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.

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.

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 ...

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.

Why Do Patients Bleed?

PubMed Central

Curnow, Jennifer; Pasalic, Leonardo; Favaloro, Emmanuel J.

2016-01-01

Patients undergoing surgical procedures can bleed for a variety of reasons. Assuming that the surgical procedure has progressed well and that the surgeon can exclude surgical reasons for the unexpected bleeding, then the bleeding may be due to structural (anatomical) anomalies or disorders, recent drug intake, or disorders of hemostasis, which may be acquired or congenital. The current review aims to provide an overview of reasons that patients bleed in the perioperative setting, and it also provides guidance on how to screen for these conditions, through consideration of appropriate patient history and examination prior to surgical intervention, as well as guidance on investigating and managing the cause of unexpected bleeding. PMID:28824979

Bleeding risks associated with inheritance of the Quebec platelet disorder.

PubMed

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

2004-07-01

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

During Pregnancy

MedlinePlus

... miscarriages or infant deaths. Top of Page Other Concerns Bleeding and Clotting Disorders : Bleeding and clotting disorders ... anyone affected, but pregnant women often have special concerns. Learn more about infections, medications, vaccinations, and toxins ...

Coagulation Factor Tests

MedlinePlus

... your coagulation factors. Coagulation factors are known by Roman numerals (I, II VIII, etc.) or by name ( ... need this test if you have a family history of bleeding disorders. Most bleeding disorders are inherited . ...

Bleeding Disorders Treatment Options

MedlinePlus

... rare bleeding disorders are usually made from human plasma and are treated to eliminate viruses like HIV ... made in the laboratory and not from human plasma, so they carry no risk of infectious disease. ...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

Hemorrhagic

MedlinePlus

... Hemorrhagic diseases are caused by bleeding, or they result in bleeding (hemorrhaging). Related topics include: Primary thrombocythemia (hemorrhagic thrombocythemia) Stroke Yellow fever Bleeding disorders Ebola fever Dengue hemorrhagic ...

Endometrial haemostasis and menstruation.

PubMed

Davies, Joanna; Kadir, Rezan A

2012-12-01

Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

Heavy Menstrual Bleeding (Menorrhagia)

MedlinePlus

... Facts Signs and Symptoms Heavy Menstrual Bleeding Research Articles & Key Findings Free Materials About Us Information For… Media Policy Makers Blood Disorders Heavy Menstrual Bleeding Recommend ...

A global quantitative survey of hemostatic assessment in postpartum hemorrhage and experience with associated bleeding disorders.

PubMed

James, Andra H; Cooper, David L; Paidas, Michael J

2017-01-01

Coagulopathy may be a serious complicating or contributing factor to postpartum hemorrhage (PPH), and should be promptly recognized to ensure proper bleeding management. This study aims to evaluate the approaches of obstetrician-gynecologists worldwide towards assessing massive PPH caused by underlying bleeding disorders. A quantitative survey was completed by 302 obstetrician-gynecologists from 6 countries (the UK, France, Germany, Italy, Spain, and Japan). The survey included questions on the use of hematologic laboratory studies, interpretation of results, laboratory's role in coagulation assessments, and experience with bleeding disorders. Overall, the most common definitions of "massive" PPH were >2,000 mL (39%) and >1,500 mL (34%) blood loss. The most common criteria for rechecking a "stat" complete blood count and for performing coagulation studies were a drop in blood pressure (73%) and ongoing visible bleeding (78%), respectively. Laboratory coagulation (prothrombin time/activated partial thromboplastin time [PT/aPTT]) and factor VIII/IX assays were performed on-site more often than were mixing studies (laboratory coagulation studies, 93%; factor VIII/IX assays, 63%; mixing studies, 22%). Most commonly consulted sources of additional information were colleagues within one's own specialty (68%) and other specialists (67%). Most respondents had consulted with a hematologist (78%; least, Germany [56%]; greatest, UK [98%]). The most common reason for not consulting was hematologist unavailability (44%). The most commonly reported thresholds for concern with PT and aPTT were 13 to 20 seconds (36%) and 30 to 45 seconds (50%), respectively. Most respondents reported having discovered an underlying bleeding disorder (58%; least, Japan [35%]; greatest, Spain [74%]). Global survey results highlight similarities and differences between countries in how PPH is assessed and varying levels of obstetrician-gynecologist experience with identification of underlying bleeding disorders and engagement of hematology consultants. Opportunities to improve patient management of PPH associated with bleeding disorders include greater familiarity with interpreting PT/aPTT test results and identification of and consistent consultation with hematologists with relevant expertise.

What Should You Know about Blood Disorders in Women?

MedlinePlus

... Articles & Key Findings About Us Do you have heavy periods? This fact sheet talks about the symptoms ... Bleeding Disorders in Women Facts Signs and Symptoms Heavy Menstrual Bleeding Research Articles & Key Findings Free Materials ...

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 ...

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

PubMed

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management

PubMed Central

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%. PMID:29333065

Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy

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

Shiraishi, Yutaka, E-mail: shiraishi@rad.med.keio.ac.jp; Hanada, Takashi; Ohashi, Toshio

2013-09-01

Purpose: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after {sup 125}I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. Methods and Materials: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose–volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUD{sub sum}) was determined by a summation ofmore » the brachytherapy and external-beam radiation therapy components. Results: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUD{sub sum} increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUD{sub sum} (P=.000) as risk factors for grade 2+ rectal bleeding. Conclusions: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.« less

Quebec platelet disorder.

PubMed

Hayward, Catherine P M; Rivard, Georges E

2011-04-01

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with a unique gain-of-function defect in fibrinolysis. In the past 5 years, there have been important advances in the understanding of the pathogenesis of QPD, including its genetic cause, which is a copy number variation mutation of PLAU, the gene for urokinase plasminogen activator (uPA). QPD is the first bleeding disorder identified to be caused by a PLAU mutation and it is also the first bleeding disorder recognized to result from a gene copy number mutation. The molecular defect of QPD leads to marked overexpression of uPA during megakaryopoiesis, producing profibrinolytic platelets that contain active forms of uPA in their α-granules. This article summarizes expert opinions on the features of QPD and recent advances in the understanding of its pathogenesis and genetic cause.

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.

75 FR 66108 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... as bleeding disorders, trauma, and diseases such as sepsis, cardiovascular disease, stroke, and..., cardiovascular disease, stroke, cancer). Treatment of bleeding disorders or trauma. Treatment of cerebral... poor prognosis. Because HCC is often associated with liver disease, traditional chemotherapy is not an...

Munchausen Syndrome Masquerading as Bleeding Disorder in a Group of Pediatric Patients

PubMed Central

Sridharan, Srivani; Shukla, Deepak; Mehta, Ritambhara; Oswal, Rajat

2011-01-01

This short communication is about Munchausen's syndrome in a group of pediatric patients and co morbid Munchausen's syndrome by proxy. A 7-year-old girl presented with spontaneous bleeding from forehead, eyes and scalp. The girl was investigated thoroughly by pediatricians at a tertiary care hospital in western India for all possible bleeding disorders, but there was no conclusive diagnosis. After two days, cases with similar complaints were reported among children residing in the same locality and with similar socioeconomic background. All of them were investigated in detail for possible causes of bleeding but nothing came out. There was a media reporting of the cases as a mysterious bleeding disorder. At this point of time, an expert opinion from the psychiatrist was demanded. Covert video surveillance and series of interviews revealed Munchausen's syndrome and possible Munchausen's syndrome by proxy. An in-depth literature review with special reference to Munchausen's syndrome was carried out to come to a final conclusive diagnosis. PMID:22021962

Munchausen syndrome masquerading as bleeding disorder in a group of pediatric patients.

PubMed

Sridharan, Srivani; Shukla, Deepak; Mehta, Ritambhara; Oswal, Rajat

2011-01-01

This short communication is about Munchausen's syndrome in a group of pediatric patients and co morbid Munchausen's syndrome by proxy. A 7-year-old girl presented with spontaneous bleeding from forehead, eyes and scalp. The girl was investigated thoroughly by pediatricians at a tertiary care hospital in western India for all possible bleeding disorders, but there was no conclusive diagnosis. After two days, cases with similar complaints were reported among children residing in the same locality and with similar socioeconomic background. All of them were investigated in detail for possible causes of bleeding but nothing came out. There was a media reporting of the cases as a mysterious bleeding disorder. At this point of time, an expert opinion from the psychiatrist was demanded. Covert video surveillance and series of interviews revealed Munchausen's syndrome and possible Munchausen's syndrome by proxy. An in-depth literature review with special reference to Munchausen's syndrome was carried out to come to a final conclusive diagnosis.

Post-partum hemorrhage in women with rare bleeding disorders.

PubMed

Peyvandi, Flora; Menegatti, Marzia; Siboni, Simona Maria

2011-02-01

Post-partum hemorrhage (PPH) accounts for a substantial fraction of maternal deaths in the general population. Among all women, however, those affected with rare bleeding disorders (RBDs) represent a particular group since to usual bleeding symptoms, they are likely to experience bleedings associated to obstetrical and gynaecological problems. Pregnancy and childbirth, two important stages in the life of a woman, pose a special clinical challenge in women with RBDs, since information about these issues are really scarce and limited to few case reports. These data show that all women with RBDs, except for FXI deficiency, have to be considered potentially at risk for developing PPH, therefore they should be monitored carefully during and immediately after pregnancy. The implication is that women with bleeding disorders may require prophylaxis and/or close observation for several weeks and should be followed by a multidisciplinary team including expertises such as laboratory haematologist, obstetrician-gynaecologist, anaesthesiologist, family physician, and laboratory technician. © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2011-09-01

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

Conditions associated with canine hypothyroidism.

PubMed

Panciera, D L

2001-09-01

Careful review of the literature regarding clinical signs caused by hypothyroidism in dogs has shown that some assumptions regarding the relation of hypothyroidism to other conditions are based on anecdotal evidence. Cutaneous manifestations are present in most hypothyroid dogs, but the specific abnormalities and breed variations remain to be clearly defined. Decreased metabolic rate manifested by obesity and lethargy is also common. Neurologic manifestations, although uncommon, clearly occur in hypothyroid dogs. Cardiac abnormalities seem to be common, but their clinical significance is questionable. The only consistent hematologic abnormality that occurs in hypothyroid dogs is anemia; evidence for acquired von Willebrand's disease or other bleeding disorders is negligible. Reproductive dysfunction secondary to hypothyroidism is unlikely to occur in male dogs, and there is no evidence to support abnormalities in female dogs. The relation of megaesophagus, laryngeal paralysis, ocular abnormalities, and gastrointestinal disorders with hypothyroidism remains to be established. Future research into canine hypothyroidism may serve to convert dogma into a more clear understanding of the manifestations and pathophysiologic findings of this common endocrinopathy.

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

PubMed Central

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

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: 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 patients with haematological disorders after chemotherapy with or without stem cell transplantation. PMID:25722651

Congenital Disorders of Platelet Function and Number.

PubMed

Sharma, Ruchika; Perez Botero, Juliana; Jobe, Shawn M

2018-06-01

Mucocutaneous bleeding symptoms and/or persistent thrombocytopenia occur in individuals with congenital disorders of platelet function and number. Apart from bleeding, these disorders are often associated with additional hematologic and clinical manifestations, including auditory, immunologic, and oncologic disease. Autosomal recessive, dominant, and X-linked inheritance patterns have been demonstrated. Precise delineation of the molecular cause of the platelet disorder can aid the pediatrician in the detection and prevention of specific disorder-associated manifestations and guide appropriate treatment and anticipatory care for the patient and family. Copyright © 2018 Elsevier Inc. All rights reserved.

Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

PubMed

Alavi, Seyed Ezatolla Rafiee; Jalalvand, Masumeh; Assadollahi, Vahideh; Tabibian, Shadi; Dorgalaleh, Akbar

2018-04-01

Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm 3 . Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding disorders, and are hence suitable for these patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Yellow fever

MedlinePlus

... the heart, liver, and kidney. Bleeding disorders, seizures, coma, and delirium may also occur. Symptoms may include: ... heartbeats (arrhythmias) Bleeding (may progress to hemorrhage) Seizures Coma

Overview of platelet physiology and laboratory evaluation of platelet function.

PubMed

Rodgers, G M

1999-06-01

Appropriate laboratory testing for the platelet-type bleeding disorders hinges on an adequate assessment in the history and physical examination. Patients with histories and screening laboratory results consistent with coagulation disorders (hemophilia, disseminated intravascular coagulation) are not appropriate candidates for platelet function testing. In contrast, patients with a lifelong history of platelet-type bleeding symptoms and perhaps a positive family history of bleeding would be appropriate for testing. Figure 6 depicts one strategy to evaluate these patients. Platelet morphology can easily be evaluated to screen for two uncommon qualitative platelet disorders: Bernard-Soulier syndrome (associated with giant platelets) and gray platelet syndrome, a subtype of storage pool disorder in which platelet granulation is morphologically abnormal by light microscopy. If the bleeding disorder occurred later in life (no bleeding with surgery or trauma early in life), the focus should be on acquired disorders of platelet function. For those patients thought to have an inherited disorder, testing for vWD should be done initially because approximately 1% of the population has vWD. The complete vWD panel (factor VIII coagulant activity, vWf antigen, ristocetin cofactor activity) should be performed because many patients will have abnormalities of only one particular panel component. Patients diagnosed with vWD should be classified using multimeric analysis to identify the type 1 vWD patients likely to respond to DDAVP. If vWD studies are normal, platelet aggregation testing should be performed, ensuring that no antiplatelet medications have been ingested at least 1 week before testing. If platelet aggregation tests are normal and if suspicion for an inherited disorder remains high, vWD testing should be repeated. The evaluation of thrombocytopenia may require bone marrow examination to exclude primary hematologic disorders. If future studies with thrombopoietin assays confirm preliminary results, however, the bone marrow examination of certain patients may be replaced by a thrombopoietin level.

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.

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.

Challenges in the Evaluation for Possible Abuse: Presentations of Congenital Bleeding Disorders in Childhood

ERIC Educational Resources Information Center

Jackson, Jami; Carpenter, Shannon; Anderst, Jim

2012-01-01

Objectives: To describe children with congenital bleeding disorders that present in a manner that may be concerning for non-accidental trauma (NAT), and to evaluate associations with disease and demographic characteristics. Methods: Ten year retrospective charts of subjects were reviewed at a Hemophilia Treatment Center. Demographic, historical,…

Bleeding from the eyes and through intact skin: physiologic, structural, spiritual, or faked?

PubMed

Bezner, Stephanie K; Buchanan, George R

2013-08-01

Patients with an apparent bleeding disorder can usually be diagnosed by a careful history, physical examination, and screening laboratory tests. However, at times the constellation of bleeding signs and symptoms fail to be explained by test results and/or our current understanding of hemostatic mechanisms. One such patient is the subject of the current report. She is a 13-year-old female with a history of striking bleeding manifestations, including spontaneous hemorrhage from her eyes, scalp, hands, and feet. She was evaluated by one of the authors at a teaching hospital in Mumbai, India in March 2009 during the filming of a National Geographic Channel documentary characterizing puzzling medical disorders encountered in India. Given her unusual bleeding manifestations, she received international media attention at the time. National Geographic and a film company in the United Kingdom subsequently expressed interest in highlighting the patient to document her seemingly rare hematologic disorder and contacted the American Society of Hematology to identify an American hematologist to further investigate the case. With consent of the family and collaboration with a hematologist practicing at a teaching hospital in Mumbai, filming commenced during March 2009 in an attempt to capture the patient's diagnosis and the cultural and medical milieu in which the bleeding events occurred. Copyright © 2013 Wiley Periodicals, Inc.

Sertraline-induced periorbital purpura: a case report.

PubMed

Kayhan, Fatih; Eken, Zahide Eriş; Uguz, Faruk

2015-08-01

The incidence of mild to severe levels of spontaneous bleeding due to the usage of selective serotonin reuptake inhibitors (SSRIs) is relatively low. Although the exact mechanism is not known, it is thought that inhibition of the serotonin transporter together with a decrease in platelet serotonin could be responsible for the bleeding. Therefore, the use of SSRIs in conjunction with anti-aggregants may predispose to or exacerbate the risk of bleeding. In this case report, we describe a 44-year-old female patient with a diagnosis of anxiety disorder who spontaneously developed periorbital purpura during treatment with sertraline. Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene.

PubMed

Paterson, Andrew D; Rommens, Johanna M; Bharaj, Bhupinder; Blavignac, Jessica; Wong, Isidro; Diamandis, Maria; Waye, John S; Rivard, Georges E; Hayward, Catherine P M

2010-02-11

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder linked to a region on chromosome 10 that includes PLAU, the urokinase plasminogen activator gene. QPD increases urokinase plasminogen activator mRNA levels, particularly during megakaryocyte differentiation, without altering expression of flanking genes. Because PLAU sequence changes were excluded as the cause of this bleeding disorder, we investigated whether the QPD mutation involved PLAU copy number variation. All 38 subjects with QPD had a direct tandem duplication of a 78-kb genomic segment that includes PLAU. This mutation was specific to QPD as it was not present in any unaffected family members (n = 114), unrelated French Canadians (n = 221), or other persons tested (n = 90). This new information on the genetic mutation will facilitate diagnostic testing for QPD and studies of its pathogenesis and prevalence. QPD is the first bleeding disorder to be associated with a gene duplication event and a PLAU mutation.

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.

Phenotypic approaches to gene mapping in platelet function disorders - identification of new variant of P2Y12, TxA2 and GPVI receptors.

PubMed

Watson, S; Daly, M; Dawood, B; Gissen, P; Makris, M; Mundell, S; Wilde, J; Mumford, A

2010-01-01

Platelet number or function disorders cause a range of bleeding symptoms from mild to severe. Patients with platelet dysfunction but normal platelet number are the most prevalent and typically have mild bleeding symptoms. The study of this group of patients is particularly difficult because of the lack of a gold-standard test of platelet function and the variable penetrance of the bleeding phenotype among affected individuals. The purpose of this short review is to discuss the way in which this group of patients can be investigated through platelet phenotyping in combination with targeted gene sequencing. This approach has been used recently to identify patients with mutations in key platelet activation receptors, namely those for ADP, collagen and thromboxane A2 (TxA2). One interesting finding from this work is that for some patients, mild bleeding is associated with heterozygous mutations in platelet proteins that are co-inherited with other genetic disorders of haemostasis such as type 1 von Willebrand's disease. Thus, the phenotype of mild bleeding may be multifactorial in some patients and may be considered to be a complex trait.

Animal Models of Hemophilia and Related Bleeding Disorders

PubMed Central

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

Quebec platelet disorder: features, pathogenesis and treatment.

PubMed

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

2008-03-01

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

Causes and Diagnosis of Abnormal Vaginal Bleeding.

PubMed

Sokol, Elizabeth; Peddinti, Radhika

2015-07-01

Abnormal vaginal bleeding in a postmenarchal adolescent patient is most often related to dysfunctional uterine bleeding. However, there are other potential etiologies, including hematologic disorders, infections, and oncologic problems. We present a 12-year-old girl who presented with prolonged vaginal bleeding and was ultimately diagnosed with rhabdomyosarcoma. In this article, we discuss the approach to a patient with vaginal bleeding along with a more in-depth review of risk stratification in rhabdomyosarcoma, including treatment options such as chemotherapy, surgery, and radiation therapy. Copyright 2015, SLACK Incorporated.

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.

Direct-to-consumer advertising for bleeding disorders: a content analysis and expert evaluation of advertising claims.

PubMed

Abel, G A; Neufeld, E J; Sorel, M; Weeks, J C

2008-10-01

In the United States, the Food and Drug Administration (FDA) requires that all direct-to-consumer advertising (DTCA) contain both an accurate statement of a medication's effects ('truth') and an even-handed discussion of its benefits and risks/adverse effects ('fair balance'). DTCA for medications to treat rare diseases such as bleeding disorders is unlikely to be given high priority for FDA review. We reviewed all DTCA for bleeding disorder products appearing in the patient-directed magazine HemeAware from January 2004 to June 2006. We categorized the information presented in each advertisement as benefit, risk/adverse effect, or neither, and assessed the amount of text and type size devoted to each. We also assessed the readability of each type of text using the Flesch Reading Ease Score (FRES, where a score of >or=65 is considered of average readability), and assessed the accuracy of the advertising claims utilizing a panel of five bleeding disorder experts. A total of 39 unique advertisements for 12 products were found. On average, approximately twice the amount of text was devoted to benefits as compared with risks/adverse effects, and the latter was more difficult to read [FRES of 32.0 for benefits vs. 20.5 for risks/adverse effects, a difference of 11.5 (95% CI: 4.5-18.5)]. Only about two-thirds of the advertising claims were considered by a majority of the experts to be based on at least low-quality evidence. As measured by our methods, print DTCA for bleeding disorders may not reach the FDA's standards of truth and fair balance.

Congenital platelet function defects

MedlinePlus

Platelet storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... This disorder may also cause severe bleeding. Platelet storage pool disorder (also called platelet secretion disorder) occurs ...

Bleeding and Blood Disorders in Clients of Voluntary Medical Male Circumcision for HIV Prevention - Eastern and Southern Africa, 2015-2016.

PubMed

Hinkle, Lawrence E; Toledo, Carlos; Grund, Jonathan M; Byams, Vanessa R; Bock, Naomi; Ridzon, Renee; Cooney, Caroline; Njeuhmeli, Emmanuel; Thomas, Anne G; Odhiambo, Jacob; Odoyo-June, Elijah; Talam, Norah; Matchere, Faustin; Msungama, Wezi; Nyirenda, Rose; Odek, James; Come, Jotamo; Canda, Marcos; Wei, Stanley; Bere, Alfred; Bonnecwe, Collen; Choge, Isaac Ang'Ang'A; Martin, Enilda; Loykissoonlal, Dayanund; Lija, Gissenge J I; Mlanga, Erick; Simbeye, Daimon; Alamo, Stella; Kabuye, Geoffrey; Lubwama, Joseph; Wamai, Nafuna; Chituwo, Omega; Sinyangwe, George; Zulu, James Exnobert; Ajayi, Charles A; Balachandra, Shirish; Mandisarisa, John; Xaba, Sinokuthemba; Davis, Stephanie M

2018-03-23

Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President's Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged ≥10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for ≥3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5).

