakus, Suleyman C

2011-12-01

Glanzman thrombasthenia is a rare hematologic disorder characterized by qualitative thrombocyte abnormality. Patients present with episodic mucocutaneous bleeding. Thrombosis is a paradox phenomenon observed in patients with Glanzman thrombasthenia and generally considered as a treatment complication. We present a 16-year-old girl referred for severe flank pain beginning after treatment of hematuria due to Glanzman thrombasthenia. The patient underwent endoscopy for further diagnosis and treatment because of the failure of radiologic evaluation. Although the resolution of the large clots was obtained with streptokinase instillation via the ureteral catheter, clot was mobilized with gentle insertion of ureteral catheter in the present case.

Crouzon’s Syndrome with Life-Threatening Ear Bleed: Ruptured Jugular Vein Diverticulum Treated by Endovascular Embolization

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

Mondel, Prabath Kumar, E-mail: prabathmondel@gmail.com; Anand, Sunanda, E-mail: sunandaanand@gmail.com; Limaye, Uday S., E-mail: uslkem@gmail.com

Crouzon’s syndrome is the commonest variety of syndromic craniosynostosis. Life-threatening ear bleed due to ruptured jugular venous diverticulum in Crouzon’s syndrome has not been described previously. In patients with syndromic craniosynostosis, definitive repair of jugular diverticulum by open surgery is fraught with high risk of bleeding, poor functional outcomes, and even death. A 24-year-old woman with Crouzon’s syndrome presented with conductive hearing loss and recurrent episodes of torrential bleeding from her left ear. On computed tomography, a defect in the roof of jugular fossa containing jugular venous diverticulum immediately inferior to the bony external auditory canal was seen. The clinicalmore » presentation, imaging features, and endovascular management of Crouzon’s syndrome due to a ruptured jugular venous diverticulum is described.« less

Outcome of Isolated Premature Menarche: A Retrospective and Follow-Up Study.

PubMed

Ejaz, Sehar; Lane, Andrew; Wilson, Thomas

2015-01-01

Isolated premature menarche is isolated or recurrent vaginal bleeding in a female in the absence of appropriate secondary sexual characters. Retrospective chart review of patients with premature menarche, followed by a telephone questionnaire. Charts of patients evaluated in the Pediatric Endocrine Clinic for premature vaginal bleeding from 1982-2013 were reviewed. Of 21 patients identified, 17 could be contacted. Five newly diagnosed patients were recruited during the course of the study. The median age at initial presentation was 7 years. Most patients presented with Tanner I sexual development. Some had more advanced breast staging, which regressed later. All had prepubertal baseline and stimulated gonadotropins. Most of the patients reported a single or few episodes of menses. Two reported continuation of irregular bleeding into adulthood. All reported an adult height within the midparental target height. Premature menarche in the absence of other appropriate secondary sexual characteristics is a benign entity. Most patients have a few isolated episodes of menses that stop spontaneously; some may continue to have periods into adulthood. Unlike true puberty, these patients do not demonstrate advanced skeletal maturation, and the adult height is normal. Fertility appears to be normal. © 2015 S. Karger AG, Basel.

Acute promyelocytic leukaemia and acquired α-2-plasmin inhibitor deficiency: a retrospective look at the use of epsilon-aminocaproic acid (Amicar) in 30 patients

PubMed Central

Wassenaar, T.; Black, J.; Kahl, B.; Schwartz, B.; Longo, W.; Mosher, D.; Williams, E.

2012-01-01

Bleeding diathesis and a hyper-fibrinolytic state often accompany a diagnosis of Acute Promyelocytic Leukaemia (APML). This complication can have grave effects if not successfully treated, with a 10–20% incidence of haemorrhagic death. We hypothesized that α-2-antiplasmin levels would correlate with the risk for bleeding, and that administration of epsilon-aminocaproic acid (EACA) would attenuate that risk. To assess this, we conducted a retrospective chart review analyzing 30 APML patients, 17 of whom were treated with EACA. Thirty patients were treated, 21 with primary induction therapy. Patients with low α-2-antiplasmin levels were treated with a coagulopathy protocol consisting of low-dose heparin, EACA and blood product support. Seventeen patients (57%) developed haemorrhagic complications during their treatment. The presence and grade of haemorrhage appeared to be associated with the α-2-antiplasmin level. There were no grade IV haemorrhages or episodes of haemorrhagic death. One episode of central venous catheter associated thromboembolism and three deaths from infection during chemotherapy were observed. α-2-Antiplasmin levels are a reliable surrogate for fibrinolysis and haemorrhagic risk in patients with APML. Treatment with EACA is a rational way to pharmacologically inhibit fibrinolysis, is associated with a low incidence of severe haemorrhagic events, and appears to be safe with a low risk of thrombosis. Randomized clinical trials further assessing the efficacy and potential toxicity of EACA in inhibiting fibrinolysis in patients with APML are needed. PMID:18613223

Plasma Cell Disorders

MedlinePlus

... Time Poses Clot Risk (News) New Hemophilia Treatment Stems Bleeding Episodes (News) Quickly Treating Mini-Stroke Can Cut Risk for Future Stroke (News) Zelboraf Approved for Rare Blood Cancer (Video) Chronic Lymphocytic Leukemia (Video) Blood Clots: Plugging the Breaks Additional Content ...

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.

[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.

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.

Unusual Clinical Presentation of Hemobilia with Recurrent Vasovagal Episodes.

PubMed

Tiwari, Abhinav; Hammad, Tariq; Sharma, Himani; Qamar, Khola; Khan, Mohammad Saud; Khan, Zubair; Nawras, Ali; Sodeman, Thomas

2017-01-01

Hemobilia is caused by the abnormal connection between a blood vessel and the bile duct, which is usually iatrogenic and caused by hepatobiliary procedures. The classic triad of hemobilia includes biliary colic, obstructive jaundice, and gastrointestinal bleeding. We present the case of an 80-year-old man who had laparoscopic cholecystectomy complicated by hemobilia. He had an unusual presentation of hemobilia in the form of transient vasovagal episodes in addition to abdominal pain and hematochezia.

Complications of fluoroscopically directed facet joint nerve blocks: a prospective evaluation of 7,500 episodes with 43,000 nerve blocks.

PubMed

Manchikanti, Laxmaiah; Malla, Yogesh; Wargo, Bradley W; Cash, Kimberly A; Pampati, Vidyasagar; Fellows, Bert

2012-01-01

Chronic spinal pain is common along with numerous modalities of diagnostic and therapeutic interventions utilized, creating a health care crisis. Facet joint injections and epidural injections are the 2 most commonly utilized interventions in managing chronic spinal pain. While the literature addressing the effectiveness of facet joint nerve blocks is variable and emerging, there is paucity of literature on adverse effects of facet joint nerve blocks. A prospective, non-randomized study of patients undergoing interventional techniques from May 2008 to December 2009. A private interventional pain management practice, a specialty referral center in the United States. Investigation of the incidence in characteristics of adverse effects and complications of facet joint nerve blocks. The study was carried out over a period of 20 months including almost 7,500 episodes of 43,000 facet joint nerve blocks with 3,370 episodes in the cervical region, 3,162 in the lumbar region, and 950 in the thoracic region. All facet joint nerve blocks were performed under fluoroscopic guidance in an ambulatory surgery center by 3 physicians. The complications encountered during the procedure and postoperatively were evaluated prospectively. This study was carried out over a period of 20 months and included over 7,500 episodes or 43,000 facet joint nerve blocks. All of the interventions were performed under fluoroscopic guidance in an ambulatory surgery center by one of 3 physicians. The complications encountered during the procedure and postoperatively were prospectively evaluated. Measurable outcomes employed were intravascular entry of the needle, profuse bleeding, local hematoma, dural puncture and headache, nerve root or spinal cord irritation with resultant injury, and infectious complications. There were no major complications. Multiple side effects and complications observed included overall intravascular penetration in 11.4% of episodes with 20% in cervical region, 4% in lumbar region, and 6% in thoracic region; local bleeding in 76.3% of episodes with highest in thoracic region and lowest in cervical region; oozing with 19.6% encounters with highest in cervical region and lowest in lumbar region; with local hematoma seen only in 1.2% of the patients with profuse bleeding, bruising, soreness, nerve root irritation, and all other effects such as vasovagal reactions observed in 1% or less of the episodes. Limitations of this study include lack of contrast injection, use of intermittent fluoroscopy and also an observational nature of the study. This study illustrate that major complications are extremely rare and minor side effects are common.

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.

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.

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.

PROPOSAL OF A CLINICAL CARE PATHWAY FOR THE MANAGEMENT OF ACUTE UPPER GASTROINTESTINAL BLEEDING.

PubMed

Franco, Matheus Cavalcante; Nakao, Frank Shigueo; Rodrigues, Rodrigo; Maluf-Filho, Fauze; Paulo, Gustavo Andrade de; Libera, Ermelindo Della

2015-12-01

Upper gastrointestinal bleeding implies significant clinical and economic repercussions. The correct establishment of the latest therapies for the upper gastrointestinal bleeding is associated with reduced in-hospital mortality. The use of clinical pathways for the upper gastrointestinal bleeding is associated with shorter hospital stay and lower hospital costs. The primary objective is the development of a clinical care pathway for the management of patients with upper gastrointestinal bleeding, to be used in tertiary hospital. It was conducted an extensive literature review on the management of upper gastrointestinal bleeding, contained in the primary and secondary information sources. The result is a clinical care pathway for the upper gastrointestinal bleeding in patients with evidence of recent bleeding, diagnosed by melena or hematemesis in the last 12 hours, who are admitted in the emergency rooms and intensive care units of tertiary hospitals. In this compact and understandable pathway, it is well demonstrated the management since the admission, with definition of the inclusion and exclusion criteria, passing through the initial clinical treatment, posterior guidance for endoscopic therapy, and referral to rescue therapies in cases of persistent or rebleeding. It was also included the care that must be taken before hospital discharge for all patients who recover from an episode of bleeding. The introduction of a clinical care pathway for patients with upper gastrointestinal bleeding may contribute to standardization of medical practices, decrease in waiting time for medications and services, length of hospital stay and costs.

Cold hematoma visualized by technetium-99m labeled red blood cells

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

Beanblossom, M.

1986-09-01

A 64-yr-old male was admitted to the hospital with severe abdominal pain associated with vomiting. Upon examination, the patients Hgb was 7.8 with a WBC count of 13.3 band cells of 7 and a recticulocyte count of 3.4, no evidence of gastrointestinal bleeding. The patient's prior history revealed involvement in an automobile accident approx. 10 days prior to this admission. At that time, he suffered multiple contusions and abrasions with a fracture to his left clavicle. Apparently there were no episodes of abdominal pain or vomiting prior to the onset of illness perceived on the day of admission. A liver/spleenmore » scan was done. Four millicuries of /sup 99m/Tc-sulfur colloid were intravenously injected using a bolus injection technique while obtaining multiple dynamic images. The flow study was unremarkable, demonstrating no abnormalities to the great vessels and good perfusion to both organs. Static images of the liver and spleen revealed a straightening or flatness to the lateral border of the spleen with a small diminished area of tracer sulfur colloid localization at the posterolateral aspect of that organ. This finding raised the suspicion that a small subcapsular hematoma had developed at the mid-posterolateral aspect of the spleen. Twenty-four hours after hospital admission, 4 units of packed RBCs were transfused into the patient. Although there was at this time still no evidence of abnormal bleeding, it was felt that because of the strong symptomatic correlation for internal bleeding, a radionuclide bleeding site study should be ordered and immediately performed.« less

Precautions and Adverse Reactions during Blood Transfusion

MedlinePlus

... Time Poses Clot Risk (News) New Hemophilia Treatment Stems Bleeding Episodes (News) Quickly Treating Mini-Stroke Can Cut Risk for Future Stroke (News) Zelboraf Approved for Rare Blood Cancer (Video) Chronic Lymphocytic Leukemia (Video) Blood Clots: Plugging the Breaks Additional Content ...

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.

ACR appropriateness Criteria® second and third trimester bleeding.

PubMed

Podrasky, Ann E; Javitt, Marcia C; Glanc, Phyllis; Dubinsky, Theodore; Harisinghani, Mukesh G; Harris, Robert D; Khati, Nadia J; Mitchell, Donald G; Pandharipande, Pari V; Pannu, Harpreet K; Shipp, Thomas D; Siegel, Cary Lynn; Simpson, Lynn; Wall, Darci J; Wong-You-Cheong, Jade J; Zelop, Carolyn M

2013-12-01

Vaginal bleeding occurring in the second or third trimesters of pregnancy can variably affect perinatal outcome, depending on whether it is minor (i.e. a single, mild episode) or major (heavy bleeding or multiple episodes.) Ultrasound is used to evaluate these patients. Sonographic findings may range from marginal subchorionic hematoma to placental abruption. Abnormal placentations such as placenta previa, placenta accreta and vasa previa require accurate diagnosis for clinical management. In cases of placenta accreta, magnetic resonance imaging is useful as an adjunct to ultrasound and is often appropriate for evaluation of the extent of placental invasiveness and potential involvement of adjacent structures. MRI is useful for preplanning for cases of complex delivery, which may necessitate a multi-disciplinary approach for optimal care.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

[Safety and efficacy of a prothrombin complex concentrate in patients with coagulopathy and hemorrhage].

PubMed

Martínez-Calle, N; Marcos-Jubilar, M; Alfonso, A; Hernández, M; Hidalgo, F; Lecumberri, R; Páramo, Ja

2014-01-01

Prothrombin complex concentrates (PCC) are approved for urgent reversal of vitamin K antagonists (VKA). Recently, PCC have been used in the management of massive bleeding-associated coagulopathy. The present work evaluates safety and efficacy of PCC in a case series of both VKA reversal and massive bleeding. Retrospective review of cases treated with CCP (January 2010 to February 2013). Safety endpoints were infusion reactions and incidence of thromboembolic events. Efficacy endpoints were: 1) VKA reversal efficacy and 2) Massive bleeding coagulopathy reversal and 24h mortality. Thirty-one patients were included (22 male), median age 61 years (range 30-86). No infusion reactions were detected, and only 1 thrombotic episode was observed. VKA reversal was effective in 100% of patients (6/6), all of them with complete reversal of INR value. In massive bleeding, 24-hour survival was 64% (16/25). Invasive hemostatic procedures were required in 28% of patients (7/25). CCP use was correlated with bleeding control in 44% of cases (11/25), and also significantly associated with survival (p=0.01). CCP are safe and effective for the novel indication of adjuvant treatment in massive bleeding patients, as well as for traditional urgent reversal of VKA.

Arterial hemorrhage from cesarean scar: a rare cause of recurring massive uterine bleeding and successful surgical management.

PubMed

Wang, Chun-Feng; Hu, Min

2015-02-01

Abnormal uterine bleeding and other gynecologic complications associated with a previous cesarean section scar are only recently being identified and described. Herein we report a rare case of a woman with recurring massive uterine bleeding after 2 cesarean sections. Curettage and hormone therapy were unsuccessfully used in an attempt to control the bleeding. After she was transferred to our hospital, she had another episode of vaginal bleeding that was successfully managed with oxytocin and hemostatic. Diagnostic hysteroscopy performed under anesthesia revealed an abnormal transected artery in the cesarean section scar with a thrombus visible. In the treatment at the beginning of laparoscopic management, we adopted temporary bilateral uterine artery occlusion with titanium clips to prevent massive hemorrhage. Secondly, with the aid of hysteroscopy, the bleeding site was opened, and then the cesarean scar was wedge resected and stitched interruptedly with 1-0 absorbable sutures. The postoperative recovery was uneventful. It would seem that the worldwide use of cesarean section delivery may contribute to the risk of gynecologic disturbances including some unrecognized and complex conditions as seen in this case. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

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.

Partial spleen embolization reduces the risk of portal hypertension-induced upper gastrointestinal bleeding in patients not eligible for TIPS implantation.

PubMed

Buechter, Matthias; Kahraman, Alisan; Manka, Paul; Gerken, Guido; Dechêne, Alexander; Canbay, Ali; Wetter, Axel; Umutlu, Lale; Theysohn, Jens M

2017-01-01

Upper gastrointestinal bleeding (UGIB) is a severe and life-threatening complication among patients with portal hypertension (PH). Covered transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for patients with refractory or recurrent UGIB despite pharmacological and endoscopic therapy. In some patients, TIPS implantation is not possible due to co-morbidity or vascular disorders. Spleen embolization (SE) may be a promising alternative in this setting. We retrospectively analyzed 9 patients with PH-induced UGIB who underwent partial SE between 2012 and 2016. All patients met the following criteria: (i) upper gastrointestinal hemorrhage with primary or secondary failure of endoscopic interventions and (ii) TIPS implantation not possible. Each patient was followed for at least 6 months after embolization. Five patients (56%) suffered from cirrhotic PH, 4 patients (44%) from non-cirrhotic PH. UGIB occured in terms of refractory hemorrhage from gastric varices (3/9; 33%), hemorrhage from esophageal varices (3/9; 33%), and finally, hemorrhage from portal-hypertensive gastropathy (3/9; 33%). None of the patients treated with partial SE experienced re-bleeding episodes or required blood transfusions during a total follow-up time of 159 months, including both patients with cirrhotic- and non-cirrhotic PH. Partial SE, as a minimally invasive intervention with low procedure-associated complications, may be a valuable alternative for patients with recurrent PH-induced UGIB refractory to standard therapy.

Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach.

PubMed

Talab, Saman Shafaat; McDougal, W Scott; Wu, Chin-Lee; Tabatabaei, Shahin

2014-08-01

This study aimed evaluate the safety and feasibility of endoscopic potassium titanyl phosphate (KTP) laser application in the management of patients with radiation-induced hemorrhagic cystitis (RHC). We retrospectively reviewed the records of 20 patients with RHC who underwent endoscopic KTP laser ablation of telangiectatic bladder vessels between October 2005 and January 2013. After initial cystoscopy, KTP laser was used to ablate the submucosal vasculature while preserving the overlying mucosa. The surgical outcome was evaluated by duration of hematuria-free interval, number of episodes of hematuria, and number of required medical and/or surgical interventions after initial treatment. Overall, 20 patients underwent 26 sessions of KTP laser ablation of bladder vessels. The procedure was able to stop bleeding 92% of the time and the average hematuria-free interval after ablation was 11.8 months, with a range of 1-37 months. In 13 patients (65%) hematuria resolved after 1 session of KTP laser treatment, whereas 5 patients (25%) required multiple sessions. Two patients (10%) with severe hematuria continued to have bleeding after laser treatment, which necessitated proximal diversion of urine with percutaneous nephrostomy tubes to control bleeding. This study suggests that KTP laser, with its unique photoselectivity property, is a safe, effective, and durable treatment with minimal side effects for ablation of submucosal bladder vessels in patients with RHC. Copyright © 2014 Elsevier Inc. All rights reserved.

Spleen and Liver Stiffness Is Positively Correlated with the Risk of Esophageal Variceal Bleeding.

PubMed

Buechter, Matthias; Kahraman, Alisan; Manka, Paul; Gerken, Guido; Jochum, Christoph; Canbay, Ali; Dechêne, Alexander

2016-01-01

Portal hypertension (PH) is a common complication of chronic liver disease and results in esophageal and gastric variceal bleeding, which is associated with a high mortality rate. Measurement of the hepatic venous pressure gradient (HVPG) is considered the gold standard for diagnosing PH and estimating the risk of varices and bleeding. In contrast, upper gastrointestinal (GI) endoscopy (UGE) can reliably demonstrate the presence of varices and bleeding. Both measures are invasive, and HVPG is mainly restricted to tertiary centers. Therefore, the development of noninvasive methods of assessing the severity of PH and the risk of variceal bleeding is warranted. We retrospectively examined the correlation of spleen stiffness (SSM) and liver stiffness measurements (LSM) with the incidence of variceal bleeding among 143 patients who underwent combined liver and spleen elastography between 2013 and 2015. For 19 of 103 patients (16.8%), upper GI variceal bleeding was diagnosed and treated endoscopically. The median SSM of all patients was 35.3 kilopascals (kPa); the median LSM, 11.7 kPa. Patients with previous bleeding episodes had significantly higher SSM (75.0 kPa) and LSM (37.3 kPa) than those without a history of bleeding (SSM, 30.6 kPa; LSM, 8.2 kPa; p < 0.0001). Seventy-five patients (66.4%) underwent UGE in addition to SSM and LSM: 25 with no esophageal varices (EVs; SSM, 29.5 kPa; LSM, 11.4 kPa), 16 with EV grade 1 (SSM, 35.9 kPa; LSM, 33.4 kPa), 21 with EV grade 2 (SSM, 67.8 kPa; LSM, 27.0 kPa) and 13 with EV grade 3 (SSM, 75.0 kPa; LSM, 26.3 kPa). No statistically significant differences were found between respective grades of EV but were found between the presence and absence of varices. At a calculated cutoff level of 42.6 kPa (with application of 95% CI), SSM had sensitivity of 89% and specificity of 64% in determining the risk of bleeding, with a negative predictive value (NPV) of 0.97 (LSM sensitivity, 84%; LSM specificity, 80%; LSM NPV, 0.96 at LSM cutoff level of 20.8 kPa). When LSM (cutoff level, 20.8 kPa) and SSM (cutoff level, 42.6 kPa) were combined, the NPV was 1 (sensitivity, 100%; specificity, 55%). SSM and LSM as determined by FibroScan (a noninvasive method of detecting PH) is positively correlated with upper GI variceal bleeding (optimal SSM cutoff level, 42.6 kPa; optimal LSM cutoff level, 20.8 kPa). No patients with both SSM and LSM below cutoff levels had a history of bleeding complications. © 2016 S. Karger AG, Basel.

An observational European study on clinical outcomes associated with current management strategies for non-variceal upper gastrointestinal bleeding (ENERGIB-Turkey).

PubMed

Mungan, Zeynel

2012-01-01

This observational, retrospective cohort study assessed outcomes of the current management strategies for nonvariceal upper gastrointestinal bleeding in several European countries (Belgium, Greece, Italy, Norway, Portugal, Spain, and Turkey) (NCT00797641; ENERGIB). Turkey contributed 23 sites to this study. Adult patients (≥18 years old) consecutively admitted to hospital and who underwent endoscopy for overt non-variceal upper gastrointestinal bleeding (hematemesis, melena or hematochezia, with other clinical/laboratory evidence of acute upper GI blood loss) were included in the study. Data were collected from patient medical records regarding bleeding continuation, re-bleeding, pharmacological treatment, surgery, and mortality during a 30-day follow-up period. A total of 423 patients (67.4% men; mean age: 57.8 ± 18.9 years) were enrolled in the Turkish study centers, of whom 96.2% were admitted to hospital with acute non-variceal upper gastrointestinal bleeding. At admission, the most common symptom was melena (76.1%); 28.6% of patients were taking aspirin, 19.9% were on non-steroidal anti-inflammatory drugs, and 7.3% were on proton pump inhibitors. The most common diagnoses were duodenal (45.2%) and gastric (27.7%) ulcers and gastritis/gastric erosions (26.2%). Patients were most often managed in general medical wards (45.4%). A gastrointestinal team was in charge of treatment in 64.8% of cases. Therapeutic procedures were performed in 32.4% of patients during endoscopy. After the endoscopy, most patients (94.6%) received proton pump inhibitors. Mean (SD) hospital stay was 5.36 ± 4.91 days. The cumulative proportions of continued bleeding/re-bleeding, complications and mortality within 30 days of the non-variceal upper gastrointestinal bleeding episode were 9.0%, 5.7% and 2.8%, respectively. In the Turkish sub-group of patients, the significant risk factors for bleeding continuation or re-bleeding were age >65 years, presentation with hematemesis or shock/syncope, and the diagnosis of duodenal ulcer. The risk of clinical complications after non-variceal upper gastrointestinal bleeding was higher in female patients older than 65 years, in patients with comorbidities, and in patients presenting with shock/syncope, and also according to time to endoscopy. The use of aspirin, non-steroidal anti-inflammatory drugs or warfarin at baseline was negatively associated with the development of bleeding or clinical complications. The risk of death within 30 days after non-variceal upper gastrointestinal bleeding was significantly higher in patients older than 65 years and in those receiving transfusions other than intravenous fluid or red blood cells within 12 hours of presentation. According to the survey results, non-variceal upper gastrointestinal bleeding in Turkey varies from that in other European countries in a number of aspects. These differences could be associated with a younger population and Helicobacter pylori incidence. Despite the diminishing need for surgical intervention and mortality rates for non-variceal upper gastrointestinal bleeding, as is the case in other European countries, non-variceal upper gastrointestinal bleeding remains a serious problem.

Acute promyelocytic leukaemia and acquired alpha-2-plasmin inhibitor deficiency: a retrospective look at the use of epsilon-aminocaproic acid (Amicar) in 30 patients.

PubMed

Wassenaar, T; Black, J; Kahl, B; Schwartz, B; Longo, W; Mosher, D; Williams, E

2008-12-01

Bleeding diathesis and a hyper-fibrinolytic state often accompany a diagnosis of Acute Promyelocytic Leukaemia (APML). This complication can have grave effects if not successfully treated, with a 10-20% incidence of haemorrhagic death. We hypothesized that alpha-2-antiplasmin levels would correlate with the risk for bleeding, and that administration of epsilon-aminocaproic acid (EACA) would attenuate that risk. To assess this, we conducted a retrospective chart review analyzing 30 APML patients, 17 of whom were treated with EACA. Thirty patients were treated, 21 with primary induction therapy. Patients with low alpha-2-antiplasmin levels were treated with a coagulopathy protocol consisting of low-dose heparin, EACA and blood product support. Seventeen patients (57%) developed haemorrhagic complications during their treatment. The presence and grade of haemorrhage appeared to be associated with the alpha-2-antiplasmin level. There were no grade IV haemorrhages or episodes of haemorrhagic death. One episode of central venous catheter associated thromboembolism and three deaths from infection during chemotherapy were observed. alpha-2-Antiplasmin levels are a reliable surrogate for fibrinolysis and haemorrhagic risk in patients with APML. Treatment with EACA is a rational way to pharmacologically inhibit fibrinolysis, is associated with a low incidence of severe haemorrhagic events, and appears to be safe with a low risk of thrombosis. Randomized clinical trials further assessing the efficacy and potential toxicity of EACA in inhibiting fibrinolysis in patients with APML are needed. Copyright (c) 2008 John Wiley & Sons, Ltd.

Upper gastrointestinal bleeding in a patient with depression receiving selective serotonin reuptake inhibitor therapy.

PubMed

Kumar, Deepak; Saaraswat, Tanuj; Sengupta, S N; Mehrotra, Saurabh

2009-02-01

Serotonin plays an important role in the normal clotting phenomenon and is released by platelets. Platelets are dependent on a serotonin transporter for the uptake of serotonin, as they cannot synthesize it themselves. Selective serotonin reuptake inhibitors (SSRIs) block the uptake of serotonin into platelets and can cause problems with clotting leading to bleeding. This case report highlights the occurrence of upper gastrointestinal bleeding in the index case on initiating SSRI therapy for depression and the prompt resolution of the same on its discontinuation on two separate occasions. SSRIs may cause upper gastrointestinal (GI) bleeding. Physicians should be aware of the same and should try to rule out previous episodes of upper GI bleed or the presence of other risk factors which might predispose to it before prescribing SSRIs; they should also warn the patients about this potential side effect. Also, the presence of thalassemia trait in the index patient deserves special attention and needs to be explored to see if it might in any way contribute in potentiating this side effect of SSRIs.

Primary aortojejunal fistula: a rare cause for massive upper gastrointestinal bleeding.

PubMed

Paulasir, Sylvester; Khorfan, Rhami; Harsant, Christina; Anderson, Harry Linne

2017-04-26

A 68-year-old man presented to the emergency department with haematemesis and shock. Upper endoscopy and selective angiography could not identify the source of bleeding. He underwent selective embolisation of the gastroduodenal artery. The patient then had a period of about 24 hours with relative haemodynamic stability before having another episode of massive upper gastrointestinal bleed. A second attempt to embolise the common hepatic artery and distal coeliac axis was unsuccessful. Hence, he was urgently taken to the operating room for exploratory laparotomy. The source of bleeding could not be identified in the operating room. The patient went into cardiac arrest and expired. Autopsy revealed a fistula between proximal jejunum and a previously unknown abdominal aortic aneurysm (AAA). We present an entity that has only been described a few times in the literature while highlighting the importance of having a broad differential with upper gastrointestinal bleeding, especially when the source is not clearly evident. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Severe Bleeding: First Aid

MedlinePlus

... 12, 2017. Jevon P, et al. Part 5 — First-aid treatment for severe bleeding. Nursing Times. 2008;104:26. Oct. 19, 2017 Original article: http://www.mayoclinic.org/first-aid/first-aid-severe-bleeding/basics/ART-20056661 . Mayo ...

How to Deal with Hemophilia

MedlinePlus

... organs, treatment is necessary. Patients with more serious cases of hemophilia often get regular shots of the factor that they're missing to prevent bleeding episodes. Kids with moderate or mild cases of hemophilia usually don't need these shots unless they have a more serious injury or ...

Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review.

PubMed

Neunert, C; Noroozi, N; Norman, G; Buchanan, G R; Goy, J; Nazi, I; Kelton, J G; Arnold, D M

2015-03-01

The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established. To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies. We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry up to May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated. We identified 118 studies that reported bleeding (n = 10 908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults (95% confidence interval [CI], 0.9-2.1%) and 0.4% for children (95% CI, 0.2-0.7%; P < 0.01), most of whom had chronic ITP. The weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1-17.1%) and 20.2% for children (95% CI, 10.0-32.9%; P < 0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable in primary studies. Two bleeding assessment tools (Buchanan 2002 for children; Page 2007 for adults) demonstrated adequate inter-rater reliability and validity in independent assessments. ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable across studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this important outcome for patients. © 2014 International Society on Thrombosis and Haemostasis.

Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review

PubMed Central

NEUNERT, C.; NOROOZI, N.; NORMAN, G.; BUCHANAN, G. R.; GOY, J.; NAZI, I.; KELTON, J. G.; ARNOLD, D. M.

2016-01-01

Summary Background The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established. Objectives To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies. Patients/Methods We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry up to May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated. Results We identified 118 studies that reported bleeding (n = 10 908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults (95% confidence interval [CI], 0.9–2.1%) and 0.4% for children (95% CI, 0.2–0.7%; P < 0.01), most of whom had chronic ITP. The weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1–17.1%) and 20.2% for children (95% CI, 10.0–32.9%; P < 0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable in primary studies. Two bleeding assessment tools (Buchanan 2002 for children; Page 2007 for adults) demonstrated adequate interrater reliability and validity in independent assessments. Conclusions ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable across studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this important outcome for patients. PMID:25495497

Near fatal spontaneous intraperitoneal bleeding: A rare manifestation in a congenital factor X deficiency carrier.

PubMed

Vinod, K V; Hitha, B; Kaaviya, R; Dutta, T K

2015-03-01

Congenital factor X (FX) deficiency is a rare coagulation disorder of autosomal recessive inheritance, characterized by bleeding of variable severity. Bleeding severity generally correlates with the level of FX functional activity and severe bleeding usually occurs in moderate and severe deficiency, when FX coagulant activity is <5%. FX activity above 10% is infrequently associated with severe bleeding. Here we report the rare occurrence of life-threatening massive spontaneous intraperitoneal bleeding with hypovolemic shock, resulting from spontaneous rupture of an ovarian luteal cyst in a 25-year-old FX deficiency carrier woman, with a FX activity of 26%. She was managed successfully conservatively, with fresh frozen plasma and packed red blood cell transfusions and she showed gradual improvement. The case is being reported to discuss the diagnosis and management of this rare inherited coagulation disorder.

Cost-utility analysis of an adjunctive recombinant activated factor VIIa for on-demand treatment of bleeding episodes in dengue haemorrhagic fever.

PubMed

Naing, Cho; Poovorawan, Yong; Mak, Joon Wah; Aung, Kyan; Kamolratankul, Pirom

2015-06-01

The present study aimed to assess the cost-utility analysis of using an adjunctive recombinant activated factor VIIa (rFVIIa) in children for controlling life-threatening bleeding in dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). We constructed a decision-tree model, comparing a standard care and the use of an additional adjuvant rFVIIa for controlling life-threatening bleeding in children with DHF/DSS. Cost and utility benefit were estimated from the societal perspective. The outcome measure was cost per quality-adjusted life years (QALYs). Overall, treatment with adjuvant rFVIIa gained QALYs, but the total cost was higher. The incremental cost-utility ratio for the introduction of adjuvant rFVIIa was $4241.27 per additional QALY. Sensitivity analyses showed the utility value assigned for calculation of QALY was the most sensitive parameter. We concluded that despite high cost, there is a role for rFVIIa in the treatment of life-threatening bleeding in patients with DHF/DSS.

Cost effectiveness of enoxaparin as prophylaxis against venous thromboembolic complications in acutely ill medical inpatients: modelling study from the hospital perspective in Germany.

PubMed

Schädlich, Peter K; Kentsch, Michael; Weber, Manfred; Kämmerer, Wolfgang; Brecht, Josef Georg; Nadipelli, Vijay; Huppertz, Eduard

2006-01-01

To estimate, from the hospital perspective in Germany, the cost effectiveness of the low-molecular-weight heparin (LMWH) subcutaneous enoxaparin sodium 40 mg once daily (ENOX) relative to no pharmacological prophylaxis (NPP) and relative to subcutaneous unfractionated heparin (UFH) 5,000 IU three times daily (low-dose UFH [LDUFH]). Each is used in addition to elastic bandages/compression stockings and physiotherapy in the prevention of venous thromboembolic events (VTE) in immobilised acutely ill medical inpatients without impaired renal function or extremes of body weight. The incremental cost-effectiveness ratios (ICERs) of the 'additional cost for ENOX per clinical VTE avoided versus NPP' and 'additional cost for ENOX per episode of major bleeding avoided versus LDUFH' were chosen as target variables. The target variables were quantified using a modelling approach based on the decision-tree technique. Resource use during thromboprophylaxis, diagnosis and treatment of VTEs, episode of major bleeding and secondary pneumonia after pulmonary embolism (PE) was collected from a hospital survey. Costs were exclusively those to hospitals incurred by staff expenses, drugs, devices, disposables, laboratory tests and equipment for diagnostic procedures. These costs were determined by multiplying utilised resource items by the price or tariff of each item as of the first quarter of 2003. Safety and efficacy values of the comparators were taken from the MEDENOX (prophylaxis in MEDical patients with ENOXaparin) and the THE-PRINCE (THromboEmbolism-PRevention IN Cardiac or respiratory disease with Enoxaparin) trials and from a meta-analysis. The evaluation encompassed 8 (6-14) days of thromboprophylaxis plus time to treat VTE and episode of major bleeding in hospital. Point estimates of all model parameters were applied exclusively in the base-case analysis. There were incremental costs of euro 1,106 for ENOX per clinical VTE avoided versus NPP (1 euro approximately equals 1.07 US dollars; average of the first quarter of 2003). ENOX dominated LDUFH: cost savings of euro 55,825 were obtained and 7.7 episodes of major bleeding were avoided by ENOX compared with LDUFH, each per 1000 patients. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. Results of this evaluation suggest that, in immobilised acutely ill medical inpatients, ENOX may offer hospitals in Germany a very cost-effective option for thromboprophylaxis compared with NPP and a cost-saving alternative compared with LDUFH.

Rhabdomyolysis in a Young Girl with Van Wyk-Grumbach Syndrome due to Severe Hashimoto Thyroiditis.

PubMed

Leonardi, Alberto; Penta, Laura; Cofini, Marta; Lanciotti, Lucia; Principi, Nicola; Esposito, Susanna

2018-04-09

Background: Autoimmune hypothyroidism (Hashimoto thyroiditis; HT) is the most common postnatal thyroid disease. Clinical manifestations of HT vary according to disease severity. Due to the pleiotropic effects of thyroid hormone, less common signs and symptoms of HT can occur, leading to a delay in diagnosis. Case presentation: A 9-year-old girl of Indian origin was admitted for a one-week history of widespread myalgia, fatigue, muscle weakness, difficulty walking, and a significant increase in weight (approximately 2 kg) without any changes in daily habits. The only relevant medical history was several intermittent vaginal bleeding episodes since four years of age. Breast development was consistent with Tanner stage 2 without pubic or axillary hair; while height and weight were at the 10th percentile and the 38th percentile; respectively. Bone age from a left wrist X-ray was delayed 1 year. Pelvic ultrasonography revealed a uterine body/neck ratio of >1 (pubertal stage) and multifollicular ovaries. Her external genitalia had a childlike appearance. Laboratory examinations showed an increased thyroid-stimulating hormone, decreased free thyroxine, and positive anti-thyroglobulin antibody titres, as well as elevation of creatine phosphokinase, myoglobin, lactate dehydrogenase, serum aspartate aminotransferase, hypercholesterolemia, and a basal serum prolactin near the upper limit of normal. Follicle stimulating hormone and estradiol were slightly and significantly elevated, respectively. Thyroid ultrasound showed an increased gland size with irregular echostructures and high vascularization. Levothyroxine replacement therapy led to complete normalization of clinical and laboratory findings, including rhabdomyolysis indices. No further vaginal bleeding episodes were reported. Conclusion: This case report highlights how various can be the clinical picture of HT in children, and how rare clinical manifestations can be the only signs of disease at presentation leading to delayed diagnosis and treatment. In this girl, a never-described association of Van Wyk-Grumbach syndrome and acute rhabdomyolysis in a young girl with previously unrecognized HT is described. The importance of recognizing the signs and symptoms of rare complications of HT in order to begin appropriate therapy is stressed.

Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature.

PubMed

Winkelhorst, Dian; Kamphuis, Marije M; de Kloet, Liselotte C; Zwaginga, Jaap Jan; Oepkes, Dick; Lopriore, Enrico

2016-05-01

The most feared bleeding complication in fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an intracranial hemorrhage (ICH). However, FNAIT may also lead to other severe bleeding problems. The aim was to analyze this spectrum and evaluate the occurrence of severe hemorrhages other than ICH in fetuses or neonates with FNAIT. A retrospective chart analysis of cases of FNAIT presenting with severe bleeding complications other than ICH at our institution from 1990 to 2015 was conducted. Additionally, a review of the literature was performed to identify case reports and case series on FNAIT presenting with extracranial hemorrhage. Of 25 fetuses or neonates with severe bleeding due to FNAIT, three had isolated severe internal organ hemorrhage other than ICH, two pulmonary hemorrhages and one gastrointestinal hemorrhage. Two of these three neonates died due to this bleeding. Eighteen cases of extracranial bleeding complications as a first presentation of FNAIT were found in the literature, including ocular, gastrointestinal, spinal cord, pulmonary, renal, subgaleal, and genitourinary hemorrhages. Bleeding complications other than ICH may be more extensive, and the presentation of FNAIT may have a greater spectrum than previously described. A high index of suspicion on the possible diagnosis of FNAIT with any bleeding complication in a fetus or neonate may enable adequate diagnostics, adequate treatment, and appropriate follow-up in future pregnancies, as is especially relevant for FNAIT. © 2016 AABB.

Dengue fever in renal transplant patients: a systematic review of literature.

PubMed

Weerakkody, Ranga Migara; Patrick, Jean Ansbel; Sheriff, Mohammed Hussain Rezvi

2017-01-13

Dengue fever in renal transplanted patients has not been studied well, and we review all the literature about episodes dengue fever in renal transplant patients. The aim was to describe clinico-pathological characteristics, immunosuppressive protocols, need renal outcome and mortality. PubMed, LILACS, Google Scholar and Research Gate were searched for "Dengue" and "Renal/Kidney Transplantation" with no date limits. Hits were analyzed by two researchers separately. Fever, myalgia, arthralgia and headache was significantly lower than normal population, while pleural effusions and ascites were observed more. Incidence of severe dengue is significantly higher among transplant patients in this review, as well as they had a significantly higher mortality (8.9% vs 3.7%, p = 0.031). Age, period after transplantation and immunosuppressive profile had no effect on disease severity, mortality or graft out come. Presence of new bleeding complications and ascites was associated with more severe disease (p < 0.001 and p = 0.005), death (p = 0.033) or graft loss (p = 0.035). Use of tacrolimus was associated with new bleeding complications (p = 0.027), and with ascites (p = 0.021), but not with thrombocytopenia. 25% of patients with primary disease fail to mount an IgG response by 15 weeks of the illness. 58.9% had graft dysfunction during illness. Postoperative transplanted patients were at risk of severe disease and unfavorable outcome. The physical and laboratory findings in dengue fever in renal transplanted patients differ from the general population. Some degree of graft dysfunction is common during the illness, but only a minority develops graft failure.

Trapezoid supracondylar femoral extension osteotomy for knee flexion contractures in patients with haemophilia.

PubMed

Mortazavi, S M J; Heidari, P; Esfandiari, H; Motamedi, M

2008-01-01

Flexion deformity of the haemophilic knee is a considerable cause of disability and may need to be managed surgically in severe cases. We have used a trapezoid supracondylar femoral extension osteotomy to correct severe knee flexion deformity. Nine severe haemophilic patients with contractures >30 degrees that were unresponsive to conservative measures underwent 11 trapezoid osteotomies. The angle of deformity was measured using anteroposterior and lateral knee X-ray films at maximum extension. Factor levels of 80-100% were achieved before the operation. A trapezoid osteotomy of the distal femur bone was performed using a lateral approach. The frontal plane angular deformity (if any) was corrected at the same time. The osteotomy site was fixed using an Arbeitsgemeinschaft für Osteo synthesefragen (AO) condylar blade plate. Following surgery, the knee was supported by a plaster splint at 20 degrees of flexion. Physiotherapy was started on third postoperative day and continued three times a week. There was no serious complication. The deformities were corrected in all of the patients and the mean range of motion increased form 68.6 degrees to 98.1 degrees . Bleeding episodes decreased in all four knees which had a bleeding score of 3 before surgery. Using the Orthopaedic Advisory Committee of the World Federation of Haemophilia scores, nine good and two fair results were obtained. All patients regained the ability to walk for both short and long distance without any aid, climb the stairs, bath, and use public transportation. Trapezoid supracondylar femoral extension osteotomy should be considered in the surgical management of severe haemophilic flexion deformity of the knee joint.

Primary aortoduodenal fistula associated with abdominal aortic aneurysm with presentation of gastrointestinal bleeding: a case report.

PubMed

Lin, Tzu-Chieh; Tsai, Chung-Lin; Chang, Yao-Tien; Hu, Sung-Yuan

2018-06-07

Primary aortoduodenal fistula (ADF) is a rare cause of gastrointestinal (GI) bleeding and is difficult to diagnose as the clinical presentation is subtle. Clinicians should keep a high level of suspicion for an unknown etiology of GI bleeding, especially in older patients with or without abdominal aortic aneurysm (AAA). Computed tomographic angiography (CTA) can be used to detect primary ADF. Open surgery or endovascular aortic repair (EVAR) for ADF with bleeding will improve the survival rate. We report a rare case of AAA complicating ADF with massive GI bleeding in a 73-year-old Taiwanese man. He presented with abdominal pain and tarry stool for 5 days and an initial upper GI endoscopy at a rural hospital showed gastric ulcer only, but hypotension with tachycardia and a drop in hemoglobin of 9 g/dl from 12 g/dl occurred the next day. He was referred to our hospital for EVAR and primary closure of fistula defect due to massive GI bleeding with shock from ADF caused by AAA. Diagnosis was made by CTA of aorta. A timely and accurate diagnosis of primary ADF may be challenging due to insidious episodes of GI bleeding, which are frequently under-diagnosed until the occurrence of massive hemorrhage. Clinical physicians should keep a high index of awareness for primary ADF, especially in elderly patients with unknown etiology of upper GI bleeding with or without a known AAA.

Dental postoperative bleeding complications in patients with suspected and documented liver disease.

PubMed

Hong, C H; Scobey, M W; Napenas, J J; Brennan, M T; Lockhart, P B

2012-10-01

The aims of this study were to determine the frequency of bleeding complications following dental procedures in patients with known or suspected chronic liver disease and whether international normalized ratio (INR) determination could aid in predicting bleeding complications in these patients. We identified 90 patients (mean age: 51 ± 9 years) in this retrospective chart review. Sixty-nine patients had a known history of chronic liver disease and 21 had suspected chronic liver disease. Descriptive statistics were determined. Independent sample t-test and one-way variance test were utilized for continuous variables and chi-square test for dichotomous variables. The mean INR value for all patients was 1.2 ± 0.3. The INR value was significantly associated with the diagnosis of liver cirrhosis, the diagnoses of Hepatitis B and C together, the presence of ascites alone, and the number of clinical signs and symptoms (i.e. ascites, jaundice and encephalopathy) present. Nine patients with INR values between 1.5 and 2 underwent invasive dental procedures without postoperative bleeding complications. There were no episodes of postoperative bleeding in patients. The findings suggest that clinicians should not rely solely on an INR value to predict post-procedure bleeding in patients with liver disease. © 2012 John Wiley & Sons A/S.

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.

Active iris vascular tufts bleeding successfully treated with argon laser photocoagulation.

PubMed

Sarmad, Ambreen; Alfaqawi, Fadi; Chakrabarti, Monali; Mitra, Arijit; Mushtaq, Bushra

2018-03-01

Iris vascular tufts (IVT) are rare biomicroscopic capillary outgrowths from the pupillary margins. Patients are usually asymptomatic until presenting with blurred vision due to spontaneous hyphema or with raised intraocular pressure. A 61-year-old woman presented to eye casualty with left eye (LE) blurred vision and discomfort for 1 day. Her external ocular examination was unremarkable and visual acuity was 6/6 in the right eye (RE) and 6/9 in the LE. Biomicroscopic examination revealed a 2-mm hyphema in her LE and bilateral multiple small IVT and active bleeding from IVT at the pupillary margin of the LE at the 5 o'clock position. Diagnosis of LE active bleeding from IVT was made and she underwent argon laser photocoagulation directed at the source of bleeding. The bleeding stopped immediately after the second burn. She was followed up for 3 months; her visual acuity was 6/5 and 6/6 in the RE and LE, respectively, with no further problems. Iris vascular tufts are benign and recurrent hemorrhages are unlikely. Therefore, definitive argon laser photocoagulation or surgical treatment are reserved to arrest further episodes of hyphema. Our case demonstrates the effective use of argon laser photocoagulation to completely arrest active bleeding from IVT and excellent recovery of hyphema with no further problems for 5 years.

Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

PubMed Central

Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

2015-01-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

Bleeding gums

MedlinePlus

... form of gum and jawbone disease known as periodontitis . Other causes of bleeding gums include: Any bleeding ... if: The bleeding is severe or long-term (chronic) Your gums continue to bleed even after treatment ...

Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003-2008).

PubMed

Marín, Liliana M; Iazbik, M Cristina; Zaldivar-Lopez, Sara; Lord, Linda K; Stingle, Nicole; Vilar, Paulo; Lara-Garcia, Ana; Alvarez, Francisco; Hosoya, Kenji; Nelson, Laura; Pozzi, Antonio; Cooper, Edward; McLoughlin, Mary A; Ball, Rebecca; Kisseberth, William C; London, Cheryl A; Dudley, Robert; Dyce, Jonathan; McMahon, Melanie; Lerche, Phillip; Bednarski, Richard; Couto, C Guillermo

2012-06-01

To determine the frequency of delayed postoperative bleeding in retired racing Greyhounds with appendicular bone tumors undergoing limb amputations. To identify if administration of epsilon-aminocaproic acid (EACA) was effective on the prevention of postoperative bleeding. Retrospective study from December 2003 to December 2008. Veterinary university teaching hospital. Forty-six retired racing Greyhounds (RRGs) diagnosed with primary appendicular bone tumors that underwent limb amputation were included in the study. None. Thirteen of 46 RRGs (28%) included in the study had delayed postoperative bleeding starting 48-72 h after surgery. Bleeding episodes included cutaneous, subcutaneous, and external bleeding that extended from the area of the surgical site that became widespread within hours, and that required administration of blood components. A paired t-test suggests that there was a significant decrease in PCV postoperatively for both dogs that bled and dogs that did not bleed (P < 0.0001). Forty of 46 RRGs (86%) received either fresh frozen plasma (FFP) or EACA or both, for the prevention of postoperative bleeding. A logistic regression model determined that dogs that did not receive EACA were 5.7 times more likely to bleed than dogs that did receive EACA, when controlling for whether or not they received FFP (95% CI: 1.02-32.15, P = 0.047). This retrospective study suggests that preemptive postoperative administration of EACA appears to be efficacious in decreasing the frequency of bleeding in RRGs undergoing limb amputation; however, a prospective study is warranted to corroborate its effectiveness. © Veterinary Emergency and Critical Care Society 2012.

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

Response to mass casualty events: from the battlefield to the Stop the Bleed campaign

PubMed Central

Knudson, M Margaret; Velmahos, George; Cooper, Zara R

2016-01-01

In the aftermath of a number of episodes of mass casualty events, we must be reminded of how important it is to be prepared and to reflect on the knowledge accumulated over the past 15 years of war in Iraq and Afghanistan. PMID:29766063

[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.

An uncommon case of antegrade stent causing serious persistent haematuria

PubMed Central

Ejikeme, Chidozie M.

2015-01-01

Introduction Transient minor bleeding after nephrostomy tube placement is very common, occurring in up to 95% of cases. Often this is due to small vessel or venous bleeding. Severe post procedure bleeding requiring transfusion or other intervention is RARE. Presentation of case A case of a 79 year old man, who had antegrade stent insertion for 10 mm left upper ureteric stone. He was alright for up to one week but developed severe haemturia requiring three way catheter. Catheter was blocking regularly and needed to go to theatre for bladder washout. No source of bleeding was found in bladder. CT renal angiogram revealed his stent has migrated into the nephrostomy tract. He was taken to theatre and had his stent changed. His haematuria settled. Discussion The severe bleeding recorded in this case could not have been attributed to the stent, though the initial bleeding following the procedure has settled it seemed likely to blame vascular injury following PCN as the cause of bleeding. Subsequent CT scan was able to point at the right source of bleeding. Conclusion All possibilities should be considered when presented with a case severe bleeding following antegrade stent insertion. PMID:25797353

An uncommon case of antegrade stent causing serious persistent haematuria.

PubMed

Ejikeme, Chidozie M

2015-01-01

Transient minor bleeding after nephrostomy tube placement is very common, occurring in up to 95% of cases. Often this is due to small vessel or venous bleeding. Severe post procedure bleeding requiring transfusion or other intervention is RARE. A case of a 79 year old man, who had antegrade stent insertion for 10mm left upper ureteric stone. He was alright for up to one week but developed severe haemturia requiring three way catheter. Catheter was blocking regularly and needed to go to theatre for bladder washout. No source of bleeding was found in bladder. CT renal angiogram revealed his stent has migrated into the nephrostomy tract. He was taken to theatre and had his stent changed. His haematuria settled. The severe bleeding recorded in this case could not have been attributed to the stent, though the initial bleeding following the procedure has settled it seemed likely to blame vascular injury following PCN as the cause of bleeding. Subsequent CT scan was able to point at the right source of bleeding. All possibilities should be considered when presented with a case severe bleeding following antegrade stent insertion. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Risk factors for unscheduled delivery in patients with placenta accreta.

PubMed

Bowman, Zachary S; Manuck, Tracy A; Eller, Alexandra G; Simons, Marilee; Silver, Robert M

2014-03-01

Patients with suspected placenta accreta have improved outcomes with scheduled delivery. Our objective was to identify risk factors for unscheduled delivery in patients with suspected placenta accreta. This was a cohort study of women with antenatally suspected placenta accreta. Women who delivered prior to a planned delivery date were compared with women who had a scheduled delivery. Data were analyzed using a Student t test, χ(2), logistic regression, and survival analyses. Variables included in the analyses were episodes of antenatal vaginal bleeding, preterm premature rupture of membranes (PPROM), uterine contractions, prior cesarean deliveries, interpregnancy interval, parity, and patient demographic factors. A value of P < .05 was considered significant. Seventy-seven women with antenatal suspicion for placenta accreta were identified. Thirty-eight (49.4%) had an unscheduled delivery. Demographics were similar between groups. Unscheduled patients delivered earlier (mean 32.3 vs 35.7 weeks, P < .001) and were significantly more likely to have had vaginal bleeding (86.8% vs 35.9%, P < .001) and uterine activity (47.4% vs 2.6%, P < .001). Each episode of antenatal vaginal bleeding was associated with an increased risk of unscheduled delivery (adjusted odds ratio, 3.8; 95% confidence interval, 1.8-7.8). Risk of earlier delivery was even greater when associated with PPROM (P < .001). Among women with suspected placenta accreta, those with antenatal vaginal bleeding were more likely to require unscheduled delivery. This risk increases further in the setting of PPROM and/or uterine contractions. These clinical factors should be considered when determining the optimal delivery gestational age for women with placental accreta. Copyright © 2014 Mosby, Inc. All rights reserved.

Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER).

PubMed

Napolitano, Mariasanta; Giansily-Blaizot, Muriel; Dolce, Alberto; Schved, Jean F; Auerswald, Guenter; Ingerslev, Jørgen; Bjerre, Jens; Altisent, Carmen; Charoenkwan, Pimlak; Michaels, Lisa; Chuansumrit, Ampaiwan; Di Minno, Giovanni; Caliskan, Umran; Mariani, Guglielmo

2013-04-01

Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (<1-45 years of age, 21 female). Severest phenotypes (central nervous system, gastrointestinal, joint bleeding episodes) were highly prevalent. Twenty-one patients received recombinant activated factor VII (24 courses), four received plasma-derived factor VII, and ten received fresh frozen plasma. Prophylactic schedules clustered into "frequent" courses (three times weekly, n=23) and "infrequent" courses (≤ 2 times weekly, n=15). Excluding courses for menorrhagia, "frequent" and "infrequent" courses produced 18/23 (78%) and 5/12 (41%) "excellent" outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on "frequent" administrations (three times weekly) and a 90 μg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency.

Recombinant von Willebrand factor: preclinical development.

PubMed

Plaimauer, B; Schlokat, U; Turecek, P L; Mitterer, A; Mundt, W; Auer, W; Pichler, L; Gritsch, H; Schwarz, H P

2001-08-01

Von Willebrand factor (vWF) is a multimeric glycoprotein (GP) that attracts platelets to the site of vascular injury, mediates platelet-platelet interaction, and stabilizes factor VIII (FVIII) in the circulation. Quantitative and qualitative defects of vWF result in von Willebrand disease (vWD), manifested by modest to severe bleeding episodes. Substitution therapy, with plasma-derived FVIII/vWF complex concentrates, is used for patients suffering the more severe forms of vWD. Efficacy of these preparations is often unsatisfactory because inadvertent proteolytic degradation during the manufacturing process causes them to lack the hemostatically most active high-molecular-weight multimers. In contrast, recombinant vWF (r-vWF), which is constitutively expressed at high yields in Chinese hamster ovary (CHO) cells and secreted into the conditioned medium under perfusion fermentation in "protein-free" medium, has high-molecular-weight multimers of extraordinary structural integrity. Functional analysis has shown that r-vWF promotes ristocetin cofactor-mediated platelet aggregation, collagen interaction and FVIII binding, and platelet-collagen adhesion under shear stress. Infusing vWF-deficient animals with r-vWF corrected vWF concentration and reduced blood loss, subsequently stabilizing endogenous FVIII associated with the reduction of bleeding time. Compared with plasma-derived vWF preparations, r-vWF was found to have a prolonged half-life, further enhancing the potential value of r-vWF as a therapeutic agent for treating patients suffering from vWD.

Venous Thromboembolism in Patients With Reduced Estimated GFR: A Population-Based Perspective

PubMed Central

Parikh, Amisha M.; Spencer, Frederick A.; Lessard, Darleen; Emery, Catherine; Baylin, Ana; Linkletter, Crystal; Goldberg, Robert J.

2011-01-01

Background An increased frequency of venous thromboembolism (VTE) has been shown among patients with reduced kidney function as measured by a decreased estimated glomerular filtration rate (eGFR). However, current practices with respect to VTE prevention and management in patients with a reduced eGFR in general population settings remain uncertain. Study Design Observational study. Setting & Participants Community investigation of 1,509 metropolitan Worcester (Massachusetts) residents with validated VTE during 1999, 2001, and 2003 with further follow-up for up to 3 years. Predictor VTE patients further classified according to their eGFR on presentation: < 30, 30-59, 60-89, or ≥ 90 ml/min/1.73m2 (reference group). Outcomes Recurrent VTE, major bleeding episodes, and all-cause mortality. Measurements Demographic and clinical characteristics, treatment practices, and study outcomes were extracted from patients’ hospital and outpatient medical records; eGFR was estimated using the Chronic Kidney Disease Epidemiology equation. Results VTE patients with eGFR < 30 ml/min/1.73m2 were at an increased risk for recurrent VTE (HR, 1.83; 95% CI, 1.03-3.25), major bleeding episodes (HR, 2.30; 95% CI, 1.28-4.16) and all-cause mortality (HR, 1.70; 95% CI, 1.12-2.57) over 3-year follow-up. Patients with reduced eGFR also presented with more co-morbidities and were less likely to be discharged on any form of anticoagulant therapy (72.6%, 81.0%, 82.1%, and 87.3% for eGFR < 30, 30-59, 60-89, and ≥ 90 mL/min/1.73m2, respectively; p<0.001). Limitations Reduced eGFR status is presumed based on creatinine values on clinical presentation. The impact of drug dosage, timing, type of anticoagulant therapy, and medication adherence on study outcomes could not be evaluated. Conclusions Severe reductions in eGFR are associated with an increased risk of long-term recurrent VTE, bleeding, and total mortality in patients with VTE. A greater frequency of serious co-morbidities, difficulties implementing available management strategies, and suboptimal VTE prophylaxis during hospital admissions likely contributed to our findings. PMID:21872977

Is the HAS-BLED score useful in predicting post-extraction bleeding in patients taking warfarin? A retrospective cohort study

PubMed Central

Kataoka, Toshiyuki; Hoshi, Keika; Ando, Tomohiro

2016-01-01

Objective Unexpected post-extraction bleeding is often experienced in clinical practice. Therefore, determining the risk of post-extraction bleeding in patients receiving anticoagulant therapy prior to surgery is beneficial. This study aimed to verify whether the HAS-BLED score was useful in predicting post-extraction bleeding in patients taking warfarin. Design Retrospective cohort study. Setting Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University. Participants Participants included 258 sequential cases (462 teeth) who had undergone tooth extraction between 1 January 2010 and 31 December 2012 while continuing warfarin therapy. Main outcome measure Post-extraction risk factors for bleeding. The following data were collected as the predicting variables for multivariate logistic analysis: the HAS-BLED score, extraction site, tooth type, stability of teeth, extraction procedure, prothrombin time-international normalised ratio value, platelet count and the use of concomitant antiplatelet agents. Results Post-extraction bleeding was noted in 21 (8.1%) of the 258 cases. Haemostasis was achieved with localised haemostatic procedures in all the cases of post-extraction bleeding. The HAS-BLED score was found to be insufficient in predicting post-extraction bleeding (area under the curve=0.548, p=0.867, multivariate analysis). The risk of post-extraction bleeding was approximately three times greater in patients taking concomitant oral antiplatelet agents (risk ratio=2.881, p=0.035, multivariate analysis). Conclusions The HAS-BLED score alone could not predict post-extraction bleeding. The concomitant use of oral antiplatelet agents was a risk factor for post-extraction bleeding. No episodes of post-extraction bleeding required more than local measures for haemostasis. However, because this was a retrospective study conducted at a single institution, large-scale prospective cohort studies, which include cases of outpatient tooth extraction, will be necessary in the future. PMID:26936909

Use of freeze-dried plasma in French intensive care unit in Afghanistan.

PubMed

Martinaud, Christophe; Ausset, Sylvain; Deshayes, Anne Virginie; Cauet, Amandine; Demazeau, Nicolas; Sailliol, Anne

2011-12-01

Modern warfare causes severe injuries, and despite rapid transportation to theater regional trauma centers, casualties frequently arrive coagulopathic and in shock. Massive hemorrhage management includes transfusion of red blood cells and plasma in a 1:1 ratio. Fresh frozen plasma requires thawing and badly fits the emergency criteria. Since 1994, the French Military Blood Bank has been producing freeze-dried plasma (FDP) and providing it for overseas operation. The aim of our study was to evaluate the use of FDP in war settings and to assess its clinical efficiency and safety. We performed a prospective study of the FDP delivered at the International Security Assistance Force Role 3 Military Medical Treatment Facility in the Kabul Afghanistan International Airport between February 2010 and February 2011. We included every patient who received at least one unit of FDP. Basic clinical data were recorded at admission. Transfusion requirements were monitored. Biological testing were performed before and after administration of FDP including hemoglobin concentration, platelets count, fibrinogen level, prothrombin time (PT), and thromboelastography. Eighty-seven casualties received FDP during 93 episodes of transfusion. On average, 3.5 FDP units were transfused per episodes of transfusion. Of the 87 patients studied, 7 died because of nonsurvivable injuries and outcomes were unavailable for 11. The other 59 patients survived. PT significantly declined by an average of 3.3 seconds after FDP transfusion. This moderate decrease in PT reflects continued bleeding and resuscitation. It nevertheless suggests improvement in hemostasis before surgical control of bleeding. All FDP users reported ease of use, clinically observed efficacy equivalent to fresh frozen plasma and the absence of adverse effects associated with FDP. Our results provide evidence of the effectiveness of FDP for the prevention or correction of coagulopathy and hemorrhage in combat casualties.

Management of Upper Gastrointestinal Bleeding in Children: Variceal and Nonvariceal.

PubMed

Lirio, Richard A

2016-01-01

Upper gastrointestinal (UGI) bleeding is generally defined as bleeding proximal to the ligament of Treitz, which leads to hematemesis. There are several causes of UGI bleeding necessitating a detailed history to rule out comorbid conditions, medications, and possible exposures. In addition, the severity, timing, duration, and volume of the bleeding are important details to note for management purposes. Despite the source of the bleeding, acid suppression with a proton-pump inhibitor has been shown to be effective in minimizing rebleeding. Endoscopy remains the interventional modality of choice for both nonvariceal and variceal bleeds because it can be diagnostic and therapeutic. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura

PubMed Central

Buchanan, George R.; Imbach, Paul; Bolton-Maggs, Paula H. B.; Bennett, Carolyn M.; Neufeld, Ellis J.; Vesely, Sara K.; Adix, Leah; Blanchette, Victor S.; Kühne, Thomas

2008-01-01

Controversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP). Drug treatment is usually administered to prevent severe hemorrhage, although the definition and frequency of severe bleeding are poorly characterized. Accordingly, the Intercontinental Childhood ITP Study Group (ICIS) conducted a prospective registry defining severe hemorrhage at diagnosis and during the following 28 days in children with ITP. Of 1106 ITP patients enrolled, 863 were eligible and evaluable for bleeding severity assessment at diagnosis and during the subsequent 4 weeks. Twenty-five children (2.9%) had severe bleeding at diagnosis. Among 505 patients with a platelet count less than or equal to 20 000/mm3 and no or mild bleeding at diagnosis, 3 (0.6%), had new severe hemorrhagic events during the ensuing 28 days. Subsequent development of severe hemorrhage was unrelated to initial management (P = .82). These results show that severe bleeding is uncommon at diagnosis in children with ITP and rare during the next 4 weeks irrespective of treatment given. We conclude that it would be difficult to design an adequately powered therapeutic trial aimed at demonstrating prevention of severe bleeding during the first 4 weeks after diagnosis. This finding suggests that future studies of ITP management should emphasize other outcomes. PMID:18698007

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.

Optimizing the time-frame for the definition of bleeding-related death after acute variceal bleeding in cirrhosis.

PubMed

Merkel, C; Gatta, A; Bellumat, A; Bolognesi, M; Borsato, L; Caregaro, L; Cavallarin, G; Cielo, R; Cristina, P; Cucci, E; Donada, C; Donadon, V; Enzo, E; Martin, R; Mazzaro, C; Sacerdoti, D; Torboli, P

1996-01-01

To identify the best time-frame for defining bleeding-related death after variceal bleeding in patients with cirrhosis. Prospective long-term evaluation of a cohort of 155 patients admitted with variceal bleeding. Eight medical departments in seven hospitals in north-eastern Italy. Non-linear regression analysis of a hazard curve for death, and Cox's multiple regression analyses using different zero-time points. Cumulative hazard plots gave two slopes, the first corresponding to the risk of death from acute bleeding, the second a baseline risk of death. The first 30 days were outside the confidence limits of the regression curve for the baseline risk of death. Using Cox's regression analysis, the significant predictors of overall mortality risk were balanced between factors related to severity of bleeding and those related to severity of liver disease. If only deaths occurring after 30 days were considered, only predictors related to the severity of liver disease were found to be of importance. Thirty days after bleeding is considered to be a reasonable time-frame for the definition of bleeding-related death in patients with cirrhosis and variceal bleeding.

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.

Knowledge, attitudes, and behaviors of youths in the US hemophilia population: results of a national survey.

PubMed

Nazzaro, Ann-Marie; Owens, Sally; Hoots, W Keith; Larson, Kelly L

2006-09-01

The National Hemophilia Foundation and the Centers for Disease Control and Prevention conducted a national survey focusing on knowledge about, attitudes toward, and behaviors associated with key prevention activities among youths with hemophilia and used the data gathered to design a health promotion campaign. A national, random sample of 459 patients was drawn from 20 hemophilia treatment centers and 8 hemophilia associations; 110 (24%) of the respondents were young people. A telephone questionnaire was used to measure knowledge, behaviors, and barriers to prevention. Thirty-six percent of the youth respondents believed that joint disease cannot be prevented; 60% managed hemophilia by avoiding physical activity. Only 31% of the respondents treated bleeding episodes within 1 hour. Although hepatitis was a clear threat to this hemophilic cohort, 78% did now know transmission routes for hepatitis C, and 67% did not know transmission routes for hepatitis B. Young people with chronic disorders need help understanding that they can prevent complications. We identified key messages for a hemophilia prevention campaign, including exercising to ensure healthy joints and treating bleeding episodes early and adequately.

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Crighton, Gemma L; Estcourt, Lise J; Wood, Erica M; Trivella, Marialena; Doree, Carolyn; Stanworth, Simon

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004 and updated in 2012 that addressed four separate questions: therapeutic-only versus prophylactic platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. We have now split this review into four smaller reviews looking at these questions individually; this review is the first part of the original review. Objectives To determine whether a therapeutic-only platelet transfusion policy (platelet transfusions given when patient bleeds) is as effective and safe as a prophylactic platelet transfusion policy (platelet transfusions given to prevent bleeding, usually when the platelet count falls below a given trigger level) in patients with haematological disorders undergoing myelosuppressive chemotherapy or stem cell transplantation. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 July 2015. Selection criteria RCTs involving transfusions of platelet concentrates prepared either from individual units of whole blood or by apheresis, and given to prevent or treat bleeding in patients with malignant haematological disorders receiving myelosuppressive chemotherapy or undergoing HSCT. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results We identified seven RCTs that compared therapeutic platelet transfusions to prophylactic platelet transfusions in haematology patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still ongoing, leaving six trials eligible with a total of 1195 participants. These trials were conducted between 1978 and 2013 and enrolled participants from fairly comparable patient populations. We were able to critically appraise five of these studies, which contained separate data for each arm, and were unable to perform quantitative analysis on one study that did not report the numbers of participants in each treatment arm. Overall the quality of evidence per outcome was low to moderate according to the GRADE approach. None of the included studies were at low risk of bias in every domain, and all the studies identified had some threats to validity. We deemed only one study to be at low risk of bias in all domains other than blinding. Two RCTs (801 participants) reported at least one bleeding episode within 30 days of the start of the study. We were unable to perform a meta-analysis due to considerable statistical heterogeneity between studies. The statistical heterogeneity seen may relate to the different methods used in studies for the assessment and grading of bleeding. The underlying patient diagnostic and treatment categories also appeared to have some effect on bleeding risk. Individually these studies showed a similar effect, that a therapeutic-only platelet transfusion strategy was associated with an increased risk of clinically significant bleeding compared with a prophylactic platelet transfusion policy. Number of days with a clinically significant bleeding event per participant was higher in the therapeutic-only group than in the prophylactic group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval (CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to determine whether there was any difference in the number of participants with severe or life-threatening bleeding between a therapeutic-only transfusion policy and a prophylactic platelet transfusion policy (two RCTs; 801 participants; risk ratio (RR) 4.91, 95% CI 0.86 to 28.12; low-quality evidence). Two RCTs (801 participants) reported time to first bleeding episode. As there was considerable heterogeneity between the studies, we were unable to perform a meta-analysis. Both studies individually found that time to first bleeding episode was shorter in the therapeutic-only group compared with the prophylactic platelet transfusion group. There was insufficient evidence to determine any difference in all-cause mortality within 30 days of the start of the study using a therapeutic-only platelet transfusion policy compared with a prophylactic platelet transfusion policy (two RCTs; 629 participants). Mortality was a rare event, and therefore larger studies would be needed to establish the effect of these alternative strategies. There was a clear reduction in the number of platelet transfusions per participant in the therapeutic-only arm (two RCTs, 991 participants; standardised mean reduction of 0.50 platelet transfusions per participant, 95% CI −0.63 to −0.37; moderate-quality evidence). None of the studies reported quality of life. There was no evidence of any difference in the frequency of adverse events, such as transfusion reactions, between a therapeutic-only and prophylactic platelet transfusion policy (two RCTs; 991 participants; RR 1.02, 95% CI 0.62 to 1.68), although the confidence intervals were wide. Authors’ conclusions We found low- to moderate-grade evidence that a therapeutic-only platelet transfusion policy is associated with increased risk of bleeding when compared with a prophylactic platelet transfusion policy in haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT. There is insufficient evidence to determine any difference in mortality rates and no evidence of any difference in adverse events between a therapeutic-only platelet transfusion policy and a prophylactic platelet transfusion policy. A therapeutic-only platelet transfusion policy is associated with a clear reduction in the number of platelet components administered. PMID:26422767

The papilla of Vater just below the pylorus presenting as recurrent duodenal ulcer bleeding.

PubMed

Sung, Hye Young; Kim, Jin Il; Park, Yong Bum; Cheung, Dae Young; Cho, Se Hyun; Park, Soo-Heon; Han, Joon-Yeol; Kim, Jae Kwang

2007-01-01

The papilla of Vater emptying into the duodenal bulb site is extremely rare and considered an aberrant condition. We report here a case with recurrent duodenal ulcer bleeding associated with this anomaly. A 42-year-old man was admitted to St. Mary Hospital because of tarry stool for three days. Despite no documented etiology to explain recurrent ulceration, the patient had about ten episodes of ulcer bleeding since 1995. On duodenoscopy, 1.0 x 0.6 cm sized active stage duodenal ulcer with oozing was observed at the posterior wall side below the pylorus. The papilla of Vater was bulging just below the pylorus. Bile juice was excreted from its opening. Pancreatic duct and common bile duct, which drained into the bulb site, were observed on ERCP. In this report, we show that recurrent duodenal ulcer can be associated with the papilla of Vater just below the pylorus.

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.

Sociodemographic differences in symptom severity and duration among women referred to secondary care for menorrhagia in England and Wales: a cohort study from the National Heavy Menstrual Bleeding Audit

PubMed Central

Gurol-Urganci, Ipek; Cromwell, David A; Bansi-Matharu, Loveleen; Shakespeare, Judy; Mahmood, Tahir; van der Meulen, Jan

2018-01-01

Objective To examine symptom severity and duration at time of referral to secondary care for heavy menstrual bleeding (HMB) by socioeconomic deprivation, age and ethnicity Design Cohort analysis of data from the National HMB Audit linked to Hospital Episode Statistics data. Setting English and Welsh National Health Services (secondary care): February 2011 to January 2012. Participants 15 325 women aged 18–60 years in England and Wales who had a new referral for HMB to a gynaecology outpatient department Methods Multivariable linear regression to calculate adjusted differences in mean symptom severity and quality of life scores at first outpatient visit. Multivariable logistic regression to calculate adjusted ORs. Adjustment for body mass index, parity and comorbidities. Primary outcome measures Mean symptom severity score (0=best, 100=worst), mean condition-specific quality of life score (0=worst, 100=best) and symptom duration (≥1 year). Results Women were on average 42 years old and 12% reported minority ethnic backgrounds. Mean symptom severity and condition-specific quality of life scores were 61.8 and 34.7. Almost three-quarters of women (74%) reported having had symptoms for ≥1 year. Women from more deprived areas had more severe symptoms at their first outpatient visit (difference −6.1; 95% CI−7.2 to −4.9, between least and most deprived quintiles) and worse condition-specific quality of life (difference 6.3; 95% CI 5.1 to 7.5). Symptom severity declined with age while quality of life improved. Conclusions Women living in more deprived areas reported more severe HMB symptoms and poorer quality of life at the start of treatment in secondary care. Providers should examine referral practices to explore if these differences reflect women’s health-seeking behaviour or how providers decide whether or not to refer. PMID:29420229

Cost-effectiveness analysis of high-dose omeprazole infusion as adjuvant therapy to endoscopic treatment of bleeding peptic ulcer.

PubMed

Lee, Kenneth K C; You, Joyce H S; Wong, Ian C K; Kwong, Sunny K S; Lau, James Y W; Chan, Thomas Y K; Lau, Joseph T F; Leung, Wilson Y S; Sung, Joseph J Y; Chung, Sydney S C

2003-02-01

Intravenous administration of proton pump inhibitors after endoscopic treatment of bleeding peptic ulcers has been shown to decrease the rate of recurrent bleeding and the need for subsequent surgery. Yet there is a relative lack of formal assessment of this practice. The aim of this study was to examine the cost-effectiveness of this therapy by using standard pharmacoeconomic methods. The present study was performed in conjunction with a randomized controlled clinical trial that included 232 patients who received either omeprazole (80 mg intravenous bolus followed by infusion at 8 mg/hour for 72 hours) or placebo after hemostasis was achieved endoscopically. A cost-effectiveness analysis was performed to evaluate the different outcomes of the trial. All related direct medical costs were identified from patient records. Cost-effectiveness ratios were calculated. Analysis by the Kolmogorov-Smirnov test showed that the direct medical cost in the omeprazole group was lower than that for the placebo group. Cost-effectiveness ratios for omeprazole and placebo groups were, respectively, HK$ 28,764 (US$ 3688) and HK$ 36,992 (US$ 4743) in averting one episode of recurrent bleeding in one patient after initial hemostasis was achieved endoscopically. Intravenous administration of high-dose omeprazole appears to be a cost-effective therapy in reducing the recurrence of bleeding and need for surgery in patients with active bleeding ulcer after initial hemostasis is obtained endoscopically.

Management of Hepatic Encephalopathy in the Hospital

PubMed Central

Leise, Michael D.; Poterucha, John J.; Kamath, Patrick S.; Kim, W. Ray

2014-01-01

Hepatic encephalopathy (HE) develops in about 50% of patients with cirrhosis and is one of the features of decompensated cirrhosis. The inpatient incidence of HE is approximately 23,000/year and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails two phases, induction and maintenance of remission. Most cases of significant hepatic encephalopathy are precipitated by infection, gastrointestinal bleeding, medications or other culprits. All patients should be evaluated for secondary triggers of HE and treatment should be initiated with a non-absorbable disaccharide (i.e. lactulose) in most cases. Rifaximin (off-label) can be added in patients not responding to lactulose. Neomycin is a less preferable alternative to rifaximin, due to its side effect profile. Other therapies including zinc, LOLA, and branch chain amino acids can be considered for patients not responding to a disaccharide and non-absorbable antibiotic. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe hepatic encephalopathy who do not respond to medical therapy. It is critically important that patients hospitalized with significant hepatic encephalopathy continue a maintenance medication(s) at the time of dismissal to prevent further episodes. Patients with a 1st time episode of HE can be placed on lactulose and careful instruction should be provided to patient and caregiver about titration of dose to achieve 3 bowel movements per day. Patients with recurrent HE episodes despite lactulose benefit from the addition of rifaximin which decreases the frequency of recurrent HE episodes and related hospitalizations. Lastly, patients and their families should be counselled about the risk of motor vehicle accidents which requires mandatory reporting to department of motor vehicles in some states. PMID:24411831

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.

Management of severe VWD with cryoprecipitate collected by repeated apheresis of a single dedicated donor.

PubMed

Pomper, Gregory J; Rick, Margaret E; Epstein, Jay S; Read, Elizabeth J; Leitman, Susan F

2003-11-01

Rare and severe forms of VWD are associated with trace or absent VWF. The feasibility of supporting a child with severe VWD from birth through age 12 with cryoprecipitate derived from DDAVP-stimulated plasma exchange of a single dedicated donor is reported. An infant with excessive hemorrhage at circumcision was found to have Type 3 VWD. His father carried an allele with a mutation at the level of VWF mRNA expression but did not have a history of bleeding. Cryoprecipitate was prepared from serial DDAVP-stimulated plasma exchanges of the father. Repeated plasma-exchange donations were performed to provide all of the VWF needed for his son. An average of 14 cryoprecipitate units was prepared from each donation, and the units contained markedly elevated levels of FVIII:C. The cryoprecipitate was stored for up to 102 months. Components tested after more than 8 years of storage showed 48 to 130 percent of original FVIII:C activity. Ninety-seven percent of the bleeding episodes, such as epistaxis, tongue-biting accidents, and other minor lacerations, were successfully managed with a single 50- to 100-percent replacement dose of FVIII. The patient experienced normal growth and development and is free of any long-term sequelae attributable to his disease. Cryoprecipitate prepared by repeated plasma exchange of a VWD carrier provided excellent hemostatic function, even after storage intervals of more than a year. Plasma exchange of a committed donor was a cost-effective and safe option for long-term management of VWD.

Colostomy is a simple and effective procedure for severe chronic radiation proctitis.

PubMed

Yuan, Zi-Xu; Ma, Teng-Hui; Wang, Huai-Ming; Zhong, Qing-Hua; Yu, Xi-Hu; Qin, Qi-Yuan; Wang, Jian-Ping; Wang, Lei

2016-06-28

To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis (CRP). Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life before treatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during follow-up. Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission (94% vs 12%), especially in control of transfusion-dependent bleeding (100% vs 0%), and offered a better control of refractory perianal pain (100% vs 0%), and a lower score of bleeding (P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding (100% vs 21.5%, P = 0.002) and severe bleeding (100% vs 0%, P < 0.001), obtained a lower score of bleeding (0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels (P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammation cells, and massive fibrosis collagen depositions under the rectal wall, which revealed potential fibrosis formation. Diverting colostomy is a simple, effective and safe procedure for severe hemorrhagic CRP. Colostomy can improve quality of life and reduce serious complications secondary to radiotherapy.

Colostomy is a simple and effective procedure for severe chronic radiation proctitis

PubMed Central

Yuan, Zi-Xu; Ma, Teng-Hui; Wang, Huai-Ming; Zhong, Qing-Hua; Yu, Xi-Hu; Qin, Qi-Yuan; Wang, Jian-Ping; Wang, Lei

2016-01-01

AIM: To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis (CRP). METHODS: Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life before treatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during follow-up. RESULTS: Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission (94% vs 12%), especially in control of transfusion-dependent bleeding (100% vs 0%), and offered a better control of refractory perianal pain (100% vs 0%), and a lower score of bleeding (P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding (100% vs 21.5%, P = 0.002) and severe bleeding (100% vs 0%, P < 0.001), obtained a lower score of bleeding (0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels (P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammation cells, and massive fibrosis collagen depositions under the rectal wall, which revealed potential fibrosis formation. CONCLUSION: Diverting colostomy is a simple, effective and safe procedure for severe hemorrhagic CRP. Colostomy can improve quality of life and reduce serious complications secondary to radiotherapy. PMID:27350738

A synopsis of current haemophilia care in Hong Kong.

PubMed

Au, W Y; Lee, Vincent; Kho, Bonnie; Ling, Alvin S C; Chan, Desmond; Chan, Eric Y T; Chan, Godfrey C F; Cheung, Winnie W W; Lau, C W; Lee, C Y; Li, Rever C H; Li, C K; Lin, S Y; Mak, Vivien; Sun, Lina; Wong, Kris H F; Wong, Raymond; Yau, Jeffrey; Yuen, H L

2011-06-01

To provide a synopsis of current haemophilia care in Hong Kong. Retrospective survey. All haematology units of the Hospital Authority in Hong Kong. All patients with haemophilia A and haemophilia B. To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further. A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.

Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

PubMed

Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

2015-12-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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

Kolber, Marcin K.; Shukla, Pratik A.; Kumar, Abhishek

PurposeRecurrent spontaneous hemarthrosis is an infrequent but debilitating late complication of joint replacement, affecting up to 1.6% of patients with arthroplasty of the affected joint. Repeated episodes of bleeding result in an inflammatory cascade that further propagates bleeding events. Open and arthroscopic synovectomy are often performed when conservative treatments fail. Transarterial embolization is increasingly utilized as a less invasive option; however, its role is not widely established. We performed a systematic literature review to report the safety and efficacy of transarterial embolization in treating recurrent hemarthrosis in the setting of prior arthroplasty.Materials and MethodsA systematic review was conducted in accordancemore » with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. A structured search was performed in PubMed, Web of Science, Embase, and SCOPUS databases of patients undergoing embolization for recurrent hemarthrosis after arthroplasty. Patients immediately post-operative, those embolized at first bleeding episode, and those with hemophilia were excluded. Demographic data, clinical information, angiographic findings, treatment, and outcomes were tabulated.ResultsThe search identified 119 titles of which 24 were deemed relevant, comprising 91 patients undergoing 99 embolization procedures. Mean time from prosthesis implantation was 32.2 months. Technical success was 99%. Mean follow-up time was 24.9 months. There were 10 recurrences (10%). Two cases were complicated by joint infection requiring arthroplasty revision.ConclusionsTransarterial embolization for recurrent spontaneous hemarthrosis may be safe and effective in patients having undergone arthroplasty of the affected joint.« less

Conservative treatment of intraosseous hemangiomas in the mandible: case report with a 17-year follow-up period.

PubMed

Frizzera, Fausto; Beccalli, Ivette; Maia, Rosa Maria Lourenço Carlos; Tonetto, Mateus Rodrigues; Zanetti, Liliane Scheidegger da Silva; de Barros, Liliana Pimenta Aparecida

2014-05-01

Intraosseous hemangiomas in the jaws are rare lesions and may lead to several complications. The authors present a case of a 12-year-old girl with a radiolucent periapical lesion between tooth 35 and 36 where nocturnal exsanguinating bleeding started to occur from periodontal sulcus during orthodontic treatment. Diagnosis of an intraosseous hemangioma in the mandible was based on positive needle aspiration for blood, computed tomography and arteriography. At first the family chose to only follow-up the lesion but episodes of nocturnal hemorrhage were becoming more frequent and a treatment was requested. Embolization and dental extraction were performed in order to treat the lesion. After a follow-up period of 17 years no more cases of hemorrhage occurred and lesion regressed.

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).

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.

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.

Assessing Abnormal Uterine Bleeding: Are Physicians Taking a Meaningful Clinical History?

PubMed

Lam, Christina; Anderson, Britta; Lopes, Vrishali; Schulkin, Jay; Matteson, Kristen

2017-07-01

Women with abnormal uterine bleeding (AUB) report significant reductions in quality of life (QOL), which can be attributed in many cases to the fear of embarrassing episodes of bleeding. We performed this study to determine whether or not during clinical encounters physicians addressed the impact of AUB on patient-reported QOL. Between October 2008 and May 2009, we conducted a cross-sectional study of members of the American College of Obstetricians and Gynecologists. Surveys were distributed using a mixed method (web- and mail-based) and included questions about physician characteristics and types of questions used when obtaining a clinical history from a patient with AUB. We calculated the proportion of physicians who endorsed asking each type of clinical question with 95% confidence intervals (CIs). Four hundred seventeen questionnaires were returned (52%). Ninety-nine percent (95% CI 98.4%-99.9%) reported always asking a bleeding heaviness question, 87.2% (95% CI 83.2%-90.5%) reported always asking a QOL question, and 17.5% (95% CI 13.6%-21.9%) reported always asking a mood associated with bleeding question. Seventy-eight percent specifically asked patients about bleeding through their clothes, and 55% asked about changing social plans because of bleeding. Only 18% endorsed that asking about QOL was most essential for the evaluation of women with AUB. No physician characteristics such as years since completing residency, geography, or gender were associated with how commonly providers reported asking questions regarding impact of bleeding on QOL. Physicians may not be optimizing patient-provider interactions during menstrual history taking with patients with AUB by failing to assess impact of AUB on QOL in a way that is meaningful to patients.

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

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

PubMed

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-03-28

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

PubMed Central

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-01-01

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency. PMID:28350321

Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia.

PubMed

Squizzato, Alessandro; Romualdi, Erica; Passamonti, Francesco; Middeldorp, Saskia

2013-04-30

Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative neoplasms that increase the risk of arterial and venous thrombosis, as well as bleeding. In addition to the different therapeutic strategies available, an antiplatelet drug is often used to reduce thrombotic risk. To quantify the benefit and harm of antiplatelet drugs for long-term primary and secondary prophylaxis of arterial and venous thrombotic events in patients with polycythaemia vera or essential thrombocythaemia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library (Issue 1 2012), MEDLINE (1966 to 2012), and EMBASE (1980 to 2012), as well as online registers of ongoing trials and conference proceedings. The date of the last search was October 2012. We included all randomised controlled trials (RCTs) comparing long-term (>6 months) use of an antiplatelet drug versus placebo or no treatment in participants with polycythaemia vera or essential thrombocythaemia, as diagnosed by established international criteria, with data for at least one of the selected outcomes. Using a pre-defined extraction form, two review authors independently screened results, extracted data, and assessed quality. We planned to analyse the following outcomes: mortality from arterial and venous thrombotic events (primary efficacy outcome), mortality from bleeding episodes (primary safety outcome), fatal and non-fatal arterial thrombotic events, fatal and non-fatal venous thrombotic events, micro-circulation events, transient neurological and ocular manifestations, major and minor bleeding episodes, and all-cause mortality and any adverse events. We based quantitative analysis of outcome data on an intention-to-treat principle. We used the pooled odds ratio (OR) with 95% confidence interval (CI) with a fixed-effect model (Mantel-Haenszel) to estimate the overall treatment effect. We identified no new studies from the updated searches. We included in this review two RCTs for a total of 630 participants. Both RCTs included participants with an established diagnosis of polycythaemia vera and with no clear indication or contraindication to aspirin therapy. We judged both studies to be of moderate quality. Published data from both studies were insufficient for a time-to-event data analysis and for some of the primary and secondary outcomes that we planned. The use of low-dose aspirin, compared with placebo, was associated with a lower risk of fatal thrombotic events (although this benefit was not statistically significant (OR 0.20, 95% CI 0.03 to 1.14; P = 0.07). No data on mortality from bleeding episodes were available. A non-significant benefit of aspirin was shown for all-cause mortality (OR 0.46, 95% CI 0.21 to 1.01; P = 0.05). No increase in the risk of major bleeding was reported in participants taking aspirin compared with those given placebo (OR 0.99, 95% CI 0.23 to 4.36; P = 0.99), and a non-significant increase with aspirin treatment was shown for minor bleeding (OR 1.85, 95% CI 0.90 to 3.79; P = 0.09). No published studies have reported findings in participants with essential thrombocythaemia or in the study of other antiplatelet drugs. For patients with polycythaemia vera who have no clear indication or contraindication to aspirin therapy, available evidence suggests that the use of low-dose aspirin, when compared with no treatment, is associated with a statistically non-significant reduction in the risk of fatal thrombotic events and all-cause mortality, without an increased risk of major bleeding.