The bleeding time may be longer in children than in adults.

PubMed

Sanders, J M; Holtkamp, C A; Buchanan, G R

1990-01-01

The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults. We have reviewed our 9 years of experience with 137 children (mean age 6.5 years) who were referred for diagnostic evaluation of a bleeding disorder but whose history and physical examination were felt by us to be inconsistent with an abnormality of hemostasis. Bleeding time values in these individuals (mean 6.0 min, 95th percentile 9.0 min) were compared with those of 85 normal adult volunteers (mean 4.4 min, 95th percentile 6.5 min). The Simplate-I disposable device and vertical (perpendicular to elbow crease) incision direction were used in both groups. This difference between the pediatric and adult bleeding time values is statistically significant (p less than 0.0001). Neither age nor sex had a significant effect on the pediatric bleeding time measurements. We conclude that the bleeding time, when performed as described, is longer in children than in adults and that pediatric standards for bleeding time should be used in order to avoid a spurious diagnosis of a primary hemostatic disorder in some normal children.

Capacity Building for Rare Bleeding Disorders in the Remote Commonwealth of the Northern Mariana Islands.

PubMed

Lin, Tiffany F; Carhill, Pam; Huang, James N; Baker, Judith R

2016-04-01

The US Pacific Commonwealth of the Northern Mariana Islands is home to an underserved hemophilia population. We developed a strategy in 2014 to build sustainable island-wide medical, patient and family, and community support for this rare disease. Collaboration with regional bleeding disorder leadership galvanized a weeklong conference series. More than 200 participants attended discipline-specific seminars; pre-post test evaluations documented educational benefits. This time-concentrated island-wide education intervention promoted the rapid identification of new cases and stimulated sustainable bleeding disorder care development. The education series proved feasible, efficient, and effective in increasing knowledge and reducing patient and professional isolation, serving as a model for improving capacity for orphan diseases (those that affect fewer than 200 000 people in any particular country) in underresourced areas.

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

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.

[Psychogenic purpura with hematuria and sexual pain disorder: a case report].

PubMed

Ozyildirim, Ilker; Yücel, Başak; Aktan, Melih

2010-01-01

Psychogenic purpura (Gardner-Diamond syndrome) is the occurrence and spontaneous recurrence of painful ecchymosis following emotional stress and minor trauma. Although the exact mechanism of this syndrome remains unknown, apart from skin lesions, different types of hemorrhaging have been reported, such as epistaxis, gastrointestinal bleeding, and bleeding from the ear canals and eyes. We report a psychogenic purpura case that presented with hematuria in addition to skin lesions. Based on the psychiatric evaluation she was diagnosed with major depressive disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Additionally, sexual pain disorder accompanied these disorders. With the help of antidepressant and supportive psychotherapy, the patient's ecchymosis and bleeding disappeared. During 8 months of follow-up the symptoms did not return. Vaginismus has not been reported in patients with psychogenic purpura. The presence of vaginismus, which is seen more frequently in eastern cultures and is thought to be related to sociocultural determinants, suggests that some cultural factors may be common to both psychogenic purpura and vaginismus. The aim of this case report was to call attention to a syndrome that is rarely seen and diagnosed, and to discuss its relationship to psychosocial factors. This syndrome should be considered in the differential diagnosis of not only ecchymotic lesions, but also various types of bleeding, including hematuria. Despite the fact that its etiology and treatment are not clearly understood, it should be noted that psychological factors play a role in this disease and therefore, psychopharmacological and psychotherapeutic approaches can be effective.

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

Effectiveness of a balance training home exercise programme for adults with haemophilia: a pilot study.

PubMed

Hill, K; Fearn, M; Williams, S; Mudge, L; Walsh, C; McCarthy, P; Walsh, M; Street, A

2010-01-01

Adults with haemophilia and other bleeding disorders often develop lower limb musculoskeletal problems associated with bleeds into joints and muscles, which may affect balance performance and increase likelihood of falling. The aim of this study was to evaluate the effectiveness of an individualized balance and strength home exercise programme on improving balance and related outcomes for adults with haemophilia and other bleeding disorders. Twenty male adults with haemophilia and other bleeding disorders (mean age 39.4 years, 95% CI = 33.7-45.1) were recruited to participate. They underwent a comprehensive clinical and force platform assessment of balance and related measures. Based on assessment findings, the assessing physiotherapist provided an individualized home exercise programme of balance, strengthening and walking exercises. Re-assessment occurred after the 4-month exercise programme. Twelve participants (60%) completed the programme and were re-assessed. There were no safety problems or dropouts associated with the exercise programme aggravating joint status. Although there were no statistically significant changes in any of the measures (adjusted for multiple comparisons), there were improvements of between 5% and 22% on 10 of the 16 measures, with the Neurocom modified Clinical Test of Sensory Interaction on Balance (P = 0.036) and Timed Sit to Stand (P = 0.064) approaching significance. A tailored home exercise programme targeting balance, strengthening and walking is feasible for adults with haemophilia and other bleeding disorders. These results suggest that positive physical outcomes including improved balance and mobility may be achieved with this type of programme.

Genetic factors contribute to bleeding after cardiac surgery.

PubMed

Welsby, I J; Podgoreanu, M V; Phillips-Bute, B; Mathew, J P; Smith, P K; Newman, M F; Schwinn, D A; Stafford-Smith, M

2005-06-01

Postoperative bleeding remains a common, serious problem for cardiac surgery patients, with striking inter-patient variability poorly explained by clinical, procedural, and biological markers. We tested the hypothesis that genetic polymorphisms of coagulation proteins and platelet glycoproteins are associated with bleeding after cardiac surgery. Seven hundred and eighty patients undergoing aortocoronary surgery with cardiopulmonary bypass were studied. Clinical covariates previously associated with bleeding were recorded and DNA isolated from preoperative blood. Matrix Assisted Laser Desorption/Ionization, Time-Of-Flight (MALDI-TOF) mass spectroscopy or polymerase chain reaction were used for genotype analysis. Multivariable linear regression modeling, including all genetic main effects and two-way gene-gene interactions, related clinical and genetic predictors to bleeding from the thorax and mediastinum. Nineteen candidate polymorphisms were assessed; seven [GPIaIIa-52C>T and 807C>T, GPIb alpha 524C>T, tissue factor-603A>G, prothrombin 20210G>A, tissue factor pathway inhibitor-399C>T, and angiotensin converting enzyme (ACE) deletion/insertion] demonstrate significant association with bleeding (P < 0.01). Adding genetic to clinical predictors results improves the model, doubling overall ability to predict bleeding (P < 0.01). We identified seven genetic polymorphisms associated with bleeding after cardiac surgery. Genetic factors appear primarily independent of, and explain at least as much variation in bleeding as clinical covariates; combining genetic and clinical factors double our ability to predict bleeding after cardiac surgery. Accounting for genotype may be necessary when stratifying risk of bleeding after cardiac surgery.

Genetics Home Reference: factor XI deficiency

MedlinePlus

... with this disorder can have heavy or prolonged menstrual bleeding (menorrhagia) or prolonged bleeding after childbirth. In ... the particular mutation and whether one or both copies of the F11 gene in each cell have ...

Nasal endoscopy

MedlinePlus

... have a bleeding disorder or take blood-thinning medicine, let your provider know so they are extra careful to decrease bleeding. If you have heart disease, there is a small risk that you could feel lightheaded or faint.

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.

Capacity Building for Rare Bleeding Disorders in the Remote Commonwealth of the Northern Mariana Islands

PubMed Central

Carhill, Pam; Huang, James N.; Baker, Judith R.

2016-01-01

The US Pacific Commonwealth of the Northern Mariana Islands is home to an underserved hemophilia population. We developed a strategy in 2014 to build sustainable island-wide medical, patient and family, and community support for this rare disease. Collaboration with regional bleeding disorder leadership galvanized a weeklong conference series. More than 200 participants attended discipline-specific seminars; pre–post test evaluations documented educational benefits. This time-concentrated island-wide education intervention promoted the rapid identification of new cases and stimulated sustainable bleeding disorder care development. The education series proved feasible, efficient, and effective in increasing knowledge and reducing patient and professional isolation, serving as a model for improving capacity for orphan diseases (those that affect fewer than 200 000 people in any particular country) in underresourced areas. PMID:26890163

Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders.

PubMed

Neerman-Arbez, Marguerite; de Moerloose, Philippe; Casini, Alessandro

2016-06-01

Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity. These disorders are caused by mutations in the three fibrinogen-encoding genes FGA, FGB, and FGG. Afibrinogenemia is associated with mild to severe bleeding, whereas hypofibrinogenemia is often asymptomatic. For these quantitative disorders, the majority of mutations prevent protein production. However, in some cases, missense or late-truncating nonsense mutations allow synthesis of the mutant fibrinogen chain, but intracellular fibrinogen assembly and/or secretion are impaired. Qualitative fibrinogen disorders are associated with bleeding, thrombosis, or both thrombosis and bleeding, but many dysfibrinogenemias are asymptomatic. The majority of cases are caused by heterozygous missense mutations. Here, we review the laboratory and genetic diagnosis of fibrinogen gene anomalies with an updated discussion of causative mutations identified. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Congenital factor V deficiency: comparison of the severity of clinical presentations among patients with rare bleeding disorders.

PubMed

Naderi, Majid; Tabibian, Shadi; Alizadeh, Shaban; Hosseini, Soudabeh; Zaker, Farhad; Bamedi, Taregh; Shamsizadeh, Morteza; Dorgalaleh, Akbar

2015-01-01

Factor V deficiency (FVD) is a rare bleeding disorder (RBD) mostly present in regions with a high rate of consanguinity. FVD after FXIII deficiency is the next more prevalent RBD in Sistan and Baluchistan (S&B) in southeastern Iran. The aim of this study was to evaluate the clinical manifestations and severity of bleeding diathesis in patients with FVD. This descriptive study was conducted on 23 patients with FVD in S&B province. FVD was diagnosed by clinical findings and routine laboratory tests. Bleeding diatheses were classified into three grades (I-III) depending on the severity of symptoms. The severity of bleeding episodes in our patients was compared with other RBDs. Based on residual plasma FV activity, 6 (26%), 16 (69.5%) and 1 (4.5%) patients had mild, moderate and severe factor deficiency, respectively. 24% of the patients had grade III life-threatening bleeding episodes which in comparison with FVII deficiency (17.4%) and FI deficiency (21%) had a higher incidence, and in comparison with FX deficiency (41.7%) and FXIII deficiency (63.1) had a lower incidence. Grade II and grade I bleeding diathesis were observed in 56.2 and 16.7% of the patients, respectively. FVD is the second most common type of RBD in S&B province and grade II bleeding episodes were the major bleeding presentation and observed in more than half of the patients. © 2014 S. Karger AG, Basel.

The Genetics of bleeding disorders: a report on the UK Haemophilia Centre Doctors' Organisation annual scientific symposium, 10th October 2003.

PubMed

Nicolle, A L; Talks, K L; Hanley, J

2004-07-01

The UK Haemophilia Centre Doctors' Organisation (UKHCDO) held its annual scientific symposium in October 2003, at the International Centre for Life, Newcastle-upon-Tyne. The educational day covered a range of topics relating to the genetics of bleeding disorders, including advances in genetics and gene therapy, antenatal diagnosis and counselling. We present the proceedings from the educational day.

Bleeding and cupping.

PubMed Central

Turk, J. L.; Allen, E.

1983-01-01

Bleeding and cupping have been used in medicine since ancient times in the treatment of fevers and local inflammatory disorders. Local bleeding, by 'wet cupping', was effected by a scarificator or by leeches. John Hunter recommended venesection in moderation but preferred leeches for local bleeding. Bleeding as an accepted therapeutic practice went out of vogue in the middle of the nineteenth century as a result of the introduction of modern scientific methods. Dry cupping and the use of leeches, as counter irritants, persisted until the middle of this century. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6338802

An unexpected cause of vaginal bleeding: the role of pelvic radiography.

PubMed

Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Theodoridis, Theodoros; Galli-Tsinopoulou, Assimina

2014-02-14

Vaginal bleeding and/or discharge in young girls may result from infection, urological problems, endocrine causes, bleeding disorders, dermatological conditions, trauma, sexual abuse, masses or foreign bodies. We report a case of excessive vaginal bleeding caused by a foreign body in a prepubertal girl with emphasis on the diagnostic challenges and pitfalls regarding imaging techniques. In our patient, although invasive and expensive investigations had been initially made, the foreign body was last detected only when a plain pelvic radiography was performed.

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

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

Factitious disorder: a rare cause of haematemesis.

PubMed

McFarlane, Michael; Eaden, Jayne; Burch, Nicola; Disney, Ben

2017-10-01

Acute upper gastrointestinal (GI) bleeding is a common condition in the UK with 50-70,000 admissions per year. In 20% of cases no cause can be found on endoscopy. Here, we present the case of a young female patient who was admitted on three occasions with large volume haematemesis and bleeding from other sites. She was extensively investigated and underwent multiple endoscopic procedures. She was eventually diagnosed with factitious disorder after concerns were raised about the inconsistent nature of her presentations. She was found to be venesecting herself from her intravenous cannula, and ingesting the blood to simulate upper GI bleeding. This is a rare cause of 'haematemesis' but perhaps not as rare as is thought.

Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery.

PubMed

Coppola, Antonio; Windyga, Jerzy; Tufano, Antonella; Yeung, Cindy; Di Minno, Matteo Nicola Dario

2015-02-09

In people with haemophilia or other congenital bleeding disorders undergoing surgical interventions, haemostatic treatment is needed in order to correct the underlying coagulation abnormalities and minimise the bleeding risk. This treatment varies according to the specific haemostatic defect, its severity and the type of surgical procedure. The aim of treatment is to ensure adequate haemostatic coverage for as long as the bleeding risk persists and until wound healing is complete. To assess the effectiveness and safety of different haemostatic regimens (type, dose and duration, modality of administration and target haemostatic levels) administered in people with haemophilia or other congenital bleeding disorders for preventing bleeding complications during and after surgical procedures. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the last search: 20 November 2014. Randomised and quasi-randomised controlled trials comparing any hemostatic treatment regimen to no treatment or to another active regimen in children and adults with haemophilia or other congenital bleeding disorders undergoing any surgical intervention. Two authors independently assessed trials (eligibility and risks of bias) and extracted data. Meta-analyses were performed on available and relevant data. Of the 16 identified trials, four (112 participants) were eligible for inclusion.Two trials evaluated 59 people with haemophilia A and B undergoing 63 dental extractions. Trials compared the use of a different type (tranexamic acid or epsilon-aminocaproic acid) and regimen of antifibrinolytic agents as haemostatic support to the initial replacement treatment. Neither trial specifically addressed mortality (one of this review's primary outcomes); however, in the frame of safety assessments, no fatal adverse events were reported. The second primary outcome of blood loss was assessed after surgery and these trials showed the reduction of blood loss and requirement of post-operative replacement treatment in people receiving antifibrinolytic agents compared with placebo. The remaining primary outcome of need for re-intervention was not reported by either trial.Two trials reported on 53 people with haemophilia A and B with inhibitors treated with different regimens of recombinant activated factor VII (rFVIIa) for haemostatic coverage of 33 major and 20 minor surgical interventions. Neither of the included trials specifically addressed any of the review's primary outcomes (mortality, blood loss and need for re-intervention). In one trial a high-dose rFVIIa regimen (90 μg/kg) was compared with a low-dose regimen (35 μg/kg); the higher dose showed increased haemostatic efficacy, in particular in major surgery, with shorter duration of treatment, similar total dose of rFVIIa administered and similar safety levels. In the second trial, bolus infusion and continuous infusion of rFVIIa were compared, showing similar haemostatic efficacy, duration of treatment and safety. There is insufficient evidence from randomised controlled trials to assess the most effective and safe haemostatic treatment to prevent bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgical procedures. Ideally large, adequately powered, and well-designed randomised controlled trials would be needed, in particular to address the cost-effectiveness of such demanding treatments in the light of the increasing present economic constraints, and to explore the new challenge of ageing patients with haemophilia or other congenital bleeding disorders. However, performing such trials is always a complex task in this setting and presently does not appear to be a clinical and research priority. Indeed, major and minor surgeries are effectively and safely performed in these individuals in clinical practice, with the numerous national and international recommendations and guidelines providing regimens for treatment in this setting mainly based on data from observational, uncontrolled studies.

Bleeding disorders

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Spontaneous thigh hematoma associated with diclofenac.

PubMed

Salemis, Nikolaos S

2009-01-01

Spontaneous nongastrointestinal bleeding in patients treated with nonsteroidal anti-inflammatory drugs is an extremely rare occurrence. Herein, the case of a 60-year-old woman with severe bilateral hip osteoarthritis treated with diclofenac sodium, who presented with manifestations of a spontaneous hematoma of the right thigh, is described. There was no history of trauma or family history of bleeding disorder. Thorough investigation excluded a hemorrhagic disorder. The patient was treated conservatively with success and was advised to discontinue diclofenac.

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.

The level of laboratory testing required for diagnosis or exclusion of a platelet function disorder using platelet aggregation and secretion assays.

PubMed

Mezzano, Diego; Quiroga, Teresa; Pereira, Jaime

2009-03-01

The major advances from research on platelet molecular and cell biology, physiology, and pathophysiology over the past decades have not been adequately translated to clinical laboratory diagnosis. Hereditary platelet function disorders (PFDs) are at least as prevalent in the general population as von Willebrand disease (VWD) although PFDs tend not be as well recognized or evaluated. Clinical mucous and skin bleeding in patients with PFDs is prototypic of primary hemostasis disorders, and the bleeding pattern is not distinguishable from that of other primary hemostasis disorders such as VWD. However, different treatment needs, between these discrete disorders, make a precise diagnosis mandatory. Currently, clinicians receive reliable laboratory reports when testing patients with severe PFDs, such as Glanzmann thrombasthenia and Bernard-Soulier syndrome, due to the distinctive laboratory defects that these disorders present, together with the availability of differential diagnostic tests. This is not the case for the majority of PFDs generically classified as "platelet secretion disorders," which are a heterogeneous group of "mild bleeding disorders," for which there are not universally accepted diagnostic criteria. An important reason for robust diagnostic tests is the high proportion (more than 50% in some reports) of patients with unequivocal bleeding who have no precise diagnosis established after a complete laboratory workup. It is paradoxical that the current "gold standard" test for PFD diagnosis, light transmission aggregometry (LTA), has not been standardized after more than four decades of worldwide clinical use. This review describes current diagnostic assays for PFD in a clinical hemostasis laboratory, relating these with current knowledge on platelet function and pathophysiology. Special emphasis will be given to LTA and platelet secretion tests, as well as to the reasons why sensitive tests are needed to explore the lesser known participation of platelets in blood clotting and fibrinolytic processes.

The role of platelets and ε-aminocaproic acid in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome associated hemorrhage

PubMed Central

Weyand, Angela C.; Lombel, Rebecca M.; Pipe, Steven W.; Shavit, Jordan A.

2015-01-01

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling Gray Platelet Syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from post-procedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. PMID:26505894

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A

PubMed Central

Huth-Kühne, Angela; Baudo, Francesco; Collins, Peter; Ingerslev, Jørgen; Kessler, Craig M.; Lévesque, Hervé; Castellano, Maria Eva Mingot; Shima, Midori; St-Louis, Jean

2009-01-01

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group. PMID:19336751

Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue

PubMed Central

Cocero, Nadia; Pucci, Fabrizio; Messina, Maria; Pollio, Berardino; Mozzati, Marco; Bergamasco, Laura

2015-01-01

Background Dental extractions in haemophiliacs may cause secondary bleeding, requiring repeated surgical and haematological interventions. As a local haemostatic, fibrin glue has recognised efficacy but, as a plasma-derived product, it carries the risk of viral infections. We, therefore, compared fibrin glue with an autologous haemostatic, plasma rich in growth factors (PRGF), in a controlled trial. Material and methods One hundred and twenty patients with different blood disorders were randomised into two cohorts to undergo dental extraction procedures without hospitalisation. Prior to the extractions, patients underwent systemic haematological treatment. Complications were defined as secondary bleeding after the 7-day follow-up period or protracting after the repair procedure. Results There were 106 extractions (7 retained 3rd molars) in the group managed with fibrin glue: secondary bleeding affected 3/60 patients (5%) on the third day after extraction and necessitated additional surgery and systemic treatment (in one case the procedure had to be repeated on the 7th day). In the PRGF arm there were 98 extractions (23 retained 3rd molars): secondary bleeding affected two patients (3.3%) on the first day after extraction and was arrested with surgery without systemic treatment. Four out of the five secondary bleeds occurred in patients with haemophilia A. Concomitant diabetes or liver disease significantly increased the bleeding risk. Discussion The bleeding rates in the study and control arm prove that PRGF works as well as fibrin glue as a local haemostatic. Further assets are that PRGF has autologous origin, does not require additional systemic treatment in post-extraction repair surgery, is associated with an earlier onset of neo-angiogenesis and, overall, can reduce patients’ distress and costs to the health system. PMID:25369587

Psychiatric disorders related to menstrual bleeding among an ultra-orthodox population: case series and literature review.

PubMed

Vishne, Tali; Misgav, Sagit; Bunzel, Michael E

2008-05-01

The relationship between menstrual cycle and obsessive-compulsive disorder (OCD) has been documented in the past and is related to sexual hormone changes. In the ultra-orthodox Jewish population menstrual bleeding is associated both with meticulous rituals of cleanliness and with stressful meanings related to sin, impurity and punishment. Those aspects of the menstrual cycle can be related to specific OCD symptoms among ultra-orthodox women. The current study presents three cases related to the development of obsessive-compulsive symptoms in relation to the menstrual cycle among ultra-orthodox women, and discusses the biological and social-cultural basis of the disorder.

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.

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.

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.

Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran.