Bleeding during Pregnancy

MedlinePlus

... in pregnancy? • What problems with the placenta can cause bleeding during pregnancy? • Can bleeding be a sign of preterm labor? • ... the hospital. What problems with the placenta can cause bleeding during pregnancy? Several problems with the placenta later in pregnancy ...

Upper gastrointestinal bleeding in severely burned patients: a case-control study to assess risk factors, causes, and outcome.

PubMed

Kim, Young Jin; Koh, Dong Hee; Park, Se Woo; Park, Sun Man; Choi, Min Ho; Jang, Hyun Joo; Kae, Sea Hyub; Lee, Jin; Byun, Hyun Woo

2014-01-01

To determine the risk factors, causes, and outcome of clinically important upper gastrointestinal bleeding that occurs in severely burned patients. The charts of all patients admitted to the burn intensive care unit were analyzed retrospectively over a 4-year period (from January 2006 to December 2009). Cases consisted of burned patients who developed upper gastrointestinal bleeding more than 24 hours after admission to the burn intensive care unit. Controls were a set of patients, in the burn intensive care unit, without upper gastrointestinal bleeding matched with cases for age and gender. Cases and controls were compared with respect to the risk factors of upper gastrointestinal bleeding and outcomes. During the study period, clinically important upper gastrointestinal bleeding occurred in 20 patients out of all 964 patients. The most common cause of upper gastrointestinal bleeding was duodenal ulcer (11 of 20 cases, 55%). In the multivariate analysis, mechanical ventilation (p = 0.044) and coagulopathy (p = 0.035) were found to be the independent predictors of upper gastrointestinal bleeding in severely burned patients. Upper gastrointestinal hemorrhage tends to occur more frequently after having prolonged mechanical ventilation and coagulopathy.

Long-term prophylaxis in severe factor VII deficiency.

PubMed

Siboni, S M; Biguzzi, E; Mistretta, C; Garagiola, I; Peyvandi, F

2015-11-01

The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pdFVII) or 20-30mcg/kg (rFVIIa) twice or three times/weeks was described to be effective. In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pdFVII) or 20-30 microg/kg (rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis. © 2015 John Wiley & Sons Ltd.

Hemophilia A Pseudoaneurysm in a Patient with High Responding Inhibitors Complicating Total Knee Arthroplasty: Embolization: A Cost-Reducing Alternative to Medical Therapy

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

Kickuth, Ralph, E-mail: ralph.kickuth@insel.ch; Anderson, Suzanne; Peter-Salonen, Kristiina

2006-12-15

Joint hemorrhages are very common in patients with severe hemophilia. Inhibitors in patients with hemophilia are allo-antibodies that neutralize the activity of the clotting factor. After total knee replacement, rare intra-articular bleeding complications might occur that do not respond to clotting factor replacement. We report a 40-year-old male with severe hemophilia A and high responding inhibitors presenting with recurrent knee joint hemorrhage after bilateral knee prosthetic surgery despite adequate clotting factor treatment. There were two episodes of marked postoperative hemarthrosis requiring extensive use of subsititution therapy. Eleven days postoperatively, there was further hemorrhage into the right knee. Digital subtraction angiographymore » diagnosed a complicating pseudoaneurysm of the inferior lateral geniculate artery and embolization was successfully performed. Because clotting factor replacement therapy has proved to be excessively expensive and prolonged, especially in patients with inhibitors, we recommend the use of cost-effective early angiographic embolization.« less

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.

Intramural esophageal bleeding in a hemodialysis patient

PubMed Central

Lien, J. W. K.; Dufresne, L. R.; Daly, D. S.

1974-01-01

A case of intramural esophageal hemorrhage in a hemodialysis patient is described. The hemorrhage followed an episode of vomiting and violent retching. Spontaneous resolution occurred with conservative management. The clinical course resembled that of previous case reports of intramural esophageal hemorrhage, whether or not associated with chronic renal failure and intermittent hemodialysis. ImagesFIG. 1FIG. 2FIG. 3 PMID:4434294

Von Willebrand factor-containing factor VIII concentrates and inhibitors in haemophilia A. A critical literature review.

PubMed

Franchini, Massimo; Lippi, Giuseppe

2010-11-01

The development of inhibitors that neutralise the function of factor VIII (FVIII) is currently not only the most challenging complication associated with the treatment of haemophilia A but it also increases the disease-related morbidity as bleeding episodes do not respond to standard therapy. The main short-term goal of the treatment of inhibitor patients is to control bleeding episodes while the long-term one is to permanently eradicate the inhibitor by immune tolerance induction, particularly in the case of high-titer antibodies. Due to some in vitro studies and clinical observations, some investigators have suggested that FVIII concentrates containing von Willebrand factor (VWF) may be less immunogenic than high-purity or recombinant FVIII products. It has also been suggested that success rates for immune tolerance induction are higher when plasma-derived FVIII products are used. The currently available data from laboratory and clinical studies on the role of VWF in inhibitor development and eradication in haemophilia A is critically analysed in this review. As a result, we have not found definitive evidence supporting a role for product type on inhibitor incidence and inhibitor eradication in haemophilia A patients.

Knowledge, Attitudes, and Behaviors of Youths in the US Hemophilia Population: Results of a National Survey

PubMed Central

Nazzaro, Ann-Marie; Owens, Sally; Hoots, W. Keith; Larson, Kelly L.

2006-01-01

Objectives. The National Hemophilia Foundation and the Centers for Disease Control and Prevention conducted a national survey focusing on knowledge about, attitudes toward, and behaviors associated with key prevention activities among youths with hemophilia and used the data gathered to design a health promotion campaign. Methods. A national, random sample of 459 patients was drawn from 20 hemophilia treatment centers and 8 hemophilia associations; 110 (24%) of the respondents were young people. A telephone questionnaire was used to measure knowledge, behaviors, and barriers to prevention. Results. Thirty-six percent of the youth respondents believed that joint disease cannot be prevented; 60% managed hemophilia by avoiding physical activity. Only 31% of the respondents treated bleeding episodes within 1 hour. Although hepatitis was a clear threat to this hemophilic cohort, 78% did now know transmission routes for hepatitis C, and 67% did not know transmission routes for hepatitis B. Conclusions. Young people with chronic disorders need help understanding that they can prevent complications. We identified key messages for a hemophilia prevention campaign, including exercising to ensure healthy joints and treating bleeding episodes early and adequately. PMID:16873741

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.

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

A comparative study of Cyclofem and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature.

PubMed

Simbar, Masoumeh; Tehrani, Fahimeh Ramezani; Hashemi, Zeinab; Zham, Hananeh; Fraser, Ian S

2007-10-01

The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem, was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding. Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques. Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 +/- 6.7 (mean +/- SD)/mm(2) before injection. This significantly decreased to 132.4 +/- 12.2 after DMPA use, and from 151.9 +/- 5.8 to 131.8 +/- 12.8 vessels/mm(2) following Cyclofem use (paired t-test, p <0.05). However, there was no significant difference between endometrial vascular density during treatment with Cyclofem or DMPA. Total bleeding days in the first and second 3-month time intervals were 28 +/- 23 and 18 +/- 12 days in DMPA users and 22 +/- 14 and 16 +/- 9 days in Cyclofem users, respectively, Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups. This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women.

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

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.

Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians.

PubMed

Nappi, Rossella E; Kaunitz, Andrew M; Bitzer, Johannes

2016-01-01

The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices.

Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians

PubMed Central

Nappi, Rossella E.; Kaunitz, Andrew M.; Bitzer, Johannes

2016-01-01

ABSTRACT Objectives: The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. Methods: We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. Results: The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Conclusions: Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices. PMID:26572318

Vitamin K deficiency bleeding of the newborn

MedlinePlus

Vitamin K deficiency bleeding (VKDB) of the newborn is a bleeding disorder in babies. It most often develops in ... A lack of vitamin K may cause severe bleeding in newborn babies. Vitamin K plays an important role in blood clotting. Babies often have a ...

Menstrual Bleeding as a Manifestation of Mini-Puberty of Infancy in Severe Prematurity

PubMed Central

Vogiatzi, Maria G.; Pitt, Michelle; Oberfield, Sharon; Alter, Craig A.

2017-01-01

We report 2 infants with severe prematurity who presented with uterine bleeding at age 6 months (approximately 2.5 months corrected for gestational age). Mini-puberty of infancy should be considered in the differential diagnosis of girls who present with uterine bleeding during the first 6 months of life. PMID:27593439

Differential Prognostic Impact on Mortality of Myocardial Infarction Compared With Bleeding Severity in Contemporary Acute Coronary Syndrome Patients.

PubMed

Caneiro-Queija, Berenice; Abu-Assi, Emad; Raposeiras-Roubín, Sergio; Manzano-Fernández, Sergio; Flores Blanco, Pedro; López-Cuenca, Ángel; Cobas-Paz, Rafael; Gómez-Molina, Miriam; Rodríguez-Rodríguez, José Manuel; Calvo-Iglesias, Francisco; Valdés-Chávarri, Mariano; Íñiguez-Romo, Andrés

2018-04-12

The impact on mortality of myocardial infarction (MI) compared with the specific degree of bleeding severity occurring after discharge in acute coronary syndrome is poorly characterized. Defining this relationship may help to achieve a favorable therapeutic risk-benefit balance. Using Cox-based shared frailty models, we assessed the relationship between mortality and postdischarge MI and bleeding severity-graded according to Bleeding Academic Research Consortium (BARC)-in 4229 acute coronary syndrome patients undergoing in-hospital coronary arteriography between January 2012 and December 2015. Both MI (HR, 5.8; 95%CI, 3.7-9.8) and bleeding (HR, 5.1; 95%CI, 3.6-7.7) were associated with mortality. Myocardial infarction had a stronger impact on mortality than BARC type 2 and 3a bleedings: (RRr, 3.8 and 1.9; P < .05), respectively, but was equivalent to BARC type 3b (RRr, 0.9; P = .88). Mortality risk after MI was significantly lower than after BARC type 3c bleeding (RRr, 0.25; P < .001). Mortality was higher after an MI in patients on dual antiplatelet therapy (DAPT) at the time of the event (HR, 2.9; 95%CI, 1.8-4.5) than in those off-DAPT (HR, 1.5; 95%CI, 0.7-3.4). In contrast, mortality was lower after a bleeding event in patients on-DAPT (HR, 1.6; 95%CI, 1.1-2.6) than in those off-DAPT (HR, 3.2; 95%CI, 1.7-5.8). The differential effect on mortality of a postdischarge MI vs bleeding largely depends on bleeding severity. The DAPT status at the time of MI or bleeding is a modifier of subsequent mortality risk. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Emergency arterial embolization of upper gastrointestinal and jejunal tumors: An analysis of 12 patients with severe bleeding.

PubMed

Zandrino, F; Tettoni, S M; Gallesio, I; Summa, M

2017-01-01

The goal of this study was to retrospectively assess the efficacy of emergency percutaneous transcatheter arterial embolization in patients with severe bleeding due to upper gastrointestinal or jejunal tumor. Twelve patients (7 men, 5 women; mean age, 74 years±14 (SD); range: 54-86 years) with severe bleeding from the upper gastrointestinal tract, with failed endoscopic treatment not eligible for emergency surgery were treated by emergency percutaneous transcatheter arterial embolization. The bleeding cause was gastric tumor in 7 patients, duodenal tumor in 4 patients and jejunal tumor in one patient. Procedure details and follow-up were reviewed. Twelve embolization procedures were performed using various embolic agents. Embolization was achieved and bleeding was stopped in all patients. Five patients underwent surgery within the 30 days following embolization. In the remaining 7 patients, no bleeding occurred at 1 month follow-up in 6 patients and bleeding recurred in one patient at 1 month. In this later patient, endoscopic treatment was successful. The results of our study suggest that transcatheter arterial embolization is safe and effective in patients with severe arterial bleeding due to upper gastrointestinal or jejunal tumor. In some patients, transcatheter arterial embolization can be used as a bridge to surgery. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding

PubMed Central

Lin, H; Tseng, G; Perng, C; Lee, F; Chang, F; Lee, S

1999-01-01

BACKGROUND—Peptic ulcers with active bleeding or a non-bleeding visible vessel require aggressive endoscopic treatment. 
AIMS—To determine whether endoscopic adrenaline injection alone or contact probe therapy following injection is a suitable treatment for peptic ulcer bleeding. 
METHODS—A total of 96 patients with active bleeding or non-bleeding visible vessels received adrenaline alone, bipolar electrocoagulation alone, or combined treatment (n=32 in each group). 
RESULTS—Initial haemostasis was not achieved in one patient in the adrenaline group, two in the gold probe group, and two in the injection gold probe group (p>0.1). Rebleeding episodes were fewer in the injection gold probe group (2/30, 6.7%) than in the gold probe group (9/30, 30%, p=0.04) and in the adrenaline group (11/31, 35.5%, p=0.01). Treatment failure (other therapy required) was rarer in the injection gold probe group (4/32, 12.5%) than in the adrenaline group (12/32, 37.5%, p=0.04). The volume of blood transfused after entry of the study was less in the injection gold probe group (mean 491 ml) than in the adrenaline group (1548ml, p<0.0001) and the gold probe group (1105 ml, p<0.01). Duration of hospital stay, numbers of patients requiring urgent surgery, and death rate were not statistically different among the three groups. 
CONCLUSIONS—For patients with peptic ulcer bleeding, combined adrenaline injection and gold probe treatment offers an advantage in preventing rebleeding and decreasing the need for blood transfusion. 

 Keywords: gold probe; haemostasis; injectional therapy; rebleeding; shock; peptic ulcer PMID:10205211

[Recurrent variceal bleeding in a patient with portal and splenic vein thrombosis secondary to complex thrombophilia].

PubMed

Ławniczak, Małgorzata; Raszeja-Wyszomirska, Joanna; Marlicz, Wojciech; Białek, Andrzej; Wiechowska-Kozłowska, Anna; Lubikowski, Jerzy; Wójcicki, Maciej; Starzyńska, Teresa

2008-08-01

Thrombophilia in adults is one of main causes of portal vein thrombosis. Esophageal and gastric varices, ascites and hypersplenism are well known complications of portal hypertension. There are controversial issues on the management, especially anticoagulant therapy and surgical treatment of these patients. We present a 42-years old woman with a history of three acute coronary episodes suffering from recurrent variceal bleeding due to portal and splenic vein thrombosis in the course of myeloproliferative disorder and protein C deficiency. It was 10 months delay of diagnosis. She was successfully treated with medical and surgical treatment (esophageal stapler transection, cardial devascularization, and splenectomy). In the paper we discuss complexity of diagnosis and surgical treatment.

Severe thrombocytopaenia in patients with vivax malaria compared to falciparum malaria: a systematic review and meta-analysis.

PubMed

Naing, Cho; Whittaker, Maxine A

2018-02-09

Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria. A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (< 50 000/mm 3 ) to very severe thrombocytopaenia (< 20 000/mm 3 ) was observed in 10.1% of patients with P. vivax infection. A meta-analysis of 11 observational studies showed an equal risk of developing severe/very severe thrombocytopaenia between the patients with P. vivax malaria and those with P. falciparum malaria (OR: 1.98, 95% CI: 0.92-4.25). This indicates that thrombocytopaenia is as equally a common manifestation in P. vivax and P. falciparum malaria patients. One study showed a higher risk of developing very severe thrombocytopaenia in children with severe P. vivax malaria than with severe P. falciparum malaria (OR: 2.80, 95% CI: 1.48-5.29). However, a pooled analysis of two studies showed an equal risk among adult severe cases (OR: 1.19, 95% CI: 0.51-2.77). This indicates that the risk of developing thrombocytopaenia in P. vivax malaria can vary with immune status in both children and adults. One study reported higher levels of urea and serum bilirubin in patients with P. vivax malaria and severe thrombocytopaenia compared with patients mild thrombocytopaenia or no thrombocytopaenia, (P < 0.001 in all comparisons). A pooled analysis of two other studies showed a similar proportion of bleeding episodes with thrombocytopaenia in severe P. vivax patients and severe P. falciparum patients (P = 0.09). This implied that both P. vivax and P. falciparum infections could present with bleeding episodes, if there had been a change in platelet counts in the infected patients. A pooled analysis of another two studies showed an equal risk of mortality with severe thrombocytopaenia in both P. vivax and P. falciparum malaria patients (OR: 1.16, 95% CI: 0.30-4.60). However, due to the low number of studies with small sample sizes within the subset of studies that provided clinically relevant information, our confidence in the estimates is limited. The current review has provided some evidence of the clinical relevance of severe thrombocytopaenia in P. vivax malaria. To substantiate these findings, there is a need for well designed, large-scale, prospective studies among patients infected with P. vivax. These should include patients from different countries and epidemiological settings with various age and gender groups represented.

Intracranial hemorrhage in congenital bleeding disorders.

PubMed

Tabibian, Shadi; Motlagh, Hoda; Naderi, Majid; Dorgalaleh, Akbar

2018-01-01

: Intracranial hemorrhage (ICH), as a life-threatening bleeding among all kinds of congenital bleeding disorders (CBDs), is a rare manifestation except in factor XIII (FXIII) deficiency, which is accompanied by ICH, early in life, in about one-third of patients. Most inherited platelet function disorders (IPFDs) are mild to moderate bleeding disorders that can never experience a severe bleeding as in ICH; however, Glanzmann's thrombasthenia, a common and severe inherited platelet function disorder, can lead to ICH and occasional death. This bleeding feature can also be observed in grey platelet syndrome, though less frequently than in Glanzmann's thrombasthenia. In hemophilia, intracerebral hemorrhage is affected by various risk factors one of which is the severity of the disease. The precise prevalence of ICH in these patients is not clear but an estimated incidence of 3.5-4% among newborns with hemophilia is largely ascertained. Although ICH is a rare phenomenon in CBDs, it can be experienced by every patient with severe hemophilia A and B, FXIII deficiency (FXIIID), FVIID, FXD, FVD, FIID, and afibrinogenemia. Upon observing the general signs and symptoms of ICH such as vomiting, seizure, unconsciousness, and headache, appropriate replacement therapies and cranial ultrasound scans must be done to decrease ICH-related morbidity and mortality.

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/.

[Massive hookworm infection as a cause of intestinal bleeding and severe anemia].

PubMed

Nair, Gayatri V; Cazorla, Ernesto; Choque, Henry; White, A Clinton; Cabada, Miguel M

2016-01-01

Overt gastrointestinal bleeding caused by hookworm infection is rarely reported. We present a 34 year old male with lower gastrointestinal bleeding with evidence of massive hookworm infection on colonoscopy and discuss the need to consider hookworm infection as a possible etiology of gastrointestinal bleed in endemic areas.

Health-related quality of life, developmental milestones, and self-esteem in young adults with bleeding disorders.

PubMed

Limperg, P F; Haverman, L; Maurice-Stam, H; Coppens, M; Valk, C; Kruip, M J H A; Eikenboom, J; Peters, M; Grootenhuis, M A

2018-01-01

The treatment of bleeding disorders improved in the last decades. However, the effect of growing up with bleeding disorders on developmental, emotional, and social aspects is understudied. Therefore, this study assesses HRQOL, developmental milestones, and self-esteem in Dutch young adults (YA) with bleeding disorders compared to peers. Ninety-five YA (18-30 years) with bleeding disorders (78 men; mean 24.7 years, SD 3.5) and 17 women (mean 25.1 years, SD 3.8) participated and completed the Pediatric Quality of Life Inventory Young Adult version, the Course of Life Questionnaire, and the Rosenberg Self-Esteem Scale. Differences between patients with bleeding disorders and their peers, and between hemophilia severity groups, were tested using Mann-Whitney U tests. YA men with bleeding disorders report a slightly lower HRQOL on the total scale, physical functioning, and school/work functioning in comparison to healthy peers (small effect sizes). YA men with severe hemophilia report more problems on the physical functioning scale than non-severe hemophilia. YA men with bleeding disorders achieved more psychosexual developmental milestones than peers, but show a delay in 'paid jobs, during middle and/or high school.' A somewhat lower self-esteem was found in YA men with bleeding disorders in comparison to peers (small effect size). For YA women with bleeding disorders, no differences were found on any of the outcomes in comparison to peers. This study demonstrates some impairments in HRQOL and self-esteem in YA men with bleeding disorders. By monitoring HRQOL, problems can be identified early, especially with regard to their physical and professional/school functioning.

Clinical impact and course of major bleeding with rivaroxaban and vitamin K antagonists.

PubMed

Eerenberg, E S; Middeldorp, S; Levi, M; Lensing, A W; Büller, H R

2015-09-01

Rivaroxaban is a new oral anticoagulant (NOAC) that can be prescribed in a fixed dose, making regular monitoring and dose adjustments unnecessary. It has been proven to be safe and effective in comparison with enoxaparin/vitamin K antagonists (LMWH/VKA) for the (extended) treatment of venous thromboembolism in the EINSTEIN studies. Nevertheless, there is a need for information regarding the clinical impact of (major) bleeding events with NOACs such as rivaroxaban. A post-hoc analysis was performed to compare the severity of clinical presentation and subsequent clinical course of major bleeding with rivaroxaban vs. LMWH/VKA. Two investigators performed a blinded classification of major bleeding using a priori defined criteria. During the EINSTEIN studies, data concerning the clinical course and measures applied were prospectively collected for each major bleed. Treatment with LMWH/VKA caused more major bleeding events (1.7%) than rivaroxaban (1.0%; hazard ratio, 0.54; 95% confidence interval [CI], 0.37-0.79). Major bleeding events during rivaroxaban therapy had a milder presentation (23% were adjudicated to the worst categories vs. 38% for LMWH/VKA; hazard ratio or HR, 0.35; 95% CI, 0.17-0.74; P = 0.0062). The clinical course was severe in 25% of all major bleeding events associated with rivaroxaban, compared with 33% of LMWH/VKA-associated bleeds (HR, 0.46; 95% CI, 0.22-0.96; P = 0.040). Rivaroxaban-associated major bleeding events occurred less frequently, had a milder presentation and appeared to take a less severe clinical course compared with major bleeding with LMWH/VKA. © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

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.

Prophylactic Transcatheter Arterial Embolization After Successful Endoscopic Hemostasis in the Management of Bleeding Duodenal Ulcer.

PubMed

Mille, Markus; Huber, Juliane; Wlasak, Rüdiger; Engelhardt, Thomas; Hillner, Yvette; Kriechling, Henri; Aschenbach, Rene; Ende, Katrin; Scharf, Jens-Gerd; Puls, Ralf; Stier, Albrecht

2015-10-01

The aim of this study was to demonstrate the new strategy of prophylactic transcatheter arterial embolization (TAE) of the gastroduodenal artery after endoscopic hemostasis of bleeding duodenal ulcers. TAE is a well-established method for the treatment of recurrent or refractory ulcer bleeding resistant to endoscopic intervention, which increasingly replaces surgical procedures. A new approach for improving outcome and reducing rebleeding episodes is the supplemental and prophylactic TAE after successful endoscopic hemostasis. This retrospective study included all patients (n=117) treated from 2008 to 2012 for duodenal ulcer bleeding. After initial endoscopic hemostasis, patients were assessed regarding their individual rebleeding risk. Patients with a low rebleeding risk (n=47) were conservatively treated, patients with a high risk for rebleeding (n=55) had prophylactic TAE of the gastroduodenal artery, and patients with endoscopically refractory ulcer bleeding received immediate TAE. The technical success of prophylactic TAE was 98% and the clinical success was 87% of cases. Rebleeding occurred in 11% of patients with prophylactic TAE and was successfully treated with repeated TAE or endoscopy. The major complication rate was 4%. Surgery was necessary in only 1 prophylactic TAE patient (0.9%) during the whole study period. Mortality associated with ulcer bleeding was 4% in patients with prophylactic TAE. Prophylactic TAE in patients with duodenal ulcers at high risk for rebleeding was feasible, effective at preventing the need for surgery, and had low major complication rates. Given these promising outcomes, prophylactic TAE should be further evaluated as a preventative therapy in high-risk patients.

Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial.

PubMed

Saxena, K; Lalezari, S; Oldenburg, J; Tseneklidou-Stoeter, D; Beckmann, H; Yoon, M; Maas Enriquez, M

2016-09-01

BAY 81-8973 (Kovaltry(®) ) is a full-length, unmodified recombinant human factor VIII (FVIII) with the same amino acid sequence as sucrose-formulated recombinant FVIII and is produced using additional advanced manufacturing technologies. To demonstrate efficacy and safety of BAY 81-8973 for treatment of bleeds and as prophylaxis based on two different potency assignments. In LEOPOLD I (ClinicalTrials.gov identifier, NCT01029340), males aged 12-65 years with severe haemophilia A and ≥150 exposure days received BAY 81-8973 20-50 IU kg(-1) two or three times per week for 12 months. Potency was based on chromogenic substrate assay per European Pharmacopoeia and label adjusted to mimic one-stage assay potency. Patients were randomized for potency sequence and crossed over potency groups after 6 months, followed by an optional 12-month extension. Primary efficacy endpoint was annualized bleeding rate (ABR). Patients also received BAY 81-8973 during major surgeries. Sixty-two patients received BAY 81-8973 prophylaxis and were included in the analysis. Median ABR was 1.0 (quartile 1, 0; quartile 3, 5.1) without clinically relevant differences between potency periods. Median ABR was similar for twice-weekly vs. three times-weekly dosing (1.0 vs. 2.0). Haemostasis was maintained during 12 major surgeries. Treatment-related adverse event (AE) incidence was ≤7% overall; no patient developed inhibitors. One patient with risk factors for cardiovascular disease developed a myocardial infarction. BAY 81-8973 was efficacious in preventing and treating bleeding episodes, irrespective of the potency assignment method, with few treatment-related AEs. Caution should be used when treating older patients with cardiovascular risk factors. © 2016 Bayer. Haemophilia Published by John Wiley & Sons Ltd.

Warfarin Side Effects: Watch for Interactions

MedlinePlus

... in treatment. Severe bleeding, including heavier than normal menstrual bleeding Red or brown urine Black or bloody ... gums after you brush your teeth Bleeding between menstrual periods Diarrhea, vomiting or inability to eat for ...

An audit of fresh frozen plasma usage in a tertiary referral centre in a developing country.

PubMed

Prathiba, R; Jayaranee, S; Ramesh, J C; Lopez, C G; Vasanthi, N

2001-06-01

This paper evaluates the practice of fresh frozen plasma (FFP) transfusion at the University Hospital, Kuala Lumpur, and analyses its usage by the various clinical departments. The aim of this study is to identify where it is inappropriately used and the clinical indications in which such misuse is common. A retrospective analysis of the blood bank request forms and work sheets during a 6-month period between January 1998 and June 1998 formed the basis of this study. Overall, 40% of 2665 units transfused were considered appropriate. However, out of the 931 episodes of FFP transfusions only 31% were for appropriate indications. The average FFP requirement when used for appropriate indication was about 4 units per episode, whereas for inappropriate indication it was 2.5 units per episode. Inappropriate use in terms of the number of units was highest by the surgical services (68%) and Orthopaedics (64%), while the Department of Paediatrics had the lowest incidence of inappropriate use (40%). When Paediatrics was used as the benchmark, the incidence of inappropriate use by other departments was significantly higher (p < 0.01). As for FFP usage in common clinical indications, there was a high incidence of inappropriate use in burns (82%), perioperative period (73%), cardiac surgery (68%), massive bleeding (62%) and trauma (60%). The findings in this study, specifically the use of FFP for volume support in trauma, massive bleeding and burns, routine requests without identified indication in cardiac bypass surgery, and prophylactic use in the perioperative period can be the basis for recommendations to minimize the inappropriate use of FFP in the future.

Community-onset candidemia at a university hospital, 1995-2005.

PubMed

Kung, Hsiang-Chi; Wang, Jiun-Ling; Chang, Shan-Chwen; Wang, Jann-Tay; Sun, Hsin-Yun; Hsueh, Po-Ren; Chen, Yee-Chun

2007-08-01

Although not all candidemias are hospital-acquired, data on clinical epidemiology for the community-onset candidemia are limited. This retrospective study was conducted to describe predisposing factors and outcomes of community-onset candidemias. Medical records of patients who were admitted to the National Taiwan University Hospital between January 1, 1995 and May 31, 2005 and had Candida isolated from their blood in the outpatient setting and/or within 48 h of hospitalization (community-onset) were reviewed. A total of 56 episodes of candidemia were reviewed, which included 8 episodes (14.3%) of true community-acquired candidemia occurring in patients with no record of hospitalization within the previous 30 days and without histories of invasive procedures either just before or at the time of admission, and 48 episodes (85.7%) that were health care-associated. The latter included 24 episodes (42.9%) in patients recently discharged from hospitals (within 2-30 days of current admission), 23 episodes (41.1%) associated with invasive procedures and/or central intravascular lines placed for outpatient therapy, and 1 episode (1.8%) in patients admitted from nursing homes. Gastrointestinal bleeding (46.4%), immunosuppressive therapy (42.9%) and previous antibiotics use (37.5%) were the most common predisposing factors. Diabetes was the single most important predisposing factor in true community-acquired candidemia (62.5%) and had a significantly higher prevalence among these patients than in those with health care-associated candidemias (p=0.035). Candida albicans was the most common isolate (39.7%), followed by Candida tropicalis (22.4%) and Candida glabrata (17.2%). The overall case fatality rate was 55.4% (31/56), and 58.1% (18/31) of this was attributable to candidemia. Multivariate analysis identified higher severity score and lack of antifungal therapy as having an independent and adverse influence on outcome. Up to 85.7% of community-onset candidemias are health care-associated. There is a conceptual and practical need for a new classification for the spectrum of acquisition of infection, wherein the new category of health care-associated infection will have implications for the selection of empirical therapy.

Origin, Clinical Characteristics and 30-Day Outcomes of Severe Hematochezia in Cirrhotics and Non-cirrhotics

PubMed Central

Khungar, Vandana; Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O.; Jutabha, Rome; Ghassemi, Kevin A.; Machicado, Gustavo A.; Dulai, Gareth S.

2017-01-01

Background The sites of origin, causes and outcomes of severe hematochezia have not been compared between cirrhotics and non-cirrhotics. In cirrhotics versus non-cirrhotics presenting with severe hematochezia, we aimed at (1) identifying the site and etiology of gastro-intestinal bleeding and independent predictors of bleeding from the upper gastrointestinal tract versus small bowel or the colon, (2) comparing 30-day clinical outcomes, and (3) proposing an algorithm for management of severe hematochezia. Methods In this cohort study from two university-based medical centers, 860 consecutive patients with severe hematochezia admitted from 1995 to 2011 were prospectively enrolled with 160 (18.6 %) cirrhotics. We studied (a) general clinical and laboratory characteristics of cirrhotics versus non-cirrhotics, (b) predictors of bleeding sites in each patient group by multiple variable regression analysis, and compared (c) 30-day outcomes, including rebleeding, surgery and deaths. Results Cirrhosis independently predicted an upper gastrointestinal source of bleeding (OR 3.47; 95 % CI 2.01–5.96) as well as history of hematemesis, melena in the past 30 days, positive nasogastric aspirate, prior upper gastrointestinal bleeding or use of aspirin or non-steroidal anti-inflammatory. The most prevalent diagnoses were esophageal varices (20 %) in cirrhotics and colon diverticular bleeding (27.1 %) in non-cirrhotics. Thirty-day rates of rebleeding, surgical interventions and deaths were 23.1 versus 15 % (P = 0.01), 14.4 versus 6.4 % (P < 0.001), and 17.5 versus 4.1 % (P < 0.001), in cirrhotics versus non-cirrhotics, respectively. Conclusions Cirrhosis predicted an upper gastrointestinal site of bleeding in patients presenting with severe hematochezia. The 30-day rates of rebleeding, surgery, and death were significantly higher in cirrhotics than in non-cirrhotics. PMID:27286877

Sociodemographic differences in symptom severity and duration among women referred to secondary care for menorrhagia in England and Wales: a cohort study from the National Heavy Menstrual Bleeding Audit.

PubMed

Kiran, Amit; Geary, Rebecca Sally; Gurol-Urganci, Ipek; Cromwell, David A; Bansi-Matharu, Loveleen; Shakespeare, Judy; Mahmood, Tahir; van der Meulen, Jan

2018-02-02

To examine symptom severity and duration at time of referral to secondary care for heavy menstrual bleeding (HMB) by socioeconomic deprivation, age and ethnicity DESIGN: Cohort analysis of data from the National HMB Audit linked to Hospital Episode Statistics data. English and Welsh National Health Services (secondary care): February 2011 to January 2012. 15 325 women aged 18-60 years in England and Wales who had a new referral for HMB to a gynaecology outpatient department METHODS: Multivariable linear regression to calculate adjusted differences in mean symptom severity and quality of life scores at first outpatient visit. Multivariable logistic regression to calculate adjusted ORs. Adjustment for body mass index, parity and comorbidities. Mean symptom severity score (0=best, 100=worst), mean condition-specific quality of life score (0=worst, 100=best) and symptom duration (≥1 year). Women were on average 42 years old and 12% reported minority ethnic backgrounds. Mean symptom severity and condition-specific quality of life scores were 61.8 and 34.7. Almost three-quarters of women (74%) reported having had symptoms for ≥1 year. Women from more deprived areas had more severe symptoms at their first outpatient visit (difference -6.1; 95% CI-7.2 to -4.9, between least and most deprived quintiles) and worse condition-specific quality of life (difference 6.3; 95% CI 5.1 to 7.5). Symptom severity declined with age while quality of life improved. Women living in more deprived areas reported more severe HMB symptoms and poorer quality of life at the start of treatment in secondary care. Providers should examine referral practices to explore if these differences reflect women's health-seeking behaviour or how providers decide whether or not to refer. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Management of hepatic encephalopathy in the hospital.

PubMed

Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray

2014-02-01

Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes despite lactulose use benefit from the addition of rifaximin, which decreases the frequency of recurrent HE episodes and related hospitalizations. Last, patients and their families should be counseled about the risk of motor vehicle accidents, which require mandatory reporting to the Department of Motor Vehicles in some states. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Pregnancy Complications: Placenta Previa

MedlinePlus

... half of pregnancy. Call your health care provider right away if you have vaginal bleeding anytime during your pregnancy. If the bleeding is severe, go to the hospital. Not all women with placenta previa have vaginal bleeding. In fact, ...

Severe gastric variceal bleeding successfully treated by emergency splenic artery embolization.

PubMed

Sankararaman, Senthilkumar; Velayuthan, Sujithra; Vea, Romulo; Herbst, John

2013-06-01

Bleeding from gastric varices due to splenic vein obstruction is extremely rare in children, but it can be catastrophic. Reported herein is the case of a teenager with splenic vein thrombosis and chronic decompensated liver disease from autoimmune hepatitis who presented with massive gastric variceal bleeding. Standard medical management did not control the bleeding. Due to decompensated liver disease and continuous active bleeding, emergency partial splenic artery embolization was preferred over splenectomy or a shunt procedure. Bleeding was successfully controlled by partial splenic artery embolization by decreasing the inflow of blood into the portal system. It is concluded that emergency partial splenic artery embolization is a safer alternative life-saving procedure to manage severe gastric variceal bleeding due to splenic vein obstruction in a patient with high surgical risk. To our knowledge, only one other patient with similar management has been reported in the pediatric age group. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

[Administration of activated recombinant factor VII (novo seven) for the control of massive bleeding in gynecology].

PubMed

Tanchev, S; Pandurski, F; Georgiev, A; Gesheva, Iu; Platikanov, V; Dinov, P

2004-01-01

We report our clinical opinion for recombinant activated factor VII (NovoSeven, Novo Nordisk, Copenhagen, Denmark) administration in gynecology patients with massive haemorrhage. 3 women with gynecology deseases and severe bleeding in recieved NovoSeven in bolus IV. The blood loss and laboratory changes in hematology and haemostasis parameters are monitored. The bleeding was ceased in all cases. Decrease in values of Hb, Er and PTT was noted. The use of recombinant factor VIIA in gynecology patients with severe bleeding is effective and safe enough and could be an alternative to the extreme surgical procedures.

Outcome in obscure gastrointestinal bleeding after capsule endoscopy.

PubMed

Cañas-Ventura, Alex; Márquez, Lucia; Bessa, Xavier; Dedeu, Josep Maria; Puigvehí, Marc; Delgado-Aros, Sílvia; Ibáñez, Ines Ana; Seoane, Agustin; Barranco, Luis; Bory, Felipe; Andreu, Montserrat; González-Suárez, Begoña

2013-11-16

To investigate the clinical impact of capsule endoscopy (CE) after an obscure gastrointestinal bleeding (OGIB) episode, focusing on diagnostic work-up, follow-up and predictive factors of rebleeding. Patients who were referred to Hospital del Mar (Barcelona, Spain) between 2007 and 2009 for OGIB who underwent a CE were retrospectively analyzed. Demographic data, current treatment with non-steroid anti-inflammtory drugs or anticoagulant drugs, hemoglobin levels, transfusion requirements, previous diagnostic tests for the bleeding episode, as well as CE findings (significant or non-significant), work-up and patient outcomes were analyzed from electronic charts. Variables were compared by χ (2) analysis and Student t test. Risk factors of rebleeding were assessed by Log-rank test, Kaplan-Meier curves and Cox regression model. There were 105 patients [45.7% women, median age of 72 years old (interquartile range 56-79)] and a median follow-up of 326 d (interquartile range 123-641) included in this study. The overall diagnostic yield of CE was 58.1% (55.2% and 63.2%, for patients with occult OGIB and overt OGIB, respectively). In 73 patients (69.5%), OGIB was resolved. Multivariate analysis showed that hemoglobin levels lower than 8 g/dL at diagnosis [hazard ratios (HR) = 2.7, 95%CI: 1.9-6.3], patients aged 70 years and above (HR = 2.1, 95%CI: 1.2-6.1) and significant findings in CE (HR = 2.4, 95%CI: 1.1-5.8) were independent predictors of rebleeding. One third of the patients presented with rebleeding after CE; risk factors were hemoglobin levels < 8 g/dL, age ≥ 70 years or the presence of significant lesions.

Breaking paradigms in severe epistaxis: the importance of looking for the S-point.

PubMed

Kosugi, Eduardo Macoto; Balsalobre, Leonardo; Mangussi-Gomes, João; Tepedino, Miguel Soares; San-da-Silva, Daniel Marcus; Cabernite, Erika Mucciolo; Hermann, Diego; Stamm, Aldo Cassol

Since the introduction of nasal endoscopy into the field of Otorhinolaryngology, the treatment paradigm for cases of severe epistaxis has shifted toward early and precise identification of the bleeding site. Although severe epistaxis is usually considered to arise from posterior bleeding, an arterial vascular pedicle in the superior portion of the nasal septum, around the axilla projection of the middle turbinate, posterior to the septal body, frequently has been observed. That vascular pedicle was named the Stamm's S-point. The aim of this study was to describe the S-point and report cases of severe epistaxis originating from it. A retrospective case series study was conducted. Nine patients with spontaneous severe epistaxis, where the S-point was identified as the source of bleeding, were treated between March 2016 and March 2017. Male predominance (77.8%) with age average of 59.3 years old were reported. Most cases presented comorbidities (88.9%) and were not taking acetylsalicylic acid (66.7%). A predominance of left sided involvement (55.6%) and anteroposterior bleeding being the principal initial presentation (77.8%) was seen. Six patients (66.7%) presented with hemoglobin levels below 10g/dL, and four (44.4%) required blood transfusion. Cauterization of S-point was performed in all patients, with complete resolution of bleeding. No patient experienced recurrence of severe epistaxis. The Stamm's S-point, a novel source of spontaneous severe epistaxis, is reported, and its cauterization was effective and safe. Otolaryngologists must actively seek this site of bleeding in cases of severe epistaxis. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Association between obesity and periodontal disease in young adults: a population-based birth cohort

PubMed Central

Dickie de Castilhos, Eduardo; Horta, Bernardo Lessa; Gigante, Denise Petrucci; Demarco, Flávio Fernando; Peres, Karen Glazer; Peres, Marco Aurélio

2012-01-01

Aim To evaluate the association between obesity and periodontal disease and the mediating effect of oral hygiene, systemic inflammation and carbohydrate intake. Material and methods Subjects born in 1982 in Pelotas, Brazil (n = 5,914), have been followed for several times. Oral health was assessed in a representative sample of 720 individuals at 24 years. Obesity, waist circumference and number of episodes with obesity between 15 and 23 years of age were the main exposures. Mediating effect of oral hygiene, C-reactive protein level and carbohydrate consumption was also assessed. Results Obese individuals were more likely to have ≥2 teeth with gingival bleeding. However, after adjusting for confounders, the association was not statistically significant [OR (obese × 2 or more teeth) 1.72 (95% CI: 0.95, 3.11)] and adjustment for potential mediators decreased the OR (OR = 1.38). The risk of presenting calculus in obese subjects was 10% higher [PR 1.10 (95% CI: 1.02, 1.18)]. The number of episodes of obesity between 15 and 23 years was associated with dental calculus. Periodontal pockets were not associated with obesity. Conclusion Systemic inflammation and oral hygiene may be mediating the association between obesity and gingivitis. Obesity was not associated with periodontal pockets in young adults in this cohort. PMID:22671969

Combination of hemostatic therapies for treatment of patients with hemophilia A and inhibitors.

PubMed

Livnat, Tami; Budnik, Ivan; Levy-Mendelovich, Sarina; Avishai, Einat; Misgav, Mudi; Barg, Assaf Arie; Lubetsky, Aharon; Brutman-Barazani, Tami; Kenet, Gili

2017-07-01

Therapy application and monitoring of patients with hemophilia A (HA) and inhibitors are challenging. In the current study, combined FVIII - bypass therapy was implemented for a cohort of severe HA patients with inhibitors. Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII, rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied. Some patients who experienced hemarthroses or required minor surgeries were treated by a combined concomitant administration of FVIII+FEIBA as IV bolus doses. TG spiking studies showed individual responses not correlated to inhibitor titer. Combinations of agents augmented TG as compared to any single agent, while combined FVIII+FEIBA yielded the highest TG, supporting it as a potential treatment. Following emergent successful surgery of child treated by concomitant FVIII+FEIBA, a total of 396 episodes in 7/15 patients were treated with concomitant FVIII+FEIBA. Five patients were treated for bleeding episodes only, whereas 2 were children undergoing immune tolerance induction (ITI) with FEIBA prophylaxis. Four minor surgeries were performed on FVIII+FEIBA repeated infusions. Neither thrombosis nor any other adverse events were documented. A combination of FVIII+FEIBA may be effective and safe as an alternative treatment option for some high-responding inhibitor patients. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Reduced bleeding events with subcutaneous administration of recombinant human factor IX in immune-tolerant hemophilia B dogs.

PubMed

Russell, Karen E; Olsen, Eva H N; Raymer, Robin A; Merricks, Elizabeth P; Bellinger, Dwight A; Read, Marjorie S; Rup, Bonita J; Keith, James C; McCarthy, Kyle P; Schaub, Robert G; Nichols, Timothy C

2003-12-15

Intravenous administration of recombinant human factor IX (rhFIX) acutely corrects the coagulopathy in hemophilia B dogs. To date, 20 of 20 dogs developed inhibitory antibodies to the xenoprotein, making it impossible to determine if new human FIX products, formulations, or methods of chronic administration can reduce bleeding frequency. Our goal was to determine whether hemophilia B dogs rendered tolerant to rhFIX would have reduced bleeding episodes while on sustained prophylactic rhFIX administered subcutaneously. Reproducible methods were developed for inducing tolerance to rhFIX in this strain of hemophilia B dogs, resulting in a significant reduction in the development of inhibitors relative to historical controls (5 of 12 versus 20 or 20, P <.001). The 7 of 12 tolerized hemophilia B dogs exhibited shortened whole blood clotting times (WBCTs), sustained detectable FIX antigen, undetectable Bethesda inhibitors, transient or no detectable antihuman FIX antibody titers by enzyme-linked immunosorbent assay (ELISA), and normal clearance of infused rhFIX. Tolerized hemophilia B dogs had 69% reduction in bleeding frequency in year 1 compared with nontolerized hemophilia B dogs (P =.0007). If proven safe in human clinical trials, subcutaneous rhFIX may provide an alternate approach to prophylactic therapy in selected patients with hemophilia B.

Rectal bleeding in a 4-month-old boy

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

Dutro, J.A.; Santanello, S.A.; Unger, F.

1986-10-24

A case of bleeding Meckel's diverticulum is described in an infant. A 4-month-old boy was seen initially with a 24-hour history of painless hematochezia. His parents had noted two episodes of maroon-colored stool that did not appear to be associated with any abdominal distress. His medical history was unremarkable, with normal growth and development. Physical examination revealed a well-nourished, well-hydrated infant in no apparent distress. Vital signs were normal. Rectal examination revealed no masses, but bright-red blood was noted on the examining finger. Findings from the remainder of the examination were normal. An upright roentgenogram of the abdomen was obtainedmore » and demonstrated no abnormalities. The abdominal technetium scan was abnormal. An exploratory laparotomy was performed later on the day of admission.« less

Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

PubMed

Pallavee, P; Samal, Sunita; Samal, Rupal

2013-01-01

The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

[Analysis of individualized primary prophylactic treatment of 19 cases of children with severe hemophilia A].

PubMed

Liu, G Q; Tang, L; Wu, X Y; Zhen, Y Z; Li, G; Chen, Z P; Wang, Y; Zhang, N N; Zhang, J S; Yu, G X; Wu, R H

2016-12-02

Objective: To study the current situation of primary prophylaxis in severe hemophilia A children and to explore rational regimen in order to provide evidence for the development of primary prophylaxis in China. Method: A retrospective clinical data collection and analysis was conducted for 19 severe hemophilia A children who received primary prophylaxis in Beijing Children's Hospital outpatient clinic between February 2011 and September 2015 and evaluated the regimen and efficacy. Result: (1) Primary prophylaxis regimen: the median beginning age 1.8 (range 0.5-2.9) years, the median FⅧ preparation using dosage 16.7 (8.0-23.5) U/(kg·time), the median using frequency was 1.0 (1.0-3.0) time/week. Eight cases among the patients received escalation of treatment intensity because of the poor bleeding control. (2) Efficacy: the median annual bleeding rate (ABR) was 1.9 (0-6.0) times/year, the median annual joint bleeding rate (AJBR) was 0 (0-3.3) times/year, without life threatening bleeding. All of them kept in 4th scale of Beijing Children Hospital daily activity level. The median annual factor consumption was 1 844 (840-5 040) U/kg. Conclusion: Low-dose primary prophylaxis regimen which were in low-dose /low frequencies and adjusted by bleeding frequency could decrease bleeding and joint bleeding frequency significantly, maintained the normal daily activity capacity and saved the factor consumption compared to standard regimen in severe hemophilia A children.

Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency.

PubMed

Kulkarni, R; James, A H; Norton, M; Shapiro, A

2018-05-01

Essentials Plasma-derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were assessed in factor X-deficient women/girls. Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related. On-demand pdFX 25 IU kg -1 was effective and safe in women/girls with factor X deficiency. Background A high-purity, plasma-derived factor X concentrate (pdFX) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective To perform post hoc assessments of pdFX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/Methods Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of < 5 IU dL -1 ) received on-demand or preventive pdFX (25 IU kg -1 ) for ≤ 2 years. Results Of 16 enrolled subjects, 10 women and girls (aged 14-58 years [median, 25.5 years]) received 267 pdFX infusions. Mean monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were treated with pdFX, with a 98% treatment success rate versus 100% in men and boys. Mean pdFX incremental recovery was similar in the two groups (2.05 IU dL -1 versus 1.91 IU dL -1 per IU kg -1 ), as was the mean half-life (29.3 h versus 29.5 h). Of 142 adverse events in women and girls, headache was the most common (12 events in six subjects). Six events (two infusion-site erythema, two fatigue, one back pain, one infusion-site pain) in two subjects were considered to be possibly pdFX-related. Following the trial, pdFX was used to successfully maintain hemostasis in two subjects undergoing obstetric delivery. Conclusions pdFX was well tolerated and effective in women and girls with FX deficiency. Although women and girls had different bleeding symptoms and sites than men and boys, their pdFX pharmacokinetic profile was comparable. © 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Measuring the hemodynamic response to primary pharmacoprophylaxis of variceal bleeding: a cost-effectiveness analysis.

PubMed

Imperiale, Thomas F; Chalasani, Naga; Klein, Robert W

2003-12-01

The hemodynamic response to ss-blockers alone or with nitrates is highly predictive of efficacy in prevention of variceal bleeding. Hemodynamic monitoring (HDM) requires catheterization of the hepatic vein and measurement of the hepatic venous pressure gradient, the difference between wedged and free hepatic venous pressure. The aim of this study was to compare HDM with no HDM in patients considered for primary pharmacoprophylaxis of esophageal variceal bleeding. A decision model was constructed to compare HDM with no HDM in cirrhotic patients with moderate to large esophageal varices. Patients intolerant to beta-blocker therapy would undergo endoscopic variceal ligation; those with an inadequate hemodynamic response (HDR) to beta-blocker therapy could have nitrates added before ligation was considered. Variceal bleeding was treated with ligation, with transjugular intrahepatic portosystemic shunt (TIPS) reserved for refractory bleeding. Probabilities of treatment responses as well as risks of bleeding and mortality were based on published literature. Only direct costs were considered during the 5-yr time horizon. Outcomes were cost in United States dollars, survival length in life-years, and proportions of patients who experienced variceal bleeding, TIPS insertion, and mortality from any cause. In the base case analysis, HDM was either cost-saving ($2,523 US dollars /life-year gained) or cost-effective (incremental cost-effectiveness ratio of $5,200 US dollars/life-year saved) compared with no HDM, depending on whether nitrates were added to beta-blocker therapy. HDM reduced variceal bleeding by nearly 60% and had a small effect on all-cause mortality. In the sensitivity analysis, HDM was sensitive to the time horizon, as it was not cost-effective for a time horizon of <22 months and was not cost-saving before 49 months. The cost-effectiveness of HDM was not sensitive to reasonable variation in the probability of HDR to beta-blocker therapy, risk of bleeding, risk reduction with pharmacotherapy, or to the costs of HDM, bleeding, ligation, or TIPS. Probabilistic sensitivity analysis indicated that HDM was more effective and less costly 100% and 57% of the time, respectively. Compared with the current standard of no HDM, measuring the hemodynamic response of primary pharmacoprophylaxis substantially reduces the number of bleeding episodes and is cost-effective or cost-saving over a wide range of sensitivity analyses. A randomized trial of HDM is needed to verify its efficacy in clinical practice.

Gastrointestinal bleeding and subsequent risk of thromboembolic events during support with a left ventricular assist device.

PubMed

Stulak, John M; Lee, Dustin; Haft, Jonathon W; Romano, Matthew A; Cowger, Jennifer A; Park, Soon J; Aaronson, Keith D; Pagani, Francis D

2014-01-01

Modern left ventricular assist devices (LVAD) require anti-coagulation (AC) with warfarin and anti-platelet therapy to prevent thromboembolic complications in patients. Gastrointestinal bleeding (GI) is a significant adverse event in these patients and treatment typically requires reduction or elimination of AC or anti-platelet therapy. It is not known whether alterations in AC to treat GI bleeding influence subsequent risk of thromboembolic (TE) events during LVAD support. Between July 2003 and September 2011, 389 patients (308 male) underwent implantation of a continuous-flow LVAD at the University of Michigan Health System and the Mayo Clinic. Median age at implant was 60 years (range 18 to 79 years). Outcomes were analyzed for the association of GI bleeding events and subsequent TE events, defined as stroke, transient ischemic attack, hemolysis or suspected or confirmed pump thrombosis. Median survival was 10 months (maximum 7.2 years, total 439 patient-years). TE events occurring within the first 30 days were not counted. Overall survival and freedom from an outcome event were assessed using the Kaplan-Meier method. Associations between GI bleeding and subsequent TE events and survival impact were analyzed as time-dependent covariates. One hundred ninety-nine GI bleeding episodes occurred in 116 of 389 patients (30%) for an event rate of 0.45 GI bleed/patient-year of support. One hundred thirty-eight TE events occurred in 97 of 389 patients (25%) for an event rate of 0.31 TE event/patient-year of support. Median time from LVAD implant to first GI bleed was 5 months (range 1 to 116 months) and to first TE event was 6 months (range 1 to 29 months). For patients who had a TE event after GI bleed, the median interval was 5 months (range 0.5 to 25 months). TE events were 7.4-fold more likely in patients who had a prior GI bleed (range 4.9- to 11.1-fold) (p < 0.001); however, neither the presence of GI bleeding (0.7 to 1.2) nor a TE event (0.8 to 2.0) portended a lower overall survival. Patients who had GI bleeding were at significantly higher risk for a subsequent TE event. Although the exact cause of this relationship is unknown, it suggests that a reduction in anti-coagulation and anti-platelet management to treat GI bleeds may contribute to this risk. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Bleeding score in Type 1 von Willebrand disease patients using the ISTH-BAT questionnaire.

PubMed

Pathare, A; Al Omrani, S; Al Hajri, F; Al Obaidani, N; Al Balushi, B; Al Falahi, K

2018-04-01

Bleeding assessment tools have evolved in the last decade to standardize the assessment of the severity of bleeding symptom in a consistent way. In 2010, the International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) was developed and validated. Our aim was to administer ISTH-BAT questionnaire to the Omani patients with type 1 VWD and obtain the bleeding score (BS). We also studied the severity of their bleeding symptoms and correlated it with the BS as well as with the laboratory parameters. Forty-eight type I VWD index cases and 52 normal subjects were interviewed and the ISTH-BAT questionnaire administered. The BS was calculated based on a history of bleeding symptoms from 12 different sites according to the standard ISTH-BAT questionnaire. Laboratory parameters were obtained from patient's medical records. The mean age of this cohort was 27 years (range, 6-49) with 60% being females. The median time to administer this questionnaire was 10 minutes with an interquartile range (IQR) from 8 to 17 minutes. Overall, the median BS was 7 (IQR; 2,11) although individual scores ranged between 0 and 36. The BS was negatively correlated with VWF: Ag, VWF: RCo, and VWF: CB and the Spearman's correlation coefficient "rho" was, respectively, -0.15, -0.08, and -0.22. The ISTH-BAT BS is designed to reflect the severity of bleeding. Our results demonstrate the inherent variability of this bleeding pattern. We also found that the ISTH-BAT BS significantly correlated with VWF: Ag and VWF: CB. © 2017 John Wiley & Sons Ltd.

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

First living-related liver transplant to cure factor VII deficiency.

PubMed

Mohan, Neelam; Karkra, Sakshi; Jolly, Anu S; Vohra, Vijay; Mohanka, Ravi; Rastogi, Amit; Soin, A S

2015-09-01

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life-threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

PubMed

Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

2017-03-01

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

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

[Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

PubMed

Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2012-03-01

Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

Endoscopic treatment of bleeding gastric varices with histoacryl (N-butyl-2-cyanoacrylate): a South European single center experience.

PubMed

Monsanto, Pedro; Almeida, Nuno; Rosa, Albano; Maçôas, Fernanda; Lérias, Clotilde; Portela, Francisco; Amaro, Pedro; Ferreira, Manuela; Gouveia, Hermano; Sofia, Carlos

2013-07-01

Endoscopic injection of N-butyl-2-cyanoacrylate is the current recommended treatment for gastric variceal bleeding. Despite the extensive worldwide use, there are still differences related to the technique, safety, and long term-results. We retrospectively evaluated the efficacy and safety of cyanoacrylate in patients with gastric variceal bleeding. Between January 1998 and January 2010, 97 patients with gastric variceal bleeding underwent endoscopic treatment with a mixture of N-butyl-2-cyanoacrylate and Lipiodol(TM). Ninety-one patients had cirrhosis and 6 had non-cirrhotic portal hypertension. Child-Pugh score at presentation for cirrhotic patients was A-12.1 %; B-53.8 %; C-34.1 % and median MELD score at admission was 13 (3-26). Successful hemostasis, rebleeding rate and complications were reviewed. Median time of follow up was 19 months (0.5-126). A median mixture volume of 1.5 mL (0.6 to 5 mL), in 1 to 8 injections, was used, with immediate hemostasis rate of 95.9 % and early rebleeding rate of 14.4 %. One or more complications occurred in 17.5 % and were associated with the use of Sengstaken-Blakemore tube before cyanoacrylate and very early rebleeding (p < 0.05). Hospital mortality rate during initial bleeding episode was 9.3 %. Very early rebleeding was a strong and independent predictor for in-hospital mortality (p < 0.001). Long-term mortality rate was 58.8 %, in most of the cases secondary to hepatic failure. N-butyl-2-cyanoacrylate is a rapid, easy and highly effective modality for immediate hemostasis of gastric variceal bleeding with an acceptable rebleeding rate. Patients with very early rebleeding are at higher risk of death.

Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa.

PubMed

Lentz, S R; Ehrenforth, S; Karim, F Abdul; Matsushita, T; Weldingh, K N; Windyga, J; Mahlangu, J N

2014-08-01

Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors. To confirm the safety and assess the efficacy of vatreptacog alfa in treating bleeding episodes in hemophilic patients with inhibitors. In this international, multicenter, randomized, double-blind, active-controlled, crossover, confirmatory phase III trial (adept(™) 2) in patients with hemophilia A or B and inhibitors, bleeds were randomized 3 : 2 to treatment with vatreptacog alfa (one to three doses at 80 μg kg(-1) ) or rFVIIa (one to three doses at 90 μg kg(-1) ). Treatment failures after three doses of trial product (TP) were managed according to the local standard of care. In the 72 patients enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave 93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa in secondary efficacy outcomes, including the number of doses used to treat a bleed and sustained bleeding control 24-48 h after the first dose. Eight patients (11%) developed antibodies against vatreptacog alfa, including four with cross-reactivity against rFVIIa and one with an in vitro neutralizing effect to vatreptacog alfa. This large randomized controlled trial confirmed the well-established efficacy and safety profile of rFVIIa, and showed that vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of the development of anti-drug antibodies, a positive benefit-risk profile is unlikely to be achieved with vatreptacog alfa. © 2014 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Standardized reporting of bleeding complications for clinical investigations in acute coronary syndromes: a proposal from the academic bleeding consensus (ABC) multidisciplinary working group.

PubMed

Rao, Sunil V; Eikelboom, John; Steg, Ph Gabriel; Lincoff, A Michael; Weintraub, William S; Bassand, Jean-Pierre; Rao, A Koneti; Gibson, C Michael; Petersen, John L; Mehran, Roxana; Manoukian, Steven V; Charnigo, Richard; Lee, Kerry L; Moscucci, Mauro; Harrington, Robert A

2009-12-01

Clinical trials of antithrombotic agents for the treatment of ACS routinely assess bleeding as a safety endpoint, but variation in bleeding definitions makes comparison of the relative safety of these agents difficult. The ABC Multidisciplinary Working Group, an informal working group comprising clinical researchers and representatives from the US Food and Drug Administration, the National Institutes of Health, and the pharmaceutical industry, sought to develop a consensus approach to measuring the incidence and severity of bleeding complications during clinical trials of acute coronary syndromes (ACS). A meeting of the ABC was convened in April 2008 in Washington, DC, with the goal of developing a consensus approach to measuring the incidence and severity of hemorrhagic complications during clinical trials of ACS. Relevant literature on bleeding was reviewed through a series of short lectures and intensive group discussion. Using existing evidence on bleeding and outcomes as well as clinical judgment, criteria for the assessment of bleeding were developed through expert consensus. This consensus statement divides bleeding-related data elements into three categories: essential, recommended, and optional. The ABC Group recommendations for collection and reporting of bleeding complications provide a framework for consistency in the collection of information on hemorrhagic complications in trials of ACS. Widespread adoption of the statement recommendations will facilitate understanding of the mechanisms of adverse outcomes after bleeding and comparisons of the relative safety of antithrombotic agents, as well as the interpretation of safety results from future studies.

Economic analysis of recombinant activated factor VII versus plasma-derived activated prothrombin complex concentrate in mild to moderate bleeds: haemophilia registry data from the Czech Republic.

PubMed

Salaj, Peter; Penka, Miroslav; Smejkal, Petr; Geierova, Vera; Ovesná, Petra; Brabec, Petr; Cetkovsky, Petr; Kubes, Radovan; Mesterton, Johan; Lindgren, Peter

2012-05-01

Several studies suggest that recombinant activated factor VII (rFVIIa) is more cost-effective than plasma-derived activated prothrombin complex concentrate (pd-aPCC) in haemophilia with inhibitors. However, most do not consider differences between treated patients. This study compared the pharmacoeconomics of rFVIIa versus pd-aPCC treatment of mild to moderate bleeds in inhibitor patients, taking co-variables into account. The HemoRec and HemIS registries capture exhaustive bleeding data in inhibitor patients in the Czech Republic. For each bleed, patient and bleed characteristics, treatment outcomes and bypassing agent use were retrospectively analysed, and direct costs of care per bleed calculated. Generalised Linear Model regression methods with cluster effect were employed to account for the possibility of several bleedings from the same patient. There were 108 and 53 mild to moderate bleeds in the rFVIIa and pd-aPCC groups, respectively. Although re-bleeding rates were similar in both groups, deeper analyses revealed significant differences in time to bleed resolution: 93.8% of bleeds treated with rFVIIa were resolved within ≤ 12 h, versus 60.4% with pd-aPCC (P < 0.001). Mean total cost/bleed was lower with rFVIIa (336,852 [median, 290,696] CZK; €12,760 [11,011]) than pd-aPCC (522,768 [341,310] CZK; €19,802 [12,928]) (P = 0.002). Results were maintained after controlling for potential co-variables (bleed nature, time to treatment, target joints). The lower total treatment costs per bleed with rFVIIa than pd-aPCC suggest that first-line rFVIIa is more cost-effective than pd-aPCC in mild to moderate bleeds. Time to bleed resolution was also significantly shorter with rFVIIa. These results were maintained when controlled for potential confounders. Copyright © 2012 Elsevier Ltd. 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.

Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial.

PubMed

Piccini, Jonathan P; Garg, Jyotsna; Patel, Manesh R; Lokhnygina, Yuliya; Goodman, Shaun G; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Nessel, Christopher C; Mahaffey, Kenneth W; Singer, Daniel E; Califf, Robert M; Fox, Keith A A

2014-07-21

There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors. Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P < 0.0001]. Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non-central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin; HR 0.89; 95% CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin; HR 0.69, 95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin (interaction P = 0.51 and 0.11). Among high-risk patients with atrial fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Perineal Pseudoaneurysm from Traumatic Foley Removal Leads to Recurrent Life-Threatening Hematuria.

PubMed

Liang, Lorraine Min-Shan; Xue, Jingbing; Erturk, Erdal

2015-01-01

Hematuria resulting from urethral traumatic catheter insertion and removal is often encountered. Usually, hematuria resolves with conservative measures. We report a case of traumatic Foley removal leading to intermittent life-threatening hematuria resulting in blood loss anemia requiring multiple transfusions and multiple episodes of hypotension requiring pressors. A pelvic angiogram revealed a pseudoaneurysm of the left pudendal artery, which was treated with microcoil embolization leading to resolution of bleeding.

IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS

PubMed Central

Zweifach, B. W.; Gordon, H. A.; Wagner, M.; Reyniers, J. A.

1958-01-01

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock. PMID:13513911

A rare cause of bleeding after laparoscopic sleeve gastrectomy : pseudo-aneurysm of the gastro-omental artery.

PubMed

Mege, D; Louis, G; Berthet, B

2013-01-01

A serious complication of laparoscopic sleeve gastrectomy (LSG) is bleeding that is primarily located along the staples lines. Bleeding may be due to several causes, including hematomas, trocar sites, or visceral pseudo-aneurysms. We reported here a case of bleeding related to a pseudo-aneurysm of the gastro-omental artery. An LSG was performed on a 43-year-old woman (BMI = 46 kg/m2) without apparent surgical complications. Fifteen days later, she was admitted to the emergency department for hematemesis and symptoms of hemorrhagic shock. Abdominal computed tomography angiography revealed blood in the stomach, without a digestive leak, and active bleeding from a pseudo-aneurysm of the gastro-omental artery. An arterial embolisation was performed with the sandwich technique and angiographic guide wires and the placement of several detachable coils. The patient was discharged two days later. We demonstrated for the first time that post-LSG bleeding may involve a pseudo-aneurysm of the gastro-omental artery.

Endocapsular hematoma: a rare form of ocular hemorrhage after thrombolysis with streptokinase.

PubMed

Dhawan, Bodhraj; Soni, Rhibhu; Singh, Rajbir; Vig, Vipan

2014-08-01

Endocapsular hematoma has previously been described as a cataract surgery complication more commonly observed in eyes receiving a combined cataract and glaucoma surgery. However, it can also be a rare form of ocular bleed following thrombolysis with streptokinase. A 65-year-old diabetic male presented to us with complain of sudden painless diminution of vision in his left eye, which he developed while he was being thrombolysed with streptokinase administered intravenously for an episode of acute myocardial infarct. On examination, left eye was pseudophakic with collection of blood in the capsular bag (Endocapsular hematoma). Endocapsular hematoma can be a rare form of ocular bleeding complicated by thrombolysis. Reporting this case becomes more relevant in the present era with increasing number of patients suffering from ischemic heart disease and likely to undergo thrombolysis.

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.

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.

Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.

PubMed

Parra Lopez, Rafael; Nemes, Laszlo; Jimenez-Yuste, Victor; Rusen, Luminita; Cid, Ana R; Charnigo, Robert J; Baumann, James A; Smith, Lynne; Korth-Bradley, Joan M; Rendo, Pablo

2015-10-01

This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).

Refractory Gastrointestinal Bleeding: Role of Angiographic Intervention

PubMed Central

2013-01-01

Although endoscopic hemostasis remains initial treatment modality for nonvariceal gastrointestinal (GI) bleeding, severe bleeding despite endoscopic management occurs in 5% to 10% of the patients, requiring surgery or transcatheter arterial embolization (TAE). TAE is now considered the first-line therapy for massive GI bleeding refractory to endoscopic management. GI endoscopists need to be familiar with indications, principles, outcomes, and complications of TAE, as well as embolic materials available. PMID:24143308

Intra-Arterial Treatment in Patients with Acute Massive Gastrointestinal Bleeding after Endoscopic Failure: Comparisons between Positive versus Negative Contrast Extravasation Groups

PubMed Central

Chang, Wei-Chou; Liu, Chang-Hsien; Hsu, Hsian-He; Huang, Guo-Shu; Tung, Ho-Jui; Hsieh, Tsai-Yuan; Tsai, Shih-Hung; Hsieh, Chung-Bao

2011-01-01

Objective To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. Materials and Methods From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Results Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemostasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Conclusion Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage. PMID:21927558

[Predicting very early rebleeding after acute variceal bleeding based in classification and regression tree analysis (CRTA).].

PubMed

Altamirano, J; Augustin, S; Muntaner, L; Zapata, L; González-Angulo, A; Martínez, B; Flores-Arroyo, A; Camargo, L; Genescá, J

2010-01-01

Variceal bleeding (VB) is the main cause of death among cirrhotic patients. About 30-50% of early rebleeding is encountered few days after the acute episode of VB. It is necessary to stratify patients with high risk of very early rebleeding (VER) for more aggressive therapies. However, there are few and incompletely understood prognostic models for this purpose. To determine the risk factors associated with VER after an acute VB. Assessment and comparison of a novel prognostic model generated by Classification and Regression Tree Analysis (CART) with classic-used models (MELD and Child-Pugh [CP]). Sixty consecutive cirrhotic patients with acute variceal bleeding. CART analysis, MELD and Child-Pugh scores were performed at admission. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the models. Very early rebleeding rate was 13%. Variables associated with VER were: serum albumin (p = 0.027), creatinine (p = 0.021) and transfused blood units in the first 24 hrs (p = 0.05). The area under the ROC for MELD, CHILD-Pugh and CART were 0.46, 0.50 and 0.82, respectively. The value of cut analyzed by CART for the significant variables were: 1) Albumin 2.85 mg/dL, 2) Packed red cells 2 units and 3) Creatinine 1.65 mg/dL the ABC-ROC. Serum albumin, creatinine and number of transfused blood units were associated with VER. A simple CART algorithm combining these variables allows an accurate predictive assessment of VER after acute variceal bleeding. Key words: cirrhosis, variceal bleeding, esophageal varices, prognosis, portal hypertension.

Prophylactic treatment of hereditary severe factor VII deficiency in pregnancy.

PubMed

Pfrepper, Christian; Siegemund, Annelie; Hildebrandt, Sven; Kronberg, Juliane; Scholz, Ute; Niederwieser, Dietger

2017-09-01

: Severe hereditary factor VII deficiency is a rare bleeding disorder and may be associated with a severe bleeding phenotype. We describe a pregnancy in a 33-year-old woman with compound heterozygous factor VII deficiency and a history of severe menorrhagia and mucocutaneous bleedings. After discontinuation of contraceptives, menstruation was covered with recombinant activated factor VII (rFVIIa), and during pregnancy, rFVIIa had to be administered in first trimester in doses ranging from 15 to 90 μg/kg per day because of recurrent retroplacental hematomas and vaginal bleedings. Thrombin generation was measured in first trimester at different doses of rFVIIa and showed an increase in lag time when doses of less than 30 μg/kg/day were administered, whereas time to thrombin peak and peak thrombin were not influenced. A low-dose rFVIIa prophylactic treatment of 15 μg/kg every other day in the late second and in the third trimester was sufficient to allow a successful childbirth in this patient with severe factor VII deficiency.

Spatiotemporal variations of severe haze episodes in China

NASA Astrophysics Data System (ADS)

Li, J.; Liao, H.

2017-12-01

Rapid economic growth and associated emissions increase in China have led to severe air pollution in recent decades. This study presents the spatial and temporal variations of severe haze episodes in China obtained from monitoring sites and the global chemical transport model GEOS-Chem. Cities in the Beijing-Tianjin-Hebei (BTH) and Yangtze River Delta (YRD) regions suffered from severe haze, with highest numbers of severe haze episodes in winter and the lowest numbers of episodes in summer. Backward trajectory analysis by the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model indicated the origins of air mass during severe haze episodes for BTH and YRD. The principal component analysis was applied for different regions to classify synoptic conditions associated with the severe haze episodes.

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

Transjugular Intrahepatic Portosystemic Shunt Placement During Pregnancy: A Case Series of Five Patients

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

Ingraham, Christopher R., E-mail: cringra@uw.edu; Padia, Siddharth A., E-mail: spadia@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu

Background and AimsComplications of portal hypertension, such as variceal hemorrhage and ascites, are associated with significant increases in both mortality and complications during pregnancy. Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating portal hypertension, but the safety of TIPS during pregnancy is largely unknown. In this series, we review five patients who underwent TIPS placement while pregnant and describe their clinical outcomes.MethodsFive pregnant patients with cirrhosis and portal hypertension underwent elective TIPS for complications of portal hypertension (four for secondary prevention of variceal bleeding and one for refractory ascites). Outcomes measured were recurrent bleeding episodes or needmore » for further paracenteses during pregnancy, estimated radiation dose to the fetus and gestational age at delivery. All patients were followed after delivery to evaluate technical and clinical success of the procedure.ResultsAll five patients survived pregnancy and went on to deliver successfully. When TIPS was performed for secondary prevention of variceal bleeding (n = 4), no patients demonstrated variceal bleeding after TIPS placement. When TIPS was performed for refractory ascites (n = 1), no further paracenteses were required. All patients delivered successfully, albeit prematurely. Average radiation dose estimated to the fetus was 16.3 mGy.ConclusionsThis series suggests that TIPS can be performed in selective pregnant patients with portal hypertension, with little added risk to the mother or fetus.« less

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

PubMed

Lauer, Peter; Metzner, Hubert J; Zettlmeissl, Gerd; Li, Meng; Smith, Austin G; Lathe, Richard; Dickneite, Gerhard

2002-12-01

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin. Results from the AMPLIFY trial.

PubMed

Bleker, Suzanne M; Cohen, Alexander T; Büller, Harry R; Agnelli, Giancarlo; Gallus, Alexander S; Raskob, Gary E; Weitz, Jeffrey I; Curto, Madelyn; Sisson, Melanie; Middeldorp, Saskia

2016-11-30

Apixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using pre-designed classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5 % of apixaban versus 44.9 % of enoxaparin/warfarin related recipients (OR 0.49, 95 % confidence interval [CI] 0.14-1.78). A severe clinical course was observed in 14.3 % and in 12.2 %, respectively (OR 1.19, 95 %CI 0.21-6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25 % of apixaban recipients compared to 22.7 % in the enoxaparin/warfarin group (OR 1.13, 95 %CI 0.65-1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.

Co-morbidities and bleeding in elderly patients with haemophilia-A survey of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH).

PubMed

Miesbach, W; Reitter-Pfoertner, S-E; Klamroth, R; Langer, F; Wolf, H-H; Tiede, A; Siegmund, B; Scholz, U; Müller, P R; Eichler, H; Pabinger, I

2017-09-01

Nowadays patients with haemophilia survive longer due to improvements in haemophilia care. It has been hypothesized that the bleeding type and frequency may vary with age and are influenced by co-morbidities and co-medication in elderly patients. To investigate a large group of patients older than 60 years of age with haemophilia concerning haemophilia treatment, bleeding pattern changes, co-morbidities, co-medication, bleeding sites and patient mortality. A retrospective multi-centre data collection study was initiated on behalf of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH). Parameters of interest were investigated over the 5 years prior to study entry. A total of 185 haemophilia patients (mean age, 69.0±7.0 years, 29% with severe haemophilia) were included in the study. Regular prophylaxis was performed in 30% of the patients with severe haemophilia. In total, the annual bleeding rate was 2.49 and in patients with severe haemophilia 5.61, mostly caused by joint bleeds. Hypertension was the most common co-morbidity, but it occurred significantly less frequently than in an age-matched general population older than 70 years; 12% of the patients suffered from ischaemic heart disease, and 13% of the patients received anticoagulant or antiplatelet therapy. Within the observation period, 17% of the patients with severe haemophilia developed a higher frequency of bleeding symptoms, which was significantly associated with the use of antiplatelet or anticoagulant drugs. The most common co-morbidity of the patient population was hypertension, a considerable part had ischemic heart disease and antiplatelet or anticoagulant drugs. © 2017 John Wiley & Sons Ltd.

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.

Effective salvage of acute massive uterine bleeding using intrauterine balloon tamponade in a uterine adenomyosis patient on dienogest.

PubMed

Nishino, Kimihiro; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

2013-03-01

We present the case of a 37-year-old nulliparous woman in whom acute massive uterine bleeding during dienogest therapy was successfully treated using intrauterine balloon tamponade. Abnormal uterine bleeding and several cases of profuse bleeding causing severe anemia in association with dienogest therapy have been reported, but this is the first reported case involving hypovolemic shock. While successful control of postpartum hemorrhage with intrauterine balloon tamponade has been well described, applications for non-obstetric bleeding, particularly in the presence of underlying diseases, such as adenomyosis, have only rarely been reported. This procedure can be easily, promptly, and safely implemented without analgesia, anesthesia, or laparotomy; it can be used with a minimally dilated external cervical os or narrow uterine cavity; and it can preserve fertility. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

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.

Occult hemorrhage in children with severe ITP.

PubMed

Flores, Adolfo; Buchanan, George R

2016-03-01

Little is known about the frequency and significance of clinically unapparent or occult hemorrhage in ITP. Therefore, we prospectively explored the sites and frequency of occult bleeding in children with severe ITP at diagnosis or upon symptomatic relapse in a prospective, single-institution cohort study of patients ≤ 18 years of age and a platelet count ≤ 10,000/mm(3) . Data collected included bleeding severity assessment, urinalysis, fecal occult blood testing, and non-contrast brain MRI. Stool and urine samples were tested within 7 days of diagnosis or symptomatic relapse. Three months after diagnosis or relapse a noncontrast brain MRI evaluated hemosiderin deposits resulting from prior localized hemorrhage. Fifty-two ITP patients were enrolled with a mean platelet count of 4,000/mm(3) . A significant occurrence of occult hemorrhage was identified in the urine (27%) compared with clinically overt hematuria (0.91%, P < 0.0005). CNS microbleeding in the superficial cortex of the left frontal lobe was identified in one child with occult bleeding in the urinary tract. There was no relationship between occult hemorrhage and bleeding manifestations on physical examination. Occult hemorrhage was not a harbinger of subsequent bleeding. Our findings suggest that occult hemorrhage occurs with greater frequency than overt bleeding in children with severe ITP. CNS microbleeding is a potential risk in this patient population. Assessment of brain microbleeds and microscopic hematuria in this patient population require additional study. © 2015 Wiley Periodicals, Inc.

Perineal Pseudoaneurysm from Traumatic Foley Removal Leads to Recurrent Life-Threatening Hematuria

PubMed Central

Xue, Jingbing; Erturk, Erdal

2015-01-01

Abstract Hematuria resulting from urethral traumatic catheter insertion and removal is often encountered. Usually, hematuria resolves with conservative measures. We report a case of traumatic Foley removal leading to intermittent life-threatening hematuria resulting in blood loss anemia requiring multiple transfusions and multiple episodes of hypotension requiring pressors. A pelvic angiogram revealed a pseudoaneurysm of the left pudendal artery, which was treated with microcoil embolization leading to resolution of bleeding. PMID:27579388

Factors associated with delayed bleeding after resection of large nonpedunculated colorectal polyps.

PubMed

Elliott, Timothy R; Tsiamoulos, Zacharias P; Thomas-Gibson, Siwan; Suzuki, Noriko; Bourikas, Leonidas A; Hart, Ailsa; Bassett, Paul; Saunders, Brian P

2018-04-06

 Delayed bleeding is the most common significant complication after piecemeal endoscopic mucosal resection (p-EMR) of large nonpedunculated colorectal polyps (NPCPs). Risk factors for delayed bleeding are incompletely defined. We aimed to determine risk factors for delayed bleeding following p-EMR.  Data were analyzed from a prospective tertiary center audit of patients with NPCPs ≥ 20 mm who underwent p-EMR between 2010 and 2012. Patient, polyp, and procedure-related data were collected. Four post p-EMR defect factors were evaluated for interobserver agreement and included in analysis. Delayed bleeding severity was reported in accordance with guidelines. Predictors of bleeding were identified.  Delayed bleeding requiring hospitalization occurred after 22 of 330 procedures (6.7 %). A total of 11 patients required blood transfusion; of these, 4 underwent urgent colonoscopy, 1 underwent radiological embolization, and 1 required surgery. Interobserver agreement for identification of the four post p-EMR defect factors was moderate (kappa range 0.52 - 0.57). Factors associated with delayed bleeding were visible muscle fibers ( P  = 0.03) and the presence of a "cherry red spot" ( P  = 0.05) in the post p-EMR defect. Factors not associated with delayed bleeding were American Association of Anesthesiologists class, aspirin use, polyp size, site, and use of argon plasma coagulation.  Visible muscle fibers and the presence of a "cherry red spot" in the resection defect were associated with delayed bleeding after p-EMR. These findings suggest evaluation and photodocumentation of the post p-EMR defect is important and, when considered alongside other patient and procedural factors, may help to reduce the incidence and severity of delayed bleeding. © Georg Thieme Verlag KG Stuttgart · New York.

Establishment of a bleeding score as a diagnostic tool for patients with rare bleeding disorders.

PubMed

Palla, Roberta; Siboni, Simona M; Menegatti, Marzia; Musallam, Khaled M; Peyvandi, Flora

2016-12-01

Bleeding manifestations among patients with rare bleeding disorders (RBDs) vary significantly between disorders and patients, even when affected with the same disorder. In response to the challenge represented by the clinical assessment of the presence and severity of bleeding symptoms, a number of bleeding score systems (BSSs) or bleeding assessment tools (BATs) were developed. The majority of these were specifically developed for patients with more common bleeding disorders than RBDs. Few RBDs patients were evaluated with these tools and without conclusive results. A new BSS was developed using data retrieved from a large group of patients with RBDs enrolled in the EN-RBD database and from healthy subjects. These data included previous bleeding symptoms, frequency, spontaneity, extent, localization, and relationship to prophylaxis and acute treatment. The predictive power of this BSS was also compared with the ISTH-BAT and examined for the severity of RBDs based on coagulant factor activity. This BSS was able to differentiate patients with RBDs from healthy individuals with a bleeding score value of 1.5 having the highest sum of sensitivity (67.1%) and specificity (73.8%) in discriminating patients with RBD from those without. An easy-to-use calculation was also developed to assess the probability of having a RBD. Its comparison with the ISTH-BAT confirmed its utility. Finally, in RBDs patients, there was a significant negative correlation between BS and coagulant factor activity level, which was strongest for fibrinogen and FXIII deficiencies. The use of this quantitative method may represent a valuable support tool to clinicians. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review.

PubMed

Desborough, Michael; Hadjinicolaou, Andreas V; Chaimani, Anna; Trivella, Marialena; Vyas, Paresh; Doree, Carolyn; Hopewell, Sally; Stanworth, Simon J; Estcourt, Lise J

2016-10-31

People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed. To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016. We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion. Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI).We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions.We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I 2 statistic and its 95% CI. The risk of bias of each study included was assessed using the Cochrane 'Risk of bias' tool. The quality of the evidence was assessed using GRADE methods. We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified.We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies.The GRADE quality of the evidence was very low to moderate across the different outcomes.There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence).There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence).There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence).There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participants, very-low quality evidence).There was no evidence for a difference in drug reactions between TPO mimetics and placebo (RR 1.12, 95% CI 0.83 to 1.51, five trials, 455 participants, low-quality evidence).No trial reported the number of days of bleeding per participant, platelet transfusion episodes, mean red cell transfusions per participant, red cell transfusion episodes, transfusion-transmitted infections, formation of antiplatelet antibodies or platelet refractoriness.In order to demonstrate a reduction in bleeding events from 26 in 100 to 16 in 100 participants, a study would need to recruit 514 participants (80% power, 5% significance). There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting.

Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review

PubMed Central

Desborough, Michael; Hadjinicolaou, Andreas V; Chaimani, Anna; Trivella, Marialena; Vyas, Paresh; Doree, Carolyn; Hopewell, Sally; Stanworth, Simon J; Estcourt, Lise J

2017-01-01

Background People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed. Objectives To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016. Selection criteria We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion. Data collection and analysis Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI). We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions. We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I2 statistic and its 95% CI. The risk of bias of each study included was assessed using the Cochrane ’Risk of bias’ tool. The quality of the evidence was assessed using GRADE methods. Main results We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified. We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies. The GRADE quality of the evidence was very low to moderate across the different outcomes. There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence). There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence). There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence). There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence). There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence). There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participants, very-low quality evidence). There was no evidence for a difference in drug reactions between TPO mimetics and placebo (RR 1.12, 95% CI 0.83 to 1.51, five trials, 455 participants, low-quality evidence). No trial reported the number of days of bleeding per participant, platelet transfusion episodes, mean red cell transfusions per participant, red cell transfusion episodes, transfusion-transmitted infections, formation of antiplatelet antibodies or platelet refractoriness. In order to demonstrate a reduction in bleeding events from 26 in 100 to 16 in 100 participants, a study would need to recruit 514 participants (80% power, 5% significance). Authors’ conclusions There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting. PMID:27797129

Excess Long-Term Mortality following Non-Variceal Upper Gastrointestinal Bleeding: A Population-Based Cohort Study

PubMed Central

Crooks, Colin John; Card, Timothy Richard; West, Joe

2013-01-01

Background It is unclear whether an upper gastrointestinal bleed is an isolated gastrointestinal event or an indicator of a deterioration in a patient's overall health status. Therefore, we investigated the excess causes of death in individuals after a non-variceal bleed compared with deaths in a matched sample of the general population. Methods and Findings Linked longitudinal data from the English Hospital Episodes Statistics (HES) data, General Practice Research Database (GPRD), and Office of National Statistics death register were used to define a cohort of non-variceal bleeds between 1997 and 2010. Controls were matched at the start of the study by age, sex, practice, and year. The excess risk of each cause of death in the 5 years subsequent to a bleed was then calculated whilst adjusting for competing risks using cumulative incidence functions. 16,355 patients with a non-variceal upper gastrointestinal bleed were matched to 81,523 controls. The total 5-year risk of death due to gastrointestinal causes (malignant or non-malignant) ranged from 3.6% (≤50 years, 95% CI 3.0%–4.3%) to 15.2% (≥80 years, 14.2%–16.3%), representing an excess over controls of between 3.6% (3.0%–4.2%) and 13.4% (12.4%–14.5%), respectively. In contrast the total 5-year risk of death due to non-gastrointestinal causes ranged from 4.1% (≤50 years, 3.4%–4.8%) to 46.6% (≥80 years, 45.2%–48.1%), representing an excess over controls of between 3.8% (3.1%–4.5%) and 19.0% (17.5%–20.6%), respectively. The main limitation of this study was potential misclassification of the exposure and outcome; however, we sought to minimise this by using information derived across multiple linked datasets. Conclusions Deaths from all causes were increased following an upper gastrointestinal bleed compared to matched controls, and over half the excess risk of death was due to seemingly unrelated co-morbidity. A non-variceal bleed may therefore warrant a careful assessment of co-morbid illness seemingly unrelated to the bleed. Please see later in the article for the Editors' Summary PMID:23637580

The portal hypertension syndrome: etiology, classification, relevance, and animal models.

PubMed

Bosch, Jaime; Iwakiri, Yasuko

2018-02-01

Portal hypertension is a key complication of portal hypertension, which is responsible for the development of varices, ascites, bleeding, and hepatic encephalopathy, which, in turn, cause a high mortality and requirement for liver transplantation. This review deals with the present day state-of-the-art preventative treatments of portal hypertension in cirrhosis according to disease stage. Two main disease stages are considered, compensated and decompensated cirrhosis, the first having good prognosis and being mostly asymptomatic, and the second being heralded by the appearance of bleeding or non-bleeding complications of portal hypertension. The aim of treatment in compensated cirrhosis is preventing clinical decompensation, the more frequent event being ascites, followed by variceal bleeding and hepatic encephalopathy. Complications are mainly driven by an increase of hepatic vein pressure gradient (HVPG) to values ≥10 mmHg (defining the presence of Clinically Significant Portal Hypertension, CSPH). Before CSPH, the treatment is limited to etiologic treatment of cirrhosis and healthy life style (abstain from alcohol, avoid/correct obesity…). When CSPH is present, association of a non-selective beta-blocker (NSBB), including carvedilol should be considered. NSBBs are mandatory if moderate/large varices are present. Patients should also enter a screening program for hepatocellular carcinoma. In decompensated patients, the goal is to prevent further bleeding if the only manifestation of decompensation was a bleeding episode, but to prevent liver transplantation and death in the common scenario where patients have manifested first non-bleeding complications. Treatment is based on the same principles (healthy life style..) associated with administration of NSBBs in combination if possible with endoscopic band ligation if there has been variceal bleeding, and complemented with simvastatin administration (20-40 mg per day in Child-Pugh A/B, 10-20 mg in Child C). Recurrence shall be treated with TIPS. TIPS might be indicated earlier in patients with: 1) Difficult/refractory ascites, who are not the best candidates for NSBBs, 2) patients having bleed under NSBBs or showing no HVPG response (decrease in HVPG of at least 20% of baseline or to values equal or below 12 mmHg). Decompensated patients shall all be considered as potential candidates for liver transplantation. Treatment of portal hypertension has markedly improved in recent years. The present day therapy is based on accurate risk stratification according to disease stage.