PubMed

Dorgalaleh, Akbar; Alavi, Sayed Ezatolla Rafiee; Tabibian, Shadi; Soori, Shahrzad; Moradi, Es'hagh; Bamedi, Taregh; Asadi, Mansour; Jalalvand, Masumeh; Shamsizadeh, Morteza

2017-05-01

Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs. In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs. For this study, all relevant publications were searched in Medlin until 2015. Iran has the highest global incidence of factor XIII deficiency. Factor VII deficiency also is common in Iran, while factor II deficiency, with a prevalence of 1 per ∼3 million, is the rarest form of RBDs. Factor activity is available for all RBDs except for factor XIII deficiency, in which clot solubility remains as a diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few recurrent, common mutations only in patients with factor XIII deficiency, and considerable novel mutations in other RBDs. Clinical manifestations of these patients are variable and patients with factor XIII, factor X and factor VII more commonly presented severe life-threatening bleeding, while patients with combined factor V and factor VIII presented a milder phenotype. Plasma-derived products are the most common therapeutic choice in Iran, used prophylactically or on-demand for the management of these patients. Since Iran has a high rate of RBDs with life-threatening bleeding, molecular studies can be used for carrier detection and, therefore, prevention of the further expansion of these disorders and their fatal consequence.

The impact of bleeding disorders on the socioeconomic status of adult patients. Results of a comparative single centre cohort study.

PubMed

Holstein, Katharina; von Mackensen, Sylvia; Bokemeyer, Carsten; Langer, Florian

2017-07-10

The impact of inherited bleeding disorders on the socioeconomic status (SES) of affected individuals is not clear. The SES of adult patients with congenital bleeding disorders (PWBD) from a centre in Germany (age 42.3 ± 15.0 years) was compared to that of a gender- and age-matched control group of patients with thrombophilia or a thrombotic event (PWT). Patients completed a questionnaire including aspects of SES, impact of the disease on their lives, and health-related quality of life (HRQoL). Forty-five patients were enrolled in each group; 71 % of PBWD had a severe form of the bleeding disorder (FVIII/IX activity < 1 % or VWD type 3), and 60 % of all PWBD were treated on-demand. PWBD had a lower monthly income (p = 0.029) and a worse occupational status (p = 0.047) than PWT, but there was no difference regarding the project-specific SES index. PWBD also reported a worse HRQoL in the physical summary component score of the SF-36 (p < 0.001). More PWBD (69.8 %) reported a high impact of the disease on their lives than PWT (33.3 %, p < 0.001). In summary, PWBD had a worse occupational status, monthly income, health behaviour, HRQoL, and impact of the disease on their lives compared to PWT, but not a significantly different SES in general.

Diagnostic laboratory for bleeding disorders ensures efficient management of haemorrhagic disorders.

PubMed

Riddell, A; Chuansumrit, A; El-Ekiaby, M; Nair, S C

2016-07-01

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described. © 2016 John Wiley & Sons Ltd.

The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage.

PubMed

Weyand, Angela C; Lombel, Rebecca M; Pipe, Steven W; Shavit, Jordan A

2016-03-01

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well-tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. © 2015 Wiley Periodicals, Inc.

The Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial

ClinicalTrials.gov

2018-04-24

Cerebral Hemorrhage; Stroke; Hypertension; Diabetes; Anticoagulant-induced Bleeding; Cerebral Vascular Disorder; Brain Disorder; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

Genetics Home Reference: MYH9-related disorder

MedlinePlus

... related disorder typically experience easy bruising, and affected women have excessive bleeding during menstruation (menorrhagia). The platelets in people with MYH9 -related disorder are larger than normal. These enlarged platelets have difficulty moving into tiny blood vessels like capillaries . As ...

Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

PubMed

Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

2016-05-01

Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. © 2016 International Society on Thrombosis and Haemostasis.

Rotorcraft convertible engines for the 1980s

NASA Technical Reports Server (NTRS)

Eisenberg, J. D.

1982-01-01

Two rotorcraft studies were executed. The goal was to identify attractive techniques for implementing convertible powerplants for the ABC, Folded Tilt Rotor, and X-wing type high speed, high-L/D rotorcraft; to determine the DOC and fuel savings benefits achieved thereby; and to define research required to bring these powerplants into existence by the 1990's. These studies are reviewed herein and the different methods of approach are pointed out as well as the key findings. Fan shaft engines using variable inlet guide vanes or torque converters, and turboprop powerplants appear attractive. Savings in DOC and fuel consumption of over 15 percent are predicted in some cases as a result of convertible engine use rather than using separate engines for the thrust and the shaft functions. Areas of required research are fan performance (including noise), integrated engine/rotorcraft control, torque converters, turbine design, airflow for rotorcraft torque control, bleed for lift flow, and transmissions and clutches.

Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.

PubMed

Napolitano, M; Di Minno, M N D; Batorova, A; Dolce, A; Giansily-Blaizot, M; Ingerslev, J; Schved, J-F; Auerswald, G; Kenet, G; Karimi, M; Shamsi, T; Ruiz de Sáez, A; Dolatkhah, R; Chuansumrit, A; Bertrand, M A; Mariani, G

2016-09-01

A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 μg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 μg kg(-1) (divided as three doses). Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies. © 2016 John Wiley & Sons Ltd.

Blood Disorders

MedlinePlus

... become hard, sticky, and shaped like a C. Thalassemia Red blood cell disorder. Von Willebrand Disease Blood ... Hemophilia Hereditary Hemorrhagic Telangiectasia (HHT) Sickle Cell Disease Thalassemia Vitamin K Deficiency Bleeding Von Willebrand Disease Women’s ...

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

PubMed

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

2018-05-01

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

Dysfunctional uterine bleeding in ovulatory women.

PubMed

Strickler, R C

1985-01-01

Ovulatory dysfunctional uterine bleeding (DUB), a disease prevalent in the latter half of the reproductive years, is diagnosed when organic causes for bleeding have been excluded by clinical, laboratory, and surgical diagnostic means. Disordered prostaglandin metabolism within the endometrium explains most cases of DUB. Nonsteroidal antiinflammatory drugs, oral contraceptives, and oral progestin are effective medical alternatives for women who wish to retain their uterus or to avoid surgery. Hysterectomy is a rapid cure for DUB and is a therapy that is acceptable to many, if not most, women.

Adherence and Coagulation Assays in Dabigatran-treated Patients With Atrial Fibrillation

ClinicalTrials.gov

2017-09-12

Atrial Fibrillation; Medication Adherence; Blood Coagulation Tests; Anticoagulants; Circulating, Hemorrhagic Disorder; Drug Effect; Drug Use; Drug Toxicity; Drug Intolerance; Blood Clot; Blood Coagulation Disorder; Laboratory Problem; Bleeding; Thrombosis

Femoral nerve dysfunction

MedlinePlus

... in the groin Diabetes or other causes of peripheral neuropathy Internal bleeding in the pelvis or belly area ( ... Editorial team. Leg Injuries and Disorders Read more Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more A. ...

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

Bros, Sebastien, E-mail: sebbros@wanadoo.fr; Chabrot, Pascal, E-mail: pchabrot@chu-clermontferrand.fr; Kastler, Adrian, E-mail: a_kastler@chu-clermontferrand.fr

Purpose: To retrospectively identify predictive factors of recurrent bleeding within 24 h after uterine artery embolization (UAE) for postpartum hemorrhage (PPH). Materials and Methods: A total of 194 patients underwent UAE for PPH between August 1999 and April 2009 at our institution. Twelve patients experienced recurrent bleeding within the next 24 h; a second attempt at UAE was thus necessary, which was successful in 10 cases. In two cases, hemostatic hysterectomy was performed. Epidemiological, gynecological-obstetrical, anatomic, and biological data were analyzed. Results: Complete data were available for 148 of the 194 (76%) included patients. Sixty-four (43%) were primiparous, 18 (12.2%)more » had a placenta accreta, 21 (14%) had a coagulopathy, and 28 (18.9%) had an anatomic variant of the uterine arterial vasculature. Mean age and pregnancy term were similar in both recurring and nonrecurrent bleeding groups. After multivariate analysis, three criteria emerged as risk factors of recurrent bleeding: primiparity (10 patients, 83%; odds ratio [OR] = 18.84; P = 0.014), coagulation disorders (6 patients, 50%; OR = 12.08; P = 0.006), and anatomic variant of the uterine arterial vasculature (28 patients; OR = 9.83; P = 0.003). Conclusions: earch for uterine collaterals must be performed before UAE for PPH. Primiparity and coagulation disorders increase the risk of recurrent bleeding after UAE for PPH.« less

Evolution of engine cycles for STOVL propulsion concepts

NASA Technical Reports Server (NTRS)

Bucknell, R. L.; Frazier, R. H.; Giulianetti, D. J.

1990-01-01

Short Take-off, Vertical Landing (STOVL) demonstrator concepts using a common ATF engine core are discussed. These concepts include a separate fan and core flow engine cycle, mixed flow STOVL cycles, separate flow cycles convertible to mixed flow, and reaction control system engine air bleed. STOVL propulsion controls are discussed.

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

PubMed

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

2013-11-01

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

Dental health and oral health-related quality of life in children with congenital bleeding disorders.

PubMed

Salem, K; Eshghi, P

2013-01-01

The purpose of this study was to investigate the dental and some other aspects of oral health status of young patients with congenital bleeding disorders (CBD) and the impact of these on their quality of life (OHR-QoL) compared with controls. DMFS-dmfs (Decayed, Missed, Filled Tooth surfaces in permanent and primary teeth) scores, Simplified oral hygiene index, occurance of hypoplasia of first permanent molars, Temporomandibular joint dysfunction and occlusion of 46 CBD patients at the age range of 2-15 years and 46 of other children as control were compared, and the impact of their oral health situation on quality of life was also investigated. Data were analysed by chi-square, t-test and Pearson correlation. Patients were significantly more caries-free with less decayed teeth in primary-permanent dentition (P = 0.03, t = -2.17).The mean scores of OHR-QoL of CBD patients and controls were not significantly different. Oral Bleeding was the significant variable in relation to 'oral health-related quality of life' in CBD groups (Pearson correlation, r = -0.56, P = 0.000). OHR-QoL in the control group was related to dmfs score (r = -0.392, P = 0.011) and male gender (r = -0.329, P = 0.026). Congenital bleeding disorder CBD patients were found to have a better dental health situation in primary dentition compared with controls; however, their 'oral health-related quality of life' was similar. Oral bleeding was the only significant factor related to OHR-QoL in CBD. It shows an overall importance of development of comprehensive care centres for CBD as the main cause of this achievement. © 2012 Blackwell Publishing Ltd.

Evaluation and Management of Adolescents with Abnormal Uterine Bleeding.

PubMed

Mullins, Tanya L Kowalczyk; Miller, Rachel J; Mullins, Eric S

2015-09-01

The International Federation of Gynecology and Obstetrics and the American Congress of Obstetricians and Gynecologists support the use of new terminology for abnormal uterine bleeding (AUB) to consistently categorize AUB by etiology. The term AUB can be further classified as AUB/heavy menstrual bleeding (HMB) (replacing the term "menorrhagia") or AUB/intermenstrual bleeding (replacing the term "metrorrhagia"). Although many cases of AUB in adolescent women are attributable to immaturity of the hypothalamic-pituitary-ovarian axis, underlying bleeding disorders should be considered in women with AUB/HMB. This article reviews the new terminology for AUB, discusses important relevant features of history and examination, presents the laboratory evaluation of HMB, and describes hormonal (oral contraceptive pills, progestin-only methods, long-acting reversible contraceptives including intrauterine systems), hematologic (tranexamic acid and desmopressin), and surgical management options for AUB/HMB. Copyright 2015, SLACK Incorporated.

Spontaneous omental bleeding in a 20-year old patient with hemophilia A. A rare cause for emergency laparotomy.

PubMed

Aumann, V; Chiapponi, C; Meyer, F; Wybranski, C; Bruns, C J; Jannasch, O

2016-11-08

Spontaneous intraabdominal hemorrhage is a very rare event even in patients with bleeding disorders like hemophilia. Nevertheless this rare case must be considered in patients with coagulopathies presenting with abdominal pain. Prompt radiologic imaging and surgical consultation are of highest priority. Here we report on a 20-year-old patient with moderate hemophilia A, who underwent emergency laparotomy for a spontaneous idiopathic bleeding of the omentum majus. There are few cases in the literature on this sort of event in patients with hemophilia, who mostly suffer from spontaneous joint bleedings. These patients require an intensive, interdisciplinary perioperative care, involving haematologists, surgeons, radiologists and anesthesists. Finally we discuss, whether an optimized, individually adapted treatment with coagulation factors might possibly have prevented this bleeding event in this patient.

National and international registries of rare bleeding disorders.

PubMed

Peyvandi, Flora; Spreafico, Marta

2008-09-01

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

The medical management of abnormal uterine bleeding in reproductive-aged women.

PubMed

Bradley, Linda D; Gueye, Ndeye-Aicha

2016-01-01

In the treatment of women with abnormal uterine bleeding, once a thorough history, physical examination, and indicated imaging studies are performed and all significant structural causes are excluded, medical management is the first-line approach. Determining the acuity of the bleeding, the patient's medical history, assessing risk factors, and establishing a diagnosis will individualize their medical regimen. In acute abnormal uterine bleeding with a normal uterus, parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options, given the appropriate clinical scenario. Heavy menstrual bleeding can be treated with a levonorgestrel-releasing intrauterine system, combined oral contraceptives, continuous oral progestins, and tranexamic acid with high efficacy. Nonsteroidal antiinflammatory drugs may be utilized with hormonal methods and tranexamic acid to decrease menstrual bleeding. Gonadotropin-releasing hormone agonists are indicated in patients with leiomyoma and abnormal uterine bleeding in preparation for surgical interventions. In women with inherited bleeding disorders all hormonal methods as well as tranexamic acid can be used to treat abnormal uterine bleeding. Women on anticoagulation therapy should consider using progestin-only methods as well as a gonadotropin-releasing hormone agonist to treat their heavy menstrual bleeding. Given these myriad options for medical treatment of abnormal uterine bleeding, many patients may avoid surgical intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of congenital quantitative fibrinogen disorders: a Delphi consensus.

PubMed

Casini, A; de Moerloose, P

2016-11-01

No evidence-based guidelines for the management of patients suffering from afibrinogenaemia and hypofibrinogenaemia are available. The aim of this study was to harmonize patient's care among invited haemophilia experts from Belgium, France and Switzerland. A Delphi-like methodology was used to reach a consensus on: prophylaxis, bleeding, surgery, pregnancy and thrombosis management. The main final statements are as follows: (i) a secondary fibrinogen prophylaxis should be started after a first life-threatening bleeding in patients with afibrinogenaemia; (ii) during prophylaxis the target trough fibrinogen level should be 0.5 g L -1 ; (iii) if an adaptation of dosage is required, the frequency of infusions rather than the fibrinogen amount should be modified; (iv) afibrinogenaemic patients undergoing a surgery at high bleeding risk should receive fibrinogen concentrates regardless of the personal or family history of bleeding; (v) moderate hypofibrinogenaemic patients (i.e. ≥0.5 g L -1 ) without previous bleeding (despite haemostatic challenges) undergoing a surgery at low bleeding risk may not receive fibrinogen concentrates as prophylaxis; (vi) monitoring the trough fibrinogen levels should be performed at least once a month throughout the pregnancy and a foetal growth and placenta development close monitoring by ultrasound is recommended; (vii) fibrinogen replacement should be started concomitantly to the introduction of anticoagulation in afibrinogenaemic patients suffering from a venous thromboembolic event; and (viii) low-molecular-weight heparin is the anticoagulant of choice in case of venous thromboembolism. The results of this initiative should help clinicians in the difficult management of patients with congenital fibrinogen disorders. © 2016 John Wiley & Sons Ltd.

Nonhepatic hyperammonemic encephalopathy due to undiagnosed urea cycle disorder.

PubMed

Mahmood, Tashfeen; Nugent, Kenneth

2015-07-01

Ornithine transcarbamoylase deficiency is the most common inherited urea cycle disorder. In adults, its phenotypes are diverse. In asymptomatic patients with late presentations, symptom onset is often associated with a precipitating factor. We present a case of a woman with urea cycle disorder diagnosed after an acute peptic ulcer bleed and fasting.

Hemophilia Care in the Pediatric Age

PubMed Central

Bertamino, Marta; Riccardi, Francesca; Banov, Laura; Svahn, Johanna; Molinari, Angelo Claudio

2017-01-01

Hemophilia is the most common of the severe bleeding disorders and if not properly managed since early infancy can lead to chronic disease and lifelong disabilities. However, it enjoys the most efficacious and safe treatment among the most prevalent monogenic disorders. Hemophilia should be considered in the neonatal period in the case of unusual bleeding or in the case of positive family history. Later, hemophilia should be suspected mainly in males because of abnormal bruising/bleeding or unusual bleeding following invasive procedures—for example, tonsillectomy or circumcision. Prophylactic treatment that is started early with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is, therefore, the gold standard of care for hemophilia A and B in most countries with adequate resources. Central venous access catheters and arterovenous fistulas play an important role in the management of hemophilia children requiring repeated and/or urgent administration of coagulation factor concentrates. During childhood and adolescence, personalized treatment strategies that suit the patient and his lifestyle are essential to ensure optimal outcomes. Physical activity is important and can contribute to better coordination, endurance, flexibility and strength. The present article focuses also on questions frequently posed to pediatric hematologists like vaccinations, day-care/school access and dental care. PMID:28534860

Labor and delivery in a patient with hemophilia B.

PubMed

Przkora, R; Euliano, T Y; Roussos-Ross, K; Zumberg, M; Robicsek, S A

2011-07-01

Hemophilia B is a rare X-linked disorder that may cause dramatic bleeding. Women account for only 3.2% of those clinically affected. The X-linked inheritance frequently delays the diagnosis in women and may expose the patient to an increased risk of adverse events. There is limited experience with these patients during labor and delivery. A 28-year-old primiparous woman with hemophilia B (bleeding phenotype) delivered a male infant by an unplanned cesarean delivery under general anesthesia following treatment with factor IX and normalization of her coagulation parameters, guided by thromboelastography. Postpartum vaginal bleeding required transfusion of two units of packed red blood cells. Factor IX supplementation continued for one week. Once diagnosed with hemophilia B, a multidisciplinary approach and advanced antenatal planning can increase the likelihood of a safe delivery. Neuraxial approaches and cesarean delivery are recommended only after normalization of the coagulation profile. The male fetus of a hemophilia A or B patient requires special attention. Operative vaginal delivery and invasive fetal monitoring should be avoided. Thromboelastography is an excellent technique to assess parturients with bleeding disorders or peripartum hemorrhage and may be underused. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hematologic Complications of Pregnancy

PubMed Central

Townsley, Danielle M.

2013-01-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

Massive oral bleeding after full-mouth extraction in a patient with B-cell lymphocytic leukemia/small lymphocytic lymphoma reversed with recombinant activated factor VII.

PubMed

Sprenker, Collin; Omar, Hesham R; Powless, R Andrew; Mangar, Devanand; Camporesi, Enrico

2016-02-01

Full-mouth extraction can be associated with intraoral bleeding, which usually is controlled with local hemostatic measures. Recombinant activated factor VII (rFVIIa) occasionally is used to stop bleeding in a variety of off-label indications, with the main argument curtailing its use being thrombotic events. The authors describe the use of rFVIIa for bleeding after full-mouth extraction in a patient with undiagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. A 72-year-old man underwent full-mouth extraction (18 teeth). The next day, the patient experienced massive oral bleeding. The authors administered tranexamic acid, aminocaproic acid, and a total of 12 units of packed red blood cells in addition to local hemostatic measures without control of bleeding. On postoperative day 10, the authors administered 5,000 micrograms of rFVIIa, and within 2 hours oral the bleeding ceased. The authors performed flow cytometry and diagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. Unexplained massive oral bleeding despite adequate local hemostatic measures should prompt further investigations for underlying bleeding or coagulation disorders. The authors describe the successful use of rFVIIa in massive oral bleeding. Further studies are mandatory to study the effectiveness of this drug for this off-label indication. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

[Vitamin K antagonists overdose].

PubMed

Groszek, Barbara; Piszczek, Paweł

2015-01-01

Nowadays, anticoagulant therapy belongs to the most commonly used forms of pharmacotherapy in modern medicine. The most important representatives of anticoagulants are heparins (unfractionated heparin and low-molecular-weight heparin) and coumarin derivatives (vitamin K antagonists--VKA). Next to the many advantages of traditional oral anticoagulants may also have disadvantages. In Poland most often used two VKA: acenocoumarol and warfarin. The aim of the work is the analysis of the causes of the occurrence of bleeding disorders and symptoms of overdose VKA in patients to be hospitalized. In the years 2012 to 2014 were hospitalized 62 patients with overdose VKA (40 women and 22 men). The average age of patients was 75.3 years) and clotting disturbances and/or bleeding. At the time of the admission in all patients a significant increase in the value of the INR was stated, in 22 patients INR result was " no clot detected", on the remaining value of the INR were in the range of 7 to 13.1. On 51 patients observed different severe symptoms of bleeding (hematuria, bleeding from mucous membranes of the nose or gums ecchymoses on the extremities, bleeding from the gastrointestinal tract--as in 5 patients has led to significant anemia and transfusion of concentrated red blood cells. Up on 33 patients kidney function disorder were found--exacerbated chronic renal failure and urinary tract infection. 8 diagnosed inflammatory changes in the airways. On 13 patients, it was found a significant degree of neuropsychiatric disorders (dementia, cognitive impairment), which made impossible the understanding the sense of treatment and cooperation with the patient. In 6 patients the symptoms of overdose were probably dependent on the interaction with the congestants at the same time (change the preparation of anticoagulant, NSAIDs, antibiotics). In 2 cases, the overdose was a suicide attempt in nature. In addition to the above mentioned disorders, on two of those patients diagnosed with a malignant disease. Two patients died, the other has been improving and anticoagulant therapy with VKA was continued, in 4 VKA were changed to low-molecular-weight heparin, and on 4 commissioned new generation anticoagulant (rivaroxaban).

Atraumatic haemarthrosis following total knee replacement treated with selective embolisation.

PubMed

Karataglis, Dimitrios; Marlow, Duncan; Learmonth, Duncan J A

2006-06-01

Spontaneous haemarthrosis in the absence of anticoagulant medication or a bleeding disorder is a very rare complication after total knee arthroplasty. A case of recurrent spontaneous haemarthrosis following total knee replacement in a 69-year-old patient is reported. Angiography was used to aid the diagnosis. It demonstrated an abnormal blush of vessels around the anterior aspect of the knee joint, that was fed by genicular branches and a recurrent branch of the anterior tibial artery. Selective embolisation of the bleeding vessels with coils led to immediate control of the bleeding. No further recurrence of haemarthrosis has been recorded.