Remission of recurrent gastrointestinal bleeding after septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy-associated acquired von Willebrand syndrome.

PubMed

Blackshear, J L; Stark, M E; Agnew, R C; Moussa, I D; Safford, R E; Shapiro, B P; Waldo, O A; Chen, D

2015-02-01

Gastrointestinal hemorrhage is considered to be a severe complication of von Willebrand disease. The optimal therapy for acquired von Willebrand syndrome and severe gastrointestinal bleeding with hypertrophic cardiomyopathy is undefined. Seventy-seven patients (median age, 67 years; interquartile range [IQR], 56-75 years; 49% women) with hypertrophic cardiomyopathy underwent von Willebrand factor multimer testing and acquisition of bleeding history. Bleeding was detected in 27 (36%) (median age, 74 years; IQR 66-76 years; 74% women), 20 with gastrointestinal bleeding, including 11 women with transfusion dependence. In these 11 women, the median duration of transfusion dependency was 36 months (IQR 18-44 months), and the median number of transfusions required was 25 (IQR 20-38). Two patients had undergone bowel resection for bleeding, one of them twice. Seven patients showed angiodysplasia, and the remainder had no endoscopic lesion. Bleeding recurred after bowel surgery or endoscopic intervention and medical therapy for hypertrophic cardiomyopathy in 10 of 11 patients. Two patients had septal myectomy, and six patients underwent alcohol septal ablation. With the exception of one patient in whom a significant gradient persisted after septal ablation, after the periprocedural period, patients after septal reduction therapy remained free of recurrent bleeding and need for transfusions. Acquired von Willebrand syndrome is common in hypertrophic cardiomyopathy. Gastrointestinal bleeding often recurs after endoscopic therapy, but may be relieved by structural cardiac repair. © 2014 International Society on Thrombosis and Haemostasis.

Lack of bleeding in patients with severe factor VII deficiency.

PubMed

Barnett, J Mark; Demel, Kurt C; Mega, Anthony E; Butera, James N; Sweeney, Joseph D

2005-02-01

Factor VII deficiency, although rare, is now recognized as the most common autosomal recessive inherited factor deficiency. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk. The general recommendation for surgery is to achieve a FVII level in excess of 15% (0.15 1U/mL). We present three cases of severe factor VII deficiency, each of whom appeared hemostatically competent based on clinical history. Subject 1 is a 33 year-old African-American female with a baseline FVII of <1%, who had a fractured tibia requiring open reduction with internal fixation without any FVII replacement and subsequently underwent successful laparoscopic knee surgery with a factor VII level measured at 6%. Subject 2 is a 58 year-old African-American female with a factor VII level of 9% who underwent an elective left total hip replacement without any factor replacement and had no excessive bleeding, but who sustained a pulmonary embolism postoperatively. Subject 3 is a 19-year-old African-American male with a baseline FVII of 1% with a history of active participation in football without noticeable injury and who underwent an emergent appendectomy without bleeding. These three cases represent individuals with the severe form of FVII deficiency who did not exhibit excessive bleeding when challenged with surgical procedures. The clinical history would appear the most valuable tool in predicting the likelihood of bleeding in these patients, and we suggest that the presumption that all patients with severe FVII deficiency should receive replacement therapy before surgical procedures may not be valid in all cases. Copyright 2005 Wiley-Liss, Inc.

Life-threatening subdural hematoma after aortic valve replacement in a patient with Heyde syndrome: a case report.

PubMed

Uchida, Tetsuro; Hamasaki, Azumi; Ohba, Eiichi; Yamashita, Atsushi; Hayashi, Jun; Sadahiro, Mitsuaki

2017-08-08

Heyde syndrome is known as a triad of calcific aortic stenosis, anemia due to gastrointestinal bleeding from angiodysplasia, and acquired type 2A von Willebrand disease. This acquired hemorrhagic disorder is characterized by the loss of the large von Willebrand factor multimers due to the shear stress across the diseased aortic valve. The most frequently observed type of bleeding in these patients is mucosal or skin bleeding, such as epistaxis, followed by gastrointestinal bleeding. On the other hand, intracranial hemorrhage complicating Heyde syndrome is extremely rare. A 77-year-old woman presented to our hospital with severe aortic stenosis and severe anemia due to gastrointestinal bleeding and was diagnosed with Heyde syndrome. Although aortic valve replacement was performed without recurrent gastrointestinal bleeding, postoperative life-threatening acute subdural hematoma occurred with a marked midline shift. Despite prompt surgical evacuation of the hematoma, she did not recover consciousness and she died 1 month after the operation. Postoperative subdural hematoma is rare, but it should be kept in mind as a devastating hemorrhagic complication, especially in patients with Heyde syndrome.

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.

Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

PubMed Central

Benagiano, Giuseppe; Carrara, Sabina; Filippi, Valentina

2009-01-01

The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel) biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic) and peripheral (cervical mucus and endometrium) levels. Levonorgestrel (LNG), alone or in combination with ethinyl estradiol (EE), is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years empirically utilized various continuous administration regimens. The first extended-cycle oral contraceptive regimen introduced in clinical practice is an 84-day regimen that results in bleeding only 4 times a year. A commercial product specifically packed for continuous use is now available in Europe and contains 30 μg EE and 150 μg LNG. In a variation of this regimen, after administration of the same combination for 84 days, women are given 7 pills containing 10 μg EE. A 6-monthly regimen has also been tested in a small study using EE 20 μg plus LNG 100 μg taken with and without a hormone-free interval. Women in the continuous group reported significantly fewer bleeding days requiring protection and were more likely to have amenorrhea; in addition they also reported significantly fewer days of bloating and menstrual pain. A yearly regimen is now being developed. Each pill of this novel formulation contains EE 20 μg and LNG 90 μg to be taken continuously for 364 days (13 cycles) per year. A phase III trial has now evaluated safety, efficacy and menses inhibition. At the end of the 1-year trial amenorrhea was present in 58.7% of the women and a complete absence of bleeding in 79.0%. Overall, the number of bleeding and spotting days per pill pack declined with time and adverse events and discontinuations were comparable to those reported for cyclic oral contraceptive regimens. PMID:19936155

Surgical bleeding in microgravity

NASA Technical Reports Server (NTRS)

Campbell, M. R.; Billica, R. D.; Johnston, S. L. 3rd

1993-01-01

A surgical procedure performed during space flight would occur in a unique microgravity environment. Several experiments performed during weightlessness in parabolic flight were reviewed to ascertain the behavior of surgical bleeding in microgravity. Simulations of bleeding using dyed fluid and citrated bovine blood, as well as actual arterial and venous bleeding in rabbits, were examined. The high surface tension property of blood promotes the formation of large fluid domes, which have a tendency to adhere to the wound. The use of sponges and suction will be adequate to prevent cabin atmosphere contamination with all bleeding, with the exception of temporary arterial droplet streams. The control of the bleeding with standard surgical techniques should not be difficult.

Current options and new developments in the treatment of haemophilia.

PubMed

Wong, Trisha; Recht, Michael

2011-02-12

Haemophilia A and B are X-linked bleeding disorders due to the inherited deficiency of factor VIII or factor IX, respectively. Of the approximately 1 per 5000-10000 male births affected by haemophilia, 80% are deficient in factor VIII and 20% are deficient in factor IX. Haemophilia is characterized by spontaneous and provoked joint, muscle, gastrointestinal and CNS bleeding leading to major morbidity and even mortality if left untreated or under-treated. The evolution of haemophilia management has been marked by tragedy and triumph over recent decades. Clotting factors and replacement strategies continue to evolve for patients without inhibitors. For patients with an inhibitor, factor replacement for acute bleeding episodes and immune tolerance, immune modulation and extracorporeal methods for inhibitor reduction are the cornerstone of care. In addition, adjuvant therapies such as desmopressin, antifibrinolytics and topical agents also contribute to improved outcomes for patients with and without inhibitors. The future direction of haemophilia care is promising with new longer-acting clotting factors and genetic therapies, including gene transfer and premature termination codon suppressors. With these current and future treatment modalities, the morbidity and mortality rates in patients with haemophilia certainly will continue to improve.

The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis.

PubMed

Gunawan, B; Runyon, B

2006-01-01

Patients with decompensated cirrhosis are at risk for hyperfibrinolysis; this is potentially fatal. epsilon-aminocaproic acid has been used to treat patients with hyperfibrinolysis; however, the data about its benefit in the setting of cirrhosis are minimal. To analyse the efficacy of epsilon-aminocaproic acid and its safety in cirrhotic patients with hyperfibrinolysis. All patients with an abnormal euglobin lysis time who were admitted to Rancho Los Amigos Medical Center from 1 January 2001 to 31 December 2002 were included in the study. Their medical records were reviewed and analysed. There were 60 cirrhotic patients with shortened euglobin lysis time. Fifty-two patients received epsilon-aminocaproic acid. Of the 52 patients, seven had one or more bleeding episodes with the subcutaneous or soft tissue bleeding as the most common indication for epsilon-aminocaproic acid use. Of the 37 patients, 34 (92%) had improvement or resolution of their bleeding. Only two (3%) patients had epsilon-aminocaproic acid treatment discontinued because of minor side effects, rash and lightheadedness. There were no thromboembolic complications of treatment. epsilon-aminocaproic acid was found to be effective and safe for treatment of hyperfibrinolysis in patients with cirrhosis.

A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding

PubMed Central

Rostampour, Noushin; Hashemipour, Mahin; Kelishadi, Roya; Hovsepian, Silva; Hekmatnia, Ali

2011-01-01

Background McCune-Albright syndrome (MAS) is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone. Case Presentation We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA) for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up. Conclusion Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty. PMID:23056821

Prevention of Portal Hypertension: from Variceal Development to Clinical Decompensation

PubMed Central

Vorobioff, Julio D.; Groszmann, Roberto J

2015-01-01

Pharmacological treatment of portal hypertension (PH) has been exclusively devoted to gastro-esophageal varices related events at different frameworks including prophylactic, emergency or preventive therapy. The goals of treatment are to avoid the first bleeding episode, stop active bleeding and prevent bleeding recurrence, respectively. The objective of pre-primary prophylaxis (PPP) is to avoid variceal development and therefore, it necessarily deals with cirrhotic patients at earlier stages of the disease. At these earlier stages, nonselective beta blocker (NSBB) have been ineffective in preventing the development of varices and other complications of PH. Therefore, treatment should not rely on NSBB. It is possible, that at these earlier stages, etiological treatment of liver disease itself could prevent the progression of PH. This review will focus mainly on early treatment of PH, because if successful, it may translate into histological-hemodynamic improvements, avoiding not only variceal development but also other PH related complications, such as ascites and porto-systemic encephalopathy (PSE). Moreover, the advent of new therapies may allow not only the prevention of the complications of PH, but also the chance of a substantial degree of regression in the cirrhotic process with the possible prevention of hepatocellular carcinoma (HCC). PMID:24913395

Low-dose aspirin for preventing recurrent venous thromboembolism.

PubMed

Brighton, Timothy A; Eikelboom, John W; Mann, Kristy; Mister, Rebecca; Gallus, Alexander; Ockelford, Paul; Gibbs, Harry; Hague, Wendy; Xavier, Denis; Diaz, Rafael; Kirby, Adrienne; Simes, John

2012-11-22

Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism. We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism. During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P=0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P=0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P=0.22) or serious adverse events. In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. (Funded by National Health and Medical Research Council [Australia] and others; Australian New Zealand Clinical Trials Registry number, ACTRN12605000004662.).

BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial.

PubMed

Ljung, R; Kenet, G; Mancuso, M E; Kaleva, V; Rusen, L; Tseneklidou-Stoeter, D; Michaels, L A; Shah, A; Hong, W; Maas Enriquez, M

2016-05-01

BAY 81-8973, a full-length, unmodified, recombinant factor VIII (FVIII) in development for treatment of haemophilia A, has the same primary amino acid sequence as Bayer's sucrose-formulated recombinant FVIII but is produced with more advanced manufacturing technologies. To demonstrate safety and efficacy of BAY 81-8973 for prophylaxis and treatment of bleeds in previously treated children. In this phase III, multicentre, open-label, nonrandomized study, boys aged ≤12 years with severe haemophilia A and ≥50 exposure days (EDs) to FVIII products received prophylaxis with BAY 81-8973 25-50 IU kg(-1) ≥2 times weekly for ≥50 EDs. The efficacy endpoint was annualized number of total bleeds. Adverse events (AEs) and immunogenicity were assessed. Fifty-one patients were treated (age: <6 years, n = 25; 6-<12 years, n = 26) with a 2× per week (43%) or >2× per week (57%) regimen at study start. Median [quartile 1; quartile 3 (Q1; Q3)] annualized number of bleeds for the combined age groups was 1.90 (0; 6.02) for total bleeds, 0 (0; 2.01) for joint bleeds and 0 (0; 0) for spontaneous bleeds. Median (Q1; Q3) annualized number of total bleeds within 48 h of previous prophylaxis infusion was 1.88 (0; 3.97) for children aged <6 years and 0 (0; 1.96) for children aged 6-<12 years. No drug-related serious AEs or inhibitors were reported. Prophylaxis with BAY 81-8973 using individualized prophylaxis regimens of 2× per week, 3× per week and every-other-day infusions was efficacious in prevention and treatment of bleeds in children with severe haemophilia A. Treatment with BAY 81-8973 was well tolerated. © 2015 John Wiley & Sons Ltd.

Longitudinal Associations Between Interpersonal Relationship Functioning and Mood Episode Severity in Youth with Bipolar Disorder

PubMed Central

Siegel, Rebecca S.; Hoeppner, Bettina; Yen, Shirley; Stout, Robert L; Weinstock, Lauren M.; Hower, Heather M.; Birmaher, Boris; Goldstein, Tina R.; Goldstein, Benjamin I.; Hunt, Jeffrey I.; Strober, Michael; Axelson, David A.; Gill, Mary Kay; Keller, Martin B.

2014-01-01

This study examined the longitudinal association between mood episode severity and relationships in BP youth. Participants were 413 Course and Outcome of Bipolar Youth study youth, aged 12.6 ± 3.3 years. Monthly ratings of relationships (parents, siblings, and friends) and mood episode severity were assessed by the Adolescent Longitudinal Interval Follow-Up Evaluation (ALIFE) Psychosocial Functioning Schedule (PFS) and Psychiatric Rating Scales (PSR) on average every 8.2 months over 5.1 years. Correlations examined whether participants with increased episode severity also reported poorer relationships, and also examined whether fluctuations in episode severity predicted fluctuations in relationships, and vice versa. Results indicated that participants with greater mood episode severity also had worse relationships. Longitudinally, participants had largely stable relationships. To the extent that there were associations, changes in parental relationships may precede changes in episode severity, although the magnitude of this finding was small. Findings have implications for relationship interventions in BP youth. PMID:25668652

Severe rectal bleeding following PPH-stapler procedure for haemorroidal disease

PubMed Central

AMMENDOLA, M.; SAMMARCO, G.; CARPINO, A.; FERRARI, F.; VESCIO, G.; SACCO, R.

2014-01-01

PPH-stapler procedure for treatment of haemorrhoidal prolapse classified P4E4 is an important improvement, but may be followed by severe postoperative complications of which haemorrhage is one of the most serious early events. We report a case of double severe rectal bleeding following PPH-stapler procedure for haemorrhoidal disease classified P4E4 according to PATE 2000 (circumferential prolapse). A 48 years old female patient was presented to our attention. She was affected by haemorrhoidal prolapse P4E4, constipation and rectal bleeding. PPH-procedure is a technique for management of the haemorrhoidal disease. Postoperative complications may be serious and haemorrhage is the most important early complication. PMID:25644731

Menstruation and the Menopause Transition

PubMed Central

Harlow, Siobán D.; Paramsothy, Pangaja

2011-01-01

SYNOPSIS This paper characterizes changes in menstrual bleeding during perimenopause, including bleeding changes that represent markers of the menopausal transition. Recent results from the Study of Women’s Health Across the Nation (SWAN), a multiethnic cohort study of midlife women, as well as data from other cohort studies of women in the midlife are reviewed. Emerging data describing subpopulation differences in the transition experience is highlighted . Early transition, defined as a persistent difference in consecutive menstrual cycle length of seven or more days, begins on average 6-8 years before the FMP. Late transition, defined by an episode of 60 or more days of amenorrhea, begins on average two years before the FMP. When treating women in the midlife, clinicians should pay careful attention to medical factors, including both conditions and treatments, that may increase menstrual blood loss or alter menstrual cycle characteristics sufficiently to obscure the onset of the menopausal transition or the FMP. PMID:21961722

Long-lasting ovulation inhibition with a new injectable progestagen ORG-2154.

PubMed

Coutinho, E M; De Souza, J C; Barbosa, I C; Dourado Silva, V

1982-06-01

A new long-acting injectable progestagen was tested in 15 women who volunteered for the study. The occurrence of ovulation was assumed by the elevation of progesterone levels above 2ng/ml following a pre-ovulatory estradiol peak. Following a 200mg injection, ovulation was inhibited in all 15 women for five to ten months. In four subjects the interval between the injection and the first progesterone peak was five months. For eight, the interval was six to eight months. In the other three women, ovulation occurred more than eight months following injection. Bleeding episodes, similar to menstruation, occurred in most patients. Bleeding intervals lasting longer than 45 days occurred in nine subjects but more prolonged amenorrhea lasting longer than 60 days was reported by only five subjects. Blood chemistry which included blood cell counts, cholesterol, glucose, alkaline phosphatase, transaminases, urea nitrogen and creatinine remained within normal limits throughout the treatment.

New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control.

PubMed

Nelson, Anita

2010-08-09

To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women's desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors.

Antibiotic prophylaxis in cirrhosis: Good and bad.

PubMed

Fernández, Javier; Tandon, Puneeta; Mensa, Jose; Garcia-Tsao, Guadalupe

2016-06-01

Patients with cirrhosis, particularly those with decompensated cirrhosis, are at increased risk of bacterial infections that may further precipitate other liver decompensations including acute-on-chronic liver failure. Infections constitute the main cause of death in patients with advanced cirrhosis, and strategies to prevent them are essential. The main current strategy is the use of prophylactic antibiotics targeted at specific subpopulations at high risk of infection: prior episode of spontaneous bacterial peritonitis, upper gastrointestinal bleeding, and low-protein ascites with associated poor liver function. Antibiotic prophylaxis effectively prevents not only the development of bacterial infections in all these indications but also further decompensation (variceal bleeding, hepatorenal syndrome) and improves survival. However, antibiotic prophylaxis is also associated with a clinically relevant and increasing drawback, the development of infections due to multidrug-resistant organisms. Several strategies have been suggested to balance the risks and benefits of antibiotic prophylaxis. Antibiotic stewardship principles such as the restriction of antibiotic prophylaxis to subpopulations at a very high risk for infection, the avoidance of antibiotic overuse, and early deescalation policies are key to achieve this balance; nonantibiotic prophylactic measures such as probiotics, prokinetics, bile acids, statins, and hematopoietic growth factors could also contribute to ameliorate the development and spread of multidrug-resistant bacteria in cirrhosis. (Hepatology 2016;63:2019-2031). © 2015 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. government employees, and their contribution is in the public domain in the U.S.A.

In-patient international normalized ratio self-testing instruction after mechanical heart valve implantation.

PubMed

Thompson, Jess L; Sundt, Thoralf M; Sarano, Maurice E; Santrach, Paula J; Schaff, Hartzell V

2008-06-01

Patient self-testing of the international normalized ratio (INR) has been shown to improve management of anticoagulation with warfarin and reduce risks of thromboembolism and bleeding. Self-testing instruction usually begins several weeks after hospital discharge. We evaluated the feasibility of in-hospital INR self-testing instruction in patients recovering from valve replacement. We instituted an education program on a self-testing device before hospital discharge in 50 adult patients (median age, 54 years; 66% men) undergoing cardiac valve replacement with mechanical prostheses. Patients were monitored for 1 month to assess their ability to self-test and the accuracy of the INR measurements. Self-testing instruction began on postoperative day 4 (range, 1 to 8 days). Each patient had an average of 3.5 teaching sessions; each session lasted approximately 20 minutes. One month after discharge, all patients (98%) but 1 were able to self-test. No patient required interval instruction. One bleeding episode occurred in a patient whose INR exceeded the therapeutic range. Once warfarin doses were stabilized, 5 patients had subtherapeutic INR values on self-testing. The mean INR test result obtained from the coagulometer correlated well with values obtained by laboratory determination (r = 0.79). This evaluation of an in-hospital education program demonstrates that patients are able to learn INR self-testing and that most will continue to use the method without the need for interval instruction. Improved anticoagulation management by early introduction of INR self-testing should reduce thromboembolic and hemorrhagic complications after valve replacement.

Uses of chitosan for treating different forms of serious obstetrics hemorrhages.

PubMed

Carles, G; Dabiri, C; Mchirgui, A; Saoudi, E O; Hcini, N; Pouget, K; Seve, B; de Matteis, B

2017-11-01

Postpartum hemorrhage is a major cause of maternal death worldwide. Many therapeutic strategies have been developed to reduce maternal morbidity and mortality like oxytocin, prostaglandin, and uterine balloons. A new member of the therapeutic arsenal has recently emerged, the chitosan (Celox ® ), used since several years by military doctors to stop bleeding of combat wounds. In 2012, a first study was reported with the successful use of chitosan-coated gauze to treat severe postpartum hemorrhage. We report here four cases of the use of chitosan to treat life-threatening obstetric bleeding. In the first case, a pelvic packing with chitosan gauze after hemostatic hysterectomy with persistent bleeding. In the second case, the use of chitosan powder in a case of severe bleeding from multiple vaginal tears. In the third case, the use of chitosan gauze in uterine packing for postpartum hemorrhage by atonia. In the fourth case, the use of chitosan powder for stop bleeding during a hemorrhagic cesarean section. Postpartum hemorrhage of uterine origin resistant to treatment with prostaglandins can be treated with chitosan-coated gauze. This treatment requires no training and its costs are one fifth those of a Bakri ® intrauterine balloon. Using these two forms of chitosan, powder and gauze, we have a new therapeutic method at our disposal for dealing with the most serious cases of bleeding. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

Treatment tailoring for factor V deficient patients and perioperative management using global hemostatic coagulation assays.

PubMed

Levy-Mendelovich, Sarina; Barg, Assaf Arie; Rosenberg, Nurit; Avishai, Einat; Luboshitz, Jacob; Misgav, Mudi; Kenet, Gili; Livnat, Tami

2018-07-01

Congenital factor V deficiency (FVD) is a rare bleeding disorder with an estimated incidence of 1 in 1000,000 in the general population. Since the common coagulation tests do not correlate with the bleeding tendency there is an unmet need to predict FVD patients' bleeding hazard prior to surgical interventions. To optimize treatment prior to surgical interventions, using global coagulation assays, thrombin generation (TG) and rotating thromboelastogram (ROTEM). Our cohort included 5 patients with FVD, 4 severe and one mild. Two of them underwent TG and ROTEM prior to surgical interventions, including ex vivo spiking assays using bypass agents and platelets spiking. All five patients exhibited prolonged PT and PTT, non-dependent on their bleeding tendency. Patient 1, who demonstrated severe bleeding phenotype, underwent surgery treated by combination of APCC (FEIBA) and platelet transfusion. Therapy was guided by global tests (TG as well as ROTEM) results. During the pre and post-operative period neither excessive bleeding nor any thrombosis was noted. In contrast, TG and ROTEM analysis of patient 4 has lead us to perform the surgery without any blood products' support. Indeed, the patient did not encounter any bleeding. Global coagulation assays may be useful ancillary tools guiding treatment decisions in FVD patients undergoing surgical procedures. Copyright © 2018 Elsevier Inc. All rights reserved.

Serendipitous Discovery of Factor VII Deficiency and the Ensuing Dilemma.

PubMed

Umakanthan, Jayadev M; Dhakal, Prajwal; Gundabolu, Krishna; Koepsell, Scott A; Baljevic, Muhamed

2018-03-01

Congenital factor VII deficiency is a challenging disorder to manage, as it is associated with varied genotypes that do not clinically correlate with a bleeding phenotype. Individuals with severe factor VII deficiency (FVII: c <1%) might be asymptomatic, while patients with moderate deficiency (FVII: c level >5%) may experience severe hemorrhages. In modern medicine, due to extensive routine pre-operative laboratory testing, clinically asymptomatic patients without any bleeding history might be incidentally discovered, raising clinical dilemmas. Careful consideration of bleeding versus thrombosis risk has to be made in such cases, especially in the elderly. Clinical history of no prior bleeding complications may be a reassuring factor. Minimal required replacement dosing of recombinant activated factor VII can be given peri-operatively in such situations, with close monitoring.

Treatment options for severe pulmonary embolism during pregnancy and the postpartum period: a systematic review.

PubMed

Martillotti, G; Boehlen, F; Robert-Ebadi, H; Jastrow, N; Righini, M; Blondon, M

2017-10-01

Essentials The evidence on how to manage life-threatening pregnancy-related pulmonary embolism (PE) is scarce. We systematically reviewed all available cases of (sub)massive PE until December 2016. Thrombolysis in such severe PE was associated with a high maternal survival (94%). The major bleeding risk was much greater in the postpartum (58%) than antepartum period (18%). Background Massive pulmonary embolism (PE) during pregnancy or the postpartum period is a rare but dramatic event. Our aim was to systematically review the evidence to guide its management. Methods We searched Pubmed, Embase, conference proceedings and the RIETE registry for published cases of severe (submassive/massive) PE treated with thrombolysis, percutaneous or surgical thrombectomy and/or extracorporeal membrane oxygenation (ECMO), occurring during pregnancy or within 6 weeks of delivery. Main outcomes were maternal survival and major bleeding, premature delivery, and fetal survival and bleeding. Results We found 127 cases of severe PE (at least 83% massive; 23% with cardiac arrest) treated with at least one modality. Among 83 women with thrombolysis, survival was 94% (95% CI, 86-98). The risk of major bleeding was 17.5% during pregnancy and 58.3% in the postpartum period, mainly because of severe postpartum hemorrhages. Fetal deaths possibly related to PE or its treatment occurred in 12.0% of cases treated during pregnancy. Among 36 women with surgical thrombectomy, maternal survival and risk of major bleeding were 86.1% (95% CI, 71-95) and 20.0%, with fetal deaths possibly related to surgery in 20.0%. About half of severe postpartum PEs occurred within 24 h of delivery. Conclusions Published cases of thrombolysis for massive PE during pregnancy and the postpartum period suggest a high maternal and fetal survival (94% and 88%). In the postpartum period, given the high risk of major bleeding with thrombolysis, other therapeutic options (catheter [or surgical] thrombectomy, ECMO) may be considered if available. © 2017 International Society on Thrombosis and Haemostasis.

Antiplatelet and anticoagulant drugs for prevention of restenosis/reocclusion following peripheral endovascular treatment.

PubMed

Robertson, Lindsay; Ghouri, Maaz A; Kovacs, Flora

2012-08-15

Peripheral arterial disease (PAD) is frequently treated by balloon angioplasty. Restenosis/reocclusion of the dilated segments occurs often, depending on length of occlusion, lower leg outflow, stage of disease and presence of cardiovascular risk factors. To prevent reocclusion, patients are treated with antithrombotic agents. This is an update of a review first published in 2005. To determine whether any antithrombotic drug is more effective in preventing restenosis or reocclusion after peripheral endovascular treatment, compared to another antithrombotic drug, no treatment, placebo or other vasoactive drugs. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched 14 February 2012) and CENTRAL (2012, Issue 1). We selected randomised controlled trials (RCTs). Participants were patients with symptomatic PAD treated by endovascular revascularisation of the pelvic or femoropopliteal arteries. Interventions were anticoagulant, antiplatelet or other vasoactive drug therapy compared with no treatment, placebo or any other vasoactive drug. Clinical endpoints were reocclusion, restenosis, amputation, death, myocardial infarction, stroke, major bleeding and other side effects, such as minor bleeding, puncture site bleeding, gastrointestinal side effects and haematoma. We independently extracted and assessed details of the number of randomised patients, treatment, study design, patient characteristics and risk of bias. Analysis was based on intention-to-treat data. To examine the effects of outcomes such as reocclusion, restenosis, amputation and major bleeding, we computed odds ratios (OR) with 95% confidence intervals (CI) using a fixed-effect model. Twenty-two trials with a total of 3529 patients are included (14 in the original review and a further eight in this update). For the majority of comparisons, only one trial was available so results were rarely combined in meta-analyses. Individual trials were generally small and risk of bias was often unclear due to limitations in reporting. Three trials reported on drug versus placebo/control; results were consistently available for a maximum follow-up of only six months. At six months post intervention, a statistically significant reduction in reocclusion was found for high-dose acetylsalicylic acid (ASA) combined with dipyridamole (DIP) (OR 0.40, 95% CI 0.19 to 0.84), but not for low-dose ASA combined with DIP (OR 0.69, 95% CI 0.44 to 1.10; P = 0.12) nor in major amputations for lipo-ecraprost (OR 0.89, 95% CI 0.44 to 1.80). The remaining trials compared different drugs; results were more consistently available for a longer period of 12 months. At 12 months post intervention, no statistically significant difference in reocclusion/restenosis was detected for any of the following comparisons: high-dose ASA versus low-dose ASA (OR 0.98, 95% CI 0.64 to 1.48; P = 0.91), ASA/DIP versus vitamin K antagonists (VKA) (OR 0.65, 95% CI 0.40 to 1.06; P = 0.08), clopidogrel and aspirin versus low molecular weight heparin (LMWH) plus warfarin (OR 0.31, 95% CI 0.06 to 1.68; P = 0.18), suloctidil versus VKA: reocclusion (OR 0.59, 95% CI 0.20 to 1.76; P = 0.34), restenosis (OR 1.87, 95% CI 0.66 to 5.31; P = 0.24) and ticlopidine versus VKA (OR 0.71, 95% CI 0.37 to 1.36; P = 0.30). Treatment with cilostazol resulted in statistically significantly fewer reocclusions than ticlopidine (OR 0.32, 95% CI 0.13 to 0.76; P = 0.01). Compared with aspirin alone, LMWH plus aspirin significantly decreased occlusion/restenosis (by up to 85%) in patients with critical limb ischaemia (OR 0.15, 95% CI 0.06 to 0.42; P = 0.0003) but not in patients with intermittent claudication (OR 1.73, 95% CI 0.97 to 3.08; P = 0.06) and batroxobin plus aspirin reduced restenosis in diabetic patients (OR 0.28, 95% CI 0.13 to 0.60). Data on bleeding and other potential gastrointestinal side effects were not consistently reported, although there was some evidence that high-dose ASA increased gastrointestinal side effects compared with low-dose ASA, that clopidogrel and aspirin resulted in fewer major bleeding episodes compared with LMWH plus warfarin, and that abciximab resulted in more severe bleeding episodes. There is limited evidence suggesting that restenosis/reocclusion at six months following peripheral endovascular treatment is reduced by use of antiplatelet drugs compared with placebo/control, but associated information on bleeding and gastrointestinal side effects is lacking. There is also some evidence of variation in effect according to different drugs with cilostazol reducing reocclusion/restenosis at 12 months compared with ticlopidine and both LMWH and batroxobin combined with aspirin appearing beneficial compared with aspirin alone. However, available trials are generally small and of variable quality and side effects of drugs are not consistently addressed. Further good quality, large-scale RCTs, stratified by severity of disease, are required.

[Massive hemorrhage of upper gastrointestinal tract caused by gastrointestinal stromal tumor of the stomach--case report].

PubMed

Lalović, Nenad; Dukić Vladicić, Nikolina; Marić, Radmil; Cuk, Mirjana; Simatović, Milan; Jokanović, Dragana

2012-01-01

Acute bleeding from the upper gastrointestinal system is a medical emergency which is followed by high mortality rate, ranging from 6 to 15% in spite of modern diagnostic methods and treatment. Bleeding from the upper gastrointestinal system may be caused by gastrointestinal stromal tumors of the stomach, which are mainly characterized by occult bleeding, while profuse bleeding rarely occurs accompanied by hemorrhagic shock. Gastrointestinal stromal tumors of stomach are the most common mesenchimal tumors of the gastrointestinal tract. In our study we showed a 60-year-old female patient with profuse bleeding from the stomach and the clinical picture of severe hemorrhagic shock, caused by gastrointestinal stromal tumor. An ovoid junction, raised towards the lumen, covered with ulcerated mucosa in several places and followed by massive arterial bleeding was found intraoperatively, after the performed gastrotomy. Histopathological examination with immunohistochemical analysis confirmed that this was a gastrointestinal stromal tumor of the stomach. Acute bleeding from the digestive system is a sudden and serious condition of the body. Urgent esophagogastroduodenoscopy is a sensitive and specific diagnostic and therapeutic method of choice. Massive bleeding from the upper gastrointestinal tract is very rarely caused by gastrointestinal stromal tumors, whose clinical picture is very heterogeneous and depends on tumor size and location. Abundant bleeding from the tumor is an indication for urgent surgical intervention. According to the literature massive hemorrhage of the upper digestive system can rarely be caused by gastrointestinal stromal tumor of the stomach. It is shown that abundant hemorrhage of the upper digestive tract can be caused with gastric gastrointestinal stromal tumor. Surgical resection is the main form of treatment of gastrointestinal stromal tumors of the digestive system and bleeding from these tumors caused by failure of endoscopic hemostasis.

[A lymphoepithelioma-like type of spinous-cell carcinoma of the cervix uteri].

PubMed

Pires, M A; Andrade, M J; Guerra, C; Silva, T S; de Oliveira, C; Beja, M

1999-01-01

Lymphoepithelioma-like carcinomas of the cervix uteri are very rare. They are poorly differentiated squamous cell carcinomas with intense stromal lymphocytic infiltration. These histologic features are similar to nasopharyngeal lymphoepithelioma and may have a better prognosis than other tumors of the cervix. A lymphoepithelioma-like lesion of the cervix uteri is described in a 33-year-old Caucasian woman who had an episode of vaginal bleeding. A review of the literature about these types of tumor is also presented.

Contraceptive efficacy and safety of estradiol valerate/dienogest in a healthy female population: a multicenter, open-label, uncontrolled Phase III study.

PubMed

Yu, Qi; Huang, Zirong; Ren, Mulan; Chang, Qing; Zhang, Zhongqi; Parke, Susanne

2018-01-01

To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women. In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study. A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG. EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population. ClinicalTrials.gov identifier: NCT01638910.

Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System

PubMed Central

KULKARNI, R.; PRESLEY, R. J.; LUSHER, J. M.; SHAPIRO, A. D.; GILL, J. C.; MANCO-JOHNSON, M.; KOERPER, M. A.; ABSHIRE, T. C.; DIMICHELE, D.; HOOTS, W. K.; MATHEW, P.; NUGENT, D. J.; GERAGHTY, S.; EVATT, B. L.; SOUCIE, J. M.

2016-01-01

Aim To describe the prevalence and complications in babies ≤2 years with haemophilia. Methods We used a standardized collection tool to obtain consented data on eligible babies aged ≤2 years with haemophilia enrolled in the Centers for Disease Control and Prevention Universal Data Collection System surveillance project at US Hemophilia Treatment Centers (HTCs). Results Of 547 babies, 82% had haemophilia A, and 70% were diagnosed within one month of birth. Diagnosis was prompted by known maternal carrier status (40%), positive family history (23%), bleeding (35%) and unknown 2%; 81% bled during the first two years. The most common events were bleeding (circumcision, soft tissue, oral bleeding) and head injury. There were 46 episodes of intracranial haemorrhage (ICH) in 37 babies (7%): 18 spontaneous, 14 delivery related, 11 traumatic, 2 procedure related and 1 unknown cause. Of the 176 central venous access devices (CVADs) in 148 (27%) babies, there were 137 ports, 22 surgically inserted central catheters and 20 peripherally inserted central catheters. Ports had the lowest complication rates. Inhibitors occurred in 109 (20%) babies who experienced higher rates of ICH (14% vs. 5%; P = 0.002), CVAD placement (61% vs. 19%; P < 0.001) and CVAD complications (44% vs. 26%; P < 0.001). The most common replacement therapy was recombinant clotting factor concentrates. Conclusion Bleeding events in haemophilic babies ≤2 years were common; no detectable difference in the rates of ICH by the mode of delivery was noted. Neonatal factor exposure did not affect the inhibitor rates. Minor head trauma, soft tissue and oropharyngeal bleeding were the leading indications for treatment. PMID:27813214

Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

PubMed

Cooke, Esther J; Zhou, Jenny Y; Wyseure, Tine; Joshi, Shweta; Bhat, Vikas; Durden, Donald L; Mosnier, Laurent O; Drygalski, Annette von

2018-06-01

Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression. Schattauer GmbH Stuttgart.

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.

Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

PubMed

Price, Jeremy G; Stone, Nelson N; Stock, Richard G

2013-08-01

To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

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

Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G., E-mail: Richard.Stock@mountsinai.org

2013-08-01

Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, andmore » treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT.« less

Adenomyosis

MedlinePlus

... normally — thickening, breaking down and bleeding — during each menstrual cycle. An enlarged uterus and painful, heavy periods ... discomfort. However, adenomyosis can cause: Heavy or prolonged menstrual bleeding Severe cramping or sharp, knifelike pelvic pain ...

ERCP

MedlinePlus

... dye, or drug used during the procedure Bleeding Hole (perforation) of the bowel Inflammation of the pancreas ( ... or severe bloating Bleeding from the rectum or black stools Fever above 100°F (37.8°C) ...

Severe retroperitoneal and intra-abdominal bleeding after stapling procedure for prolapsed haemorrhoids (PPH); diagnosis, treatment and 6-year follow-up of the case.

PubMed

Safadi, Wajdi; Altshuler, Alexander; Kiv, Sakal; Waksman, Igor

2014-10-30

Procedure for prolapsed haemorrhoids (PPH) is a popular treatment of haemorrhoids. PPH has the advantages of a shorter operation time, minor degree of postoperative pain, shorter hospital stay and quicker recovery but may be followed by several postoperative complications. Rectal bleeding, acute pain, chronic pain, rectovaginal fistula, complete rectal obliteration, rectal stenosis, rectal pocket, tenesmus, faecal urgency, faecal incontinence, rectal perforation, pelvic sepsis and rectal haematoma have all been reported as postoperative complications of PPH. Additionally, one rare complication of the procedure is intra-abdominal bleeding. There are a few case reports describing intra-abdominal bleeding after the procedure. We report a case of a 26-year-old man who developed severe intra-abdominal and retroperitoneal haemorrhage after PPH. The diagnosis was made on the second postoperative day by CT of the abdomen and pelvis. The patient was treated conservatively and had an uneventful recovery. 2014 BMJ Publishing Group Ltd.

Postoperative Chylothorax of Unclear Etiology in a Patient with Right-sided Subclavian Central Venous Catheter Placement

PubMed Central

Asghar, Samie; Shamim, Faisal

2017-01-01

A young male underwent decompressive craniotomy for an intracerebral bleed. A right-sided subclavian central venous catheter was placed in the operating room after induction of anesthesia. Postoperatively, he was shifted to Intensive Care Unit (ICU) for mechanical ventilation due to low Glasgow coma scale. He had an episode of severe agitation and straining on the tracheal tube in the evening same day. On the 2nd postoperative day in ICU, his airway pressures were high, and chest X-ray revealed massive pleural effusion on right side. Under ultrasound guidance, 1400 milky white fluid was aspirated. It was sent for analysis (triglycerides) that confirmed chyle and hence, chylothorax was made as diagnosis. A duplex scan was done which ruled out thrombosis in subclavian vein. The catheter had normal pressure tracing with free aspiration of blood from all ports. Enteral feeding was continued as it is a controversial matter in the literature and he was monitored clinically and radiologically. PMID:29284881

Postoperative Chylothorax of Unclear Etiology in a Patient with Right-sided Subclavian Central Venous Catheter Placement.

PubMed

Asghar, Samie; Shamim, Faisal

2017-01-01

A young male underwent decompressive craniotomy for an intracerebral bleed. A right-sided subclavian central venous catheter was placed in the operating room after induction of anesthesia. Postoperatively, he was shifted to Intensive Care Unit (ICU) for mechanical ventilation due to low Glasgow coma scale. He had an episode of severe agitation and straining on the tracheal tube in the evening same day. On the 2 nd postoperative day in ICU, his airway pressures were high, and chest X-ray revealed massive pleural effusion on right side. Under ultrasound guidance, 1400 milky white fluid was aspirated. It was sent for analysis (triglycerides) that confirmed chyle and hence, chylothorax was made as diagnosis. A duplex scan was done which ruled out thrombosis in subclavian vein. The catheter had normal pressure tracing with free aspiration of blood from all ports. Enteral feeding was continued as it is a controversial matter in the literature and he was monitored clinically and radiologically.

Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate.

PubMed

Abdel-Aziz, Mahmoud I; Ali, Mostafa A Sayed; Hassan, Ayman K M; Elfaham, Tahani H

2016-01-01

The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications. © 2015, The American College of Clinical Pharmacology.

Temporal relations in hormone-withdrawal migraines and impact on prevention- a diary-based pilot study in combined hormonal contraceptive users.

PubMed

Merki-Feld, Gabriele S; Epple, Gina; Caveng, Nina; Imthurn, Bruno; Seifert, Burkhardt; Sandor, Peter; Gantenbein, Andreas R

2017-08-25

Menstrually related migraine (MRM) in the hormone-free interval (HFI) of combined hormonal contraceptives (CHC) are according to the ICHD definition also estrogen withdrawal migraines (EWH). MRMs are less responsive to acute medication. Therefore short-term prevention, initiated 1-2 days before onset of the anticipated bleeding and continued for 6 days, is recommended. Such a long prophylactic triptan use might increase the risk for medication overuse headache in women suffering in addition from non-menstrual migraines. In CHC users onset of hormone decline is predictable. It is however unknown, whether the EWHs are rather associated with onset of hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention. For this observational diary-based pilot study we collected data from daily conducted headache diaries of CHC users with MRM in at least two of three cycles, visiting our clinic from 2009 to 2015. We analyzed frequency of migraines for each hormone free day, onset of migraine, onset of bleeding and the relation of migraine to onset of bleeding in the 7-day period following estrogen withdrawal. We identified in addition the onset of migraine attacks lasting more than 1 day (episodes). Forty patient charts met the inclusion criteria, what allowed us to analyze 103 cycles. The mean number of migraine days in the HFI was 2.2 ± 1.6. Migraine started typically on days 1-5 and bleeding on days 3-5. In relation to first day of bleeding, migraines started on days -1 to 4. Almost half of the migraine attacks lasted longer than 24 h, despite the use of rescue medication. MRM in CHC users starts on bleeding days -1 to 4, what differs from findings in the natural cycle. Referring to the HFI interval migraine started mostly on days 1-5. According to these data, it seems to be reasonable to initiate short-term prevention at the last day of pill use or the first day of the HFI and continue for 5 days.

Measurement of utility values in the UK for health states related to immune thrombocytopenic purpura.

PubMed

Szende, Agota; Brazier, John; Schaefer, Caroline; Deuson, Robert; Isitt, John J; Vyas, Paresh

2010-08-01

To measure utility values associated with immune (idiopathic) thrombocytopenic purpura (ITP), as perceived by the United Kingdom (UK) general public. A multi-step process, including clinical trial data, literature review, and patient focus group, was used to develop ITP health states valued in a web survey. Six ITP health states were defined based on platelet levels, risk of bleeding and key adverse events/disease complications. Clinical trial data on bleeding and ITP-specific quality of life data were key sources for developing health-state descriptions. 359 respondents, randomly selected from a managed web panel in the UK, completed the web-based Time Trade-Off survey. Wilcoxon signed-rank test was used to compare differences between each pair of health states. Sample characteristics (mean age: 47.9 +/- 16.9 years; 54% female) were comparable to the UK general population. ITP health states were valued as significantly worse than perfect health. Experiencing bleeding episodes was a more important driver than low platelet levels in valuing a health state to be worse. Substantial disutilities were associated with surviving an intracranial haemorrhage. Mean (SD) utility values for each ITP health state are: HS1: platelets >or=50 x 10(9)/L, no outpatient bleed: 0.863 +/- 0.15; HS2: platelets >or=50 x 10(9)/L, outpatient bleed: 0.734 +/- 0.19; HS3: platelets <50 x 10(9)/L, no outpatient bleed: 0.841 +/- 0.19; HS4: platelets <50 x 10(9)/L, outpatient bleed: 0.732 +/- 0.19; HS5: intracranial haemorrhage (2-6 months): 0.038 +/- 0.46; HS6: steroid treatment adverse events: 0.758 +/- 0.20. Potential limitations relate to web user population characteristics and lack of comparative testing of web-based TTO methods. Results provide evidence that the UK general population associate substantial loss of value living with ITP, suggesting an important role for new ITP treatments. Utility values based on these health states may be useful in future cost-effectiveness studies of existing and/or new ITP treatments.

Contraceptive efficacy and tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study.

PubMed

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-04-01

The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexible(MIB)) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen. This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18-35 years) to the following regimens: flexible(MIB) (24-120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexible(MIB) only). Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexible(MIB) vs the conventional regimen [41.0±29.1 (95% CI 38.8-43.3) vs 65.8±27.0 (95% CI 62.2-69.4) days, p<0.0001; treatment difference -24.8 (95% CI -29.2 to -20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9-67.9) days. The Pearl Index for the flexible(MIB) regimen was 0.64 (95% CI 0.28-1.26). All regimens had comparable tolerability profiles. EE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexible(MIB) also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexible(MIB) regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding.

Role of platelet transfusion in children with bleeding in dengue fever.

PubMed

Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

2015-12-01

The indications for platelet transfusion in dengue fever are clearly defined in World Health Organization (WHO) guidelines (2011) for dengue fever, but physicians face practical difficulty in its implementation in an epidemic setting. On one hand there is an intense social pressure created by the panic-struck parents to transfuse platelets in presence of bleeding and on the other hand there is a need for its judicious use as the requirement is more than its availability. The study was aimed to assess the clinico-hematological parameters, and the requirement and need for platelet transfusion in children with dengue fever. All children (0-12 yr of age) diagnosed and confirmed with dengue fever at a tertiary care hospital in Puducherry between 1 August 2012 and 31 January 2015 were reviewed retrospectively from hospital case records as per the revised WHO guidelines for dengue fever. The diagnosis was confirmed by NS1 antigen- based ELISA test or dengue serology for IgM and IgG antibodies and the data were analyzed using SPSS 16.0 statistical software. Out of 261 cases of dengue fever, hemorrhagic manifestations were observed in 52 children (19.9%), which mainly included petechiae (38.5%), gum bleeding (34.6%) and melena (26.9%). Thrombocytopenia was seen in 211 (80.8%) cases. Bleeding manifestations were present in 20(39.2%), 8(15.7%), 13(25.5%) and 11(21.6%) cases with platelet count <50,000/mm3, 50,000-100,000/mm3, 1-1.50,000/mm3, and >1.50,000/mm3 respectively. Bleeding manifestations did not always correlate with platelet count in non-severe dengue infection in comparison to severe dengue infection. The most common mode of presentation of severe dengue infection was shock with 102(39.1%) cases and among them only 22 children (21.6%) had bleeding. About 17 children (6.5%) with severe dengue infection required platelet transfusion and out of them, 12 children (70.6%) had a platelet count <20,000/ mm3 whereas five children (29.4%) had platelet count in the range of 20,000-50,000/mm3. Platelet transfusion was required in children with severe dengue infection in the form of significant spontaneous bleed, shock and severe thrombocytopenia. Bleeding should not be considered only indicator to transfuse platelets as it occurred in children even with normal platelet counts. The community and treating physicians should be educated regarding the judicious transfusion of platelets. Unnecessary and empirical use of platelets should be completely avoided especially during an epidemic when there is scarcity in its availability.

Combined variants in factor VIII and prostaglandin synthase-1 amplify hemorrhage severity across three generations of descendants.

PubMed

Nance, D; Campbell, R A; Rowley, J W; Downie, J M; Jorde, L B; Kahr, W H; Mereby, S A; Tolley, N D; Zimmerman, G A; Weyrich, A S; Rondina, M T

2016-11-01

Essentials Co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. We determined pathogenic variants in a three-generational pedigree with excessive bleeding. Bleeding occurred with concurrent variants in prostaglandin synthase-1 (PTGS-1) and factor VIII. The PTGS-1 variant was associated with functional defects in the arachidonic acid pathway. Background Inherited human variants that concurrently cause disorders of primary hemostasis and coagulation are uncommon. Nevertheless, rare cases of co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. Objective We prospectively sought to determine pathogenic variants in a three-generational pedigree with excessive bleeding. Patients/methods Platelet number, size and light transmission aggregometry to multiple agonists were evaluated in pedigree members. Transmission electron microscopy determined platelet morphology and granule content. Thromboxane release studies and light transmission aggregometry in the presence or absence of prostaglandin G 2 assessed specific functional defects in the arachidonic acid pathway. Whole exome sequencing (WES) and targeted nucleotide sequence analysis identified potentially deleterious variants. Results Pedigree members with excessive bleeding had impaired platelet aggregation with arachidonic acid, epinephrine and low-dose ADP, as well as reduced platelet thromboxane B 2 release. Impaired platelet aggregation in response to 2MesADP was rescued with prostaglandin G 2 , a prostaglandin intermediate downstream of prostaglandin synthase-1 (PTGS-1) that aids in the production of thromboxane. WES identified a non-synonymous variant in the signal peptide of PTGS-1 (rs3842787; c.50C>T; p.Pro17Leu) that completely co-segregated with disease phenotype. A variant in the F8 gene causing hemophilia A (rs28935203; c.5096A>T; p.Y1699F) was also identified. Individuals with both variants had more severe bleeding manifestations than characteristic of mild hemophilia A alone. Conclusion We provide the first report of co-existing variants in both F8 and PTGS-1 genes in a three-generation pedigree. The PTGS-1 variant was associated with specific functional defects in the arachidonic acid pathway and more severe hemorrhage. © 2016 International Society on Thrombosis and Haemostasis.

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

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.

Long-term tolerability, immunogenicity and efficacy of Nuwiq® (human-cl rhFVIII) in children with severe haemophilia A.

PubMed

Klukowska, A; Szczepański, T; Vdovin, V; Knaub, S; Bichler, J; Jansen, M; Dzhunova, I; Liesner, R J

2018-03-26

Nuwiq ® (human-cl rhFVIII, simoctocog alfa) is a 4th generation recombinant human FVIII, without chemical modification or fusion with any other protein, produced in a human cell line. This study (GENA-13) was an extension of the GENA-03 study in which previously treated children aged 2-12 years with severe haemophilia A received Nuwiq ® prophylaxis for ≥6 months. GENA-13 examined long-term tolerability, immunogenicity and efficacy of Nuwiq ® prophylaxis in children. Of 59 patients enrolled in GENA-03, 49 continued Nuwiq ® prophylaxis in GENA-13 for a median (range) of 30.0 (9.5-52.0) months. No patient withdrew due to drug-related adverse events or developed inhibitors. Only 2 of 20 518 infusions were associated with possibly related adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR) was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for all bleeds. Younger children (2-5 years) had lower ABRs than children aged 6-12 years. Annualized bleeding rates were reduced in GENA-13 vs GENA-03, especially for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 [95% CI: 0.11, 0.74]). Nuwiq ® efficacy was rated as excellent/good in the treatment of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq ® was rated as excellent for all 17 assessed procedures. Long-term treatment with Nuwiq ® for the prevention of bleeds in children with severe haemophilia A was well tolerated, effective and reduced spontaneous bleeding by up to 70% compared with GENA-03. © 2018 The Authors. Haemophilia published by John Wiley & Sons Ltd.

One hundred and one over-the-scope-clip applications for severe gastrointestinal bleeding, leaks and fistulas.

PubMed

Wedi, Edris; Gonzalez, Susana; Menke, Detlev; Kruse, Elena; Matthes, Kai; Hochberger, Juergen

2016-02-07

To investigate the efficacy and clinical outcome of patients treated with an over-the-scope-clip (OTSC) system for severe gastrointestinal hemorrhage, perforations and fistulas. From 02-2009 to 10-2012, 84 patients were treated with 101 OTSC clips. 41 patients (48.8%) presented with severe upper-gastrointestinal (GI) bleeding, 3 (3.6%) patients with lower-GI bleeding, 7 patients (8.3%) underwent perforation closure, 18 patients (21.4%) had prevention of secondary perforation, 12 patients (14.3%) had control of secondary bleeding after endoscopic mucosal resection or endoscopic submucosal dissection (ESD) and 3 patients (3.6%) had an intervention on a chronic fistula. In 78/84 patients (92.8%), primary treatment with the OTSC was technically successful. Clinical primary success was achieved in 75/84 patients (89.28%). The overall mortality in the study patients was 11/84 (13.1%) and was seen in patients with life-threatening upper GI hemorrhage. There was no mortality in any other treatment group. In detail OTSC application lead to a clinical success in 35/41 (85.36%) patients with upper GI bleeding and in 3/3 patients with lower GI bleeding. Technical success of perforation closure was 100% while clinical success was seen in 4/7 cases (57.14%) due to attendant circumstances unrelated to the OTSC. Technical and clinic success was achieved in 18/18 (100%) patients for the prevention of bleeding or perforation after endoscopic mucosal resection and ESD and in 3/3 cases of fistula closure. Two application-related complications were seen (2%). This largest single center experience published so far confirms the value of the OTSC for GI emergencies and complications. Further clinical experience will help to identify optimal indications for its targeted and prophylactic use.

Endoscopic Obliteration for Bleeding Peptic Ulcer

PubMed Central

Zawadzki, J.J. J.; Gajda, A.G. G.; Kamiński, P. Ł.; Lembas, L.; Bielecki, K.

1997-01-01

A group of 133 patients treated for bleeding peptic ulcer in our Department, is reviewed. Within several hours of admission, all patients underwent upper gastrointestinal tract gastroscopy and obliteration of the bleeding ulcer. Bleeding gastric ulcers were found in 41 patients, and duodenal ulcers in 92 patients. Patients were classified according to the Forrest scale: IA – 11 patients, IB – 49 patients, IIA – 35 patients, lIB – 40 patients. In 126 (94.7%) patients the bleeding was stopped, and 7 required urgent surgery: 3 patients with gastric ulcer underwent gastrectomy, and 4 with duodenal ulcer – truncal vagotomy with pyloroplasty and had the bleeding site underpinned. Fifty-five patients underwent elective surgery: gastrectomy and vagotomy (18 patients with gastric ulcer), highly selective vagotomy (25 patients with duodenal ulcer) and truncal vagotomy and pyloroplasty (12 patients with duodenal ulcer). None of the patients was observed to have recurrent bleeding. PMID:18493453

Abnormal excessive per vagina (PV) bleeding on Esmya–selective progesterone receptor modulator (SPRM) in a symptomatic patient with uterine fibroid

PubMed Central

Matytsina-Quinlan, Lyubov; Matytsina, Laura

2015-01-01

A woman in her late 40s presented with excessive per vagina (PV) bleeding and uterine fibroid. She reported excessive PV bleeding after starting Esmya; she was brought in by ambulance to the emergency department with profuse bleeding. Abnormal uterine bleeding (AUB) developed after selective progesterone receptor modulator (SPRM) administration in this symptomatic patient with uterine fibroid. The drug was withheld and surgical treatment considered. Progressive deterioration of PV bleeding after receiving SPRM led to an urgent laparoscopic total hysterectomy, which had to be postponed due to severe anaemia. Surgery took place regardless because the excessive bleeding continued. Histology revealed a 6 cm submucosal uterine fibroid (SMUF) and adenomyosis. Physicians prescribing SPRMs to stop PV bleeding should be aware of potential AUB, which could lead to urgent hysterectomy. The mechanism of action of SPRMs is not clearly understood. Awareness of the side effects of Esmya, such as AUB, must be kept in mind when administering SPRMs. PMID:25976198

Abnormal excessive per vagina (PV) bleeding on Esmya-selective progesterone receptor modulator (SPRM) in a symptomatic patient with uterine fibroid.

PubMed

Matytsina-Quinlan, Lyubov; Matytsina, Laura

2015-05-14

A woman in her late 40s presented with excessive per vagina (PV) bleeding and uterine fibroid. She reported excessive PV bleeding after starting Esmya; she was brought in by ambulance to the emergency department with profuse bleeding. Abnormal uterine bleeding (AUB) developed after selective progesterone receptor modulator (SPRM) administration in this symptomatic patient with uterine fibroid. The drug was withheld and surgical treatment considered. Progressive deterioration of PV bleeding after receiving SPRM led to an urgent laparoscopic total hysterectomy, which had to be postponed due to severe anaemia. Surgery took place regardless because the excessive bleeding continued. Histology revealed a 6 cm submucosal uterine fibroid (SMUF) and adenomyosis. Physicians prescribing SPRMs to stop PV bleeding should be aware of potential AUB, which could lead to urgent hysterectomy. The mechanism of action of SPRMs is not clearly understood. Awareness of the side effects of Esmya, such as AUB, must be kept in mind when administering SPRMs. 2015 BMJ Publishing Group Ltd.

Protein C deficiency related obscure gastrointestinal bleeding treated by enteroscopy and anticoagulant therapy.

PubMed

Hsu, Wei-Fan; Tsang, Yuk-Ming; Teng, Chung-Jen; Chung, Chen-Shuan

2015-01-21

Obscure gastrointestinal bleeding is an uncommonly encountered and difficult-to-treat clinical problem in gastroenterology, but advancements in endoscopic and radiologic imaging modalities allow for greater accuracy in diagnosing obscure gastrointestinal bleeding. Ectopic varices account for less than 5% of all variceal bleeding cases, and jejunal variceal bleeding due to extrahepatic portal hypertension is rare. We present a 47-year-old man suffering from obscure gastrointestinal bleeding. Computed tomography of the abdomen revealed multiple vascular tufts around the proximal jejunum but no evidence of cirrhosis, and a visible hypodense filling defect suggestive of thrombus was visible in the superior mesenteric vein. Enteroscopy revealed several serpiginous varices in the proximal jejunum. Serologic data disclosed protein C deficiency (33.6%). The patient was successfully treated by therapeutic balloon-assisted enteroscopy and long-term anticoagulant therapy, which is normally contraindicated in patients with gastrointestinal bleeding. Diagnostic modalities for obscure gastrointestinal bleeding, such as capsule endoscopy, computed tomography enterography, magnetic resonance enterography, and enteroscopy, were also reviewed in this article.

A successful treatment of life-threatening bleeding from polycystic kidneys with antifibrinolytic agent tranexamic acid.

PubMed

Vujkovac, Bojan; Sabovic, Miso

2006-10-01

We describe a successful treatment of a severe, persistent bleeding from both kidneys in a patient with autosomal dominant polycystic kidney disease (ADPKD) with tranexamic acid (TXA), a potent antifibrinolytic agent. The bleeding could not be controlled by intensive conservative treatment, it became life-threatening and urgent bilateral nephrectomy was intended. Since local and systemic hyperfibrinolysis play a role in bleeding in ADPKD patients, we tried TXA treatment. In fact, the massive bleeding promptly stopped, and haematuria gradually ceased. Removal of both kidneys was prevented. After 5 days both ureters became obstructed by blood clots, but placing J-catheters in each pyelon successfully solved this complication. Our case shows that it is reasonable to try antifibrinolytic treatment with TXA in such devastating uncontrolled bleeding.

Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.

PubMed

Hsieh, J-T; Klein, K; Batstone, M

2017-09-01

Dental extractions challenge the body's haemostatic mechanism. Postoperative bleeding from dental extraction can be prolonged, or even life threatening in patients with inherited bleeding disorders. Pre- and postoperative clotting factor replacements or systemic desmopressin (ddAVP) have been advocated at our institution to prevent bleeding complications in these patients. This study aimed to assess the postoperative bleeding rate in patients with inherited bleeding disorders that underwent dental extractions at our institution between 2003 and 2012. Patients with inherited bleeding disorders such as haemophilia A, haemophilia B, and von Willebrand's disease were included. Retrospective chart review was conducted. The result showed 53 extraction events occurred in 45 patients over the 10-year period. Ten out of 53 extraction events (18.9%) had postoperative bleeding requiring further factor replacement or ddAVP. Postoperative bleeding in one patient with mild haemophilia A was complicated by the development of inhibitors. Type and severity of bleeding disorder, bone removal, and use of a local haemostatic agent did not have any significant effect on postoperative bleeding. Despite the use of perioperative factors and desmopressin, the postoperative bleeding rates remain high for patients with inherited bleeding disorders. More studies are required to assess the safety and effectiveness of using local haemostatic control to achieve haemostasis following extractions. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

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

More complications in patients with septic shock treated with dextran compared with crystalloids.

PubMed

Rasmussen, Anders Mølgaard; Jakobsen, Rasmus; Strøm, Thomas; Carlsson, Marcela; Dahler-Eriksen, Bjarne; Toft, Palle

2015-02-01

In recent years, the safety-profile of synthetic colloids has been questioned. The purpose of the present study was to elucidate the safety-profile of the colloid dextran-70 in relation to acute kidney injury (AKI) and death. We conducted a retrospective, observational study of patients admitted to our intensive care unit with septic shock and treated with dextran-70 in the period from 1 January 2009 to 31 December 2009. The controls were included from 1 March 2012 to 28 February 2013 when dextran-70 was replaced with crystalloids. There were 91 patients in the dextran group and 150 patients in the non-dextran group. The urinary output was 17.93 ml/kg/24 h in the dextran group and 27.87 in the non-dextran group (p < 0.05). Continuous renal replacement therapy (CRRT) was used in 48% in the dextran group and in 23% in the non-dextran group (p < 0.05). Major bleeding episodes occurred in 32% in the dextran group compared with 15% in the control group (p < 0.05). The 90-day mortality was 42% in the dextran group and 35% in the non-dextran group (p = 0.08). Patients in the dextran group had significantly more bleeding episodes, a higher need for CRRT and a lower urinary output than patients in the non-dextran group. Due to study design, it cannot be concluded that the use of dextran-70 is causally related to the development of AKI.

Comparative study of vaginal danazol vs diphereline (a synthetic GnRH agonist) in the control of bleeding during hysteroscopic myomectomy in women with abnormal uterine bleeding: a randomized controlled clinical trial.

PubMed

Sayyah-Melli, M; Bidadi, S; Taghavi, S; Ouladsahebmadarek, E; Jafari-Shobeiri, M; Ghojazadeh, M; Rahmani, V

2016-01-01

To compare the usefulness of vaginal danazol and diphereline in the management of intra-operative bleeding during hysteroscopy. Randomized controlled clinical trial. University hospital. One hundred and ninety participants of reproductive age were enrolled for operative hysteroscopy. Thirty women were excluded from the study. One hundred and sixty participants with submucous myomas were allocated at random to receive either vaginal danazol (200mg BID, 30 days before surgery) or intramuscular diphereline (twice with a 28-day interval). Severity of intra-operative bleeding, clarity of the visual field, volume of media, operative time, success rate for completion of operation and postoperative complications. Overall, 145 patients completed the study. In the danazol group, 78.1% of patients experienced no intra-operative uterine bleeding, and 21.9% experienced mild bleeding. In the diphereline group, 19.4% of patients experienced no intra-operative uterine bleeding, but mild, moderate and severe bleeding was observed in 31.9%, 45.8% and 2.8% of patients, respectively. The difference between the groups was significant (p<0.001). A clear visual field was reported more frequently in the danazol group compared with the diphereline group (98.6% vs 29.2%, p<0.001). The mean operative time was 10.9 min and 10.6 min in the danazol and diphereline groups, respectively (p=0.79). The mean volume of infused media was 2.0L in both groups (p=0.99). The success rate was 100% for both groups with no intra-operative complications. Both vaginal danazol and diphereline were effective in controlling uterine bleeding during operative hysteroscopy. However, vaginal danazol provided a clearer visual field. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy of standard prophylaxis versus on-demand treatment with bayer's sucrose-formulated recombinant FVIII (rFVIII-FS) in Chinese children with severe hemophilia A.

PubMed

Zhao, Yongqiang; Xiao, Juan; Yang, Renchi; Wu, Runhui; Hu, Yu; Beckmann, Horst; Wu, Junde; Hou, Qingsong; Sun, Jing

2017-04-01

In China, care of patients with severe hemophilia primarily involves insufficient dosing of on-demand treatment and secondary low-dose prophylaxis (10 IU/kg 2× /wk). We sought to evaluate 3× /wk, standard-dose prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS; Bayer) compared with on-demand treatment in Chinese children with severe hemophilia A. Children and adolescents aged 2-16 years with severe hemophilia A, no inhibitors, and no prophylaxis for >6 consecutive months before study entry were eligible for this 24-week, interventional, sequential-treatment study. Patients received rFVIII-FS on demand for 12 weeks followed by a 12-week prophylaxis period (25 IU/kg 3× /wk). The primary efficacy endpoint was comparison of the annualized bleeding rate (ABR) of all bleeds in the prophylaxis versus on-demand phase. Additional variables included ABR of joint bleeds, school attendance/activity, daily activity, and hemophilia Joint Health Score (HJHS). Thirty patients (median age, 12 years) were treated and analyzed. Compared with on-demand treatment, prophylaxis reduced median (quartile [Q1; Q3]) ABR of all bleeds (57.5 [44.5; 73.9] vs 0 [0; 4.0]) and joint bleeds (34.5 [26.1; 56.5] vs 0 [0; 4.0]). Median (range) total HJHS improved after both the prophylaxis and on-demand phases (8.0 [0-48.0] and 11.0 [0-55.0], respectively) compared with baseline (16.0 [0-56.0]). School attendance/activity and daily activity improved with prophylaxis versus on demand. No inhibitors or treatment-related adverse events were reported. In this first prospective, standard-dose, secondary prophylaxis study in China, rFVIII-FS prophylaxis reduced bleeding and improved health outcomes versus on-demand treatment in children with severe hemophilia A.

The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia.

PubMed

Shamberger, R C; Weinstein, H J; Delorey, M J; Levey, R H

1986-02-01

The treatment of acute leukemia in childhood has been increasingly successful. Infectious complications are the major cause of morbidity and mortality among these patients receiving aggressive chemotherapy. In particular, neutropenic enterocolitis or typhlitis has had a reported mortality of 50% to 100%. The authors reviewed a series of 77 previously untreated patients with acute myelogenous leukemia begun on treatment from March 1976 to June 1984 to better define the characteristics of typhlitis and its optimum management. Twenty-five patients had episodes of typhlitis, characterized by fever, abdominal pain, and tenderness, occurring during periods of neutropenia. Ten of these patients had watery diarrhea as a major additional symptom, and nine patients had a significant episode of gastrointestinal bleeding. In seven instances, blood culture results were positive, all for intestinal flora. The episodes of typhlitis occurred most frequently during the induction therapy (19 patients). Five patients experienced typhlitis during maintenance therapy, and one patient had acute appendicitis. Two patients had typhlitis during their reinduction therapy, and of note, one had had abdominal symptoms during her initial induction. All patients were treated initially with broad-spectrum antibiotics and bowel rest. Four criteria have been used for surgical intervention: (1) persistent gastrointestinal bleeding after resolution of neutropenia and thrombocytopenia and correction of clotting abnormalities; (2) evidence of free intraperitoneal perforation; (3) clinical deterioration requiring support with vasopressors, or large volumes of fluid, suggesting uncontrolled sepsis; and (4) development of symptoms of an intra-abdominal process, in the absence of neutropenia, which would normally require surgery. Using these criteria, five patients required surgical intervention for typhlitis or its sequelae and one for acute appendicitis. There was one perioperative death resulting from miliary tuberculosis. Among the 21 patients managed medically, there was 1 death resulting from typhlitis in a patient in whom surgery was deferred because of her multiple failures to enter remission.

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

PubMed

Parks, Anna L; Fang, Margaret C

2017-07-01

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[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.

Periprocedural Management of Non-Vitamin K Oral Anticoagulants in Chronic Kidney Disease: A Review of Existing Heterogeneity and Contemporary Evidence.

PubMed

Gunasekaran, Prasad; Parashara, Deepak K

2015-12-01

Non vitamin-K oral anticoagulants (NOAC) have considerably enhanced anticoagulation practice for non-valvular atrial fibrillation with specific advantages of fixed dosing, non-fluctuant therapeutic levels and obviation of therapeutic level monitoring. NOAC pharmacology is remarkable for considerable renal excretion. Heterogeneity in the precise time cut-offs for discontinuation of NOACs prior to elective surgical or percutaneous procedures arise from the non-linear variations of drug excretion with different levels of creatinine clearances as in chronic kidney disease. Multiple authors have suggested cut-offs leading to ambiguity among practicing clinicians. Recent data pertaining to systemic thromboembolism, stroke and major bleeding derived from randomized controlled clinical trials have simplified the periprocedural management of NOACs. This review focusses on heterogeneity in the management of NOACs in patients with CKD in this peculiar scenario and highlights the contemporary evidence to support a unified approach towards perioperative management of NOACs. Multiple antidotes targeted towards binding of specific NOACs have been developed and are in the testing phase, thereby offering immense potential for rapid and complete reversal of NOAC activity in emergent procedures and major bleeding episodes. Targeted research on thromboembolism, stroke and major bleeding following temporary periprocedural interruption of NOACs using multicentric registries could further expand the clinical utility of these agents.

Gastric heterotopia of rectum in a child: a mimicker of solitary rectal ulcer syndrome.

PubMed

Al-Hussaini, Abdulrahman; Lone, Khurram; Al-Sofyani, Medhat; El Bagir, Asim

2014-01-01

Bleeding per rectum is an uncommon presentation in pediatric patients. Heterotopic gastric mucosa in the rectum is a rare cause of rectal bleeding. Here, we report a 3-year-old child with a bleeding rectal ulcer that was initially diagnosed and managed as a solitary rectal ulcer syndrome. After 1 month, the patient persisted to have intermittent rectal bleed and severe anal pain. Repeat colonoscopy showed the worsening of the rectal ulcer in size. Pediatric surgeon excised the ulcer, and histopathological examination revealed a gastric fundic-type mucosa consistent with the diagnosis of gastric heterotopia of the rectum. Over the following 18 months, our patient had experienced no rectal bleeding and remained entirely asymptomatic. In conclusion, heterotopic gastric mucosa of the rectum should be considered in the differential diagnosis of a bleeding rectal ulcer.

Endovascular treatment of a bleeding secondary aorto-enteric fistula. A case report with 1-year follow-up.

PubMed

Brountzos, Elias N; Vasdekis, Spyros; Kostopanagiotou, Georgia; Danias, Nikolaos; Alexopoulou, Efthymia; Petropoulou, Konstantina; Gouliamos, Athanasios; Perros, Georgios

2007-01-01

We report a patient with life-threatening gastrointestinal bleeding caused by a secondary aorto-enteric fistula. Because the patient had several comorbid conditions, we succesfully stopped the bleeding by endovascular placement of a bifurcated aortic stent-graft. The patient developed periaortic infection 4 months later, but he was managed with antibiotics. The patient is well 1 year after the procedure.

Clinical Outcomes of the Marginal Ulcer Bleeding after Gastrectomy: As Compared to the Peptic Ulcer Bleeding with Nonoperated Stomach

PubMed Central

Chung, Woo Chul; Jeon, Eun Jung; Lee, Kang-Moon; Paik, Chang Nyol; Oh, You Suk; Lee, Yang Woon; Kim, Sang Bae; Jun, Kyong-Hwa; Chin, Hyung Min

2012-01-01

Background. Marginal ulcer is a well-known complication after gastrectomy. Its bleeding can be severe, but the severity has rarely been reported. We aim to evaluate the clinical outcomes of marginal ulcer bleeding (MUB) as compared to peptic ulcer bleeding (PUB) with nonoperated stomach. Methods. A consecutive series of patients who had nonvariceal upper gastrointestinal bleeding and admitted to the hospital between 2005 and 2011 were retrospectively analyzed. A total of 530 patients were enrolled in this study, and we compared the clinical characteristics between 70 patients with MUB and 460 patients with PUB. Results. Patients with MUB were older (mean age: 62.86 ± 10.59 years versus 53.33 ± 16.68 years, P = 0.01). The initial hemoglobin was lower (8.16 ± 3.05 g/dL versus 9.38 ± 2.49 g/dL, P = 0.01), and the duration of admission was longer in MUB (7.14 ± 4.10 days versus 5.90 ± 2.97 days, P = 0.03). After initial hemostasis, the rebleeding rate during admission was higher (16.2% versus 6.5%, P = 0.01) in MUB. However, the mortality rate did not differ statistically between MUB and PUB groups. Helicobacter pylori-positive rate with MUB was lower than that of PUB (19.4% versus 54.4%, P = 0.01). Conclusions. Clinically, MUB after gastrectomy is more severe than PUB with nonoperated stomach. Infection with H. pylori might not appear to play an important role in MUB after gastrectomy. PMID:23304127

New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control

PubMed Central

Nelson, Anita

2010-01-01

Aim: To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. Methods: This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. Results: The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. Conclusion: The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women’s desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors. PMID:21072303

Radiological Diagnosis and Management of Epistaxis

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

Krajina, Antonín, E-mail: antonin.krajina@fnhk.cz; Chrobok, Viktor, E-mail: viktor.chrobok@fnhk.cz

The majority of episodes of spontaneous posterior epistaxis treated with embolisation are idiopathic in nature. The angiographic findings are typically normal. Specific angiographic signs are rare and may include the following: a tumour blush, telangiectasia, aneurysm, and/or extravasation. Selective internal carotid artery (ICA) angiography may show rare causes of epistaxis, such as traumatic or mycotic aneurysms, which require different treatment approaches. Complete bilateral selective external and internal carotid angiograms are essential to evaluation. The images should be analysed for detection of central retinal blush in the external carotid artery (ECA) and anastomoses between the branches of the ECA and ICA.more » Monocular blindness and stroke are two of the most severe complications. Embolisation aims to decrease flow to the bleeding nasal mucosa while avoiding necrosis of the nasal skin and palate mucosa. Embolisation is routinely performed with a microcatheter positioned in the internal maxillary artery distal to the origin of the meningeal arteries. A guiding catheter should be placed in the proximal portion of the ECA to avoid vasospasm. Embolisation with microparticles is halted when the peripheral branches of the sphenopalatine artery are occluded. The use of coils is not recommended because recurrent epistaxis may occur due to proximal embolization; moreover, the option of repeat distal embolisation is lost. The success rate of embolisation therapy (accounting for late recurrence of bleeding) varies between 71 and 94 %. Results from endoscopic surgery are quite comparable. When epistaxis is refractory to nasal packing or endoscopic surgery, embolisation is the treatment of choice in some centres.« less

Physical activity in individuals with haemophilia and experience with recombinant factor VIII Fc fusion protein and recombinant factor IX Fc fusion protein for the treatment of active patients: a literature review and case reports.

PubMed

Wang, Michael; Álvarez-Román, María Teresa; Chowdary, Pratima; Quon, Doris V; Schafer, Kim

2016-10-01

The World Federation of Hemophilia and the National Hemophilia Foundation encourage people with haemophilia (PWH) to participate in routine physical activity. The benefits of physical activity for PWH include improvements in joint, bone, and muscle health. Accordingly, a number of studies suggest that levels of physical activity among PWH are similar to those of their healthy peers, especially among individuals who began prophylaxis at an early age (≤3 years). Importantly, several studies found either no increased risk or only a transient increase in risk of bleeding with more intensive physical activity compared with less intensive physical activity. Data on optimal prophylaxis regimens for PWH who participate in physical/sporting activities; however, remain sparse. Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) and recombinant factor IX Fc fusion protein (rFIXFc) demonstrated efficacy for the prevention and treatment of bleeding episodes in Phase 3 clinical trials of participants with haemophilia A and B, respectively, with most individuals able to maintain or increase their physical activities. This manuscript reviews the current literature that describes physical activity in PWH. Additionally, case studies are presented to provide supplemental information to clinicians illustrating the use of rFVIIIFc and rFIXFc in physically active patients with haemophilia A and B, respectively. These case reports demonstrate that it is possible for patients to be physically active and maintain good control of their haemophilia with extended interval prophylactic dosing using rFVIIIFc or rFIXFc.

Physical activity in individuals with haemophilia and experience with recombinant factor VIII Fc fusion protein and recombinant factor IX Fc fusion protein for the treatment of active patients: a literature review and case reports

PubMed Central

Wang, Michael; Álvarez-Román, María Teresa; Chowdary, Pratima; Quon, Doris V.; Schafer, Kim

2016-01-01

The World Federation of Hemophilia and the National Hemophilia Foundation encourage people with haemophilia (PWH) to participate in routine physical activity. The benefits of physical activity for PWH include improvements in joint, bone, and muscle health. Accordingly, a number of studies suggest that levels of physical activity among PWH are similar to those of their healthy peers, especially among individuals who began prophylaxis at an early age (≤3 years). Importantly, several studies found either no increased risk or only a transient increase in risk of bleeding with more intensive physical activity compared with less intensive physical activity. Data on optimal prophylaxis regimens for PWH who participate in physical/sporting activities; however, remain sparse. Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) and recombinant factor IX Fc fusion protein (rFIXFc) demonstrated efficacy for the prevention and treatment of bleeding episodes in Phase 3 clinical trials of participants with haemophilia A and B, respectively, with most individuals able to maintain or increase their physical activities. This manuscript reviews the current literature that describes physical activity in PWH. Additionally, case studies are presented to provide supplemental information to clinicians illustrating the use of rFVIIIFc and rFIXFc in physically active patients with haemophilia A and B, respectively. These case reports demonstrate that it is possible for patients to be physically active and maintain good control of their haemophilia with extended interval prophylactic dosing using rFVIIIFc or rFIXFc. PMID:27116081

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

Evaluation of factor IX deficiency by interdigitated electrode (IDE)

NASA Astrophysics Data System (ADS)

Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

2017-03-01

Factor IX deficiency is the main cause of hemophilia A and B. This a severe excessive bleeding disorder that can even kill the patient if not treated with the right prescription of Factor IX hormone to stop the bleeding. The bleeding can be caused by an injury or even a sudden bleeding in some very rare cases. To find the Factor IX effectiveness and to understand the deficiency more carefully for the future of medicine, experiments are conducted to test the Factor IX using the Interdigitated Electrode (IDE) and gold Nanoparticle with the help of Nanoelectrical technology.

[Hepatic artery pseudoaneurysm following blunt abdominal injury].

PubMed

Kargl, S; Breitwieser, J; Gitter, R; Pumberger, W

2012-12-01

Posttraumatic hepatic artery pseudoaneurysms are a rare but life-threatening complication of blunt abdominal trauma with liver damage. We report the case of a child who developed a pseudoaneurysm of the right hepatic artery after a bicycle accident with central liver rupture. After an episode of hemodynamically relevant hemobilia due to delayed bleeding, the asymptomatic pseudoaneurysm was diagnosed coincidentally by ultrasound. Because of the progression in size angiographic coiling was performed and led to thrombotic occlusion of the pseudoaneurysm. After a symptom-free period of 1 month the child required surgery because of acute cholecystitis.

[Mesenteric-cava shunt's results with autologous jugular vein graft in children with pre-sinusoidal portal hypertension].

PubMed

Leal, N; López Santamaría, M; Gámez, M; Murcia, J; Andolfi, G; Berrocal, T; Frauca, E; Jara, P; Tovar, J

2002-07-01

Presinusoidal portal hypertension (PPH) in children evaluates without functional hepatic damage, and with the time, trends to compensate through the creation of spontaneous portosystemic shunts. Nevertheless, some patients suffer episodes of gastrointestinal bleeding (GIB) that because of its frequency or severity, force to propose the change of surgical treatment. To evaluate the results of the mesocaval shunt (MCS) with autologous jugular vein in children with PPH. Among the 32 children with PPH treated in our Hospital in the last 7 years, 10 had episodes of GIB that forced to perform a surgical shunt. The types of shunt were distal splenorenal in 3 patients and mesocaval in 7. These 7 cases are the material of this study. The origin of the PPH was a cavernomatosis transformation of the portal vein in 6 cases and a congenital hepatic fibrosis in 1. Before the surgery the average number of episodes of GIB was 9 (range 2-15); all the patients needed transfusion of blood products and variceal sclerosis. In 2 cases a tamponade with the Sengtaken balloon was required and 5 patients were treated with somatostatin and propranolol. The Doppler ultrasounds revealed and intense hepatofugal collateral circulation in all the cases. The initial flow through the shunt was adequate in all the patients except one who required a percutaneous balloon dilatation. Only this patient has suffered an episode of GIB. The hyperesplenism signs disappeared or improved in all the seven cases and the collateral circulation was significantly reduced. The pressure in the splenic territory decreased around 50% in the 4 patients that was measured. There were no cases of encephalopasty and only one child with congenital hepatic fibrosis shows signs of mild hepatic disfunction. The medium follow up post-shunt is 32 months (range 8 m-6 years). The MCS prevents the GIB in the PPH not responsive to the conservative treatment; its effectiveness is related with an adequate permeability though the graft and at least in the cases with portal cavernomatosis (the most frequent in children) doesn't produce hepatic dysfunction. Doppler ultrasounds give a very precise information about the post-surgical situation and are an excellent method of follow up.

[Management of placenta previa and accreta].

PubMed

Kayem, G; Keita, H

2014-12-01

Produce recommendations for the management of placenta previa and placenta accrete. A literature search was conducted using Medline and the Cochrane Library over a period from 1950 to 31/12/2013. Recommendations of the latest scientific societies have also been consulted. In cases of placenta previa, if bleeding episode before 34weeks gestation occurs, a short hospitalization and tocolysis may help stop bleeding (grade C). Vaginal delivery is preferable when the distance between the internal cervical os and the placental edge is greater than 20mm. When this distance is less than 20mm, vaginal delivery is possible (professional consensus). Caesarean section is recommended in cases of placenta overlapping the internal os (professional consensus). Antenatal screening placenta accreta could improve care (EL3). Upon discovery of a placenta accreta during childbirth, it is better to avoid a forced removal of the placenta (grade C). Conservative treatment or cesarean hysterectomy are possible (grade C). The management of placental abnormalities should be planned and managed with a multidisciplinary team (professional consensus). The use of blood-saving techniques such as "cell saver" is possible in situations where early intraoperative bleeding would be>1500mL (grade C). There are no studies that have sufficient methodological value to recommend an anesthetic technique [general anaesthesia (GA) or neuraxial anaesthesia] over another in the context of placental abnormalities (grade B). When a major bleeding risk is identified, GA can be chosen in order to avoid emergency conversions in difficult conditions (professional consensus). Placental insertion abnormalities require anesthetic and obstetric coordination. Delivery must be planned in a suitable structure. Copyright © 2014. Published by Elsevier Masson SAS.

Assessment of safety of performing percutaneous coronary intervention after a recent episode of gastrointestinal bleeding.

PubMed

Karim, Saima; Ador-Dionisio, Sweetheart T; Karim, Munira; Karim, Mohammad; Khan, Sadaf S; Atreja, Ashish; Ellis, Stephen

2016-03-01

Little literature exists on the risk of performing coronary intervention (PCI) on patients who have had recent gastrointestinal bleeding (GIB), although bleeding after PCI has been identified as a risk factor for long-term mortality. Patients within the Cleveland Clinic PCI database who had acute GIB within 30 days preceding PCI during the same hospitalization (n = 79) were retrospectively compared to those who had PCI without recent GIB (n = 10 979) for mortality and need for revascularization. Baseline characteristics, laboratory values, procedures, morbidities, and mortality were compared using chi-square test for categorical variables and using Wilcoxon rank sum test for continuous variables. Mortality data was obtained using Social Security Death Index and demonstrated using Kaplan-Meier method. The GIB group had more prevalent history of peptic ulcer disease, GIB, gastrointestinal or liver disease (P < 0.0001), transient ischemic accident (P = 0.017), peripheral vascular disease (P = 0.0002), significant carotid artery occlusion (P = 0.023), and myocardial infarction (P < 0.0001). 47% of patients had upper GIB with 20% needing endoscopic intervention. This group had more anemia (P < 0.0001), heart failure (P = 0.0001), cardiogenic shock (10% versus 1.4%, P < 0.001), cardiac arrest (7.6% versus 1%, P < 0.001). GIB group had worse in-hospital mortality (P < 0.0001), long-term mortality (P < 0.001), and a 7.6% re-bleeding incidence. Overall, the patients who had GIB preceding PCI had higher in-hospital mortality and long-term mortality compared with those without GIB before PCI.

Empiric transcatheter arterial embolization for massive bleeding from duodenal ulcers: efficacy and complications.

PubMed

Ichiro, Ikushima; Shushi, Higashi; Akihiko, Ishii; Yasuhiko, Iryo; Yasuyuki, Yamashita

2011-07-01

To evaluate the efficacy and safety of empiric transcatheter arterial embolization (TAE) for patients with massive bleeding from duodenal ulcers. During January 2000 and December 2009, 59 patients with duodenal ulcer bleeding in whom TAE was attempted after endoscopic therapy failed were retrospectively analyzed. The patients were divided into empiric TAE (n = 36) and identifiable TAE (n = 23) groups according to angiographic findings with or without identification of the bleeding sites. The technical and clinical success rate, recurrent bleeding rate, procedure-related complications, and clinical outcomes were evaluated. The technical and clinical success rates of TAE were 100% and 83%. The recurrent bleeding rate, clinical success, duodenal stenosis, and 30-day mortality after TAE were not significantly different between the empiric and identifiable TAE groups. A high rate of technical and clinical success was obtained with empiric TAE comparable to identifiable TAE in patients with massive bleeding from duodenal ulcers. There were no severe complications. Empiric TAE is an effective and safe method when a bleeding site cannot determined by angiography. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

[Ischemic Changes in the Electrocardiogram and Circulatory Collapse Accompanied by Severe Anemia Owing to the Delay of Red Blood Cell Concentrate Transfusion in Two Patients with Intraoperative Massive Bleeding].

PubMed

Horiuchi, Toshinori; Noguchi, Teruo; Kurita, Naoko; Yamaguchi, Ayako; Takeda, Masafumi; Sha, Keiichi; Nagahata, Toshihiro

2016-01-01

We present two patients developing intraoperative massive bleeding and showed ischemic changes in the electrocardiogram and circulatory collapse accompanied by severe anemia owing to the delay of red blood cell concentrate transfusion. One patient underwent hepatectomy and the other pancreaticoduodenectomy. Their lowest hemoglobin concentration was around 2 g x dl(-1), and they showed ischemic changes in the electrocardiogram and severe decreases in blood pressure. The former received compatible red blood cell concentrate and the latter received uncrossmatched same blood group red blood cell concentrate immediately, and their electrocardiogram and blood pressure quickly improved. To avoid life-threatening anemia, emergency red blood cell concentrate transfusion including compatible different blood group transfusion should be applied for intraoperative massive bleeding.