47 CFR 79.102 - Closed caption decoder requirements for digital television receivers and converter boxes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... COMMISSION (CONTINUED) BROADCAST RADIO SERVICES ACCESSIBILITY OF VIDEO PROGRAMMING Apparatus § 79.102 Closed... separated from the underlying video by a sufficient number of background pixels to insure the foreground is... the trailing “white” pixels of the last character on a row do not bleed into the underlying video. (i...

47 CFR 79.102 - Closed caption decoder requirements for digital television receivers and converter boxes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... COMMISSION (CONTINUED) BROADCAST RADIO SERVICES CLOSED CAPTIONING AND VIDEO DESCRIPTION OF VIDEO PROGRAMMING... separated from the underlying video by a sufficient number of background pixels to insure the foreground is... the trailing “white” pixels of the last character on a row do not bleed into the underlying video. (i...

47 CFR 79.102 - Closed caption decoder requirements for digital television receivers and converter boxes.

Code of Federal Regulations, 2013 CFR

2013-10-01

... COMMISSION (CONTINUED) BROADCAST RADIO SERVICES CLOSED CAPTIONING AND VIDEO DESCRIPTION OF VIDEO PROGRAMMING... separated from the underlying video by a sufficient number of background pixels to insure the foreground is... the trailing “white” pixels of the last character on a row do not bleed into the underlying video. (i...

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

PubMed

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

2017-04-01

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

Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders.

PubMed

Malouf, Reem; Ashraf, Asma; Hadjinicolaou, Andreas V; Doree, Carolyn; Hopewell, Sally; Estcourt, Lise J

2018-05-14

Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries. To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders. We searched for randomised controlled trials (RCTs), non-RCTs, and controlled before-after studies (CBAs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2017, Issue 9), Ovid MEDLINE (from 1946), Ovid Embase (from 1974), PubMed (e-publications only), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 12 October 2017. We included RCTs, non-RCTs, and CBAs that involved the transfusion of platelet concentrates (prepared either from individual units of whole blood or by apheresis any dose, frequency, or transfusion trigger) and given to treat or prevent bleeding among people with congenital or acquired bone marrow failure disorders.We excluded uncontrolled studies, cross-sectional studies, and case-control studies. We excluded cluster-RCTs, non-randomised cluster trials, and CBAs with fewer than two intervention sites and two control sites due to the risk of confounding. We included all people with long-term bone marrow failure disorders that require platelet transfusions, including neonates. We excluded studies of alternatives to platelet transfusion, or studies of people receiving intensive chemotherapy or a stem cell transplant. We used the standard methodological procedures outlined by Cochrane. Due to the absence of evidence we were unable to report on any of the review outcomes. We identified one RCT that met the inclusion criteria for this review. The study enrolled only nine adults with MDS over a three-year study duration period. The trial was terminated due to poor recruitment rate (planned recruitment 60 participants over two years). Assessment of the risk of bias was not possible for all domains. The trial was a single-centre, single-blind trial. The clinical and demographic characteristics of the participants were never disclosed. The trial outcomes relevant to this review were bleeding assessments, mortality, quality of life, and length of hospital stay, but no data were available to report on any of these outcomes.We identified no completed non-RCTs or CBAs.We identified no ongoing RCTs, non-RCTs, or CBAs. We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.

Platelet Aggregometry Testing: Molecular Mechanisms, Techniques and Clinical Implications

PubMed Central

Koltai, Katalin; Kesmarky, Gabor; Feher, Gergely; Tibold, Antal

2017-01-01

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing. PMID:28820484

Rare platelet GPCR variants: what can we learn?

PubMed

Nisar, S P; Jones, M L; Cunningham, M R; Mumford, A D; Mundell, S J

2015-07-01

Platelet-expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti-platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders. © 2014 The British Pharmacological Society.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

PubMed

van Galen, Karin P M; Engelen, Eveline T; Mauser-Bunschoten, Evelien P; van Es, Robert J J; Schutgens, Roger E G

2015-12-24

Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and The Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2015. Randomised and quasi-randomised controlled trials in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. While there were no eligible trials in people with Von Willebrand disease identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of epsilon aminocaproic acid published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference of -0.64 (95% confidence interval -0.93 to - 0.36) and the EACA trial a risk difference of -0.50 (95% confidence interval 0.77 to -0.22). The combined risk difference of both trials was -0.57 (95% confidence interval -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping epsilon aminocaproic acid (combined risk difference of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the epsilon aminocaproic acid trial, but overall the risk of bias appeared to be low for both trials. Despite the discovery of a beneficial effect of systemically administered tranexamic acid and epsilon aminocaproic acid in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with Von Willebrand disease.

Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report.

PubMed

Lei, Hongen; Guan, Xing; Han, Hu; Qian, Xiaosong; Zhou, Xiaoguang; Zhang, Xiaodong; Tian, Long

2018-06-01

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of cutaneous port wine capillary malformations, varicose veins, and hemihypertrophy of bone and soft tissues. To report on a rare case of KTS in an adult man manifested by painless urethral bleeding during penile erection briefly review the clinical presentation and management of the genitourinary forms of this syndrome. On presentation, the clinical features of this patient, including medical history, signs and symptoms, and imaging examinations, were recorded. After diagnosis and initial treatment, a literature review of the urethral features of KTS was performed and is discussed in this report. A 35-year-old man with KTS presented with painless urethral bleeding during penile erection that was associated with posterior urethral vascular malformations. The coagulation method was used to treat the malformation, and no urethral bleeding or gross hematuria occurred during a postoperative follow-up period of 6 months. This case demonstrates that coagulation therapy and careful follow-up can be adequate treatment approaches for urethral features of KTS. However, the long-term efficacy of coagulation for this disorder should be investigated further. Lei H, Guan X, Han H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180-183. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Granulocytes and Vascularization Regulate Uterine Bleeding and Tissue Remodeling in a Mouse Menstruation Model

PubMed Central

Menning, Astrid; Walter, Alexander; Rudolph, Marion; Gashaw, Isabella; Fritzemeier, Karl-Heinrich; Roese, Lars

2012-01-01

Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery. PMID:22879894

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.

Abnormal uterine bleeding unrelated to structural uterine abnormalities: management in the perimenopausal period.

PubMed

Sabbioni, Lorenzo; Zanetti, Isabella; Orlandini, Cinzia; Petraglia, Felice; Luisi, Stefano

2017-02-01

Abnormal uterine bleeding (AUB) is one of the commonest health problems encountered by women and a frequent phenomenon during menopausal transition. The clinical management of AUB must follow a standardized classification system to obtain the better diagnostic pathway and the optimal therapy. The PALM-COEIN classification system has been approved by the International Federation of Gynecology and Obstetrics (FIGO); it recognizes structural causes of AUB, which can be measured visually with imaging techniques or histopathology, and non-structural entities such as coagulopathies, ovulatory dysfunctions, endometrial and iatrogenic causes and disorders not yet classified. In this review we aim to evaluate the management of nonstructural causes of AUB during the menopausal transition, when commonly women experience changes in menstrual bleeding patterns and unexpected bleedings which affect their quality of life.

Variability in platelet dense granule adenosine triphosphate release findings amongst patients tested multiple times as part of an assessment for a bleeding disorder.

PubMed

Badin, M S; Graf, L; Iyer, J K; Moffat, K A; Seecharan, J L; Hayward, C P M

2016-12-01

Lumi-aggregometry quantification of platelet dense granule adenosine triphosphate (ATP) release is commonly used for diagnosing platelet function disorders. As the test findings show considerable variability for healthy controls, we postulated that patient findings might also be variable and investigated patients who were assessed for dense granule ATP release defects more than once. Analyses were performed on prospectively collected data for first and second tests for subjects tested for dense granule ATP release defects more than once by the Hamilton Regional Laboratory Program (HRLMP) between January 2007 and June 2013 (cohort I). Similar analyses were performed for subjects who were recruited to a platelet disorder study (cohort II) and were assessed for ATP release defects more than once before October 2015. A total of 150 unique subjects had multiple ATP release tests. Results with individual agonists were variable for many subjects. While normal findings with all tested agonists were often confirmed by the second test (cohort I: 83%; cohort II: 100%), impaired release with multiple agonists was confirmed in only some subjects (cohort I: 34%; cohort II: 54%). Inconsistent findings were common (cohort I: 36%; cohort II: 39%). ISTH bleeding scores showed no relationship to the test findings. The finding of impaired ATP release with 2 or more agonists on both tests was not associated with an increased likelihood of a definite bleeding disorder. The variability in platelet dense granule ATP release findings amongst patients assessed for diagnostic purposes suggests that the test has limited value for diagnosing platelet disorders. © 2016 John Wiley & Sons Ltd.

Emergency department care for patients with hemophilia and von Willebrand disease.

PubMed

Singleton, Tammuella; Kruse-Jarres, Rebecca; Leissinger, Cindy

2010-08-01

Patients with bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease (VWD) are routinely treated at home, with their care managed in specialized centers. In emergency situations, these patients often present to their local emergency department (ED), where their management can represent a challenge to the emergency physicians and staff who rarely encounter them. Delays in diagnosis and administration of replacement therapy are the factors most commonly identified as predictive of death. Patients and family members are often very well educated in the disease and its management, which can significantly reduce morbidity and mortality. Children with bleeding disorders confer different challenges to the emergency physician and staff: they may present with no obvious signs of trauma or they may present with bruises consistent with non-accidental injury. All possible causes of bruising/bleeding should be investigated, although treatment should be administered promptly. The initial presentation of a bleeding disorder in the pediatric population is often made in the ED. Treatment of hemophilia A and B requires rapid replacement of the deficient clotting factor, with the desired factor level and dosage dependent on the product used and the hemorrhagic situation encountered. In patients with VWD, the main treatments are desmopressin or intravenous infusion of plasma-derived concentrates containing factor VIII and von Willebrand factor. The aim of this review is to outline some of the issues facing emergency physicians and the options available for the treatment of patients with hemophilia A, hemophilia B, and VWD. Copyright 2010. Published by Elsevier Inc.

Increased Plasma Clot Permeability and Susceptibility to Lysis Are Associated with Heavy Menstrual Bleeding of Unknown Cause: A Case-Control Study

PubMed Central

Szczepaniak, Piotr; Zabczyk, Michał; Undas, Anetta

2015-01-01

Background Formation of compact and poorly lysable clots has been reported in thromboembolic disorders. Little is known about clot properties in bleeding disorders. Objectives We hypothesized that more permeable and lysis-sensitive fibrin clots can be detected in women with heavy menstrual bleeding (HMB). Methods We studied 52 women with HMB of unknown cause and 52 age-matched control women. Plasma clot permeability (Ks), turbidity and efficiency of fibrinolysis, together with coagulation factors, fibrinolysis proteins, and platelet aggregation were measured. Results Women with HMB formed looser plasma fibrin clots (+16% [95%CI 7–18%] Ks) that displayed lower maximum absorbancy (-7% [95%CI -9 – -1%] ΔAbsmax), and shorter clot lysis time (-17% [95%CI -23 – -11%] CLT). The HMB patients and controls did not differ with regard to coagulation factors, fibrinogen, von Willebrand antigen, thrombin generation markers and the proportion of subjects with defective platelet aggregation. The patients had lower platelet count (-12% [95%CI -19 – -2%]), tissue plasminogen activator antigen (-39% [95%CI -41 – -29%] tPA:Ag), and plasminogen activator inhibitor-1 antigen (-28% [95%CI -38 – -18%] PAI-1:Ag) compared with the controls. Multiple regression analysis upon adjustment for age, body mass index, glucose, and fibrinogen showed that decreased tPA:Ag and shortened CLT were the independent predictors of HMB. Conclusions Increased clot permeability and susceptibility to fibrinolysis are associated with HMB, suggesting that altered plasma fibrin clot properties might contribute to bleeding disorders of unknown origin. PMID:25909989

Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry.

PubMed

Baudo, Francesco; Collins, Peter; Huth-Kühne, Angela; Lévesque, Hervé; Marco, Pascual; Nemes, László; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul

2012-07-05

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

Levonorgestrel-Releasing Intrauterine Device Use in Female Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders: Single Institution Review.

PubMed

Adeyemi-Fowode, Oluyemisi A; Santos, Xiomara M; Dietrich, Jennifer E; Srivaths, Lakshmi

2017-08-01

To identify complications and efficacy of the levonorgestrel-releasing intrauterine device (LNgIUD) in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD). A retrospective chart review of 13 postmenarchal adolescent girls with HMB/BD who underwent placement of an LNgIUD. Placement of an LNgIUD. Primary outcome was to identify complications from placement of an LNgIUD. Secondary outcome was to evaluate the efficacy of the LNgIUD in adolescents with BD. Thirteen patients met study criteria. The mean age of diagnosis of HMB was 14.08 ± 1.75 years. BD or bleeding risk factor diagnoses included low von Willebrand (VW) activity in 5, type I VW disease in 5, type IIM VW disease in 1, low VW activity and factor 7 deficiency in 1, and acquired VW disease and factor 7 deficiency in 1. Before LNgIUD placement, other hormonal therapy (n = 13) and hemostatic therapy (antifibrinolytic agents, desmopressin acetate; n = 8) yielded poor control of HMB. The LNgIUD was placed using anesthesia with periprocedure hemostatic therapy with no complications. All patients reported significant improvement in HMB after LNgIUD placement and 60% achieved amenorrhea, with mean time to improvement of 94 ± 69 days. Mean hemoglobin and ferritin levels increased after LNgIUD placement compared with before LNgIUD placement values (P = .02, P = .0085, respectively). Use of supplemental hormonal and hemostatic agents decreased (n = 4) after LNgIUD placement. None required LNgIUD removal; 1 spontaneously expelled the LNgIUD with subsequent replacement. Study results indicated the LNgIUD is an effective therapeutic option in postmenarchal adolescents with HMB due to BD/bleeding risk factor with minimal complications, high compliance rate, improvement in HMB and anemia, and no periprocedural bleeding with hemostatic management. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Acquired hemophilia A: a review of recent data and new therapeutic options.

PubMed

Franchini, Massimo; Vaglio, Stefania; Marano, Giuseppe; Mengoli, Carlo; Gentili, Sara; Pupella, Simonetta; Liumbruno, Giancarlo Maria

2017-10-01

Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function. We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments. The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently. The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.

The FIGO systems for nomenclature and classification of causes of abnormal uterine bleeding in the reproductive years: who needs them?

PubMed

Munro, Malcolm G; Critchley, Hilary O D; Fraser, Ian S

2012-10-01

In November 2010, the International Federation of Gynecology and Obstetrics formally accepted a new classification system for causes of abnormal uterine bleeding in the reproductive years. The system, based on the acronym PALM-COEIN (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy, ovulatory disorders, endometrial causes, iatrogenic, not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation that relates to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding and the various symptoms that comprise abnormal bleeding has also been included. This article describes the rationale, the structured methods that involved stakeholders worldwide, and the suggested use of the International Federation of Gynecology and Obstetrics system for research, education, and clinical care. Investigators in the field are encouraged to use the system in the design of their abnormal uterine bleeding-related research because it is an approach that should improve our understanding and management of this often perplexing clinical condition. Copyright © 2012. Published by Mosby, Inc.

Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

PubMed

Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

2013-03-01

Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

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.

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

[Haemothorax after blunt thoracic trauma].

PubMed

Siller, J; Havlícek, K

2009-05-01

Haemothorax is frequent consequence of blunt and penetrating thoracic trauma and is usually associated with pneumothorax. The occurence of haemothorax in blunt thoracic trauma patients is estimated between 25-75%. The reason of bleeding is impairment of intercostal arteries or lung parenchyma after trauma of the ribs. Uncontrolled bleeding is the main cause of the death. The article is focused on the treatment of this injury. There were enrolled 238 patients with thoracic trauma, who were admitted into our department, into the study. The average age of the patients was 42.5 years. The ISS > or = 16 were in 101 patients. Forty two patients were artefitially ventilated. Conservative treatment prevails, almost in 65%. Special care was indicated in patients with haemothorax (fluidotoraxem). Clinically and based on other screening methods the presence of the fluid in thoracic cavity was in 131 patients. Surgical treatment (punction, drainage, videothoracoscopy and thoracotomy) was necessary in 47 (35.0%). Thoracotomy for the bleeding was indicated in seven cases (5.3 %). In diagnostics and in treatment of the bleeding in thoracic trauma patients the most important factor is clinical status of the patient. Indication for thoracotomy must be unambigous. Massive haemotorax leads to restrictive ventilation disorder with decreased preload and can be activator of the haemocolaguation disorders. This fact decreases chance for the survival of the patient.

Anorectal emergencies.

PubMed

Lohsiriwat, Varut

2016-07-14

Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up.

Understanding extractive bleed : wood extractives: distribution, properties, and classes

Treesearch

Edward Burke; Norm Slavik; Tony Bonura; Dennis Connelly; Tom Faris; Arnie Nebelsick; Brent Stuart; Sam Williams; Alex C. Wiedenhoeft

2010-01-01

Color, odor, and natural durability of heartwood are characteristics imparted by a class of chemicals in wood known collectively extractives. Wood is converted by the tree from sapwood to heartwood by the deposition of extractives, typically many years after the growth ring undergoing this change was formed by the tree. Extractives are thus not a part of the wood...

Etiology and Outcome of Acute Gastrointestinal Bleeding in Iran:A Review Article

PubMed Central

Masoodi, Mohsen; Saberifiroozi, Mehdi

2012-01-01

Upper gastrointestinal bleeding (UGIB) is defined as bleeding that results from lesions located above the ligament of Treitz and is a common cause for emergency hospital admissions in patients with gastrointestinal disorders. UGIB also increases the risk of morbidity and mortality in patients already hospitalized for other reasons. According to epidemiological surveys of acute UGIB in Iran, peptic ulcer is the most common endoscopic diagnosis. Gastric and duodenal erosion accounts for 16.4%-25% of etiologies. Other relatively common causes of UGIB are variceal hemorrhage, Mallory-Weiss tears, and arterial and venous malformations. However, in 9%-13.3% of patients, the endoscopy is normal. PMID:24829656

Rectal Bleeding After High-Dose-Rate Brachytherapy Combined With Hypofractionated External-Beam Radiotherapy for Localized Prostate Cancer: The Relationship Between Dose-Volume Histogram Parameters and the Occurrence Rate

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

Okamoto, Masahiko, E-mail: masaoka@showa.gunma-u.ac.jp; Ishikawa, Hitoshi; Ebara, Takeshi

2012-02-01

Purpose: To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis. Methods and Materials: The records of 216 patients treated with HDR-BT combined with EBRT were analyzed. The treatment protocols for HDR-BT were 5 Gy Multiplication-Sign five times in 3 days or 7 Gy Multiplication-Sign three, 10.5 Gy Multiplication-Sign two, or 9 Gy Multiplication-Sign two in 2 days. The EBRT doses ranged from 45 to 51 Gy with a fractional dose of 3 Gy. Results: In 20 patients Grade 2more » or worse rectal bleeding developed, and the cumulative incidence rate was 9% at 5 years. By converting the HDR-BT and EBRT radiation doses into biologic effective doses (BED), the BED{sub 3} at rectal volumes of 5% and 10% in the patients who experienced bleeding were significantly higher than those in the remaining 196 patients. Univariate analysis showed that a higher rectal BED{sub 3-5%} and the use of fewer needles in brachytherapy were correlated with the incidence of bleeding, but BED{sub 3-5%} was found to be the only significant factor on multivariate analysis. Conclusions: The radiation dose delivered to small rectal lesions as 5% is important for predicting Grade 2 or worse rectal bleeding after HDR-BT combined with EBRT for prostate cancer.« less

Hematologic complications of pregnancy.

PubMed

Townsley, Danielle M

2013-07-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This review discusses specifically the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations; however, care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist, and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy, and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. Published by Elsevier Inc.

Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines

PubMed Central

Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

2017-01-01

Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd). PMID:19415721

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.

Protein Replacement Therapy and Gene Transfer in Canine Models of Hemophilia A, Hemophilia B, von Willebrand Disease, and Factor VII Deficiency

PubMed Central

Nichols, Timothy C.; Dillow, Aaron M.; Franck, Helen W.G.; Merricks, Elizabeth P.; Raymer, Robin A.; Bellinger, Dwight A.; Arruda, Valder R.; High, Katherine A.

2011-01-01

Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders. PMID:19293459

Congenital spherocytic anemia

MedlinePlus

... cells and bleeding disorders. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Pharmacologic Agents in the Management of Bleeding Disorders

DTIC Science & Technology

1990-01-01

and the antifibrinolytic drugs tranexamic acid in preinfusion plasma,2 2 increase platelet adheience.23 (AMCA) and epsilon- aminocaproic acid (EACA...215-9. aminocaproic acid in the treatment of patients with acute pro- 54. Schulman S, Johnsson H, Egberg N, Blomback M. DDAVP- myclocytie leukemia and...shortens the bleeding time in storage pool 79. Gardner Fli, Helmer RE Ill. Aminocaproic acid . Use in control deficiency. Ann Intern Med 1988;108:65-7. of

The experience of girls and young women with inherited bleeding disorders.

PubMed

Khair, K; Holland, M; Pollard, D

2013-09-01

Haemophilia carriers and women with inherited bleeding disorders (IBD) experience menorrhagia, bleed following dentistry, surgery, injury or childbirth. Symptoms are easily treated leading to full and active lives. Nevertheless, some girls and women suffer with abnormal bleeding for many years before diagnosis. We explored the experiences of girls and young women (aged 9-34 years) with IBD by means of focus groups which consisted of moderated discussion addressing specific aspects of bleeding, management and coping strategies. Subsequently, these issues were explored further though a paper-based questionnaire distributed via five specialist haemophilia centres in the UK. The study suggested that young women with IBD who are managed at haemophilia centres receive appropriate care and feel well supported. Although the clinic-based literature available to these women is "fit for purpose", it does not fully address the perceived needs specifically regarding sex, menorrhagia, conception and childbirth, the Pill, tattoos/piercings and so on, leading many to turn to other information sources. Most of those who responded to our survey are confident in their lives, able to manage their IBD and take pragmatic views towards the inherited nature of their condition. But there is a substantial subgroup of women who experience stigmatization, isolation and bullying and express concerns relating to fertility and conception. Overall, this cohort would benefit from opportunities for mutual support. This could be via Internet-based social networking and may be of particular value to those who are unable to seek help from traditional medical services due to religious or other cultural barriers. © 2013 John Wiley & Sons Ltd.