What to do when she's bleeding through: the recognition, evaluation, and management of abnormal uterine bleeding in adolescents.

PubMed

Bennett, Alyssa R; Gray, Susan H

2014-08-01

This article reviews the current understanding and management of abnormal uterine bleeding (AUB) in adolescents. The readers will learn a practical approach to the evaluation and treatment of mild-to-severe uterine bleeding. In 2011, a new classification system was proposed to standardize the terminology used to describe AUB. This system is based on the pattern and etiology of bleeding and has been adopted by other organizations. The term dysfunctional uterine bleeding has been replaced by AUB. The negative effect of AUB on adolescents' quality of life is now well established. The levonorgestrel-releasing intrauterine system is considered a first-line treatment for heavy menstrual bleeding and should be considered, especially in those adolescents who may also need contraception. AUB is a common adolescent complaint that can vary from mild to life-threatening if not recognized and treated promptly. This article reviews the appropriate assessment and management of AUB and proposes a practical algorithm that can be used in an office or hospital setting.

An Alternative Technique in the Control of Massive Presacral Rectal Bleeding: Fixation of GORE-TEX® Aortic Patch.

PubMed

Ozsoy, Mustafa; Ozsoy, Zehra; Sahin, Suleyman; Arikan, Yüksel

2018-01-01

The presacral venous system is located under the pelvic fascia covering the anterior of the sacrum and consists of two lateral sacral veins, middle sacral vein, and the veins that communicate them. The presacral venous system can be easily damaged and causes serious bleeding which is difficult to control and may cause intraoperative mortality. Its incidence varies between 3% and 9.4%. Although several methods have been tried to control presacral bleeding, the definitive method of treatment has not yet been identified. We present here our alternative technique in control of massive presacral massive bleeding developed from the presacral plexus secondary to the traction of the specimen during the dissection. The bleeding could not be controlled despite the use of all technical possibilities such as packing, ligation, and hemostatic agents. Bleeding control was provided by GORE-TEX ® graft. We conclude that fıxatıon of GORE-TEX ® aortic patch should be kept in mind for uncontrolled massive presacral bleeding.

The role of oral anticoagulants in epistaxis.

PubMed

Buchberger, A M S; Baumann, A; Johnson, F; Peters, N; Piontek, G; Storck, K; Pickhard, A

2018-06-23

The purpose of this retrospective study was to identify the impact of oral anticoagulants on epistaxis with the focus on new oral anticoagulants. The study was conducted at the Department  for Ear- Nose- and Throat (ENT), Head and Neck Surgery, Technical University Munich, Germany. All patients presenting in 2014 with the diagnosis of epistaxis to a specialized ENT accident and emergency department were identified and analyzed in clinical data and medication. 600 adult cases, with a median age of 66.6 years were identified with active bleeding. 66.8% of all cases were anticoagulated. Classic oral anticoagulants (COAC) were three times more common in patients than new-generation oral anticoagulants (NOAC). Recurrent bleeding was significantly associated with oral anticoagulants (OAC) (p = 0.014) and bleeding location was most often anterior (p = 0.006). In contrast, severe cases, which required surgery or embolization were significantly more likely in non-anticoagulated middle-aged patients with posterior bleedings (p < 0.05). In our epistaxis cohort, OAC were highly overrepresented (40%) when compared to the general German population (1%) but COAC as well as NOAC played only a minor role in severe courses of epistaxis. Oral anticoagulation, especially with new-generation drugs, is not associated with more complicated and severe courses of epistaxis, but rather with recurrent bleeding. One should keep this information in mind when triaging the patient in the emergency room and when planning further procedures.

[Newborn with phocomelia and thrombocytopenia. Case report].

PubMed

Maas, C; Arand, J; Orlikowsky, Th; Goelz, R

2002-01-01

Associated malformations and symptoms may be decisive in the differential diagnosis of neonatal phocomelia. We report on a neonate with phocomelia, petechiae and thrombocytopenia. This constellation is typical for the phocomelia-thrombocytopenia-syndrome, a variant of the thrombocytopenia-absent radius-(TAR) syndrome. During the neonatal period platelet transfusions were necessary. Relevant bleeding and development delays were not evident until the age of seven months. Cardinal symptoms of the TAR syndrome are bilaterally absent radius and neonatal thrombocytopenia. The patient presented with phocomelia of the upper extremities which occurs in only 5 - 10 % of the patients with TAR syndrome. Further abnormalities include additional bone and joint disorders and haematopoietic problems, such as thrombocytopenia. Bleeding episodes mainly occur in the first year of life, hence platelet transfusions may be necessary during this period. A new experimental approach is the Interleukin-6-mediated stimulation of thrombopoiesis. Usually platelet counts reach normal values in adults. The main problem remains a satisfactory management of various limb defects.

Blood, sweat and tears: androgenic-anabolic steroid misuse and recurrent primary post-tonsillectomy haemorrhage

PubMed Central

Fox, Richard; Varadharajan, Kiran; Patel, Bhavesh; Beegun, Issa

2014-01-01

A 30-year-old male body builder and androgenic-anabolic steroid and insulin abuser was admitted for day case elective tonsillectomy (bipolar). He returned with primary post-tonsillectomy haemorrhage 18 h after the operation and required bipolar cautery to the multiple small bleeding points in the right and left tonsillar fossa. Thorough coagulation screen was normal. Recurrent primary haemorrhage occurred 3 h post-operatively requiring immediate surgical intervention, removal of the inferior poles, precautionary throat packs, intubation and observation on the intensive treatment unit (ITU). Re-examination in theatre revealed a bleeding left superior pole that was under-run to achieve haemostasis and the patient returned to ITU. Hypertensive episodes were noted in the emergency department and intraoperatively including one recording >200 mm Hg. Haemostasis was eventually achieved once the blood pressure was adequately controlled. A slow wean of steroids was also instigated and the patient was managed on a surgical ward for 2 weeks post-tonsillectomy. PMID:25398921

Blood, sweat and tears: androgenic-anabolic steroid misuse and recurrent primary post-tonsillectomy haemorrhage.

PubMed

Fox, Richard; Varadharajan, Kiran; Patel, Bhavesh; Beegun, Issa

2014-11-14

A 30-year-old male body builder and androgenic-anabolic steroid and insulin abuser was admitted for day case elective tonsillectomy (bipolar). He returned with primary post-tonsillectomy haemorrhage 18 h after the operation and required bipolar cautery to the multiple small bleeding points in the right and left tonsillar fossa. Thorough coagulation screen was normal. Recurrent primary haemorrhage occurred 3 h post-operatively requiring immediate surgical intervention, removal of the inferior poles, precautionary throat packs, intubation and observation on the intensive treatment unit (ITU). Re-examination in theatre revealed a bleeding left superior pole that was under-run to achieve haemostasis and the patient returned to ITU. Hypertensive episodes were noted in the emergency department and intraoperatively including one recording >200 mm Hg. Haemostasis was eventually achieved once the blood pressure was adequately controlled. A slow wean of steroids was also instigated and the patient was managed on a surgical ward for 2 weeks post-tonsillectomy. 2014 BMJ Publishing Group Ltd.

Transcatheter Arterial Embolization for Spontaneous Rupture of the Omental Artery

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

Matsumoto, Tomohiro, E-mail: t-matsu@koto.kpu-m.ac.jp; Yamagami, Takuji; Morishita, Hiroyuki

We encountered a rare case of spontaneous rupture of the omental artery. A 25-year-old man without any episode of abdominal trauma or bleeding disorders came to the emergency unit with left upper abdominal pain. Hematoma with extravasation of the greater omentum and a hemoperitoneum was confirmed on abdominal contrast-enhanced computed tomography. Bleeding from the omental artery was suspected based on these findings. Transcatheter arterial embolization was successfully performed after extravasation of the omental artery, which arises from the left gastroepiploic artery, was confirmed on arteriography. Partial ometectomy was performed 10 days after transcatheter arterial embolization, revealing that the hematoma measuredmore » 10 cm in diameter in the greater omentum. Pathological examination showed rupture of the branch of an omental artery without abnormal findings, such as an aneurysm or neoplasm. Thus, we diagnosed him with spontaneous rupture of the omental artery. The patient recovered and was discharged from the hospital 10 days after the surgery, with a favorable postoperative course.« less

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.

Outcome Measures for Heavy Menstrual Bleeding

PubMed Central

Quinn, Stephen D; Higham, Jenny

2016-01-01

Heavy menstrual bleeding is one of the most commonly encountered gynecological problems. While accurate objective quantification of menstrual blood loss is of value in the research setting, it is the subjective assessment of blood loss that is of greater importance when assessing the severity of heavy menstrual bleeding and any subsequent response to treatment. In this review the various approaches to objective, subjective and semi-subjective assessment of menstrual blood loss will be discussed. PMID:26693585

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.

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.

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

[Severe Bleeding from the Middle Ear Cavity after Myringotomy: Review Based on a Case Report].

PubMed

Hofmann, Veit M; Niehues, Stefan M; Albers, Andreas E; Pudszuhn, Annett

2017-03-01

Report of a rare case of severe bleeding from the middle ear cavity after myringotomy. On the basis of the case report, the procedure for such bleeding is discussed in the context of the literature. A 6-year-old boy received a revision myringotomy in an ambulant setting. During the procedure a severe bleeding occurred. The external auditory canal was adequately packed. The patient was extubated and transferred to the clinic as an emergency. Computer tomography of the temporal bone showed the anatomical variant of a dehiscent high jugular bulb, which had been injured. Because no rebleeding occurred, the packing of the ear canal was removed and an explorative tympanoscopy was performed on the third postoperative day. When the tympanomeatal flap was lifted, the defect in the jugular bulb was found. The lesion was covered with Tutopatch ® pads and fibrin glue and the auditory canal was packed again. After removal of the packing three weeks postoperatively a properly healed situs was found. No further measures were taken. The injury of a dehiscent jugular bulb in the course of ear surgeries leads to a massive hemorrhage. The case describes the diagnostic and therapeutic procedure for this relatively rare but severe complication. © Georg Thieme Verlag KG Stuttgart · New York.

Interventional Algorithms for the Control of Coagulopathic Bleeding in Surgical, Trauma, and Postpartum Settings

PubMed Central

Rodrigues, Anabela; Gomes, Manuela; Carrilho, Alexandre; Nunes, António Robalo; Orfão, Rosário; Alves, Ângela; Aguiar, José; Campos, Manuel

2014-01-01

Several clinical settings are associated with specific coagulopathies that predispose to uncontrolled bleeding. With the growing concern about the need for optimizing transfusion practices and improving treatment of the bleeding patient, a group of 9 Portuguese specialists (Share Network Group) was created to discuss and develop algorithms for the clinical evaluation and control of coagulopathic bleeding in the following perioperative clinical settings: surgery, trauma, and postpartum hemorrhage. The 3 algorithms developed by the group were presented at the VIII National Congress of the Associação Portuguesa de Imuno-hemoterapia in October 2013. They aim to provide a structured approach for clinicians to rapidly diagnose the status of coagulopathy in order to achieve an earlier and more effective bleeding control, reduce transfusion requirements, and improve patient outcomes. The group highlights the importance of communication between different specialties involved in the care of bleeding patients in order to achieve better results. PMID:25424528

Modelling the occurrence and severity of enoxaparin-induced bleeding and bruising events

PubMed Central

Barras, Michael A; Duffull, Stephen B; Atherton, John J; Green, Bruce

2009-01-01

AIMS To develop a population pharmacokinetic–pharmacodynamic model to describe the occurrence and severity of bleeding or bruising as a function of enoxaparin exposure. METHODS Data were obtained from a randomized controlled trial (n = 118) that compared conventional dosing of enoxaparin (product label) with an individualized dosing regimen. Anti-Xa concentrations were sampled using a sparse design and the size, location and type of bruising and bleeding event, during enoxaparin therapy, were collected daily. A population pharmacokinetic–pharmacodynamic analysis was performed using nonlinear mixed effects techniques. The final model was used to explore how the probability of events in patients with obesity and/or renal impairment varied under differing dosing strategies. RESULTS Three hundred and forty-nine anti-Xa concentrations were available for analysis. A two-compartment first-order absorption and elimination model best fit the data, with lean body weight describing between-subject variability in clearance and central volume of distribution. A three-category proportional-odds model described the occurrence and severity of events as a function of both cumulative enoxaparin AUC (cAUC) and subject age. Simulations showed that individualized dosing decreased the probability of a bleeding or major bruising event when compared with conventional dosing, which was most noticeable in subjects with obesity and renal impairment. CONCLUSIONS The occurrence and severity of a bleeding or major bruising event to enoxaparin, administered for the treatment of a thromboembolic disease, can be described as a function of both cAUC and subject age. Individualized dosing of enoxaparin will reduce the probability of an event. PMID:19916994

Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation

PubMed Central

Desborough, Michael; Estcourt, Lise J; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Stanworth, Simon J; Murphy, Michael F

2016-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made in platelet transfusion therapy since the mid-1970s, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. Objectives To determine whether agents that can be used as alternatives, or adjuncts, to platelet transfusions for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation are safe and effective at preventing bleeding. Search methods We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 4), MEDLINE (OvidSP, 1946 to 19 May 2016), Embase (OvidSP, 1974 to 19 May 2016), PubMed (e-publications only: searched 19 May 2016), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 19 May 2016). Selection criteria We included randomised controlled trials in people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII, desmopressin (DDAVP), or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard care or platelet transfusion). We excluded studies of antifibrinolytic drugs, as they were the focus of another review. Data collection and analysis Two review authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two review authors assessed risk of bias in the included studies and extracted data independently. Main results We identified 16 eligible trials. Four trials are ongoing and two have been completed but the results have not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding. No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin. Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO). One trial compared platelet-poor plasma to platelet transfusion. We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported. We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI -5.39 to -0.61, one trial, 120 participants, very low quality evidence). No deaths occurred in either group after 30 days (one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce all-cause mortality at 90 days (OR 1.00, 95% CI 0.24 to 4.20, one trial, 120 participants, very low quality evidence). No thromboembolic events occurred for participants treated with TPO mimetics or control at 30 days (two trials, 209 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed or quality of life. One trial with 18 participants compared platelet-poor plasma transfusion with platelet transfusion. We are very uncertain whether platelet-poor plasma reduces the number of participants with any bleeding episode (OR 16.00, 95% CI 1.32 to 194.62, one trial, 18 participants, very low quality evidence). We are very uncertain whether platelet-poor plasma reduces the number of participants with severe or life-threatening bleeding (OR 4.00, 95% CI 0.56 to 28.40, one trial, 18 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed, number of platelet transfusions, all-cause mortality, thromboembolic events or quality of life. Authors’ conclusions There is insufficient evidence to determine if platelet-poor plasma or TPO mimetics reduce bleeding for participants with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation. To detect a decrease in the proportion of participants with clinically significant bleeding from 12 in 100 to 6 in 100 would require a trial containing at least 708 participants (80% power, 5% significance). The six ongoing trials will provide additional information about the TPO mimetic comparison (424 participants) but this will still be underpowered to demonstrate this level of reduction in bleeding. None of the included or ongoing trials include children. There are no completed or ongoing trials assessing artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin in people undergoing intensive chemotherapy or stem cell transplantation for haematological malignancies. PMID:27548292

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.

Doppler endoscopic probe as a guide to risk stratification and definitive hemostasis of peptic ulcer bleeding.

PubMed

Jensen, Dennis M; Ohning, Gordon V; Kovacs, Thomas O G; Ghassemi, Kevin A; Jutabha, Rome; Dulai, Gareth S; Machicado, Gustavo A

2016-01-01

For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUB), we used a Doppler endoscopic probe (DEP) for (1) detection of blood flow underlying stigmata of recent hemorrhage (SRH), (2) quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and (3) comparing risks of rebleeding and actual 30-day rebleed rates for spurting arterial bleeding (Forrest [F] IA) and oozing bleeding (F IB). Prospective cohort study of 163 consecutive patients with severe PUB and different SRH. All blood flow detected by the DEP was arterial. Detection rates were 87.4% in major SRH-spurting arterial bleeding (F IA), non-bleeding visible vessel (F IIA), clot (F IIB)-and were significantly lower at 42.3% (P < .0001) for an intermediate group of oozing bleeding (F IB) or flat spot (F IIC). For spurting bleeding (F IA) versus oozing (F IB), baseline DEP arterial flow was 100% versus 46.7%, residual blood flow detected after endoscopic hemostasis was 35.7% versus 0%, and 30-day rebleed rates were 28.6% versus 0% (all P < .05). (1) For major SRH versus oozing or spot, the arterial blood flow detection rate by the DEP was significantly higher, indicating a higher rebleed risk. (2) Before and after endoscopic treatment, spurting (F IA) PUB had significantly higher rates of blood flow detection than oozing (F IB) PUB and a significantly higher 30-day rebleed rate. (3) The DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUB. Published by Elsevier Inc.

Doppler Endoscopic Probe as a Guide to Risk Stratification and Definitive Hemostasis of Peptic Ulcer Bleeding

PubMed Central

Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas OG; Ghassemi, Kevin A.; Jutabha, Rome; Dulai, Gareth S.; Machicado, Gustavo A.

2015-01-01

Background and Aims For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUBs), we used Doppler endoscopic probe (DEP) for: 1. detection of blood flow underlying stigmata of recent hemorrhage (SRH), 2. quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and 3. comparing risks of rebleeding and actual 30 day rebleed rates for spurting arterial bleeding (Forrest – FIA) and oozing bleeding (FIB). Methods Prospective cohort study of 163 consecutive patients with severe PUBs and different SRH. Results All blood flow detected by DEP was arterial. Detection rates were 87.4% in major SRH - spurting arterial bleeding (FIA), non bleeding visible vessel (FIIA), clot (FIIB) - and significantly lower at 42.3% (p<0.0001) for intermediate group of oozing bleeding (FIB) or flat spot (FIIC). For spurting bleeding (FIA) vs. oozing (FIB), baseline DEP arterial flow was 100% vs. 46.7%; residual blood flow detected after endoscopic hemostasis was 35.7% vs. 0%; and 30 day rebleed rates were 28.6% vs. 0% (all p<0.05). Conclusions 1. For major SRH vs. oozing or spot, the arterial blood flow detection rates by DEP was significantly higher, indicating a higher rebleed risk. 2. Before and after endoscopic treatment, spurting FIA PUB’s had significantly higher rates of blood flow detection than oozing FIB PUB’s and a significantly higher 30 rebleed rate. 3. DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUBs. PMID:26318834

Severe Gastrointestinal Haemorrhage: Summary of a National Quality of Care Study with Focus on Radiological Services

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

McPherson, Simon J., E-mail: simon.mcpherson@nhs.net, E-mail: smcpherson@ncepod.org.uk; Sinclair, Martin T.; Smith, Neil C. E.

Purpose of StudyTo identify the remediable factors in the quality of care provided to patients with severe gastrointestinal (GI) bleeding.MethodAll hospital admissions in the first four months of 2013 with ICD10 coding for GI bleeding who received a transfusion of 4 units or more of blood. Up to five cases/hospital randomly selected for structured case note peer review. National availability of GI bleeding services data derived from organisational questionnaire completed by all hospitals.Results4563/29,796 (15.3%) of GI bleeds received 4 or more units of blood with a mortality rate of 20.2% compared to 7.3% without blood transfusion. 30.8% of GI bleedsmore » received a blood transfusion. 32% (60/185) of hospitals admitting acute GI bleeds lacked 24/7 endoscopy. 26% (48/185) had on-site embolisation 24/7 with a further 34% (64/185) accessing embolisation by transfer within a validated formal network. Blood product use was inappropriate in 20% (84/426). Improved management, principally earlier senior gastroenterologist review and/or endoscopy, would have reduced blood product use in 25% (113/457). 14.5% (90/618) had a CT scan which identified the site of bleeding in 32% (29/90). 7.8% (36/459) underwent an Interventional Radiology (IR) procedure but a further 6.3% (21/33) should have had IR. 6% (36/586) underwent surgery with 21/36 for uncontrolled bleeding. In 20/35 IR was not considered despite the majority being suitable for IR. Overall 44% (210/476) received an acceptable standard of care according to peer review.Conclusions26 recommendations were made to improve the quality of care in GI bleeding, with six principle recommendations.« less

A study of clinical and endoscopic profile of acute upper, gastrointestinal bleeding.

PubMed

Dewan, K R; Patowary, B S; Bhattarai, S

2014-01-01

Acute Upper Gastrointestinal Bleeding is a common medical emergency with a hospital mortality of approximately 10 percent. Higher mortality rate is associated with rebleeding. Rockall scoring system identifies patients at higher risk of rebleed and mortality. To study the clinical and endoscopic profile of acute upper gastrointestinal bleed to know the etiology, clinical presentation, severity of bleeding and outcome. This is a prospective, descriptive hospital based study conducted in Gastroenterology unit of College of Medical Sciences and Teaching Hospital, Bharatpur, Nepal from January 2012 to January 2013. It included 120 patients at random presenting with manifestations of upper gastrointestinal bleed. Their clinical and endoscopic profiles were studied. Rockall scoring system was used to assess their prognosis. Males were predominant (75%). Age ranged from 14 to 88 years, mean being 48.76+17.19. At presentation 86 patients (71.7%) had both hematemesis and malena, 24 patients (20%) had only malena and 10 patients (8.3%) had only hematemesis. Shock was detected in 21.7%, severe anemia and high blood urea were found in 34.2% and 38.3% respectively. Upper Gastrointestinal Bleeding endoscopy revealed esophageal varices (47.5%), peptic ulcer disease (33.3%), erosive mucosal disease (11.6%), Mallory Weiss tear (4.1%) and malignancy (3.3%). Median hospital stay was 7.28+3.18 days. Comorbidities were present in 43.3%. Eighty six patients (71.7%) had Rockall score < 5 and 34 (28.3%) had >6. Five patients (4.2%) expired. Risk factors for death being massive rebleeeding, comorbidities and Rockall score >6. Acute Upper Gastrointestinal bleeding is a medical emergency. Mortality is associated with massive bleeding, comorbidities and Rockall score >6. Urgent, appropriate hospital management definitely helps to reduce morbidity and mortality.

Low, fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation.

PubMed

Bagal, Bhausaheb; Chandrasekharan, Arun; Chougle, Aliya; Khattry, Navin

2018-03-01

Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD. We retrospectively evaluated 511 patients who underwent stem cell transplant at our center from November 2007 and December 2015. All patients received ursodeoxycholic acid as VOD prophylaxis. Modified Seattle criterion was used for diagnosis and severity grading of VOD. Patients developing VOD were initially treated with furosemide and adequate analgesia. Defibrotide was started within 12 to 24 hours of diagnosis of VOD. All adult patients received defibrotide at a fixed dose of 200mg twice daily while two children were given dose of 100mg and 50mg twice daily. Nine (1.7%) of our patients developed VOD. Daily dose of defibrotide ranged from 5mg/kg/d to 20mg/kg/d till resolution of VOD. All patients had complete resolution of VOD. None of our patients required ventilator support or dialysis. No episodes of bleeding were observed. No dose response relationship was observed between defibrotide dose and time to resolution of VOD. Low fixed dose defibrotide initiated early seems to be effective and safe in treatment of VOD. This is relevant in a resource limited setting and warrants prospective evaluation. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Comparison of the Safety and Effectiveness of Apixaban versus Warfarin in Patients with Severe Renal Impairment.

PubMed

Stanton, Brooke E; Barasch, Naomi S; Tellor, Katie B

2017-04-01

The U.S. Food and Drug Administration approval of the use of apixaban in patients with a creatinine clearance (CrCl) of < 15 ml/minute or in those receiving dialysis is based only on pharmacokinetic data as clinical trials of apixaban excluded patients with a CrCl of < 25 ml/minute or a serum creatinine concentration (SCr) of > 2.5 mg/dl. Thus, the objective of this study was to evaluate the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment. Retrospective, matched-cohort study. Community hospital. A total of 146 adults who received at least one dose of apixaban (73 patients) or warfarin (73 patients) while hospitalized between January 30, 2014, and December 31, 2015, and had a CrCl of < 25 ml/minute or SCr of > 2.5 mg/dl, or who received peritoneal dialysis or hemodialysis, were included. Patients who were taking warfarin and had a therapeutic international normalized ratio on admission were matched consecutively in a 1:1 fashion in chronologic order to patients taking apixaban based on renal function and indication for anticoagulation. The primary outcome was major bleeding. Secondary outcomes included the composite of bleeding (major bleeding, clinically relevant nonmajor bleeding, and minor bleeding) in addition to documented ischemic stroke or recurrent venous thromboembolism. A nonsignificant difference in the occurrence of major bleeding and composite bleeding was observed between patients who received apixaban compared with those who received warfarin (9.6% vs 17.8%, p=0.149, and 21.9% vs 27.4%, p=0.442, respectively). The occurrence of stroke was similar between the groups (7.5% in each group), and no recurrent venous thromboembolism events were noted in either group during the study period. Apixaban appears to be a reasonable alternative to warfarin in patients with severe renal impairment. © 2017 Pharmacotherapy Publications, Inc.

Post-tonsillectomy hemorrhage--some facts will never change.

PubMed

Windfuhr, Jochen P; Verspohl, Berit C; Chen, Yue-Shih; Dahm, Julia D; Werner, Jochen A

2015-05-01

Bleeding remains the most significant complication following tonsillectomy (TE), sometimes requiring revision surgery under general anesthesia. This study was undertaken to verify whether or not bleeding rates changed after bipolar coagulation was replaced by suture ligation to achieve hemostasis at a single institution. The charts of all patients who had undergone tonsillectomy between April 1, 2007, and April 30, 2013, at our institution were reviewed. The tonsils were bluntly dissected with scissors and a rasp. While hemostasis was achieved with bipolar coagulation during the first 36 months (group A), this method was replaced after a transition period of 1 month by intraoperative suture ligation (group B) during the last 36 months. Group A encompassed 2,137 patients including 963 children scheduled for adenotonsillectomy (ATE), and group B consisted of 1,521 patients and included 435 ATE cases. Bleeding from the tonsillar wounds occurred in 111/2,137 group A (5.2 %) and 68/1,521 group B patients (4.5 %). The difference was not found to be significant (p = 0.317). The incidence of primary bleeding (PB) and secondary bleeding (SB) was significantly (p = 0,000) associated with the method to achieve hemostasis: PB prevailed in group B and SB prevailed in group A. The overall incidence of post-tonsillectomy hemorrhage (PTH) varied at different ages, but the difference was not significant in group A (p = 0.401) and group B (p = 0.661). Repeated episodes of PTH occurred in 11/111 group A (9.9 %) and 8/68 group B (11.7 %) patients. The statistical difference was not found to be significant (p = 0.725). However, there were significantly more male patients with bleeding complications in both groups. Despite the strongest efforts to avoid it, the potential risk of PTH remains a fact to be accepted by surgeons and patients. An increased surgical precision achieved by introduction of a surgical microscope as well as replacing bipolar cautery by suture ligation to achieve hemostasis could only reduce the overall rate of PTH. Another fact remains unchanged: PB occurs predominantly when electrosurgical means are avoided and SB prevails, whenever surgeons use them. We will continue our research on refined methods of cold steel microsurgical TE including suture techniques.

Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

PubMed

Oldenburg, Johannes; Mahlangu, Johnny N; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U; Young, Guy; Santagostino, Elena; Kruse-Jarres, Rebecca; Negrier, Claude; Kessler, Craig; Valente, Nancy; Asikanius, Elina; Levy, Gallia G; Windyga, Jerzy; Shima, Midori

2017-08-31

Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C. A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (P<0.001). A total of 22 participants in group A (63%) had zero bleeding events, as compared with 1 participant (6%) in group B. Among 24 participants in group C who had participated in a noninterventional study, emicizumab prophylaxis resulted in a bleeding rate that was significantly lower by 79% than the rate with previous bypassing-agent prophylaxis (P<0.001). Overall, 198 adverse events were reported in 103 participants receiving emicizumab prophylaxis; the most frequent events were injection-site reactions (in 15% of participants). Thrombotic microangiopathy and thrombosis were reported in 2 participants each (in the primary analysis) who had received multiple infusions of activated prothrombin complex concentrate for breakthrough bleeding. No antidrug antibodies were detected. Emicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no prophylaxis among participants with hemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).

Contraceptive efficacy and tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study

PubMed Central

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-01-01

Background The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexibleMIB) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen. Study design This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18–35 years) to the following regimens: flexibleMIB (24–120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexibleMIB only). Results Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexibleMIB vs the conventional regimen [41.0±29.1 (95% CI 38.8–43.3) vs 65.8±27.0 (95% CI 62.2–69.4) days, p<0.0001; treatment difference −24.8 (95% CI −29.2 to −20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9–67.9) days. The Pearl Index for the flexibleMIB regimen was 0.64 (95% CI 0.28–1.26). All regimens had comparable tolerability profiles. Conclusions EE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexibleMIB also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexibleMIB regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding. PMID:22454003

Management of Patients with Acute Lower Gastrointestinal Bleeding

PubMed Central

Strate, Lisa L.; Gralnek, Ian M.

2016-01-01

This guideline provides recommendations for the management of patients with acute overt lower gastrointestinal hemorrhage. Hemodynamic status should be initially assessed with intravascular volume resuscitation started as needed. Risk stratification based upon clinical parameters should be performed to help distinguish patients at high and low-risk of adverse outcomes. Hematochezia associated with hemodynamic instability may be indicative of an upper GI bleeding source and thus warrants an upper endoscopy. In the majority of patients, colonoscopy should be the initial diagnostic procedure and should be performed within 24 hours of patient presentation after adequate colon preparation. Endoscopic hemostasis therapy should be provided to patients with high risk endoscopic stigmata of bleeding including active bleeding, non-bleeding visible vessel, or adherent clot. The endoscopic hemostasis modality used (mechanical, thermal, injection or combination) is most often guided by the etiology of bleeding, access to the bleeding site, and endoscopist experience with the various hemostasis modalities. Repeat colonoscopy, with endoscopic hemostasis performed if indicated, should be considered for patients with evidence of recurrent bleeding. Radiographic interventions (tagged red blood cell scintigraphy, CT angiography, angiography) should be considered in high-risk patients with ongoing bleeding who do not respond adequately to resuscitation, and who are unlikely to tolerate bowel preparation and colonoscopy. Strategies to prevent recurrent bleeding should be considered. NSAID use should be avoided in patients with a history of acute lower GI bleeding particularly if secondary to diverticulosis or angioectasia. In patients with established cardiovascular disease who require aspirin (secondary prophylaxis), aspirin should not be discontinued. The exact timing depends on the severity of bleeding, perceived adequacy of hemostasis and the risk of a thromboembolic event. Surgery for the prevention of recurrent lower gastrointestinal bleeding should be individualized and the source of bleeding should be carefully localized prior to resection. PMID:26925883

Treatment of Recurrent Hemarthrosis after Total Knee Arthroplasty

PubMed Central

Yoo, Ju-Hyung; Oh, Hyun-Cheol; Park, Sang-Hoon; Lee, Sanghyeon; Lee, Yunjae

2018-01-01

Purpose The purpose of this study is to evaluate the incidence and treatment of recurrent hemarthrosis after total knee replacement (TKR). Materials and Methods Among a total of 5,510 patients who underwent TKR from March 2000 to October 2016, patients who had two or more bleeding 2 weeks after surgery were studied. Conservative treatments were performed for all cases with symptoms. In patients who did not respond to conservative treatment several times, embolization was performed. We retrospectively evaluated the postoperative bleeding time, bleeding frequency, treatment method, and outcome. Results Seventeen (0.3%) of the 5,510 patients developed recurrent hemarthrosis. Bleeding occurred at an average of 2 years 3 months after the operation. Joint aspiration was performed 3.5 times (range, 2 to 10 times) on average, and 14 cases (82.3%) were treated with conservative treatment. In 3 patients with severe bleeding and hemorrhage, embolization was performed. Conclusions Recurrent hemarthrosis after TKR is a rare disease with a low incidence of 0.3% and usually could be treated by conservative treatment. If recurrences occur repeatedly, embolization through angiography or surgical treatment may be considered, but the results are not satisfactory and careful selection of treatment modalities is warranted. PMID:29715715

After-effects reported by women having follow-up cervical cytology tests in primary care: a cohort study within the TOMBOLA trial.

PubMed

Cotton, Seonaidh; Sharp, Linda; Cochran, Claire; Gray, Nicola; Cruickshank, Maggie; Smart, Louise; Thornton, Alison; Little, Julian

2011-06-01

Although it is recognised that some women experience pain or bleeding during a cervical cytology test, few studies have quantified physical after-effects of these tests. To investigate the frequency, severity, and duration of after-effects in women undergoing follow-up cervical cytology tests, and to identify subgroups with higher frequencies in Grampian, Tayside, and Nottingham. Cohort study nested with a multi-centre individually randomised controlled trial. The cohort included 1120 women, aged 20-59 years, with low-grade abnormal cervical cytology who completed a baseline sociodemographic questionnaire and had a follow-up cervical cytology test in primary care 6 months later. Six weeks after this test, women completed a postal questionnaire on pain, bleeding, and discharge experienced after the test, including duration and severity. The adjusted prevalence of each after-effect was computed using logistic regression. A total of 884 women (79%) completed the after-effects questionnaire; 30% of women experienced one or more after-effect: 15% reported pain, 16% bleeding, and 7% discharge. The duration of discharge was ≤2 days for 66%, 3-6 days for 22%, and ≥7 days for 11% of women. Pain or bleeding lasted ≤2 days in more than 80% of women. Severe after-effects were reported by <1% of women. The prevalence of pain decreased with increasing age. Bleeding was more frequent among nulliparous women. Discharge was more common among oral contraceptive users. Pain, bleeding, and discharge are not uncommon in women having follow-up cervical cytology tests. Informing women about possible after-effects could better prepare them and provide reassurance, thereby minimising potential non-adherence with follow-up or non-participation with screening in the future.

After-effects reported by women having follow-up cervical cytology tests in primary care: a cohort study within the TOMBOLA trial

PubMed Central

Cotton, Seonaidh; Sharp, Linda; Cochran, Claire; Gray, Nicola; Cruickshank, Maggie; Smart, Louise; Thornton, Alison; Little, Julian

2011-01-01

Background Although it is recognised that some women experience pain or bleeding during a cervical cytology test, few studies have quantified physical after-effects of these tests. Aim To investigate the frequency, severity, and duration of after-effects in women undergoing follow-up cervical cytology tests, and to identify subgroups with higher frequencies in Grampian, Tayside, and Nottingham. Design Cohort study nested with a multi-centre individually randomised controlled trial. Method The cohort included 1120 women, aged 20–59 years, with low-grade abnormal cervical cytology who completed a baseline sociodemographic questionnaire and had a follow-up cervical cytology test in primary care 6 months later. Six weeks after this test, women completed a postal questionnaire on pain, bleeding, and discharge experienced after the test, including duration and severity. The adjusted prevalence of each after-effect was computed using logistic regression. Results A total of 884 women (79%) completed the after-effects questionnaire; 30% of women experienced one or more after-effect: 15% reported pain, 16% bleeding, and 7% discharge. The duration of discharge was ≤2 days for 66%, 3–6 days for 22%, and ≥7 days for 11% of women. Pain or bleeding lasted ≤2 days in more than 80% of women. Severe after-effects were reported by <1% of women. The prevalence of pain decreased with increasing age. Bleeding was more frequent among nulliparous women. Discharge was more common among oral contraceptive users. Conclusion Pain, bleeding, and discharge are not uncommon in women having follow-up cervical cytology tests. Informing women about possible after-effects could better prepare them and provide reassurance, thereby minimising potential non-adherence with follow-up or non-participation with screening in the future. PMID:21801512

PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A.

PubMed

Lissitchkov, T; Rusen, L; Georgiev, P; Windyga, J; Klamroth, R; Gercheva, L; Nemes, L; Tiede, A; Bichler, J; Knaub, S; Belyanskaya, L; Walter, O; Pasi, K J

2017-09-01

Nuwiq ® (human-cl rhFVIII) is a 4 th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq ® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg -1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. PK-guided personalized prophylaxis with Nuwiq ® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Abnormal uterine bleeding in reproductive-aged women.

PubMed

Matthews, Michelle L

2015-03-01

Abnormal uterine bleeding is a common medical condition with several causes. The International Federation of Gynecology and Obstetrics published guidelines in 2011 to develop universally accepted nomenclature and a classification system. In addition, the American College of Obstetrics and Gynecology recently updated recommendations on evaluation of abnormal uterine bleeding and indications for endometrial biopsies. This article reviews both medical and surgical treatments, including meta-analysis reviews of the most effective treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

Appendicular bleeding: an excepcional cause of lower hemorrhage.

PubMed

Magaz Martínez, Marta; Martín López, Javier; De la Revilla Negro, Juan; González Partida, Irene; de Las Heras, Tania; Sánchez Yuste, María Rosario; Ríos Garcés, Roberto; Salas Antón, Clara; Abreu García, Luis Esteban

2016-07-01

Chronic complications of acute appendicitis managed in a conservative manner are not frequent. We present a case of acute lower gastrointestinal hemorrhage in a young patient with a previous acute appendicitis without surgical intervention. The colonoscopy detected an appendicular bleeding which was surgically treated. The anatomopathological diagnosis was granulomatous appendicitis. The clinical evolution of the patient was favorable without bleeding recurrence. Appendicular hemorrhage can be an unusual complication-however potentially severe-of acute appendicitis not treated surgically.

BE EMPOWERED, a specialty pharmacy education program for hemophilia B patients, impacts adult joint bleeds and pediatric use of RICE.

PubMed

Blankenship, Crystal S; Tortella, Bartholomew J; Bruno, Marianna

2014-02-01

Traditional education about hemophilia B in hemophilia treatment centers (HTCs) and episodic contact with HTCs limit the amount of education patients and their caregivers receive. Specialty care providers have frequent, continuing contact with patients. Each contact with a specialty care provider (e.g., coordinating a refill or addressing a patient inquiry) is another opportunity to support patient self-management of the disease and to give counsel on appropriate medication administration. The role of specialty pharmacy in improving patient self-management and supporting medication management and adherence is well established and reported with rheumatoid arthritis, multiple sclerosis, and renal transplant. With hemophilia, specialty pharmacies can support educational reinforcement of HTCs as well as support patient self-management and education of medication therapy. Utilization of patient education materials and programs can facilitate such a role. BE EMPOWERED, a specialty pharmacy education program for hemophilia B patients, is a multimodule education program coupled with frequent telephonic outreach.   To provide education about hemophilia B, based upon discrete curriculum modules, facilitated by a specialty pharmacy-based nurse educator.   Patients with hemophilia B (or, for children, their caregivers) were enrolled in the BE EMPOWERED program, and data were prospectively collected regarding bleeding and hemophilia-specific quality of life (QoL) outcomes (n = 21 caregivers, n = 17 adults).  BE EMPOWERED was associated with a statistically significant impact on the use of RICE (rest, ice, compression, and elevation) by caregivers whose utilization increased from 81% to 95% (P = 0.05). Adults in the BE EMPOWERED program experienced a statistically significant drop in the annualized bleeding rate (ABR), decreasing from 4.7 to 2.5 for total bleeds and decreasing from 3.5 to 1.7 for joint bleeds (P ≤ 0.02). For children with hemophilia B, bleeds were less common overall, as reported by their caregivers, with a mean ABR of 1.1 before and 1.2 following the program. Regarding QoL scores, adults had lower scores compared with children enrolled in the program.  Completion of the BE EMPOWERED program was associated with a decrease in total bleeds and in joint bleeds in adults and with increased RICE utilization in children, as reported by caregivers. QoL scores were lower in adults compared with children, and further research is warranted to understand this difference. Future studies may focus on the effect of specialty pharmacy as an educational vehicle with potential cost benefits. 

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.

Warfarin or aspirin in embolism prevention in patients with mitral valvulopathy and atrial fibrillation.

PubMed

Lavitola, Paulo de Lara; Sampaio, Roney Orismar; Oliveira, Walter Amorim de; Bôer, Berta Napchan; Tarasoutchi, Flavio; Spina, Guilherme Sobreira; Grinberg, Max

2010-12-01

Atrial fibrillation (AF) associated to rheumatic mitral valve disease (RMVD) increases the incidence of thromboembolism (TE), with warfarin being the standard therapy, in spite of difficulties in treatment adherence and therapeutic control. To compare the effectiveness of Aspirin vs Warfarin in TE prevention in patients with AF and RMVD. A total of 229 patients (pts) with AF and RMVD were followed in a prospective and randomized study. The first group consisted of 110 pts receiving Aspirin - 200 mg/day (Group Aspirin - GA) and the second group consisted of 119 pts receiving Warfarin at individually-adjusted doses (Group Warfarin - GW). There were 15 embolic events in GA and 24 in GW (p = 0.187), of which 21 presented INR < 2.0. Thus, after excluding patients with inadequate INR, there was a higher number of embolic events in GA than in GW (15 vs 3) (p < 0.0061). The GW showed lower treatment adherence (p = 0.001). Neither group presented episodes of major bleeding. Small bleeding episodes were more frequent in the GW (p < 0.01). Increased serum levels of cholesterol and triglycerides constituted a risk factor for a higher number of thromboembolic events in the studied population, with no difference between the groups. In patients presenting RMVD with AF for less than a year and no previous embolism, Aspirin is little effective in preventing TE. Patients with lower-risk mitral valvulopathy (mitral regurgitation and mitral biological prosthesis), especially in cases presenting contraindication to or low adherence to Warfarin, Aspirin use can present some benefit in TE prevention.

Seventeen-month-long paracorporeal biventricular mechanical support as a bridge to transplantation for severe dilated cardiomyopathy.

PubMed

Kitamura, Tadashi; Torii, Shinzo; Oka, Norihiko; Horai, Tetsuya; Itatani, Keiichi; Yoshii, Takeshi; Nakamura, Yuki; Shibata, Miyuki; Tamura, Tomoki; Araki, Haruna; Matsunaga, Yoshikiyo; Miyaji, Kagami

2015-03-01

The long-term management of paracorporeal biventricular assist devices (BiVAD) is difficult because of significant risks of bleeding, thrombosis, and infection. Here we report the case of a 41-year-old woman with severe dilated cardiomyopathy who developed serious cerebral bleeding after receiving a paracorporeal BiVAD but recovered well after treatment. She eventually underwent cardiac transplantation 17 months after implantation of the paracorporeal BiVAD.

A 34-Week Size Uterus with a Complete Hydatidiform Mole: Hook Effect and Severe Anemia with No Vaginal Bleeding.

PubMed

McLaren, Rodney; Bayya, Vijaya; Irani, Mohamad

2018-01-01

Complete hydatidiform mole is an abnormal pregnancy that usually presents with vaginal bleeding and markedly elevated serum ß-hCG levels. We report a rare case of complete hydatidiform mole occurring in a 16-year-old nulligravid who presented with a 34-week size uterus and a relatively low serum ß-hCG level (722 IU/L)-likely related to the "hook effect"-and severe anemia (hemoglobin: 6.1 g/dL) despite the absence of vaginal bleeding. She also reported right flank pain and was diagnosed with moderate right hydronephrosis owing to the compression exerted by the enlarged uterus on the right ureter. The patient received a total of 6 units of packed red blood cells and was managed by dilation and evacuation followed by serial monitoring of serum ß-hCG levels. Therefore, complete mole can present with symptoms related to an enlarged uterus and severe anemia before the occurrence of vaginal bleeding. It is also important to note that a negative urine pregnancy test or relatively low serum ß-hCG level should prompt repeating the measurement on diluted sample to prevent the "hook effect."