Both hemophilia health care providers and hemophilia a carriers report that carriers have excessive bleeding.

PubMed

Paroskie, Allison; Oso, Olatunde; Almassi, Benjamin; DeBaun, Michael R; Sidonio, Robert F

2014-05-01

Hemophilia A, the result of reduced factor VIII activity, is an X-linked recessive bleeding disorder. Previous reports of hemophilia A carriers suggest an increased bleeding tendency. Our objective was to determine the attitudes and understanding of the hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey were used as preliminary data for an ongoing prospective study. An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers, and hemophilia A carriers who were members of Hemophilia Federation of America. The questions focused on the clinical understanding of bleeding symptoms and management of hemophilia A carriers, and the timing and intensity of carrier testing. Our survey indicates that 51% (36/51) of providers compared with 78% (36/46) of carriers believe that hemophilia A carriers with normal factor VIII activity have an increased bleeding tendency (P<0.001); 72% (33/36) of hemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of hemophilia A carriers prefer testing to be done before this age (P<0.001). Hemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status.

Haemoglobin responses to transfusion in severe iron deficiency anaemia: potential impact of gastrointestinal disorders.

PubMed

Bosch, X; Montori, E; Guerra-García, M; Costa-Rodríguez, J; Quintanilla, M H; Tolosa-Chapasian, P E; Moreno, P; Guasch, N; López-Soto, A

2017-04-01

Red blood cell (RBC) transfusion may be justified in iron deficiency anaemia (IDA) when an increase in oxygen delivery is needed, as sometimes occurs in subjects with haemoglobin <8·0 mg/dL, serious comorbidities or at risk of cardiovascular instability. Earlier investigations showed that some patients with severe IDA requiring transfusion had lower than expected post-transfusion haemoglobin levels with poorer clinical outcomes than other patients. After hypothesizing that haemoglobin responses to transfusion were different and that the underlying gastrointestinal (GI) disorders causing IDA could be a confounder explaining this association, these responses were analysed in a prospective cohort of IDA adults referred for outpatient GI investigation. Transfused patients with proven IDA, baseline haemoglobin at referral <9·0 g/dL and no extraintestinal bleeding were eligible. To assess a homogeneous population, only GI disorders known to cause occult bleeding were considered. Haemoglobin increments per 100 mL of RBCs were investigated. In total, 2818 patients were enrolled over 10·5 years. On multivariable regression, diffuse angiodysplasias and GI cancer independently predicted for reduced increments in post-transfusion haemoglobin [adjusted regression coefficients: -0·082 (95% confidence interval, -0·093 to -0·072) and -0·073 (95% confidence interval, -0·081 to -0·066), respectively, P < 0·001 in both]. Haemoglobin responses in the remaining bleeding disorders were adequate and agreed with the principle that one RBC unit increases the haemoglobin an average of 1 g/dL. The potential differential impact of GI disorders on changes in haemoglobin levels after RBC transfusion could be useful for transfusing physicians, especially for diagnostic purposes. © 2017 International Society of Blood Transfusion.

Bleeding Disorders in Women

MedlinePlus

... Emergency Preparedness & Response Environmental Health Healthy Living Injury, Violence & Safety Life Stages & Populations Travelers’ Health Workplace Safety & Health Features Media Sign up for Features Get Email Updates To ...

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.

[Haemophilia--then and now].

PubMed

Nilsson, I M

1994-01-01

Haemophilia is a bleeding disorder which has always attracted wide interest both among physicians and the laity--uncontrollable haemorrhage, blood that fails to coagulate and heredity with only males affected. The disease is probably best known to the public through its appearance in European royal families and in the Russian Imperial family. The oldest known description of haemophilia is to be found in the Talmud, the collection of ancient Judaic books from the early centuries of our era. The first clinical account of haemophilia was published by the American, Otto, in 1803. He described the disease as an inheritable bleeding disorder occurring only in males, and transmitted by female carriers who are not themselves affected. The disease manifests itself in early childhood, joint bleedings being its most characteristic feature. Otto called the male patients "bleeders". The term, haemophilia, originated with a German, Friedrich Hopff (1828), who coined the name "haemorrhaphilia" which was later abbreviated to haemophilia. ... As to future prospects, it is hoped that it will soon be possible to cure the disease by means of gene therapy, and to this end promising experimental work is already in progress.

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

Familiy Planning and Pregnancy

MedlinePlus

... should be managed to reduce risks to both mother and child; the options available for conception , prenatal diagnosis , and fetal sex determination . Updated November 2012 Bleeding Disorders The Clotting ...

Reticulocyte count

MedlinePlus

Anemia - reticulocyte ... A higher than normal reticulocytes count may indicate: Anemia due to red blood cells being destroyed earlier than normal ( hemolytic anemia ) Bleeding Blood disorder in a fetus or newborn ( ...

Association of past and recent major depression and menstrual characteristics in midlife: Study of Women's Health Across the Nation.

PubMed

Bromberger, Joyce T; Schott, Laura L; Matthews, Karen A; Kravitz, Howard M; Randolph, John F; Harlow, Sioban; Crawford, Sybil; Green, Robin; Joffe, Hadine

2012-09-01

The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women. Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors. One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD. Midlife women with a history of MD are more likely to report heavy bleeding.

Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies.

PubMed

Shatzel, J J; Olson, S R; Tao, D L; McCarty, O J T; Danilov, A V; DeLoughery, T G

2017-05-01

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib. © 2017 International Society on Thrombosis and Haemostasis.

Von Hippel-Lindau Disease: A Rare Familiar Multi-System Disorder and the Impact of the Clinical Nurse Specialist

DTIC Science & Technology

1993-01-01

would undergo removal of both adrenal glands, the renal cell carcinomas, a cholecystectomy and a choledochoduodenostomy for biliary drainage . The...bleeding, renal failure, and pancreatitis. After recovery, a craniotomy would be done to remove the hemangioblastoma that had been bleeding. The...analgesia. After a three month convalescence, the patient had a craniotomy and was home within a week. The patient’s siblings have all had negative eye

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).

Anorectal emergencies

PubMed Central

Lohsiriwat, Varut

2016-01-01

Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up. PMID:27468181

Menstrual Disorders

MedlinePlus

... prostaglandins, naturally occurring chemicals that cause cramps. Oral contraceptives can also be used to relieve severe menstrual cramps. Hormone treatments, such as oral contraceptives, can also be used for dysfunctional uterine bleeding. ...

PALM-COEIN Nomenclature for Abnormal Uterine Bleeding.

PubMed

Deneris, Angela

2016-05-01

Approximately 30% of women will experience abnormal uterine bleeding (AUB) during their life time. Previous terms defining AUB have been confusing and imprecisely applied. As a consequence, both clinical management and research on this common problem have been negatively impacted. In 2011, the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Group (FMDG) published PALM-COEIN, a new classification system for abnormal bleeding in the reproductive years. Terms such as menorrhagia, menometrorrhagia, metrorrhagia, dysfunctional uterine bleeding, polymenorrhea, oligomenorrhea, and uterine hemorrhage are no longer recommended. The PALM-COEIN system was developed to standardize nomenclature to describe the etiology and severity of AUB. A brief description of the PALM-COEIN nomenclature is presented as well as treatment options for each etiology. Clinicians will frequently encounter women with AUB and should report findings utilizing the PALM-COEIN system. © 2016 by the American College of Nurse-Midwives.

Does non-acetylated salicylate inhibit thromboxane biosynthesis in human platelets?

PubMed

Danesh, B J; McLaren, M; Russell, R I; Lowe, G D; Forbes, C D

1988-08-01

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.

Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

PubMed

Breivik, H; Bang, U; Jalonen, J; Vigfússon, G; Alahuhta, S; Lagerkranser, M

2010-01-01

Central neuraxial blocks (CNBs) for surgery and analgesia are an important part of anaesthesia practice in the Nordic countries. More active thromboprophylaxis with potent antihaemostatic drugs has increased the risk of bleeding into the spinal canal. National guidelines for minimizing this risk in patients who benefit from such blocks vary in their recommendations for safe practice. The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) appointed a task force of experts to establish a Nordic consensus on recommendations for best clinical practice in providing effective and safe CNBs in patients with an increased risk of bleeding. We performed a literature search and expert evaluation of evidence for (1) the possible benefits of CNBs on the outcome of anaesthesia and surgery, for (2) risks of spinal bleeding from hereditary and acquired bleeding disorders and antihaemostatic drugs used in surgical patients for thromboprophylaxis, for (3) risk evaluation in published case reports, and for (4) recommendations in published national guidelines. Proposals from the taskforce were available for feedback on the SSAI web-page during the summer of 2008. Neuraxial blocks can improve comfort and reduce morbidity (strong evidence) and mortality (moderate evidence) after surgical procedures. Haemostatic disorders, antihaemostatic drugs, anatomical abnormalities of the spine and spinal blood vessels, elderly patients, and renal and hepatic impairment are risk factors for spinal bleeding (strong evidence). Published national guidelines are mainly based on experts' opinions (weak evidence). The task force reached a consensus on Nordic guidelines, mainly based on our experts' opinions, but we acknowledge different practices in heparinization during vascular surgery and peri-operative administration of non-steroidal anti-inflammatory drugs during neuraxial blocks. Experts from the five Nordic countries offer consensus recommendations for safe clinical practice of neuraxial blocks and how to minimize the risks of serious complications from spinal bleeding. A brief version of the recommendations is available on http://www.ssai.info.

Both Hemophilia Health Care Providers and Hemophilia A Carriers Report that Carriers have Excessive Bleeding

PubMed Central

Paroskie, Allison; Oso, Olatunde; DeBaun, Michael R.; Sidonio, Robert F

2014-01-01

Introduction Hemophilia A, the result of reduced factor VIII (FVIII) activity, is an X-linked recessive bleeding disorder. Previous reports of Hemophilia A carriers suggest an increased bleeding tendency. Our objective was to determine the attitudes and understanding of the Hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey was used as preliminary data for an ongoing prospective study. Material and Methods An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers (HTC), and Hemophilia A carriers who were members of Hemophilia Federation of America. Questions focused on the clinical understanding of bleeding symptoms and management of Hemophilia A carriers, and the timing and intensity of carrier testing. Results Our survey indicates that 51% (36/51) of providers compared to 78% (36/46) of carriers believe that Hemophilia A carriers with normal FVIII activity have an increased bleeding tendency (p<0.001); 72% (33/36) of Hemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of Hemophilia A carriers prefer testing to be done prior to this age (p<0.001). Discussion Hemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status. PMID:24309601

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

Study of Tranexamic Acid During Air Medical Prehospital Transport (STAAMP) Trial

DTIC Science & Technology

2017-10-01

Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an...ABSTRACT Multi-center, prospective, randomized, blinded, controlled interventional trial focusing on patients with concern for bleeding who are ...retraining scenarios were provided and are currently being converted into a quiz for distribution to the pre-hospital crews). 4. KEY RESEARCH

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 and management of von Willebrand's syndrome.

PubMed

Rick, M E

1994-05-01

von Willebrand's disease is the most common of the inherited bleeding disorders. It is caused by quantitative and/or qualitative abnormalities of von Willebrand factor, and it usually presents with bleeding from mucosal surfaces. The diagnosis is confirmed by measuring von Willebrand factor activity and antigen levels, factor VIII activity, and performing a multimer analysis of von Willebrand factor. Treatment may require plasma-derived concentrates, but can often be accomplished with DDAVP, a vasopressin analogue that causes transient release of von Willebrand factor from body storage sites.

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

PubMed

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

2015-11-01

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

Prothrombin time (PT)

MedlinePlus

... of a blood clotting or bleeding disorder Normal Results PT is measured in seconds. Most of the ... meaning of your specific test results. What Abnormal Results Mean If you are not taking blood thinning ...

Derivation and validation of a novel risk score for safe discharge after acute lower gastrointestinal bleeding: a modelling study.

PubMed

Oakland, Kathryn; Jairath, Vipul; Uberoi, Raman; Guy, Richard; Ayaru, Lakshmana; Mortensen, Neil; Murphy, Mike F; Collins, Gary S

2017-09-01

Acute lower gastrointestinal bleeding is a common reason for emergency hospital admission, and identification of patients at low risk of harm, who are therefore suitable for outpatient investigation, is a clinical and research priority. We aimed to develop and externally validate a simple risk score to identify patients with lower gastrointestinal bleeding who could safely avoid hospital admission. We undertook model development with data from the National Comparative Audit of Lower Gastrointestinal Bleeding from 143 hospitals in the UK in 2015. Multivariable logistic regression modelling was used to identify predictors of safe discharge, defined as the absence of rebleeding, blood transfusion, therapeutic intervention, 28 day readmission, or death. The model was converted into a simplified risk scoring system and was externally validated in 288 patients admitted with lower gastrointestinal bleeding (184 safely discharged) from two UK hospitals (Charing Cross Hospital, London, and Hammersmith Hospital, London) that had not contributed data to the development cohort. We calculated C statistics for the new model and did a comparative assessment with six previously developed risk scores. Of 2336 prospectively identified admissions in the development cohort, 1599 (68%) were safely discharged. Age, sex, previous admission for lower gastrointestinal bleeding, rectal examination findings, heart rate, systolic blood pressure, and haemoglobin concentration strongly discriminated safe discharge in the development cohort (C statistic 0·84, 95% CI 0·82-0·86) and in the validation cohort (0·79, 0·73-0·84). Calibration plots showed the new risk score to have good calibration in the validation cohort. The score was better than the Rockall, Blatchford, Strate, BLEED, AIMS65, and NOBLADS scores in predicting safe discharge. A score of 8 or less predicts a 95% probability of safe discharge. We developed and validated a novel clinical prediction model with good discriminative performance to identify patients with lower gastrointestinal bleeding who are suitable for safe outpatient management, which has important economic and resource implications. Bowel Disease Research Foundation and National Health Service Blood and Transplant. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bleeding Disorders

MedlinePlus

... functionality. ------------------------------------------------------------ Find a Health Center ------------------------------------------------------------ Share this page: Twitter MySpace Technorati Facebook StumbleUpon Delicious Email to friend ... such as 20002), address, state, or place Share Twitter Facebook Email to friend Embed Code Embed this ...

Rates and Predictors of Conversion to Schizophrenia or Bipolar Disorder Following Substance-Induced Psychosis.

PubMed

Starzer, Marie Stefanie Kejser; Nordentoft, Merete; Hjorthøj, Carsten

2018-04-01

The authors investigated the rates of conversion to schizophrenia and bipolar disorder after a substance-induced psychosis, as well as risk factors for conversion. All patient information was extracted from the Danish Civil Registration System and the Psychiatric Central Research Register. The study population included all persons who received a diagnosis of substance-induced psychosis between 1994 and 2014 (N=6,788); patients were followed until first occurrence of schizophrenia or bipolar disorder or until death, emigration, or August 2014. The Kaplan-Meier method was used to obtain cumulative probabilities for the conversion from a substance-induced psychosis to schizophrenia or bipolar disorder. Cox proportional hazards regression models were used to calculate hazard ratios for all covariates. Overall, 32.2% (95% CI=29.7-34.9) of patients with a substance-induced psychosis converted to either bipolar or schizophrenia-spectrum disorders. The highest conversion rate was found for cannabis-induced psychosis, with 47.4% (95% CI=42.7-52.3) converting to either schizophrenia or bipolar disorder. Young age was associated with a higher risk of converting to schizophrenia. Self-harm after a substance-induced psychosis was significantly linked to a higher risk of converting to both schizophrenia and bipolar disorder. Half the cases of conversion to schizophrenia occurred within 3.1 years after a substance-induced psychosis, and half the cases of conversion to bipolar disorder occurred within 4.4 years. Substance-induced psychosis is strongly associated with the development of severe mental illness, and a long follow-up period is needed to identify the majority of cases.

Iron Deficiency Anemia in Adolescents Who Present with Heavy Menstrual Bleeding.

PubMed

Cooke, Amanda G; McCavit, Timothy L; Buchanan, George R; Powers, Jacquelyn M

2017-04-01

To assess the clinical severity and initial treatment of iron deficiency anemia (IDA) in female adolescents with heavy menstrual bleeding (HMB) in our center. Retrospective cohort study of electronic medical records via search of administrative records using International Classification of Diseases Ninth Revision codes for IDA or unspecified anemia and disorders of menstruation. Children's Medical Center in Dallas, Texas. One hundred seven patients with HMB and concomitant IDA (median age, 14.4 years) who presented to the outpatient, emergency department, and/or inpatient settings. The median initial hemoglobin concentration for all patients (n = 107) was 7.4 g/dL, and most (74%, n = 79) presented to the emergency department or via inpatient transfer. Symptomatic IDA was treated with blood transfusion in 46 (43%, n = 46). Ferrous sulfate was the most commonly prescribed oral iron therapy. Seven patients received intravenous iron therapy either initially or after oral iron treatment failure. Combined oral contraceptives were commonly prescribed for abnormal uterine bleeding, yet 10% of patients (n = 11) received no hormonal therapy during their initial management. Evaluation for underlying bleeding disorders was inconsistent. Severe anemia because of IDA and HMB resulting in urgent medical care, including hospitalization and blood transfusion, is a common but underemphasized problem in adolescent girls. In addition to prevention and early diagnosis, meaningful efforts to improve initial management of adolescents with severe HMB and IDA are necessary. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

PHARMACOKINETIC STUDY OF ORAL ε-AMINOCAPROIC ACID IN THE NORTHERN ELEPHANT SEAL (MIROUNGA ANGUSTIROSTRIS).

PubMed

Kaye, Sarrah; Johnson, Shawn; Arnold, Robert D; Nie, Ben; Davis, Joshua T; Gulland, Frances; Abou-Madi, Noha; Fletcher, Daniel J

2016-06-01

ε-Aminocaproic acid (EACA) is a lysine analogue antifibrinolytic drug used to treat bleeding disorders in humans and domestic animals. Its use in zoological medicine is rare, and dosage is anecdotal. One possible application of EACA is to treat bleeding associated with prepatent Otostrongylus arteritis in Northern elephant seals ( Mirounga angustirostris ) presenting to wildlife rehabilitation centers. This study used an in vitro model of hyperfibrinolysis and a thromboelastograph-based assay to estimate the therapeutic plasma concentration of EACA in elephant seals (85 μg/ml, 95% confidence interval = 73.8-96.8 μg/ml). A concurrent pharmacokinetic study of orally administered, single-dose EACA found that doses of 75 and 100 mg/kg achieved therapeutic plasma concentrations (>85 μg/ml), but the drug was rapidly eliminated and remained in the therapeutic range for only 0.4 and 1.5 hr, respectively. Models of repeated oral dosing at 100 mg/kg every 6 hr predict that therapeutic plasma concentration will be maintained for 31.7% (7.6 hr) of a 24-hr period. More frequent dosing would be required to maintain continuous therapeutic concentrations but would be impractical in a wildlife rehabilitation setting. Further pharmacodynamic studies to evaluate the duration of action of EACA in elephant seals and a prospective, placebo-controlled study are needed to determine if EACA is effective in decreasing bleeding associated with prepatent Otostrongylus arteritis and other bleeding disorders in this species.

A systematic review of the management and outcomes of pregnancy in Glanzmann thrombasthenia.

PubMed

Siddiq, S; Clark, A; Mumford, A

2011-09-01

Glanzmann Thrombasthenia (GT) is a rare autosomal recessive disorder which usually manifests as severe mucocutaneous bleeding and is caused by deficiency of the platelet glycoprotein IIb-IIIa. Pregnancy in women with GT presents particular challenges as there is increased risk of both maternal and foetal bleeding. To improve understanding and clarify the optimum management of pregnancy in this disorder, we performed a systematic review of the world literature of pregnancy and GT. This identified three single-centre case series of patients with GT that included brief descriptions of women in pregnancy and 31 detailed case reports of 40 pregnancies in 35 women that resulted in 38 live births. Among the detailed case reports, ante-natal bleeding was described in 50% of pregnancies but was usually mild and occurred at mucocutaneous sites. Primary postpartum haemorrhage (PPH) was reported in 34% of pregnancies and secondary PPH in 24%. PPH was frequently severe and occurred up to 20 days after delivery. There was a wide variation in approach to prevention and treatment of PPH but most women received platelet transfusion, sometimes with additional recombinant FVIIa and anti-fibrinolytics. Maternal alloimmunization against platelet antigens was reported in 73% of pregnancies and was associated with four neonatal deaths. These data emphasize the need for multidisciplinary management of pregnancy in women with GT. Delivery plans should recognize the need for prevention and aggressive treatment of PPH and should minimize foetal bleeding risk in pregnancies complicated by alloimmunization. © 2011 Blackwell Publishing Ltd.

Red cell-derived microparticles (RMP) as haemostatic agent.

PubMed

Jy, Wenche; Johansen, Max E; Bidot, Carlos; Horstman, Lawrence L; Ahn, Yeon S

2013-10-01

Among circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 µm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.

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.

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.

Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

PubMed

Kahr, W H; Zheng, S; Sheth, P M; Pai, M; Cowie, A; Bouchard, M; Podor, T J; Rivard, G E; Hayward, C P

2001-07-15

The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

Health of Women after Wartime Deployments: Correlates of Risk for Selected Medical Conditions among Females after Initial and Repeat Deployments to Afghanistan and Iraq, Active Component, U.S. Armed Forces

DTIC Science & Technology

2012-07-01

719.xx Peripheral enthesopathies, allied syndromes 726.xx Reproductive system disorders Disorders of menstruation /other abnormal bleeding 626.xx...range, 2.0%-2.8%), while the percentages diagnosed with “disorders of menstruation ” remained stable (range, 7.6%-8.0%), with increasing number...between the condi- tions. For example, in multivariate analyses, MSMR Vol. 19 No. 7 July 2012Page 6 Reproductive system disorders Menstruation

Genetics Home Reference: factor V deficiency

MedlinePlus

... Twitter Home Health Conditions Factor V deficiency Factor V deficiency Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Factor V deficiency is a rare bleeding disorder. The signs ...

Genetics Home Reference: X-linked thrombocytopenia

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked thrombocytopenia X-linked thrombocytopenia Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description X-linked thrombocytopenia is a bleeding disorder that primarily ...

Genetics Home Reference: factor X deficiency

MedlinePlus

... Twitter Home Health Conditions Factor X deficiency Factor X deficiency Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Factor X deficiency is a rare bleeding disorder that varies ...

Intracellular activation of the fibrinolytic cascade in the Quebec Platelet Disorder.

PubMed

Sheth, Prameet M; Kahr, Walter H A; Haq, M Anwar; Veljkovic, Dragoslava Kika; Rivard, Georges E; Hayward, Catherine P M

2003-08-01

The Quebec Platelet Disorder (QPD) is an unusual bleeding disorder associated with increased platelet stores of urokinase-type plasminogen activator (u-PA) and proteolysis of platelet alpha-granule proteins. The increased u-PA and proteolyzed plasminogen in QPD platelets led us to investigate possible contributions of intracellular plasmin generation to QPD alpha-granule proteolysis. ELISA indicated there were normal amounts of plasminogen and plasmin-alpha(2)-antiplasmin (PAP) complexes in QPD plasmas. Like normal platelets, QPD platelets contained only a small proportion of the blood plasminogen, however, they contained an increased amount of PAP complexes compared to normal platelets (P < 0.005). The quantities of plasminogen stored in platelets were important to induce QPD-like proteolysis of normal alpha-granule proteins by two chain u-PA (tcu-PA) in vitro. Moreover, adding supplemental plasminogen to QPD, but not to control, platelet lysates, triggered further alpha-granule protein proteolysis to forms that comigrated with plasmin degraded proteins. These data suggest the generation of increased but limiting amounts of plasmin within platelets is involved in producing the unique phenotypic changes to alpha-granule proteins in QPD platelets. The QPD is the only known bleeding disorder associated with chronic, intracellular activation of the fibrinolytic cascade.

EFFECT OF ε-AMINOCAPROIC ACID ON FIBRINOLYSIS IN PLASMA OF ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

PubMed

Kaye, Sarrah; Abou-Madi, Noha; Fletcher, Daniel J

2016-06-01

ε-Aminocaproic acid (EACA) is a lysine analogue antifibrinolytic drug used to treat bleeding disorders in humans and domestic animals. Use in zoological medicine is rare and dose recommendations are anecdotal, but EACA may be a valuable therapeutic option for bleeding disorders in exotic species, including Asian elephants ( Elephas maximus ). This study used an in vitro model of hyperfibrinolysis and a thromboelastograph-based assay to estimate the therapeutic plasma concentration of EACA in Asian elephants (61.5 μg/ml, 95% CI = 34.6-88.5 μg/ml). Substantial but incomplete inhibition of lysis was seen at relatively low concentrations of EACA (40 μg/ml). Asian elephants appear sensitive to EACA-mediated inhibition of hyperfibrinolysis. Doses published for domestic animals, targeting higher plasma concentrations, may be inappropriate in this species.

Downhill oesophageal variceal bleeding: A rare complication in Behçet's disease-related superior vena cava syndrome.

PubMed

Ennaifer, Rym; B'chir Hamzaoui, Saloua; Larbi, Thara; Romdhane, Hayfa; Abdallah, Maya; Bel Hadj, Najet; M'rad, Sander

2015-03-01

Behçet's disease (BD) is a multisystemic disorder that involves vessels of all sizes. Superior vena cava (SVC) thrombosis is a rare complication that can lead to the development of various collateral pathways. A 31-year-old man presented with SVC syndrome. He had a history of recurrent genital aphthosis. Computed tomography revealed extensive thrombosis of the right internal jugular, axillary, and subclavian veins with collateral circulation. The patient was diagnosed with BD, and he was started on anticoagulation and immunosuppressive therapy. One week later, he presented with haematemesis. Upper gastrointestinal endoscopy disclosed varices in the upper third of the oesophagus with stigmata of recent bleeding. Portal hypertension was ruled out. Anticoagulation therapy was discontinued. He was discharged on immunosuppressive therapy. Bleeding from downhill oesophageal varices should be suspected in any patient presenting with upper gastrointestinal bleeding and a history of SVC syndrome due to BD. Copyright © 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Nano- and micro-materials in the treatment of internal bleeding and uncontrolled hemorrhage.

PubMed

Gaston, Elizabeth; Fraser, John F; Xu, Zhi Ping; Ta, Hang T

2018-02-01

Internal bleeding is defined as the loss of blood that occurs inside of a body cavity. After a traumatic injury, hemorrhage accounts for over 35% of pre-hospital deaths and 40% of deaths within the first 24 hours. Coagulopathy, a disorder in which the blood is not able to properly form clots, typically develops after traumatic injury and results in a higher rate of mortality. The current methods to treat internal bleeding and coagulopathy are inadequate due to the requirement of extensive medical equipment that is typically not available at the site of injury. To discover a potential route for future research, several current and novel treatment methods have been reviewed and analyzed. The aim of investigating different potential treatment options is to expand available knowledge, while also call attention to the importance of research in the field of treatment for internal bleeding and hemorrhage due to trauma. Copyright © 2017 Elsevier Inc. All rights reserved.

Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

PubMed

Bahia, Malkeet S; Silakari, Om

2010-05-01

Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

Platelet von Willebrand factor in Hermansky-Pudlak syndrome.

PubMed

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

1998-10-01

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

Genetics Home Reference: factor VII deficiency

MedlinePlus

... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

A rare combination: congenital factor VII deficiency with Chiari malformation.

PubMed

Bay, Ali; Aktekin, Elif; Erkutlu, Ibrahim

2015-12-01

Congenital factor (VII) deficiency is a rare bleeding disorder. We present a patient with congenital FVII deficiency and congenital hydrocephalus who underwent a ventriculoperitoneal shunt operation and needed no prophylaxis after the procedure.

Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding

PubMed Central

Warner, P.; Guttinger, A.; Glasier, A.F.; Lee, R.J.; Nickerson, S.; Brenner, R.M.; Critchley, H.O.D.

2010-01-01

BACKGROUND The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS. METHODS CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19–49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%). RESULTS Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (−11% points, 95% CI −19 to −2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1–18). CONCLUSIONS The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72. PMID:19897857

Physiotherapy home exercise program for haemophiliacs.

PubMed

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

2011-05-01

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

SP-100 system thaw and start-up strategies

NASA Astrophysics Data System (ADS)

Kirpich, A.; Choe, H.

The authors review several strategies that have been considered during calendar year 1990 for SP-100 system start-up and thaw, and provide results of screening analyses. Screening studies have identified three concepts which are capable of thawing the SP-100 system: (1) a heat pipe approach in which reactor-heated heat pipes are routed to equipment enclosed within a thaw cavity; (2) a bleed-tube approach in which perforated tubes routed through ducting and components achieve thaw progressively as the result of successively thawing bleed-holes; and (3) a NaK traceline approach in which reactor-heated NaK is routed along ducting and components and achieves lithium thaw by both radiative and conductive coupling methods. Key issues have been identified in connection with pump start-up, reactor and power converter transient behavior, and hydraulic circuit stability. Pump start-up stability is accomplished by a linked-pump hydraulic arrangement.

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 ...

Hemophilia Data and Statistics

MedlinePlus

... View public health webinars on blood disorders Data & Statistics Language: English (US) Español (Spanish) Recommend on Facebook ... genetic testing is done to diagnose hemophilia before birth. For the one-third ... rates and hospitalization rates for bleeding complications from hemophilia ...

Single-platelet nanomechanics measured by high-throughput cytometry

NASA Astrophysics Data System (ADS)

Myers, David R.; Qiu, Yongzhi; Fay, Meredith E.; Tennenbaum, Michael; Chester, Daniel; Cuadrado, Jonas; Sakurai, Yumiko; Baek, Jong; Tran, Reginald; Ciciliano, Jordan C.; Ahn, Byungwook; Mannino, Robert G.; Bunting, Silvia T.; Bennett, Carolyn; Briones, Michael; Fernandez-Nieves, Alberto; Smith, Michael L.; Brown, Ashley C.; Sulchek, Todd; Lam, Wilbur A.

2017-02-01

Haemostasis occurs at sites of vascular injury, where flowing blood forms a clot, a dynamic and heterogeneous fibrin-based biomaterial. Paramount in the clot's capability to stem haemorrhage are its changing mechanical properties, the major drivers of which are the contractile forces exerted by platelets against the fibrin scaffold. However, how platelets transduce microenvironmental cues to mediate contraction and alter clot mechanics is unknown. This is clinically relevant, as overly softened and stiffened clots are associated with bleeding and thrombotic disorders. Here, we report a high-throughput hydrogel-based platelet-contraction cytometer that quantifies single-platelet contraction forces in different clot microenvironments. We also show that platelets, via the Rho/ROCK pathway, synergistically couple mechanical and biochemical inputs to mediate contraction. Moreover, highly contractile platelet subpopulations present in healthy controls are conspicuously absent in a subset of patients with undiagnosed bleeding disorders, and therefore may function as a clinical diagnostic biophysical biomarker.

Developing a public health research agenda for women with blood disorders.

PubMed

Byams, Vanessa R; Beckman, Michele G; Grant, Althea M; Parker, Christopher S

2010-07-01

Bleeding and clotting in women is an issue that directly affects the life of every woman, child, and family worldwide. This article summarizes recent activities undertaken by the Division of Blood Disorders (DBD) at the Centers for Disease Control and Prevention (CDC) to identify risk factors through evidence-based research and surveillance to prevent complications of blood disorders in women. Specific focus is given to our efforts to improve early identification and diagnosis of blood disorders among women, improve our understanding of maternal and infant outcomes, and develop surveillance systems to monitor the prevalence and incidence of these events.

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.

Celiac disease and dysfunctional uterine bleeding; the efficiency of gluten free diet.

PubMed

Ehsani-Ardakani, M J; Fallahian, M; Rostami, K; Rostami-Nejad, M; Lotfi, S; Mohaghegh-Shalmani, H; Dabiri, R; Norouzinia, M; Azizpour-Shoobi, F; Zali, M R

2014-01-01

The aim of this study was to investigate the relation between Celiac disease (CD) and unexplained dysfunctional uterine bleeding (DUB) in celiac women. The celiac patients were selected from women who were referred to celiac department. Controls were selected from those women without any signs of celiac disease and matched with age. Meanwhile, a trained physician was ready to explain the study, and then in case of their allowance, a questionnaire was completed by the physician. 24 % of celiac women reported a past history of at least one menstrual cycle disorder vs 10 % of controls reported these problems (p=0.038) and higher percentage of unexplained DUB has been observed in celiac women. All celiac patients were undertaking gluten free diet for at least 3 months and the celiac patients who reported the history of DUB were again interviewed for any signs of unexplained DUB. From 12 celiac women with DUB, 10 patients reported no more unexplained DUB after getting gluten-free diet (83.3 %). The occurrence of a significant correlation between CD and DUB suggests the possibility of considering CD as one of the potential causes of abnormal uterine bleeding. Therefore, celiac disease must be seriously considered in the screening of patients with reproductive disorders (Tab. 2,Ref. 23).

Leidos Biomed Teams with NCI, DOE, and Argonne National Lab to Support National X-Ray Resource | Poster

Cancer.gov

Scientists are making progress in understanding a bleeding disorder caused by prescription drug interactions, thanks to a high-tech research facility involving two federal national laboratories, Argonne and Frederick.

[Relapse of bleeding ulcer in a 15 year-old boy with collagenous gastritis].

PubMed

Haase, Anne-Mette; Kelsen, Jens

2012-06-18

Collagenous gastritis (CG) is a rare disorder. Two patient groups are known: 1) Children and young adults, presenting with anaemia and abdominal pain, and 2) adults presenting with watery diarrhoea. In the latter group, CG is frequently associated with collagenous colitis and/or coeliac disease. This case concerns a 15-year-old boy with a bleeding ulcer. The biopsies from corpus ventriculi showed a thickened subepithelial collagen band (> 10 micrometres), and the patient was diagnosed with CG. Ulcers are rarely linked to CG. CG should be considered when ulcers are found in children and young adults.

Two Cases of Lethal Complications Following Ultrasound-Guided Percutaneous Fine-Needle Biopsy of the Liver

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

Drinkovic, Ivan; Brkljacic, Boris

1996-09-15

Two cases with lethal complications are reported among 1750 ultrasound (US)-guided percutaneous fine-needle liver biopsies performed in our department. The first patient had angiosarcoma of the liver which was not suspected after computed tomography (CT) and US studies had been performed. The other patient had hepatocellular carcinoma in advanced hepatic cirrhosis. Death was due to bleeding in both cases. Pre-procedure laboratory tests did not reveal the existence of major bleeding disorders in either case. Normal liver tissue was interposed in the needle track between the liver capsule and the lesions which were targeted.

Chinese guidelines for treatment of adult primary immune thrombocytopenia.

PubMed

Liu, Xin-Guang; Bai, Xiao-Chuan; Chen, Fang-Ping; Cheng, Yun-Feng; Dai, Ke-Sheng; Fang, Mei-Yun; Feng, Jian-Ming; Gong, Yu-Ping; Guo, Tao; Guo, Xin-Hong; Han, Yue; Hong, Luo-Jia; Hu, Yu; Hua, Bao-Lai; Huang, Rui-Bing; Li, Yan; Peng, Jun; Shu, Mi-Mi; Sun, Jing; Sun, Pei-Yan; Sun, Yu-Qian; Wang, Chun-Sen; Wang, Shu-Jie; Wang, Xiao-Min; Wu, Cong-Ming; Wu, Wen-Man; Yan, Zhen-Yu; Yang, Feng-E; Yang, Lin-Hua; Yang, Ren-Chi; Yang, Tong-Hua; Ye, Xu; Zhang, Guang-Sen; Zhang, Lei; Zheng, Chang-Cheng; Zhou, Hu; Zhou, Min; Zhou, Rong-Fu; Zhou, Ze-Ping; Zhu, Hong-Li; Zhu, Tie-Nan; Hou, Ming

2018-06-01

Primary immune thrombocytopenia (ITP) is a bleeding disorder commonly encountered in clinical practice. The International Working Group (IWG) on ITP has published several landmark papers on terminology, definitions, outcome criteria, bleeding assessment, diagnosis, and management of ITP. The Chinese consensus reports for diagnosis and management of adult ITP have been updated to the 4th edition. Based on current consensus positions and new emerging clinical evidence, the thrombosis and hemostasis group of the Chinese Society of Hematology issued Chinese guidelines for management of adult ITP, which aim to provide evidence-based recommendations for clinical decision making.

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.

Renal biopsy practice: What is the gold standard?

PubMed

Brachemi, Soumeya; Bollée, Guillaume

2014-11-06

Renal biopsy (RB) is useful for diagnosis and therapy guidance of renal diseases but incurs a risk of bleeding complications of variable severity, from transitory haematuria or asymptomatic hematoma to life-threatening hemorrhage. Several risk factors for complications after RB have been identified, including high blood pressure, age, decreased renal function, obesity, anemia, low platelet count and hemostasis disorders. These should be carefully assessed and, whenever possible, corrected before the procedure. The incidence of serious complications has become low with the use of automated biopsy devices and ultrasound guidance, which is currently the "gold standard" procedure for percutaneous RB. An outpatient biopsy may be considered in a carefully selected population with no risk factor for bleeding. However, controversies persist on the duration of observation after biopsy, especially for native kidney biopsy. Transjugular RB and laparoscopic RB represent reliable alternatives to conventional percutaneous biopsy in patients at high risk of bleeding, although some factors limit their use. This aim of this review is to summarize the issues of complications after RB, assessment of hemorrhagic risk factors, optimal biopsy procedure and strategies aimed to minimize the risk of bleeding.

Novel thrombin and factor Xa inhibitors: challenges to reversal of their anticoagulation effects.

PubMed

Yates, Sean; Sarode, Ravi

2013-11-01

Warfarin has been the sole oral anticoagulant used in the management of thromboembolic disorders for over 60 years. Target-specific oral anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because they do not require laboratory monitoring. Nevertheless, with the rising use of TSOAs, there is growing concern among clinicians regarding management of bleeding in patients taking them. Unlike warfarin, there is no antidote or reversal agent for TSOAs. This review summarizes recent developments and attempts to provide a systematic approach to patients on TSOAs presenting with bleeding complications. Currently, data involving clinical management of TSOAs are limited and primarily based on ex-vivo or animal models using hemostatic agents with uncertain implications in bleeding patients. There is a pressing need for randomized clinical trials evaluating the safety and efficacy of hemostatic agents. Without evidence-based guidelines for TSOA management, appropriate patient care requires an understanding of TSOA pharmacology, their effect on coagulation tests and, hence, a correct interpretation of test results, as well as a systematic approach to bleeding complications.

[New knowledge on the diverticular disease of colon].

PubMed

Dolejsí, Mojmír

2011-01-01

The article is a summary paper aimed at new knowledge, concerning the classification, diagnostics, medication and endoscopic treatment of diverticular disease of colon. Briefly mentioned are the issues of functional disorder in the field of diverticulosis--symptomatic uncomplicated diverticular disease of colon. Diverticular bleeding is explained in terms of its pathogenesis and diagnostics. The problem with estimation the ration of diverticular bleedings in the total number of bleedings into the lower digestive tract is caused by diverse criteria for selecting patients and two levels of diagnostic of diverticular bleeding (definite and presumptive). Attention is paid also to diverticular colitis. Synonyms, endoscopic and histological classification are listed. The main endoscopic findings represent areas of erythema, which are visible on the mucosa between diverticula. Diverticulitis is seen as the most significant complication and the diagnostics of diverticulitis is discussed in detail. The first recommended step in the diagnosis is an urgent abdominal ultrasound; the gold standard is a CT examination of the abdomen, in special situations, some other imaging methods should be used: MRI, colonoscopy. The article ends with an overview of modern therapeutic options in the treatment of diverticular colitis and diverticulitis, particularly the use of antibiotics, probiotics, mesalasine and antispasmodics. Negative effect of NSAIDs on the course of diverticulitis and induction diverticular bleeding is listed.

Abnormal uterine bleeding in perimenopause.

PubMed

Goldstein, S R; Lumsden, M A

2017-10-01

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

An unusual cause of stridor in a neonate.

PubMed

Fah, K K; Tan, H K

1994-01-01

We report an unusual case of unilateral vocal fold palsy due to intracranial haemorrhage in a neonate with undiagnosed haemophilia A. Bleeding disorders in neonates are briefly discussed and the importance of a systemic investigation of stridor in children is emphasized.

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).

Extended and continuous use of hormonal contraceptives to reduce menstruation.

PubMed

Wiegratz, Inka; Kissler, Stefan; Kuhl, Herbert; Kaufmann, Manfred

2006-09-01

During the use of long-cycle regimens of monophasic oral contraceptives, the total number of bleeding and cycle-dependent complaints is considerably lower than during conventional treatment with oral contraceptives. Despite an initially higher rate of irregular bleeding, the majority of women prefer the long-cycle treatment since it may improve quality of life. As this regimen provides an enhanced ovarian suppression, it may prevent pregnancies, especially in noncompliant women or patients who are concomitantly treated with drugs that may impair the efficacy of oral contraceptives. Postponement or suppression of withdrawal bleeding also reduces menses-associated disorders such as menorrhagia and dysmenorrhea, and has beneficial effects in patients with hemorrhagic diathesis, endometriosis, uterine leiomyomas and polycystic ovary syndrome. Long-term studies are necessary to assess the impact of long-term use of extended regimens of oral contraceptives on safety, for example, the risk of cancer and cardiovascular disease, and on fertility after discontinuation of treatment.

PSYCHOLOGICAL FACTORS IN 155 PATIENTS WITH FUNCTIONAL UTERINE BLEEDING.

PubMed

DUTTON, W A

1965-02-20

One hundred and fifty-five women with functional uterine bleeding were studied to evaluate the importance of concomitant psychological disorders. Psychological illnesses were diagnosed in 128 patients (82.6%), most of which arose from problems directly related to sexual or reproductive functions. The remaining 27 patients (17.4%) were different in that they were psychologically stable and all but two were at puberty or approaching the menopause.Histological studies of endometrial samples from 135 of these patients indicated little evidence of abnormal sex hormone activity; 77 (57%) showed normal secretory phase endometrium and 32 (23.7%), proliferative phase endometrium. The remaining 26 (19.2%) showed evidence of some endocrine dysfunction, 15 such specimens being obtained from psychologically stable patients.It is probable that psychological disturbances are the principal cause of functional uterine bleeding during the prime reproductive years. The psychological component of the illness is the most important and determines the ultimate prognosis.

Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

PubMed Central

Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

2018-01-01

Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

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

PubMed

Nijkeuter, M; Huisman, M V

2004-09-01

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

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.

Curative effects of two new endometrial ablation procedures using radiofrequency thermocoagulation for the treatment of severe abnormal uterine bleeding.

PubMed

Yin, Geping; Li, Juan; Zhu, Tongyu; Chen, Ming

2013-07-01

Severe Abnormal Uterine Bleeding (SAUB) is a common gynecological disorder. The clinical characteristics include disordered menstrual cycle and massive bleeding that can cause anemia or secondary infection. Current treatment mainly relies on drug therapy or surgical removal of the uterus, each having its significant disadvantages. How to preserve the uterus, reduce the pain from surgery, and achieve better treatment effects have been well known but remaining as unresolved issues. This study aims at evaluating two types of radiofrequency (RF) thermocoagulation procedures for the treatment of SAUB: the RF-A procedure group included 25 SAUB patients ≥45 years of age treated for amenorrhea; the RF-B procedure group included 51 patients at <45 years of age treated for the control of excessive bleeding. Post-treatment ratings of menstrual satisfaction and pre-/post-treatment menstrual scores-pictorial blood loss assessment chart (PBAC)-and hemoglobin levels were collected; and the mean length of follow-up was 72 months. Also, 38 SAUB patients treated with standard drug regimens served as a control group. The results of the study showed that following RF treatment, the average long-term patient menstrual satisfaction was greater than 92 %. In both the RF groups, PBAC scores and hemoglobin levels were significantly improved from baseline (p < .05). Compared with the control group, PBAC scores and hemoglobin levels were also significantly better for the RF groups at 6-24-month post-operation. Patients experienced no hysterectomy in association with the RF procedures. In conclusion, this pilot study suggests that the novel RF procedures are both safe and effective in treating patients with SAUB. Further investigation is necessary to evaluate their application in broader clinical indication.