Invasive and non-invasive techniques for detecting portal hypertension and predicting variceal bleeding in cirrhosis: a review.

PubMed

Zardi, Enrico Maria; Di Matteo, Francesco Maria; Pacella, Claudio Maurizio; Sanyal, Arun J

2014-02-01

Portal hypertension is a severe syndrome that may derive from pre-sinusoidal, sinusoidal, and post-sinusoidal causes. As a consequence, several complications (i.e. ascites, oesophageal varices) may develop. In sinusoidal portal hypertension, hepatic venous pressure gradient (HVPG) is a reliable method for defining the grade of portal pressure, establishing the effectiveness of the treatment, and predicting the occurrence of complications; however, some questions exist regarding its ability to discriminate bleeding from non-bleeding varices in cirrhotic patients. Other imaging techniques (transient elastography, endoscopy, endosonography, and duplex Doppler sonography) for assessing causes and complications of portal hypertensive syndrome are available and may be valuable for the management of these patients. In this review, we evaluate invasive and non-invasive techniques currently employed to obtain a clinical prediction of deadly complications, such as variceal bleeding in patients affected by sinusoidal portal hypertension, in order to create a diagnostic algorithm to manage them. Again, HVPG appears to be the reference standard to evaluate portal hypertension and monitor the response to treatment, but its ability to predict several complications and support management decisions might be further improved through the diagnostic combination with other imaging techniques.

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.

Approach to assessing the economic impact of insulin-related hypoglycaemia using the novel Local Impact of Hypoglycaemia Tool.

PubMed

Parekh, W A; Ashley, D; Chubb, B; Gillies, H; Evans, M

2015-09-01

To provide estimates of the costs of severe and non-severe insulin-related hypoglycaemia in the UK using the Local Impact of Hypoglycaemia Tool. Rates of hypoglycaemia were extracted from the UK Hypoglycaemia Study Group observational study. The costs of severe and non-severe hypoglycaemic episodes in insulin-treated adults with Type 1 and Type 2 diabetes were estimated from UK data sources. The rates and costs were then applied to specific populations to give an estimate of the cost of insulin-related hypoglycaemia for the UK, a specific locality, or a user-defined population. User-specific rates and costs could also be applied. The estimated cost of a hypoglycaemic episode can range from as much as £2,152 for severe episodes (for which the patient is admitted to hospital) to as little as £1.67 for non-severe episodes. With a UK population of 64.1 million, the total estimated cost of managing insulin-related hypoglycaemia is £468.0 m per year (£295.9 m for severe episodes, £172.1 m for non-severe episodes). On a local health economy level, using a hypothetical general population of 100 000, the total cost of managing insulin-related hypoglycaemia is estimated to be £730,052 per year (£461,658 for severe and £268,394 for non-severe episodes). The Local Impact of Hypoglycaemia Tool highlights the economic burden of insulin-related hypoglycaemia. Non-severe episodes are often overlooked because of their low individual cost, but their high frequency makes the cumulative cost substantial. The Local Impact of Hypoglycaemia Tool also shows clinicians and budget-holders the economic impact of lower rates of hypoglycaemia. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Use of global assays to understand clinical phenotype in congenital factor VII deficiency.

PubMed

Greene, L A; Goldenberg, N A; Simpson, M L; Villalobos-Menuey, E; Bombardier, C; Acharya, S S; Santiago-Borrero, P J; Cambara, A; DiMichele, D M

2013-09-01

Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy. Global assays of coagulation and fibrinolysis may better characterize overall haemostatic balance and aid in haemorrhagic risk assessment. We evaluated the ability of novel global assays to better understand clinical bleeding severity in congenital FVII deficiency. Subjects underwent central determination of factor VII activity (FVII:C) as well as clot formation and lysis (CloFAL) and simultaneous thrombin and plasmin generation (STP) global assay analysis. A bleeding score was assigned to each subject through medical chart review. Global assay parameters were analysed with respect to bleeding score and FVII:C. Subgroup analyses were performed on paediatric subjects and subjects with FVII ≥ 1 IU dL(-1). CloFAL fibrinolytic index (FI2 ) inversely correlated with FVII:C while CloFAL maximum amplitude (MA) and STP maximum velocity of thrombin generation (VT max) varied directly with FVII:C. CloFAL FI2 directly correlated with bleeding score among subjects in both the total cohort and paediatric subcohort, but not among subjects with FVII ≥ 1 IU dL(-1) . Among subjects with FVII ≥ 1 IU dL(-1), STP time to maximum velocity of thrombin generation and time to maximum velocity of plasmin generation inversely correlated with bleeding score. These preliminary findings suggest a novel potential link between a hyperfibrinolytic state in bleeding severity and congenital FVII deficiency, an observation that should be further explored. © 2013 John Wiley & Sons Ltd.

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.

ACG Clinical Guideline: Management of Patients With Acute Lower Gastrointestinal Bleeding.

PubMed

Strate, Lisa L; Gralnek, Ian M

2016-04-01

This guideline provides recommendations for the management of patients with acute overt lower gastrointestinal bleeding. Hemodynamic status should be initially assessed with intravascular volume resuscitation started as needed. Risk stratification based on clinical parameters should be performed to help distinguish patients at high- and low-risk of adverse outcomes. Hematochezia associated with hemodynamic instability may be indicative of an upper gastrointestinal (GI) bleeding source and thus warrants an upper endoscopy. In the majority of patients, colonoscopy should be the initial diagnostic procedure and should be performed within 24 h of patient presentation after adequate colon preparation. Endoscopic hemostasis therapy should be provided to patients with high-risk endoscopic stigmata of bleeding including active bleeding, non-bleeding visible vessel, or adherent clot. The endoscopic hemostasis modality used (mechanical, thermal, injection, or combination) is most often guided by the etiology of bleeding, access to the bleeding site, and endoscopist experience with the various hemostasis modalities. Repeat colonoscopy, with endoscopic hemostasis performed if indicated, should be considered for patients with evidence of recurrent bleeding. Radiographic interventions (tagged red blood cell scintigraphy, computed tomographic angiography, and angiography) should be considered in high-risk patients with ongoing bleeding who do not respond adequately to resuscitation and who are unlikely to tolerate bowel preparation and colonoscopy. Strategies to prevent recurrent bleeding should be considered. Nonsteroidal anti-inflammatory drug use should be avoided in patients with a history of acute lower GI bleeding, particularly if secondary to diverticulosis or angioectasia. Patients with established high-risk cardiovascular disease should not stop aspirin therapy (secondary prophylaxis) in the setting of lower GI bleeding. [corrected]. The exact timing depends on the severity of bleeding, perceived adequacy of hemostasis, and the risk of a thromboembolic event. Surgery for the prevention of recurrent lower gastrointestinal bleeding should be individualized, and the source of bleeding should be carefully localized before resection.

The management of lower gastrointestinal bleeding.

PubMed

Marion, Y; Lebreton, G; Le Pennec, V; Hourna, E; Viennot, S; Alves, A

2014-06-01

Lower gastrointestinal (LGI) bleeding is generally less severe than upper gastrointestinal (UGI) bleeding with spontaneous cessation of bleeding in 80% of cases and a mortality of 2-4%. However, unlike UGI bleeding, there is no consensual agreement about management. Once the patient has been stabilized, the main objective and greatest difficulty is to identify the location of bleeding in order to provide specific appropriate treatment. While upper endoscopy and colonoscopy remain the essential first-line examinations, the development and availability of angiography have made this an important imaging modality for cases of active bleeding; they allow diagnostic localization of bleeding and guide subsequent therapy, whether therapeutic embolization, interventional colonoscopy or, if other techniques fail or are unavailable, surgery directed at the precise site of bleeding. Furthermore, newly developed endoscopic techniques, particularly video capsule enteroscopy, now allow minimally invasive exploration of the small intestine; if this is positive, it will guide subsequent assisted enteroscopy or surgery. Other small bowel imaging techniques include enteroclysis by CT or magnetic resonance imaging. At the present time, exploratory surgery is no longer a first-line approach. In view of the lesser gravity of LGI bleeding, it is most reasonable to simply stabilize the patient initially for subsequent transfer to a specialized center, if minimally invasive techniques are not available at the local hospital. In all cases, the complexity and diversity of LGI bleeding require a multidisciplinary collaboration involving the gastroenterologist, radiologist, intensivist and surgeon to optimize diagnosis and treatment of the patient. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Bleeding and starving: fasting and delayed refeeding after upper gastrointestinal bleeding.

PubMed

Fonseca, Jorge; Meira, Tânia; Nunes, Ana; Santos, Carla Adriana

2014-01-01

Early refeeding after nonvariceal upper gastrointestinal bleeding is safe and reduces hospital stay/costs. The aim of this study was obtaining objective data on refeeding after nonvariceal upper gastrointestinal bleeding. From 1 year span records of nonvariceal upper gastrointestinal bleeding patients that underwent urgent endoscopy: clinical features; rockall score; endoscopic data, including severity of lesions and therapy; feeding related records of seven days: liquid diet prescription, first liquid intake, soft/solid diet prescription, first soft/solid intake. From 133 patients (84 men) Rockall classification was possible in 126: 76 score ≥5, 50 score <5. One persistent bleeding, eight rebled, two underwent surgery, 13 died. Ulcer was the major bleeding cause, 63 patients underwent endoscopic therapy. There was 142/532 possible refeeding records, no record 37% patients. Only 16% were fed during the first day and half were only fed on third day or later. Rockall <5 patients started oral diet sooner than Rockall ≥5. Patients that underwent endoscopic therapy were refed earlier than those without endotherapy. Most feeding records are missing. Data reveals delayed refeeding, especially in patients with low-risk lesions who should have been fed immediately. Nonvariceal upper gastrointestinal bleeding patients must be refed earlier, according to guidelines.

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

Functional Reconstruction with Latissimus Dorsi Flap following Resection of an Extensive Basal Cell Carcinoma in the Shoulder Region: A Case Report

PubMed Central

Paprottka, Felix J.; Klimas, Dalius; Hebebrand, Detlev

2018-01-01

Large and ulcerating skin tumors have become a rarity in the modern Western world. However, these conditions can cause serious life-threatening complications. The case of a 60-year-old male Caucasian patient is reported, who had suffered from an extensive basal cell carcinoma in the right shoulder region for several years. The patient kept the lesion secret from his friends and family and delayed presentation to health care services. After an episode of tumor-related heavy bleeding, the patient was referred to our clinic and received a radical surgical tumor resection—followed by defect coverage with a latissimus dorsi myocutaneous flap. An alternative treatment option that could be offered to the patient would have been a mutilating surgical procedure with an arm amputation. By using this plastic reconstructive surgical technique, the main function of the shoulder joint was conserved. The presented case demonstrates options for defect coverage of problematic wounds in anatomically complex body regions—like the shoulder—by using a functional reconstruction using myocutaneous flaps. PMID:29896564

[Gastrointestinal bleeding from capillary hemangioma of the ileum detected by 99mTc-HSAD scintigraphy].

PubMed

Asano, Y; Ishii, K; Sagiuchi, T; Aoki, Y; Yanaihara, H; Hayakawa, K

2001-05-01

It has been well-known that technetium-99m-human serum albumin-diethylenetriaminepenta-acetic acid (99mTc-HSAD) scintigraphy is useful for diagnosis of the localization of the gastrointestinal arterial or venous bleeding. In this report, we describe a case of venous bleeding from capillary hemangioma of the ileum end detected by 99mTc-HSAD scintigraphy. This patient was a 9-year-old girl with severe anemia. Gastrointestinal bleeding was suspected from her clinical course and laboratory tests. Immediately after melena occurred, 99mTc-HSAD scintigraphy showed the extravasation of RI suggesting gastrointestinal bleeding in the ileum end. Abdominal angiography immediately after 99mTc-HSAD scintigraphy, however, could not show the extravasation of contrast agent. Because the condition of the patient became worse, laparotomy was performed on the basis of 99mTc-HSAD scintigraphy findings. At surgery, venous bleeding from capillary hemangioma in the ileum end was observed. It was suggested that 99mTc-HSAD scintigraphy was very useful for identifying the gastrointestinal venous bleeding.

The use of antifibrinolytics in pediatric patients with hypoproliferative thrombocytopenia.

PubMed

Delaney, Meghan; Matthews, Dana C; Gernsheimer, Terry B

2017-12-01

Despite the use of evidence-based platelet transfusion therapy during periods of hypoproliferative thrombocytopenia, a large proportion of pediatric hematology/oncology patients continue to suffer from clinically significant bleeding. Antifibrinolytic (AF) drugs have been shown in certain surgical and trauma settings to decrease bleeding, blood transfusion, and improve survival. We conducted a retrospective assessment of the safety of using AF drugs in pediatric patients with hypoproliferative thrombocytopenia at our center as well as the impact on bleeding occurrence and severity. © 2017 Wiley Periodicals, Inc.

Older adults who persistently present to the emergency department with severe, non-severe, and indeterminate episode patterns.

PubMed

Kaskie, Brian; Obrizan, Maksym; Jones, Michael P; Bentler, Suzanne; Weigel, Paula; Hockenberry, Jason; Wallace, Robert B; Ohsfeldt, Robert L; Rosenthal, Gary E; Wolinsky, Fredric D

2011-10-21

It is well known that older adults figure prominently in the use of emergency departments (ED) across the United States. Previous research has differentiated ED visits by levels of clinical severity and found health status and other individual characteristics distinguished severe from non-severe visits. In this research, we classified older adults into population groups that persistently present with severe, non-severe, or indeterminate patterns of ED episodes. We then contrasted the three groups using a comprehensive set of covariates. Using a unique dataset linking individual characteristics with Medicare claims for calendar years 1991-2007, we identified patterns of ED use among the large, nationally representative AHEAD sample consisting of 5,510 older adults. We then classified one group of older adults who persistently presented to the ED with clinically severe episodes and another group who persistently presented to the ED with non-severe episodes. These two groups were contrasted using logistic regression, and then contrasted against a third group with a persistent pattern of ED episodes with indeterminate levels of severity using multinomial logistic regression. Variable selection was based on Andersen's behavioral model of health services use and featured clinical status, demographic and socioeconomic characteristics, health behaviors, health service use patterns, local health care supply, and other contextual effects. We identified 948 individuals (17.2% of the entire sample) who presented a pattern in which their ED episodes were typically defined as severe and 1,076 individuals (19.5%) who typically presented with non-severe episodes. Individuals who persistently presented to the ED with severe episodes were more likely to be older (AOR 1.52), men (AOR 1.28), current smokers (AOR 1.60), experience diabetes (AOR (AOR 1.80), heart disease (AOR 1.70), hypertension (AOR 1.32) and have a greater amount of morbidity (AOR 1.48) than those who persistently presented to the ED with non-severe episodes. When contrasted with 1,177 individuals with a persistent pattern of indeterminate severity ED use, persons with severe patterns were older (AOR 1.36), more likely to be obese (AOR 1.36), and experience heart disease (AOR 1.49) and hypertension (AOR 1.36) while persons with non-severe patterns were less likely to smoke (AOR 0.63) and have diabetes (AOR 0.67) or lung disease (AOR 0.58). We distinguished three large, readily identifiable groups of older adults which figure prominently in the use of EDs across the United States. Our results suggest that one group affects the general capacity of the ED to provide care as they persistently present with severe episodes requiring urgent staff attention and greater resource allocation. Another group persistently presents with non-severe episodes and creates a considerable share of the excess demand for ED care. Future research should determine how chronic disease management programs and varied co-payment obligations might impact the use of the ED by these two large and distinct groups of older adults with consistent ED use patterns.

Lung and heart pathology in fatal drug addiction. A consecutive autopsy study.

PubMed

Kringsholm, B; Christoffersen, P

1987-01-01

Lung and heart sections from 33 drug addicts submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen were studied together with tissue sections from 20 'normal' persons. In the drug addict cases focal bleedings in lung tissue were found in 94%, signs of earlier bleedings, haemosiderin containing histiocytes, were seen in 91%, and focal fibrosis in 46%. The bleeding episodes may be due to hypoxia in connection with heroin intake. In 94% of the drug addicts birefringent material in lung tissue was demonstrated, in 58% in granulomas and giant cells, in 27% in giant cells only and in 9% in isolated histiocytes. The material was localized in the wall of pulmonar arteries and/or in the interstitial tissue, undoubtedly depending on the duration of the abuse. In 18% angiothrombosis was seen, in all cases granulomas/giant cells were observed in the wall of the vessel concerned. The results indicate periodical intravenous injection of dissolved tablets in addition to heroin. Histological signs of pulmonary hypertension were not seen, possibly due to the fact that abuse of central stimulants is very rare in Denmark. Regarding heart alterations no significant differences were demonstrated between drug addicts and controls. The only note-worthy finding was focal infiltration of lymphocytes in the atrio-ventricular bundle in two drug addicts, the meaning of which is uncertain.

Menstrual symptoms: the importance of social factors in women's experiences

PubMed Central

O'Flynn, Norma

2006-01-01

Background Menstrual disorders are a common presentation in primary care. Heavy menstrual bleeding is the most common concern, and is often treated by medical and surgical means despite lack of pathology. Aim To explore women's experiences of menstrual disorders. Design of study Two qualitative studies using semi-structured interviews. Setting Inner-city London. Method An initial study recruited women with heavy menstrual bleeding via their GPs. A follow-up study recruited women with a variety of menstrual problems via general practice and the community. Interviews were taped and transcribed then analysed using the constant comparative method. Results Management of menstruation was a prominent theme in interviews. Women acted to comply with a strong social message that menstruation should be concealed, although this behaviour was often ‘taken for granted.’ The need to conceal evidence or reminders of menstrual bleeding was particularly important. Onset of menstrual symptoms often challenged established strategies for menstrual management. Menstrual management then became a conscious problem and a source of continuing stress. The breakdown of management strategies, by real or threatened episodes of leaking or staining, influenced consultation behaviour and decisions about treatment. Conclusion The social pressure to maintain concealment of menstruation is a strong influence on women's health-related behaviour in response to menstrual concerns. Women's choices may be better understood if attention is paid to the social context in which they live. PMID:17132384

Postauthorization safety study of Clottafact® , a triply secured fibrinogen concentrate in acquired fibrinogen deficiency: a prospective observational study.

PubMed

Négrier, C; Ducloy-Bouthors, A-S; Piriou, V; De Maistre, E; Stieltjes, N; Borel-Derlon, A; Colson, P; Picard, J; Lambert, T; Claeyssens, S; Boileau, S; Bertrand, A; André, M-H; Fourrier, F; Ozier, Y; Sié, P; Gruel, Y; Tellier, Z

2018-02-01

A postauthorization safety study was performed between 2009 and 2012 to describe the use of Clottafact ® in acquired fibrinogen deficiency in real-life medical practice in France. One hundred and fifty patients were planned for 28 days of prospective follow-up after infusion. The analysis of this observational study was descriptive and performed according to the type of treatment (curative or preventive) and the origin of the bleed. One hundred and fifty-six patients (16-87 years) were included in 13 centres and treated in five different medical bleeding situations: postpartum (59), other gynaecological/obstetrical (6), trauma (34), liver (13), cardiovascular (23) and other various bleeding situations (21). The mean follow-up time was 18·9 ± 12·3 days. Two patients presented adverse drug reactions: one a pulmonary embolism and the other a four-site venous thromboembolic episode. All were serious with a dubious causal relationship with the study treatment. Efficacy data were collected as a secondary objective. In 150 patients receiving curative treatment, 117 of 159 infusions (73·6%) were considered as successful by the investigators, 35 as moderate (22%) and seven as no response (4·4%). The Clottafact ® safety profile observed during the study matched the known profile of fibrinogen during use. © 2017 International Society of Blood Transfusion.

Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies.

PubMed

Diener, Hans-Christoph; Gold, Morris; Hagen, Martina

2014-11-19

Most patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints. Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were 'all headache episodes' and those with 'severe pain at baseline'. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities. 6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p < 0.0001), and similarly for those severe at baseline (20.2% vs. 12.1% and 10.8%; p ≤ 0.0003). A similar pattern of superiority was observed for secondary endpoints. The triple combination was generally well tolerated. The combination of acetylsalicylic acid, acetaminophen and caffeine is effective and well tolerated in episodic tension-type headache, and significantly superior to acetaminophen with regard to being pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline.

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.

Endometrial Shedding Effect on Conception and Live Birth in Women With Polycystic Ovary Syndrome

PubMed Central

Diamond, Michael P.; Kruger, Michael; Santoro, Nanette; Zhang, Heping; Casson, Peter; Schlaff, William; Coutifaris, Christos; Brzyski, Robert; Christman, Gregory; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Steinkampf, Michael P.; Gosman, Gabriella G.; Nestler, John E.; Carson, Sandra; Myers, Evan E.; Eisenberg, Esther; Legro, Richard S.

2013-01-01

Objective To estimate whether progestin-induced endometrial shedding, prior to ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). Methods A secondary analysis of the data from 626 women with PCOS from the National Institutes of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). Results While ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live birth per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; p<0.001). The difference was more marked when rate was calculated per ovulation (live birth per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; p < .001). Conclusion Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared to anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin prior to ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS. PMID:22525900

Recombinant factor VIIa (eptacog alfa): a review of its use in congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders.

PubMed

Croom, Katherine F; McCormack, Paul L

2008-01-01

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is structurally similar to human plasma-derived coagulation factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa interacts with thrombin-activated platelets to produce a thrombin burst leading to accelerated fibrin clot formation localized to the site of vascular injury. It is approved in many countries for use as an intravenous hemostatic agent in patients with congenital hemophilia with inhibitors, and also for acquired hemophilia, factor VII deficiency, and Glanzmann thrombasthenia in some countries. Studies have shown it to be effective and generally well tolerated when used intravenously to treat bleeding episodes or provide hemostatic cover during surgery in patients with congenital hemophilia with inhibitors, acquired hemophilia, factor VII deficiency or Glanzmann thrombasthenia. Based on available data, its efficacy in terms of patient-assessed response may be similar to that of activated prothrombin complex concentrate (aPCC), but treatment with a single 270 microg/kg dose of recombinant factor VIIa might reduce the need for rescue therapy compared with aPCC. Recombinant factor VIIa is not immunogenic in patients with hemophilia, does not produce an anamnestic response in hemophilia patients with inhibitors, and has very low thrombogenicity. It is recommended in guidelines as the treatment of choice for bleeds in patients with hemophilia B with high-responding inhibitors and for patients with factor VII deficiency, and is also a first-line therapeutic option for high-responder hemophilia A patients with inhibitors and those with acquired hemophilia. Cost data from pharmacoeconomic analyses support its use in hemophilia patients with inhibitors. Thus, recombinant factor VIIa is a valuable treatment option for patients with these rare, but potentially serious, bleeding disorders.

Long-term mortality and causes of death in endoscopically verified upper gastrointestinal bleeding: comparison of bleeding patients and population controls.

PubMed

Miilunpohja, S; Jyrkkä, J; Kärkkäinen, J M; Kastarinen, H; Heikkinen, M; Paajanen, H; Rantanen, T; Hartikainen, Jek

2017-11-01

Upper gastrointestinal bleeding (UGIB) is a common emergency, with in-hospital mortality between 3 and 14%. However, the long-term mortality and causes of death are unknown. We investigated the long-term mortality and causes of death in UGIB patients in a retrospective single-centre case-control study design. A total of 569 consecutive patients, aged ≥18 years, admitted to Kuopio University Hospital for their first endoscopically verified UGIB during the years 2009-2011 were identified from hospital records. For each UGIB patient, an age, sex and hospital district matched control patient was identified from the Statistics Finland database. Data on endoscopy procedures, laboratory values, comorbidities and medication were obtained from patient records. Data on deaths and causes of death were obtained from Statistics Finland. In-hospital mortality of UGIB patients was low at 3.3%. The long-term (mean follow-up 32 months) mortality of UGIB patients was significantly higher than controls (34.1 versus 12.1%, p < .001). During the 6 months following UGIB, the risk of death compared to controls was highest (HR 19.2, 95% CI 7.0-52.4, p < .001) and remained higher up to 3 years after the bleeding. Beyond 3 years' follow-up, there was no difference in mortality between the groups (HR 0.7, 95% CI 0.4-1.6, p = .436). During the first 3 months after the UGIB episode, mortality was related to gastrointestinal diseases; after 3 months, the causes of death were related to comorbidities and did not differ from causes of death in controls. UGIB patients have three times higher long-term mortality than population controls.

[Transjugular intrahepatic portosystemic shunting with covered stents in children: a preliminary study of safety and patency].

PubMed

Zurera, L J; Espejo, J J; Canis, M; Bueno, A; Vicente, J; Gilbert, J J

2014-01-01

To retrospectively analyze the safety and efficacy of transjugular intrahepatic portosystemic shunting (TIPS) using covered stents in children. We present 6 children (mean age, 10.6 years; mean weight, 33.5kg) who underwent TIPS with 8mm diameter Viatorr(®) covered stents for acute (n=4) or recurrent (n=2) upper digestive bleeding that could not be controlled by endoscopic measures. Five of the children had cirrhosis and the other had portal vein thrombosis with cavernous transformation. We analyzed the relapse of upper digestive bleeding, the complications that appeared, and the patency of the TIPS shunt on sequential Doppler ultrasonography or until transplantation. A single stent was implanted in a single session in each child; none of the children died. The mean transhepatic gradient decreased from 16mmHg (range: 12-21mmHg) before the procedure to 9mmHg (range: 1-15mmHg) after TIPS. One patient developed mild encephalopathy, and the girl who had portal vein thrombosis with cavernous transformation developed an acute occlusion of the TIPS that resolved after the implantation of a coaxial stent. Three children received transplants (7, 9, and 10 months after the procedure, respectively), and the patency of the TIPS was confirmed at transplantation. In the three remaining children, patency was confirmed with Doppler ultrasonography 1, 3, and 5 months after implantation. None of the children had new episodes of upper digestive bleeding during follow-up after implantation (mean: 8.1 months). Our results indicate that TIPS with 8mm diameter Viatorr(®) covered stents can be safe and efficacious for the treatment of upper digestive bleeding due to gastroesophageal varices in cirrhotic children; our findings need to be corroborated in larger series. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

Episodic acidification of small streams in the northeastern united states: ionic controls of episodes

USGS Publications Warehouse

Wigington, P.J.; DeWalle, David R.; Murdoch, Peter S.; Kretser, W.A.; Simonin, H.A.; Van Sickle, J.; Baker, J.P.

1996-01-01

As part of the Episodic Response Project (ERP), we intensively monitored discharge and stream chemistry of 13 streams located in the Northern Appalachian region of Pennsylvania and in the Catskill and Adirondack Mountains of New York from fall 1988 to spring 1990. The ERP clearly documented the occurrence of acidic episodes with minimum episodic pH ??? 5 and inorganic monomeric Al (Alim) concentrations >150 ??g/L in at least two study streams in each region. Several streams consistently experienced episodes with maximum Alim concentrations >350 ??g/L. Acid neutralizing capacity (ANC) depressions resulted from complex interactions of multiple ions. Base cation decreases often made the most important contributions to ANC depressions during episodes. Organic acid pulses were also important contributors to ANC depressions in the Adirondack streams, and to a lesser extent, in the Catskill and Pennsylvania streams. Nitrate concentrations were low in the Pennsylvania streams, whereas the Catskill and Adirondack study streams had high NO3- concentrations and large episodic pulses (???54 ??eq/L). Most of the Pennsylvania study streams also frequently experienced episodic pulses of SO42- (???78 ??eq/L), whereas the Adirondack and Catskill streams did not. High baseline concentrations of SO42- (all three study areas) and NO3- (Adirondacks and Catskills) reduced episodic minimum ANC, even when these ions did not change during episodes. The ion changes that controlled the most severe episodes (lowest minimum episodic ANC) differed from the ion changes most important to smaller, more frequent episodes. Pulses of NO3- (Catskills and Adirondacks), SO42- (Pennsylvania), or organic acids became more important during major episodes. Overall, the behavior of streamwater SO42- and NO4- is an indicator that acidic deposition has contributed to the severity of episodes in the study streams.

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report

PubMed Central

2010-01-01

Introduction We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity. Case presentation As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region. Conclusion Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever. PMID:20525295

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report.

PubMed

Ezzat, Rajan Fuad; Hussein, Hiwa A; Baban, Trifa Shawkat; Rashid, Abbas Tahir; Abdullah, Khaled Musttafa

2010-06-03

We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity. As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region. Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever.

Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.

PubMed

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G; Ferrazzi, Paolo; Gardner, Timothy J; Latini, Roberto; Libby, Peter; Lombardi, Federico; O'Gara, Patrick T; Page, Richard L; Tavazzi, Luigi; Tognoni, Gianni

2012-11-21

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results. To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events. In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00970489.

Severe methemoglobinemia complicating topical benzocaine use during endoscopy in a toddler: a case report and review of the literature.

PubMed

Dahshan, Ahmed; Donovan, G Kevin

2006-04-01

Severe methemoglobinemia resulting from the use of topical benzocaine has been reported in adults as a rare complication. Here we report a case of severe acquired methemoglobinemia resulting from topical use of benzocaine spray during diagnostic upper gastrointestinal endoscopy in a 3-year-old boy with repeated episodes of hematemesis 3 weeks posttonsillectomy. He developed marked cyanosis and became increasingly agitated immediately after completion of his unremarkable endoscopic procedure, which was performed under intravenous sedation. He did not respond to maximum supplemental oxygen and had increased respiratory effort. His pulse oximetry dropped to 85%, but simultaneous arterial blood-gas analysis showed marked hypoxemia (Po2 = 29%) and severe methemoglobinemia (methemoglobin = 39%). His cyanosis and altered mental status promptly resolved after intravenous administration of methylene blue. In patients with methemoglobinemia, pulse oximetry tends to overestimate the actual oxygen saturation and is not entirely reliable. Posttonsillectomy bleeding is a rare but occasionally serious complication that could occur weeks after the surgery, although it more commonly occurs within the first few days. Physicians should remain aware of the possibility of its late onset. This case illustrates the severity of acquired methemoglobinemia that may result from even small doses of topical benzocaine and highlights the fact that prompt treatment of the disorder can be life saving. We question the rationale for routine use of topical anesthetic spray for sedated upper gastrointestinal endoscopy in children. By bringing the attention of pediatricians to this rare but serious complication, we hope that it will result in its improved recognition and possible prevention.

Acquired Uterine Arteriovenous Malformation and Retained Placenta Increta.

PubMed

Roach, Michelle K; Thomassee, May S

2015-09-01

Uterine arteriovenous malformations are rare and have been reported to occur after uterine trauma (eg, surgery, gestational trophoblastic disease, malignancy). A 33-year-old woman, gravida 3 para 3, presented 4 weeks post-cesarean delivery with episodic profuse vaginal bleeding. Pelvic ultrasonography and magnetic resonance imaging revealed a left uterine arteriovenous malformation. After consideration of all treatment options, total laparoscopic hysterectomy was performed. Acquired uterine arteriovenous malformations and placental ingrowth into the myometrium are increasingly reported after surgical uterine procedures. This case of a postpartum patient with both uterine arteriovenous malformation and retained placenta increta suggests a correlation between the two complications.

Inflammatory myoglandular polyp--a rare but distinct type of colorectal polyps.

PubMed

Becheanu, Gabriel; Stamm, Bernhard

2003-01-01

The aim of this paper was to report another example of a rare type of colorectal polyps, the inflammatory myoglandular polyp, and to reaffirm this type of polyp as a distinct entity. This solitary pedunculated polyp was detected after a single episode of rectal bleeding. It was situated in the sigmoid colon, measured 2.5 cm in greatest diameter, and was composed almost exclusively of smooth muscles and hyperplastic glands. The patient had neither chronic colitis nor diverticula. Clinical presentation, localization, and histology give this type of polyp a unique appearance and justify its designation as a separate entity.

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.

Delayed bleeding and hemorrhage of mucosal defects after gastric endoscopic submucosal dissection on second-look endoscopy.

PubMed

Ono, Shoko; Ono, Masayoshi; Nakagawa, Manabu; Shimizu, Yuichi; Kato, Mototsugu; Sakamoto, Naoya

2016-04-01

Although second-look endoscopy is performed within several days after gastric endoscopic submucosal dissection (ESD), there has been no evidence supporting the usefulness of the intervention. We investigated the relationship between delayed bleeding and hemorrhage of mucosal defects after ESD on second-look endoscopy and analyzed risk factors of active bleeding on second-look endoscopy. A total of 441 consecutive ESD cases with gastric cancer or adenoma were retrospectively analyzed. Second-look endoscopy was performed in the morning after the day of ESD. Bleeding of mucosal defects on second-look endoscopy was classified according to the Forrest classification, and active bleeding was defined as Forrest Ia or Ib. Delayed bleeding was defined as hematemesis or melena after second-look endoscopy. A total of 406 second-look endoscopies were performed, and delayed bleeding occurred in 11 patients. The incidence rate of delayed bleeding after second-look endoscopy in patients with Forrest Ia or Ib was significantly higher than that in patients with Forrest IIa, IIb or III (7.69 vs. 2.02 %, p < 0.05). Complication of a histological ulcer, large size of the resected specimen and long ESD procedure time were shown to be risk factors for hemorrhage of mucosal defects after ESD on second-look endoscopy by univariate analysis. Multivariate analysis indicated that only large size of the resected specimen was a risk factor. In a specimen size of >35 mm, the odds ratio of active bleeding on second-look endoscopy was 1.9. Active bleeding of mucosal defects on second-look endoscopy is a risk factor for delayed bleeding.

Hemostatic abnormalities in Noonan syndrome.

PubMed

Artoni, Andrea; Selicorni, Angelo; Passamonti, Serena M; Lecchi, Anna; Bucciarelli, Paolo; Cerutti, Marta; Cianci, Paola; Gianniello, Francesca; Martinelli, Ida

2014-05-01

A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score <2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K-dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P < .01 for all aggregating agents). Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients. Copyright © 2014 by the American Academy of Pediatrics.

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.

Bleeding score in type 1 von Willebrand disease patients using the condensed MCMDM-1 vWD validated questionnaire.

PubMed

Pathare, A; Al Hajri, F; Al Omrani, S; Al Obaidani, N; Al Balushi, B; Al Falahi, K

2018-05-13

Assessment of the severity of bleeding symptom has led to the evolution of bleeding assessment tools which are now validated. To administer the condensed molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease VWD (MCMDM-1 vWD) questionnaire to the Omani type 1 vWD patients and correlate it with the laboratory parameters. Patients and controls were personally interviewed and the condensed MCMDM-1 vWD questionnaire administered by a single investigator. Bleeding score (BS) was calculated, based on the presence or absence of the bleeding symptoms according to a standard validated questionnaire in both the patients and the controls. The median age of the patient cohort was 27 (range, 7-49) years with 60.87% of females. The median time to administer condensed MCMDM-1 BS questionnaire was 11 minutes (interquartile range-IQR;7,16). Overall, bleeding from the oral cavity was the most predominant symptom (63%). The median BS was 5 (IQR;1,8) although individual scores ranged between 0 and 29. However, there was no statistically significant difference in BS between genders (males: median 4; IQR 1,6 and females: median 5, IQR 1,10) (P > .05, Kruskal-Wallis test) The Spearman's correlation value of BS was weak with FVIII:C levels and von Willebrand Ristocetin co-factor activity; very weak with von Willebrand Antigen level, and moderate with vonWillebrand Collagen Binding activity being -0.29, -0.28, -0.14 and -0.43, respectively. The BS reflects the severity of bleeding among the vWD patients. Although the BS was abnormal, it did not correlate significantly with the surrogate laboratory parameters [P > .05]. © 2018 John Wiley & Sons Ltd.

Transarterial embolization for the treatment of massive bleeding in gynecologic and obstetric emergencies: a single center experience.

PubMed

Hongsakul, Keerati; Songjamrat, Apiradee; Rookkapan, Sorracha

2014-08-01

Delayed treatment of the massive bleeding in gynecologic and obstetric conditions can cause high morbidity and mortality. The aim of this study is to assess the angiographic findings and outcomes of transarterial embolization in cases of massive hemorrhage from underlying gynecological and obstetrical conditions. This is a retrospective study of 18 consecutive patients who underwent transarterial embolization of uterine and/or hypogastric arteries due to massive bleeding from gynecological and obstetrical causes from January 2006 to December 2011. The underlying causes of bleeding, angiographic findings, technical success rates, clinical success rates, and complications were evaluated. Massive gynecological and obstetrical bleeding occurred in 12 cases and 6 cases, respectively. Gestational trophoblastic disease was the most common cause of gynecological bleeding. The most common cause of obstetrical hemorrhage was primary post-partum hemorrhage. Tumor stain was the most frequent angiographic finding (11 cases) in the gynecological bleeding group. The most common angiographic findings in obstetrical patients were extravasation (2 cases) and pseudoaneurysm (2 cases). Technical and final clinical success rates were found in all 18 cases and 16 cases. Collateral arterial supply, severe metritis, and unidentified cervical laceration were causes of uncontrolled bleeding. Only minor complications occurred, which included pelvic pain and groin hematoma. Percutaneous transarterial embolization is a highly effective and safe treatment to control massive bleeding in gynecologic and obstetric emergencies.

Understanding the experience of caring for children with haemophilia: cross-sectional study of caregivers in the United States.

PubMed

DeKoven, M; Karkare, S; Kelley, L A; Cooper, D L; Pham, H; Powers, J; Lee, W C; Wisniewski, T

2014-07-01

Congenital haemophilia is an inherited bleeding disorder typically diagnosed at birth or shortly thereafter. Haemophilia imposes a significant burden on patients and their caregivers. The aim of the study was to quantify the overall burden of haemophilia on caregivers in the USA using a novel disease-specific questionnaire and the previously validated CarerQol. Targeted literature review and a previous survey conducted by the authors was used to develop an online questionnaire with six burden domains of interest to caregivers (emotional stress, financial, sacrifice, medical management, child's pain and transportation) and several visual analogue scales (VAS). Content validity of the questionnaire was confirmed by three haemophilia caregivers. The study sample consisted of caregivers of children with haemophilia identified via a previously developed opt-in research database. Descriptive statistics were employed for demographic and clinical characteristics; a generalized linear model (GLM) was used to identify factors influencing caregiver burden. A total of 310 caregivers completed the survey (45.5% response rate). Most of the participating caregivers were mothers of a child with haemophilia (88%), between 35 and 44 years of age (48%), and with a college education or a postgraduate degree (63%). 'Child's pain' was identified as the most burdensome domain to caregivers (median score = 3.50 out of 5), followed by 'emotional stress' (2.67), 'financial' (2.40), 'transportation' (2.33), 'sacrifice' (2.17) and 'medical management' (2.00) domains. Although higher income exhibited a protective effect, episodes of bleeds, current presence of an inhibitor and lower caregiver productivity in the past month negatively affected caregiver burden per GLM results. Training and educational programs should potentially be developed to address caregiver burden. © 2014 John Wiley & Sons Ltd.

Hemostatic efficacy of local chitosan linear polymer granule in an experimental sheep model with severe bleeding of arteria and vena femoralis.

PubMed

Ersoy, Gürkan; Rodoplu, Ülkümen; Yılmaz, Osman; Gökmen, Necati; Doğan, Alper; Dikme, Özgür; Aydınoğlu, Aslı; Orhon, Okyanus

2016-05-01

The aim of the present study was to evaluate the hemostatic effect of chitosan linear polymer in a sheep model with femoral bleeding. Following induction of anesthesia and intubation of sheep, groin injury was induced to initiate hemorrhage. Animals were randomly assigned to study and control groups. In the control group, absorbent pads were packed on the wound, and pressure was supplied by a weight placed over the dressing. In the study group, chitosan linear polymer was poured onto the bleeding site; absorbent pads and pressure were applied in the same manner. At 5-min intervals, bleeding was evaluated. Primary endpoint was time to hemostasis. Bleeding had stopped by the 1st interval in 5 members of the study group, and by the 2nd interval in 1 member. One sheep was excluded. The bleeding stopped after the 1st interval in 1 member of the control group and after the 2nd interval in 4 members. Bleeding stopped in 2 cases following ligation of the bleeding vessel. Hemostasis was achieved earlier in the study group, compared to the control group, and the difference was statistically significant. Hemostasis was achieved earlier following application of chitosan linear polymer.

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.

Epistaxis grading in Osler's disease: comparison of comprehensive scores with detailed bleeding diaries.

PubMed

Parzefall, Thomas; Wolf, Axel; Frei, Klemens; Kaider, Alexandra; Riss, Dominik

2017-03-01

Use of reliable grading scores to measure epistaxis severity in hereditary hemorrhagic telangiectasia (HHT) is essential in clinical routine and for scientific purposes. For practical reasons, visual analog scale (VAS) scoring and the Epistaxis Severity Score (ESS) are widely used. VAS scores are purely subjective, and a potential shortcoming of the ESS is that it is based on self-reported anamnestic bleeding data. The aim of this study was to validate the level of correlation between VAS scores, the ESS, and actual bleeding events, based on detailed epistaxis diaries of patients. Records from daily epistaxis diaries maintained by 16 HHT patients over 112 consecutive days were compared with the monthly ESS and daily VAS scores in the corresponding time period. The Spearman rank correlation coefficient, analysis of variance models, and multiple R 2 measures were used for statistical analysis. Although the ESS and VAS scores generally showed a high degree of correlation with actual bleeding events, mild events were underrepresented in both scores. Our results highlight the usefulness of the ESS as a standard epistaxis score in cohorts with moderate to severe degrees of epistaxis. The use of detailed epistaxis diaries should be considered when monitoring patients and cohorts with mild forms of HHT. © 2016 ARS-AAOA, LLC.

Ileal Varices Treated with Balloon-Occluded Retrograde Transvenous Obliteration

PubMed Central

Sato, Takahiro; Yamazaki, Katsu; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi; Akaike, Jun

2009-01-01

A 55-year-old man with hepatitis B virus antigen-positive liver cirrhosis was admitted to our hospital with anal bleeding. Colonoscopy revealed blood retention in the entire colon, but no bleeding lesion was found. Computed tomography images showed that vessels in the ileum were connected to the right testicular vein, and we suspected ileal varices to be the most probable cause of bleeding. We immediately performed double balloon enteroscopy, but failed to find any site of bleeding owing to the difficulty of fiberscope insertion with sever adhesion. Using a balloon catheter during retrograde transvenous venography, we found ileal varices communicating with the right testicular vein (efferent vein) with the superior mesenteric vein branch as the afferent vein of these varices. We performed balloon occluded retrograde transvenous obliteration by way of the efferent vein of the varices and have detected no further bleeding in this patient one year after treatment. PMID:27956966

Ileal Varices Treated with Balloon-Occluded Retrograde Transvenous Obliteration.

PubMed

Sato, Takahiro; Yamazaki, Katsu; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi; Akaike, Jun

2009-04-01

A 55-year-old man with hepatitis B virus antigen-positive liver cirrhosis was admitted to our hospital with anal bleeding. Colonoscopy revealed blood retention in the entire colon, but no bleeding lesion was found. Computed tomography images showed that vessels in the ileum were connected to the right testicular vein, and we suspected ileal varices to be the most probable cause of bleeding. We immediately performed double balloon enteroscopy, but failed to find any site of bleeding owing to the difficulty of fiberscope insertion with sever adhesion. Using a balloon catheter during retrograde transvenous venography, we found ileal varices communicating with the right testicular vein (efferent vein) with the superior mesenteric vein branch as the afferent vein of these varices. We performed balloon occluded retrograde transvenous obliteration by way of the efferent vein of the varices and have detected no further bleeding in this patient one year after treatment.