A case of coffee-ground emesis in an elderly patient

PubMed Central

De Palma, Giovanni D; Persico, Marcello; Forestieri, Pietro

2014-01-01

Key Clinical Message Black esophagus is an exceeding rare disorder with a multifactorial etiology. Clinical presentation is generally related to upper gastrointestinal bleeding. Diagnosis is based on endoscopic images. Overall mortality is largely related to the underlying medical condition. PMID:25356232

Gastritis

MedlinePlus

... Less common causes are: Autoimmune disorders (such as pernicious anemia) Backflow of bile into the stomach (bile reflux) ... causing bleeding from the lining of the stomach, symptoms may include: Black stools Vomiting blood ... Complete blood count (CBC) to check for anemia or low blood count Examination of the stomach ...

Sexual harassment and menstrual disorders among Italian university women: A cross-sectional observational study.

PubMed

Romito, P; Cedolin, C; Bastiani, F; Beltramini, L; Saurel-Cubizolles, M J

2017-07-01

Menstrual disorders and sexual harassment are common among young women and interfere with their life and activities. We aimed to describe the association of sexual harassment and menstrual disorders among female university students. This cross-sectional, observational study examined the association between sexual harassment and menstrual disorders in a sample of 349 university students in Italy. Students answered an anonymous self-administered questionnaire. Descriptive bivariate analyses and logistic regression analyses were performed. Main outcome measures were associations between levels of exposure to sexual harassment (none, levels 1 and 2) and five menstrual disorders (premenstrual symptoms, heavy bleeding, pain, irregular cycles, and amenorrhea). Among the women interviewed (mean age 20.4 ± 1.45 years), 146 (41.8%) had experienced sexual harassment in the previous 12 months: 91 (26.1%) level 1 and 55 (15.7%) level 2. The frequency of premenstrual symptoms was 31.9% ( n=110); heavy bleeding, 35.3% ( n=124); pain, 51.4% ( n=181); irregular cycles, 55.5% ( n=195); and amenorrhea, 6.7% ( n=23). After adjustment for age, place of birth, being in a couple relationship and receiving hormone therapy, the frequency of menstrual disorders, except for amenorrhea, was increased with sexual harassment, with a regular gradient from no harassment to level 2 harassment. Introducing factors of depression, specific gynaecological problems and lifetime sexual violence did not change the results. For instance, the adjusted odds ratios of premenstrual symptoms were 2.10 [1.19-3.68] for women with level 1 harassment and 3.58 [1.83-7.03] for women with level 2 compared with women without harassment exposure. Sexual harassment is related to the prevalence of menstrual disorders. Healthcare providers should encourage dialogue with patients and address the issue of sexual violence or harassment.

Definition of an organisational model for the prevention and reduction of health and social impacts of inherited bleeding disorders.

PubMed

Calizzani, Gabriele; Menichini, Ivana; Candura, Fabio; Lanzoni, Monica; Profili, Samantha; Tamburrini, Maria Rita; Fortino, Antonio; Vaglio, Stefania; Marano, Giuseppe; Facco, Giuseppina; Oliovecchio, Emily; Franchini, Massimo; Coppola, Antonio; Arcieri, Romano; Bon, Cinzia; Saia, Mario; Nuti, Sabina; Morfini, Massimo; Liumbruno, Giancarlo M; Di Minno, Giovanni; Grazzini, Giuliano

2014-04-01

Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network.

The incidence, risk and functional outcomes of intracranial haemorrhage in children with inherited bleeding disorders at one haemophilia center.

PubMed

Bladen, M; Main, E; Khair, K; Hubert, N; Koutoumanou, E; Liesner, R

2016-07-01

Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation. © 2016 John Wiley & Sons Ltd.

Definition of an organisational model for the prevention and reduction of health and social impacts of inherited bleeding disorders

PubMed Central

Calizzani, Gabriele; Menichini, Ivana; Candura, Fabio; Lanzoni, Monica; Profili, Samantha; Tamburrini, Maria Rita; Fortino, Antonio; Vaglio, Stefania; Marano, Giuseppe; Facco, Giuseppina; Oliovecchio, Emily; Franchini, Massimo; Coppola, Antonio; Arcieri, Romano; Bon, Cinzia; Saia, Mario; Nuti, Sabina; Morfini, Massimo; Liumbruno, Giancarlo M.; Di Minno, Giovanni; Grazzini, Giuliano

2014-01-01

Introduction Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. Material and methods The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. Results In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. Conclusions The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network. PMID:24922299

The Comprehensive Geriatric Assessment and the multidimensional approach. A new look at the older patient with gastroenterological disorders.

PubMed

Pilotto, Alberto; Addante, Filomena; D'Onofrio, Grazia; Sancarlo, Daniele; Ferrucci, Luigi

2009-01-01

The Comprehensive Geriatric Assessment (CGA) is a multidimensional, usually interdisciplinary, diagnostic process intended to determine an elderly person's medical, psychosocial, and functional capacity and problems with the objective of developing an overall plan for treatment and short- and long-term follow-up. The potential usefulness of the CGA in evaluating treatment and follow-up of older patients with gastroenterological disorders is unknown. In the paper we reported the efficacy of a Multidimensional-Prognostic Index (MPI), calculated from information collected by a standardized CGA, in predicting mortality risk in older patients hospitalized with upper gastrointestinal bleeding and liver cirrhosis. Patients underwent a CGA that included six standardized scales, i.e. Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Short-Portable Mental Status Questionnaire (SPMSQ), Mini-Nutritional Assessment (MNA), Exton-Smith Score (ESS) and Comorbity Index Rating Scale (CIRS), as well as information on medication history and cohabitation, for a total of 63 items. The MPI was calculated from the integrated total scores and expressed as MPI 1=low risk, MPI 2=moderate risk and MPI 3=severe risk of mortality. Higher MPI values were significantly associated with higher short- and long-term mortality in older patients with both upper gastrointestinal bleeding and liver cirrhosis. A close agreement was found between the estimated mortality by MPI and the observed mortality. Moreover, MPI seems to have a greater discriminatory power than organ-specific prognostic indices such as Rockall and Blatchford scores (in upper gastrointestinal bleeding patients) and Child-Plugh score (in liver cirrhosis patients). All these findings support the concept that a multidimensional approach may be appropriate for the evaluation of older patients with gastroenterological disorders, like it has been reported for patients with other pathological conditions.

Von Willebrand's disease: case report and review of literature.

PubMed

Echahdi, Hanae; El Hasbaoui, Brahim; El Khorassani, Mohamed; Agadr, Aomar; Khattab, Mohamed

2017-01-01

Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to the symptoms, the child was on a normal diet and was thriving appropriately. The child presented one days before his admission trauma to the inner face of the lower lip that caused an external acute bleeding loss. The laboratory data showed unfortunately, the most severe form of Von Willebrand's Disease; Type 3. The management was based on erythrocyte and fresh-frozen plasma (FFP) transfusions with administration of factor VII with good evolution.

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

Complete Blood Count: MedlinePlus Lab Test Information

MedlinePlus

... your lungs and to the rest of your body Hematocrit , a measurement of how much of your blood is made ... Internet]. Bethesda (MD): U.S. Department of Health and Human Services; Your Guide to Anemia; [cited ... MedlinePlus Health Topics Bleeding Disorders Blood Count ...

Leidos Biomed Teams with NCI, DOE, and Argonne National Lab to Support National X-Ray Resource | FNLCR Staging

Cancer.gov

Scientists are making progress in understanding a bleeding disorder caused by prescription drug interactions, thanks to a high-tech research facility involving two federal national laboratories, Argonne and Frederick. Miroslawa Dauter is a Senior Res

Management of tooth extraction in a patient with a rare bleeding disorder associated with Hermansky-Pudlak syndrome: a case report.

PubMed

Minkin, Patton; Bertetti, Richard; Lindsey, Sean; Bovino, Brian

2015-02-01

This report describes the case of a 27-year-old man who had been diagnosed with Hermansky-Pudlak syndrome shortly after birth. Because the patient had a major bleeding disorder associated with his syndrome, local and systemic hemostatic protection recommendations had to be considered before tooth extraction. Synthetic vasopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) was transfused intravenously before surgery. During surgery the patient was transfused with 1 U of human leukocyte antigen (HLA)-matched apheresis platelets. A hemostatic packing of Avitene and Gelfoam was adapted to the extraction site. Treatment with DDAVP, HLA-matched platelets, and local application of a packing with Avitene and Gelfoam resulted in sustained hemostasis and an excellent healing response. Surgical and routine extractions appear to be safe procedures in patients with Hermansky-Pudlak syndrome when appropriate local and systemic hemostatic measures are used. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The impact of coagulopathy on traumatic splenic injuries.

PubMed

Smalls, Norma; Obirieze, Augustine; Ehanire, Imudia

2015-10-01

Patients with pre-injury coagulopathy have worse outcomes than those without coagulopathy. This article investigated the risk-adjusted effect of pre-injury coagulopathy on outcomes after splenic injuries. Review of the National Trauma Data Bank from 2007 to 2010 comparing mortality and complications between splenic injury patients with and without a pre-injury bleeding disorder. Of 58,896 patients, 2% had a bleeding disorder. Coagulopathic patients had higher odds of mortality (odds ratio, 1.3), sepsis (odds ratio, 2.0), acute respiratory distress syndrome (odds ratio, 2.6), acute renal failure (odds ratio, 1.5), cardiac arrest (odds ratio, 1.5), and overall complications (odds ratio, 2.4). The higher odds of myocardial infarction did not achieve statistical significance (odds ratio, 1.6). Pre-injury coagulopathy in patients with splenic injury has a negative impact on cardiac arrest, sepsis, acute respiratory distress syndrome, acute renal failure, and mortality. The higher likelihood of myocardial infarction did not reach statistical significance. Copyright © 2015 Elsevier Inc. 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.

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

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

PubMed

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

2005-01-01

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

Reference intervals of citrated-native whole blood thromboelastography in premature neonates.

PubMed

Motta, Mario; Guaragni, Brunetta; Pezzotti, Elena; Rodriguez-Perez, Carmen; Chirico, Gaetano

2017-12-01

Bleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated. To evaluate TEG in preterm neonates, and to assess their reference ranges. One hundred and eighteen preterm neonates were analyzed for TEG in a retrospective cohort study. Double-sided 95% reference intervals were calculated using a bootstrap method after Box-Cox transformation. TEG parameters were compared between early-preterm and moderate-/late-preterm neonates and between bleeding and non-bleeding preterm neonates. Comparing early-preterm with moderate-/late-preterm neonates, TEG parameters were not statistically different, except for fibrinolysis which was significantly higher in early preterm neonates. Platelet count significantly correlated with α angle and MA parameters. Bleeding and non-bleeding neonates had similar TEG values. These results reinforce the concept that in stable preterm neonates, in spite of lower concentration of pro- and anti-coagulants proteins, the hemostasis is normally balanced and well functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Juvenile polyposis syndrome: An unusual case report of anemia and gastrointestinal bleeding in young infant.

PubMed

Hsiao, Yi-Han; Wei, Chin-Hung; Chang, Szu-Wen; Chang, Lung; Fu, Yu-Wei; Lee, Hung-Chang; Liu, Hsuan-Liang; Yeung, Chun-Yan

2016-09-01

Juvenile polyposis syndrome, a rare disorder in children, is characterized with multiple hamartomatous polyps in alimentary tract. A variety of manifestations include bleeding, intussusception, or polyp prolapse. In this study, we present an 8-month-old male infant of juvenile polyposis syndrome initially presenting with chronic anemia. To the best of our knowledge, this is the youngest case reported in the literature. We report a rare case of an 8-month-old male infant who presented with chronic anemia and gastrointestinal bleeding initially. Panendoscopy and abdominal computed tomography showed multiple polyposis throughout the entire alimentary tract leading to intussusception. Technetium-99m-labeled red blood cell (RBC) bleeding scan revealed the possibility of gastrointestinal tract bleeding in the jejunum. Histopathological examination on biopsy samples showed Peutz-Jeghers syndrome was excluded, whereas the diagnosis of juvenile polyposis syndrome was established. Enteroscopic polypectomy is the mainstay of the treatment. However, polyps recurred and occupied the majority of the gastrointestinal tract in 6 months. Supportive management was given. The patient expired for severe sepsis at the age of 18 months. Juvenile polyposis syndrome is an inherited disease, so it is not possible to prevent it. Concerning of its poor outcome and high mortality rate, it is important that we should increase awareness and education of the parents at its earliest stages.

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

Menstrual management and reproductive concerns in adolescent and young adult women with underlying hematologic or oncologic disease.

PubMed

Quinn, Sheila M; Louis-Jacques, Jennifer

2016-08-01

Heavy menstrual bleeding is common among adolescent and young adult women, and can affect health-related quality of life. The cause of heavy menstrual bleeding is not uncommonly because of an underlying hematologic or oncologic disease process, which substantially influences the way patients are counseled and treated. Options for menstrual management are more numerous today than ever before and range from minimizing monthly blood loss to suppressing the cycle altogether. However, an underlying bleeding disorder or malignancy can introduce many nuances and limits in individual patient care, which this review highlights. Additionally, because survival rates for adolescent and young adult cancers are improving, more of these patients are planning for lives after their disease, which may include starting or adding to a family. Options for fertility preservation during cancer therapy regimens are solidifying and both primary practitioners and subspecialists should be aware of the possibilities. Patients with underlying hematologic or oncologic disease require management of menstrual bleeding, but also deserve a comprehensive evaluation and counseling regarding their individualized contraceptive needs and fertility preservation options during their reproductive years. This review employs the latest evidence from current literature to help guide clinicians caring for this unique demographic.

Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders

PubMed Central

Estcourt, Lise J; Desborough, Michael; Brunskill, Susan J; Doree, Carolyn; Hopewell, Sally; Murphy, Michael F; Stanworth, Simon J

2016-01-01

Background People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. 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 1950) and ongoing trial databases to 07 March 2016. Selection criteria We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. Data collection and analysis Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration’s ‘Risk of bias’ tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. Main results We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA. Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology. Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity. We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) −0.37 to 3.77: consolidation; 18 participants; MD −1.50 bleeding events, 95% CI −3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies. Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence). All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD −5.60 platelet units, 95% CI −9.02 to −2.18: induction; 38 participants, MD −1.00 platelet units, 95% CI −9.11 to 7.11; very low-quality evidence). Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence). None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). Authors’ conclusions Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020. PMID:26978005

A Synthetic Fibrin-Crosslinking Polymer for Modulating Clot Properties and Inducing Hemostasis

PubMed Central

Chan, Leslie W.-G.; Wang, Xu; Wei, Hua; Pozzo, Lilo D.; White, Nathan J.; Pun, Suzie H.

2015-01-01

Clotting factor replacement is the standard management of acute bleeding in congenital and acquired bleeding disorders. We present a synthetic approach to hemostasis using an engineered hemostatic polymer (PolySTAT) that circulates innocuously in the blood, identifies sites of vascular injury, and promotes clot formation to stop bleeding. PolySTAT induces hemostasis by crosslinking the fibrin matrix within clots, mimicking the function of the transglutaminase Factor XIII. Furthermore, synthetic PolySTAT binds specifically to fibrin monomers and is uniformly integrated into fibrin fibers during fibrin polymerization, resulting in a fortified, hybrid polymer network with enhanced resistance to enzymatic degradation. In vivo hemostatic activity was confirmed in a rat model of trauma and fluid resuscitation in which intravenous administration of PolySTAT improved survival by reducing blood loss and resuscitation fluid requirements. PolySTAT-induced fibrin crosslinking is a novel approach to hemostasis utilizing synthetic polymers for non-invasive modulation of clot architecture with potentially wide-ranging therapeutic applications. PMID:25739763

Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

PubMed

Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

2016-03-01

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

Isolated acquired factor VII deficiency: review of the literature.

PubMed

Mulliez, Sylvie M N; Devreese, Katrien M J

2016-04-01

Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

[Coagulation Monitoring and Bleeding Management in Cardiac Surgery].

PubMed

Bein, Berthold; Schiewe, Robert

2018-05-01

The transfusion of allogeneic blood products is associated with increased morbidity and mortality. An impaired hemostasis is frequently found in patients undergoing cardiac surgery and may in turn cause bleeding and transfusions. A goal directed coagulation management addressing the often complex coagulation disorders needs sophisticated diagnostics. This may improve both patients' outcome and costs. Recent data suggest that coagulation management based on a rational algorithm is more effective than traditional therapy based on conventional laboratory variables such as PT and INR. Platelet inhibitors, cumarins, direct oral anticoagulants and heparin need different diagnostic and therapeutic approaches. An algorithm specifically developed for use during cardiac surgery is presented. Georg Thieme Verlag KG Stuttgart · New York.

Fitness and quality of life in children with haemophilia.

PubMed

Broderick, C R; Herbert, R D; Latimer, J; Curtin, J A

2010-01-01

Prior to the introduction of prophylactic clotting factor, children with haemophilia were discouraged from physical activity due to the risk of bleeds. Reports of children with haemophilia having lower levels of fitness and strength than their healthy peers were therefore well accepted. This study aimed to establish whether these deficits continued, and specifically, whether Australian boys with haemophilia and von Willebrand disorder had lower strength and aerobic capacity than their peers, despite widespread use of prophylaxis. Forty-four boys aged 6.1-17.0 years (mean 10.9, SD 3.2) with haemophilia A and B and von Willebrand disorder participated in the study. Fitness, strength and body mass index (BMI) measures were compared with age- and gender-matched data from a representative cohort of school children. Quality of Life was measured using the Haemo-QoL to obtain baseline measures in an Australian population. There were no statistically significant or clinically important differences in aerobic fitness or BMI between the boys with haemophilia and controls in any age category. Boys with haemophilia in Years 4, 6 and 10 had greater strength than their peers. Australian boys with bleeding disorders do not have impaired aerobic capacity or strength compared with their peers. Quality of life in Australian boys with haemophilia is comparable to their European counterparts.

Laparoscopic management of retroperitoneal injuries from penetrating abdominal trauma in haemodynamically stable patients.

PubMed

Koto, Modise Zacharia; Matsevych, Oleh Y; Mosai, Fusi; Balabyeki, Moses; Aldous, Colleen

2018-02-27

Laparoscopy is increasingly utilised in the trauma setting. However, its safety and reliability in evaluating and managing retroperitoneal injuries are not known. The aim of this study was to analyse our experience with laparoscopic management of retroperitoneal injuries due to penetrating abdominal trauma (PAT) and to investigate its feasibility, safety and accuracy in haemodynamically stable patients. Over a 4-year period, patients approached laparoscopically with retroperitoneal injuries were analysed. Mechanism, location and severity of injuries were recorded. Surgical procedures, conversion rate and reasons for conversion and outcomes were described. Of the 284 patients with PAT, 56 patients had involvement of retroperitoneum. Stab wounds accounted 62.5% of patients. The mean Injury Severity Score was 7.4 (4-20). Among retroperitoneal injuries, the colon (27%) was the most commonly involved hollow viscera followed by duodenum (5%). The kidney (5%) and the pancreas (4%) were the injured solid organs. The conversion rate was 19.6% and was mainly due to active bleeding (73%). Significantly more patients with gunshot wound were converted to laparotomy (38% vs. 9%). Therapeutic laparoscopy was performed in 36% of patients. There were no recorded missed injuries or mortality. Five (9%) patients developed the Clavien-Dindo Grade 3 complications, three were managed with reoperation, one with drainage/debridement and one with endovascular technique. Laparoscopic management of retroperitoneal injuries is safe and feasible in haemodynamically stable patients with PAT. However, a high conversion rate indicates difficulties in managing these injuries. The requirements are the dexterity in laparoscopy and readiness to convert in the event of bleeding.

Coagulopathy in Zellweger spectrum disorders: a role for vitamin K.

PubMed

Zeynelabidin, Sara; Klouwer, Femke C C; Meijers, Joost C M; Suijker, Monique H; Engelen, Marc; Poll-The, Bwee Tien; van Ommen, C Heleen

2018-03-01

Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD. Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined. In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation. Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation.

Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis.

PubMed

Diamandis, M; Adam, F; Kahr, W H A; Wang, P; Chorneyko, K A; Arsenault, A L; Rivard, G E; Hayward, C P M

2006-05-01

The Quebec platelet disorder (QPD) is inherited and characterized by delayed-onset bleeding following hemostatic challenge. Other characteristics include increased expression and storage of active urokinase-type plasminogen activator (u-PA) in platelets in the setting of normal to increased u-PA in plasma. There is also consumption of platelet plasminogen activator inhibitor-1 and increased generation of plasmin in platelets accompanied by proteolysis of stored alpha-granule proteins, including Factor V. Although fibrinolysis has been proposed to contribute to QPD bleeding, the effects of QPD blood and platelets on clot lysis have not been evaluated. We used thromboelastography (TEG), biochemical evaluations of whole blood clot lysis, assessments of clot ultrastructure, and perfusion of blood over preformed fibrin to gain insights into the disturbed hemostasis in the QPD. Thromboelastography was not sensitive to the increased u-PA in QPD blood. However, there was abnormal plasmin generation in QPD whole blood clots, generated at low shear, with biochemical evidence of increased fibrinolysis. The incorporation of QPD platelets into a forming clot led to progressive disruption of fibrin and platelet aggregates unless drugs were added to inhibit plasmin. In whole blood perfusion studies, QPD platelets showed normal adherence to fibrin, but their adhesion was followed by accelerated fibrinolysis. The QPD is associated with "gain-of-function" abnormalities that increase the lysis of forming or preformed clots. These findings suggest accelerated fibrinolysis is an important contributor to QPD bleeding.

Strategies to encourage physical activity in patients with hemophilia to improve quality of life

PubMed Central

Goto, Miwa; Takedani, Hideyuki; Yokota, Kazuhiko; Haga, Nobuhiko

2016-01-01

Hemophilia is a bleeding disorder caused by a congenital abnormality of blood coagulation. Until the mid-1970s, patients with hemophilia (PWH) were advised to refrain from physical activity (PA) because of a perceived increased risk of bleeding. Since then, PA, which is recognized as being essential for health maintenance, is now recommended by the World Federation of Hemophilia. Moreover, a number of studies reported that PA can improve treatment efficacy and prevent bleeding in PWH. Physical assessment and intervention in PA are currently used in clinical practice. However, the necessity of PA is not emphasized, and many PWH generally have low- to- no PA. Therefore, a behavior change approach to encourage patient motivation is becoming ever more important. In this article, we review articles addressing PA in PWH and discuss strategies to encourage PA through a behavior change approach by focusing on factors relevant to hemophilia, such as benefits and bleeding risk of PA, risk management of bleeding, PA characteristics, and difficulty with exercise adherence. The trust relationship between clinicians and patients, a transtheoretical model of behavior change, and motivation theory as approaches to promote PA are introduced. Finally, we review a case report of the clinical success of a behavior change approach to promote PA. Many PWH find it difficult to continue PA because of aging, fear of bleeding, insufficient recognition of PA benefits, and psychological problems. Therefore, it is essential and important to perform prophylaxis with PWH and to heighten their understanding of the benefits and risks of PA, before initiating the exercise regimen. For those patients who find it difficult to participate in PA, it is necessary to plan individual-based behavior change approach and encourage self-efficacy. PMID:27274330

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.

Iron Deficiency without Anemia: A Common Yet Under-Recognized Diagnosis in Young Women with Heavy Menstrual Bleeding.

PubMed

Johnson, Stephen; Lang, Abigail; Sturm, Mollie; O'Brien, Sarah H

2016-12-01

To assess the proportion of iron deficiency that is not detected with a screening hemoglobin or complete blood count (CBC) alone in young women with heavy menstrual bleeding. Retrospective review of electronic medical records. Nationwide Children's Hospital in Columbus, Ohio. One hundred fourteen young women aged 9-19 years consecutively referred to a young women's hematology clinic with a complaint of heavy menstrual bleeding. Fifty-eight (50.9%) of all patients had ferritin <20 ng/mL indicating iron deficiency. Of the 58 patients with iron deficiency, only 24 (41.4%) were anemic and 25 (46.3%) were microcytic. The sensitivity of hemoglobin alone and CBC alone for identifying women with ferritin <20 ng/mL was 41.4% (95% confidence interval [CI], 28.7-54.1) and 46.3% (95% CI, 33.0-59.6), respectively. Both tests had reasonable specificity at 91.1% (95% CI, 83.6-98.5) for hemoglobin and 83.9% for CBC (95% CI, 74.3-93.6). Patients had significantly higher odds of having iron deficiency if they were overweight or obese (odds ratio, 2.81; 95% CI, 1.25-6.29) compared with patients with normal body mass index. Age at presentation for heavy menstrual bleeding, presence of an underlying bleeding disorder, and median household income were not significantly associated with iron deficiency. In adolescents with heavy menstrual bleeding, fewer than half of iron deficiency cases are detected when screening is performed with hemoglobin or blood count alone. Measuring ferritin levels in at-risk patients might allow for earlier implementation of iron therapy and improvement in symptoms. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Molecular aspects in clinical hemostasis research at Karolinska Institutet.

PubMed

Blombäck, Margareta

2010-05-21

The development of hemostasis research at Karolinska Institutet is described, focusing first on the initial findings of the fibrinogen structure and the hereditary bleeding disorders, hemophilia A and von Willebrand's disease. Basic research has focused on new biomarkers for cardiovascular/thromboembolic disorders, such as myocardial infarction and stroke, including preeclampsia and diabetes, with studies on the importance of decreased fibrinolysis in these disorders. Since long, the structure of the fibrin network has been evaluated, and recently the influence of aspirin and new thrombin and factor Xa inhibitors has been investigated. Research on the contact pathway of coagulation has also started at the Unit. 2010 Elsevier Inc. All rights reserved.

Coagulation management in patients undergoing neurosurgical procedures.

PubMed

Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

2017-10-01

Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

Bleeding prevalence and transfusion requirement in patients with thrombocytopenia in the emergency department.

PubMed

Turvani, Fabrizio; Pigozzi, Luca; Barutta, Letizia; Pivetta, Emanuele; Pizzolato, Elisa; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

2014-10-01

Thrombocytopenia is the most common coagulation disorder in critically ill patients. No studies have investigated the epidemiology and clinical impact of this condition in emergency department (ED) patients. We aimed to investigate epidemiological features, incidence of bleeding, and diagnostic and therapeutic requirements of patients with thrombocytopenia admitted to the ED. We performed a retrospective observational study enrolling all patients admitted to the medical-surgical ED of the "Città della Salute e della Scienza di Torino" Hospital with a platelet count <150×10(9) PLTs/L, during four non-consecutive months. There were no exclusion criteria. The study included 1218 patients. The percentage of patients with severe (<50×10(9) PLTs/L) or very severe (<20×10(9) PLTs/L) thrombocytopenia was about 12%. Thrombocytopenia associated with liver cirrhosis was the most represented etiology. On the contrary, the most frequent cause in patients with newly recognized low platelet count was disseminated intravascular coagulation/sepsis. The incidence of bleeding and hypovolemia, as well as the need of transfusional support and mechanical, surgical or endoscopic hemostasis progressively increased with the severity of thrombocytopenia. Our results suggest that the detection of a platelet count lower than 50×10(9) PLTs/L may help to identify patients with higher bleeding risk in the ED setting. Additional studies are required to evaluate whether, in this setting, thrombocytopenia may represent an independent risk factor for bleeding episodes and increased mortality.

Hawthorn Herb Increases the Risk of Bleeding after Cardiac Surgery: An Evidence-Based Approach.

PubMed

Rababa'h, Abeer M; Altarabsheh, Salah E; Haddad, Osama; Deo, Salil V; Obeidat, Yagthan; Al-Azzam, Sayer

2016-08-22

Hawthorn extract consumption is becoming more widespread among the Jordanian population with cardiovascular disorders. We conducted this prospective observational longitudinal study to determine the impact of hawthorn extract on bleeding risk in patients who undergo cardiac surgery. A prospective observational study was performed on 116 patients who underwent cardiac surgery in the period between June 2014 and May 2015. Patients were divided into two groups: Group I (patients recently consumed hawthorn extract) and Group II (patients never consumed hawthorn extract). Endpoint measures included the rates of reopening to control bleeding, early mortality, duration of intensive care unit stay, total in-hospital stay period, and duration and amount of chest tube drainage. Hawthorn patients had a significantly higher rate of postoperative bleeding necessitating take back to the operating room compared to the control group (10% versus 1%; P = .03) respectively. The overall mortality rate for group I and II was 4% and 0% respectively; P = .17. Chest tubes were kept in for longer times in group I compared to group II (54 ± 14.6 versus 49 ± 14.7 hours respectively; P = .01). Group I stayed longer in the intensive care unit compared to group II (24 versus 22 hours respectively; P = .01). The total in-hospital stay period was comparable between the two groups. Hawthorn extract consumption does increase the potential for bleeding and the amount of chest tube output after cardiac surgery.

A novel mutation in the P2Y12 receptor and a function-reducing polymorphism in protease-activated receptor 1 in a patient with chronic bleeding.

PubMed

Patel, Y M; Lordkipanidzé, M; Lowe, G C; Nisar, S P; Garner, K; Stockley, J; Daly, M E; Mitchell, M; Watson, S P; Austin, S K; Mundell, S J

2014-05-01

The study of patients with bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets. We have identified a patient with a chronic bleeding disorder expressing a homozygous P2RY(12) mutation, predicting an arginine to cysteine (R122C) substitution in the G-protein-coupled P2Y(12) receptor. This mutation is found within the DRY motif, which is a highly conserved region in G-protein-coupled receptors (GPCRs) that is speculated to play a critical role in regulating receptor conformational states. To determine the functional consequences of the R122C substitution for P2Y(12) function. We performed a detailed phenotypic analysis of an index case and affected family members. An analysis of the variant R122C P2Y(12) stably expressed in cells was also performed. ADP-stimulated platelet aggregation was reduced as a result of a significant impairment of P2Y(12) activity in the patient and family members. Cell surface R122C P2Y(12) expression was reduced both in cell lines and in platelets; in cell lines, this was as a consequence of agonist-independent internalization followed by subsequent receptor trafficking to lysosomes. Strikingly, members of this family also showed reduced thrombin-induced platelet activation, owing to an intronic polymorphism in the F2R gene, which encodes protease-activated receptor 1 (PAR-1), that has been shown to be associated with reduced PAR-1 receptor activity. Our study is the first to demonstrate a patient with deficits in two stimulatory GPCR pathways that regulate platelet activity, further indicating that bleeding disorders constitute a complex trait. © 2014 International Society on Thrombosis and Haemostasis.

Juvenile polyposis syndrome

PubMed Central

Hsiao, Yi-Han; Wei, Chin-Hung; Chang, Szu-Wen; Chang, Lung; Fu, Yu-Wei; Lee, Hung-Chang; Liu, Hsuan-Liang; Yeung, Chun-Yan

2016-01-01

Abstract Background: Juvenile polyposis syndrome, a rare disorder in children, is characterized with multiple hamartomatous polyps in alimentary tract. A variety of manifestations include bleeding, intussusception, or polyp prolapse. In this study, we present an 8-month-old male infant of juvenile polyposis syndrome initially presenting with chronic anemia. To the best of our knowledge, this is the youngest case reported in the literature. Methods: We report a rare case of an 8-month-old male infant who presented with chronic anemia and gastrointestinal bleeding initially. Panendoscopy and abdominal computed tomography showed multiple polyposis throughout the entire alimentary tract leading to intussusception. Technetium-99m-labeled red blood cell (RBC) bleeding scan revealed the possibility of gastrointestinal tract bleeding in the jejunum. Histopathological examination on biopsy samples showed Peutz-Jeghers syndrome was excluded, whereas the diagnosis of juvenile polyposis syndrome was established. Results: Enteroscopic polypectomy is the mainstay of the treatment. However, polyps recurred and occupied the majority of the gastrointestinal tract in 6 months. Supportive management was given. The patient expired for severe sepsis at the age of 18 months. Conclusion: Juvenile polyposis syndrome is an inherited disease, so it is not possible to prevent it. Concerning of its poor outcome and high mortality rate, it is important that we should increase awareness and education of the parents at its earliest stages. PMID:27631205

Medical Surveillance Monthly Report (MSMR). Volume 18, Number 12, December 2011

DTIC Science & Technology

2011-12-01

pregnancy complications were “other specifi ed complications of preg- nancy” (code 646.8, which includes “fatigue during pregnancy” and “ herpes ...bleeding disorders 623.8, 626.5, 626.6,626.8, 626.9 Pain associated with female genital organs 625.0, 625.3, 625.5, 625.9 Inpatient procedure codes

Building our global family--achieving treatment for all.

PubMed

Skinner, M W

2010-07-01

Building our global family by reaching out to women, children and youth and those in sub-Saharan Africa to achieve Treatment for All. The World Federation of Hemophilia (WFH) has committed to recognizing and incorporating the critical and important challenges that are faced by women with bleeding disorders within our global family. The next crucial steps include the development of outreach and registry programmes which can be adapted globally to accelerate the identification of such women, and to educate and guide them to the appropriate clinical care setting. Equally important, awareness must be raised within the broader medical community where women would typically first present with clinical symptoms. Family practitioners, nurse-midwives, obstetricians, gynaecologists and community health clinics will increasingly be strategic and central to WFH outreach efforts, in addition to serving as new care partners essential to the multidisciplinary model of care. Adapting and implementing the WFH development model regionally within Africa is proving to be a successful approach both for the introduction as well as the development of sustainable national care programmes for patients with bleeding disorders. The targeted development of solid national programmes such as in South Africa, Senegal and Kenya has expanded the training capacity of the WFH, as well as providing key regional examples. Local medical professionals are now responsible for providing the training in many regional programmes. Children with bleeding disorders in low-income countries are at great risk of dying young. WFH data demonstrate that among such patients, as the economic capacity of a country decreases so does the ratio of adults to children. The organization of care, training of a multi-disciplinary healthcare team, and education of patients and their families lead to improved mortality independent of economic capacity or increased clotting factor concentrate availability. Additionally, through enhanced youth education, awareness and engagement, we will assure continuity within WFH national member organizations, build greater unity within our global family and capture the innovation and creativity of their ideas to improve Treatment for All.

Albinism and lung fibrosis in a young man - the first case of adult Hermansky-Pudlak Syndrome reported in Malaysia.

PubMed

Liza, A F; Aziah, A M

2012-12-01

A young gentleman of Indian descent with oculacutaneous albinism (OCA) was found to have severe pulmonary fibrosis at first presentation. Following investigations, he was diagnosed with Hermansky-Pudlak Syndrome (HPS). It is a genetic condition characterised by albinism, bleeding diathesis and multisystem disorder observed in individuals of particular descents. Although there is no curative treatment apart from lung transplantation, preventive measures to minimise pulmonary insult may change the natural history of the disease. Therefore HPS should be actively sought, monitored and risk factors addressed in individuals with OCA and bleeding diathesis particularly those of Indian descent as they may develop serious complications such as pulmonary fibrosis in the future.

[Anterior seromyotomy of the body and the functional part of the stomach combined with posterior truncal vagotomy and ulcer excision in the surgical treatment of complicated stomach ulcer].

PubMed

Petrov, V I; Sytnik, A P; Gorbunov, V N; KOrenev, N N; Naumov, B A; Gordeev, S A

1990-07-01

Anterior seromyotomy of the body and fundus of the stomach was combined with posterior truncal vagotomy and excision of the ulcer in 23 patients with gastric ulcer complicated by bleeding or perforation. Seventeen patients had chronic ulcers of the body of the stomach (type I), 3 patients had concurrent ulcers (type II), and 3 more patients had acute ulcers of the body of the stomach. Operation was undertaken for active bleeding from the ulcer in 20 patients and for perforating ulcer in 3 patients. One patient died. Mild disorders of evacuation of an aqueous barium sulfate suspension from the stomach were noted in 4 patients.

[Nursing measures against adverse reaction from anti-cancer chemotherapy].

PubMed

Goto, Setsuko; Mori, Machiko; Fukaya, Youko; Nakamura, Keiko

2003-06-01

Combination chemotherapy for leukemia develops bone marrow suppression. Infection or hemorrhage disorders the treatment, and may influence the clinical result. The caring staff must understand the pathology of bone marrow suppression. Visitors observe the hospital rules. Foods are also limited, city water and uncooked foods are prohibited. To keep oral cavity clean, pretreatment of some decayed teeth, and frequent gargling with sterilized water are needed. Defecation control is important. Sitz bath or shower toilet is helpful. Hand cleaning is essential for before a meal, after defecation and after a going out. Bathing is fundamental to cleaning body. No bathing is dirty. Medical catheters are checked up every day. Thrombocytopenia(< 30,000/microliter) develops a spontaneous bleeding. Severe thrombocytopenia(< 10,000/microliter) does a fatal organ bleeding.

[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.

8(th) Symposium on Hemostasis: Translational and Basic Science Discoveries.

PubMed

Margaritis, Paris; Key, Nigel S

2016-05-01

It has been 14 years since the first symposium on hemostasis at UNC Chapel Hill that focused primarily on the tissue factor (TF) and Factor VIIa (FVIIa) biology, biochemistry and translational work for the treatment of bleeding. Concepts, mechanistic data and therapeutic agents have since emerged that permeate not only aspects of the TF and FVIIa functions, but also broader processes in hemostasis and thrombosis. These processes involve circulating proteins, receptors, cells and cellular components that interact within the coagulation system as well as with additional systems that are dysregulated in disorders seemingly unrelated to bleeding/thrombosis. The reviews in this symposium provide the research background to understand such interactions and integrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular and functional aspects of menstruation in the macaque.

PubMed

Brenner, Robert M; Slayden, Ov D

2012-12-01

Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

Vitamin K antagonists and direct thrombin inhibitors: present and future.

PubMed

Pineo, Graham F; Hull, Russell D

2005-02-01

Warfarin and related compounds are efficacious and safe in a variety of clinical thrombotic disorders; however, these drugs have a narrow therapeutic window, whereby inadequate therapy is associated with an increased thrombotic risk and overanticoagulation is associated with bleeding. Therefore, attempts have been made to develop alternatives to warfarin. Ximelagatran, an oral direct thrombin inhibitor, has been shown to be as efficacious and safe as warfarin for the prevention and treatment of different thrombotic disorders. This article reviews the pharmacology of the coumarins, the most commonly used vitamin K antagonists, and the practical aspects regarding their use in the management of thrombotic disorders. The future role of the oral direct thrombin inhibitor ximelagatran also is reviewed.

Haemophilia A carriers experience reduced health-related quality of life.

PubMed

Gilbert, L; Paroskie, A; Gailani, D; Debaun, M R; Sidonio, R F

2015-11-01

Haemophilia A is an X-linked recessive bleeding disorder that primarily affects males. Emerging data support evidence for increased bleeding in female haemophilia A carriers despite factor VIII activity within the normal range. Data regarding the effect of increased bleeding on health-related quality of life (HR-QOL) in haemophilia A carriers is sparse. We tested the hypothesis that haemophilia A carriers have reduced HR-QOL related to bleeding symptoms. We conducted a cross-sectional study at Vanderbilt University. Case subjects were obligate or genetically verified haemophilia A carriers age 18-60 years. Control subjects were mothers of children with cancer who receive care at the Vanderbilt paediatric haematology-oncology clinic. Trained interviewers administered the Rand 36-Item Health Survey 1.0, a validated questionnaire evaluating eight health concepts that may affect HR-QOL, to each study participant. Mann-Whitney U-tests were used to compare median scores for the eight health domains between the case and control groups. Forty-two haemophilia A carriers and 36 control subjects were included in analyses. Haemophilia A carriers had significantly lower median scores for the domains of 'Pain' (73.75 vs. 90; P = 0.02) and 'General health' (75 vs. 85; P = 0.01) compared to control subjects. Haemophilia A carriers in our study demonstrated significantly lower median scores on the Rand 36-item Health Survey 1.0 in the domains of 'Pain' and 'General Health' compared to women in the control group. Our findings highlight the need for further investigation of the effect of bleeding on HR-QOL in this population. © 2015 John Wiley & Sons Ltd.

Gamma Knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part I: Differences in epidemiologic, morphologic, and clinical characteristics, permanent complications, and bleeding in the latency period

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

Nicolato, Antonio; Lupidi, Francesco; Section of Stereotactic and Functional Neurosurgery, University of Verona and University Hospital, Verona

Purpose: To compare the epidemiologic, morphologic, and clinical characteristics of 92 children/adolescents (Group A) and 362 adults (Group B) with cerebral arteriovenous malformations (cAVMs) considered suitable for radiosurgery; to correlate radiosurgery-related permanent complication and post-radiosurgery bleeding rates in the 75 children/adolescents and 297 adults available for follow-up. Methods and Materials: Radiosurgery was performed with a model C 201-source Co{sup 6} Leksell Gamma Unit (Elekta Instruments, Stockholm, Sweden). Fisher exact two-tailed, Wilcoxon rank-sum, and two-sample binomial exact tests were used for statistical analysis. Results: There were significant differences between the two populations in sex (p = 0.015), clinical presentation (p =more » 0.001), and location (p = 0.008). The permanent complication rate was lower in younger (1.3%) than in older patients (5.4%), although the difference was not significant (p = 0.213). The postradiosurgery bleeding rate was lower in Group A (1.3%) than in Group B (2.7%) (p = 0.694), with global actuarial bleeding rates of 0.56% per year and 1.15% per year, respectively. Conclusions: The different characteristics of child/adolescent and adult cAVMs suggest that they should be considered two distinct vascular disorders. The similar rates of radiosurgery-related complications and latency period bleeding in the two populations show that gamma knife radiosurgery does not expose young patients to a higher risk of sequelae than that for older patients.« less

Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project

PubMed Central

Soucie, J. Michael; Gill, Joan Cox

2017-01-01

This analysis of the US Hemophilia Treatment Center Network and the Centers for Disease Control and Prevention surveillance registry assessed trends in prophylaxis use and its impact on key indicators of arthropathy across the life-span among participants with severe hemophilia A. Data on demographics, clinical characteristics, and outcomes were collected prospectively between 1999 and 2010 at annual clinical visits to 134 hemophilia treatment centers. Trends in treatment and outcomes were evaluated using cross-sectional and longitudinal analyses. Data analyzed included 26 614 visits for 6196 males; mean age at first registry visit was 17.7 years; and median was 14 (range, 2 to 69). During this time, prophylaxis use increased from 31% to 59% overall, and by 2010, 75% of children and youths <20 years were on prophylaxis. On cross-sectional analysis, bleeding rates decreased dramatically for the entire population (P < .001) in parallel with increased prophylaxis usage, possibly because frequent bleeders adopted prophylaxis. Joint bleeding decreased proportionately with prophylaxis (22%) and nonprophylaxis (23%), and target joints decreased more with prophylaxis (80% vs 61%). Joint, total, and target joint bleeding on prophylaxis were 33%, 41%, and 27%, respectively, compared with nonprophylaxis. On longitudinal analysis of individuals over time, prophylaxis predicted decreased bleeding at any age (P < .001), but only prophylaxis initiation prior to age 4 years and nonobesity predicted preservation of joint motion (P < .001 for each). Using a national registry, care providers in a specialized health care network for a rare disorder were able to detect and track trends in outcomes over time. PMID:28183693

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

Idiopathic portal hypertension and extrahepatic portal venous obstruction.

PubMed

Khanna, Rajeev; Sarin, Shiv Kumar

2018-02-01

Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are non-cirrhotic vascular causes of portal hypertension (PHT). Variceal bleed and splenomegaly are the commonest presentations. The present review is intended to provide the existing literature on etiopathogenesis, clinical profile, diagnosis, natural history and management of IPH and EHPVO. IPH and EHPVO are both characterized by normal hepatic venous pressure gradient, moderate to massive splenomegaly with preserved liver synthetic functions. While the level of block in IPH is presinusoidal, in EHPVO it is at prehepatic level. Infections, autoimmunity, drugs, immunodeficiency and prothrombotic states are possible etiological agents in IPH. Contrastingly in EHPVO, prothrombotic disorders and local factors around the portal vein are the incriminating factors. Diagnosis is often clinical, supported by simple radiological tools. Natural history is defined by episodes of variceal bleed and symptoms related to enlarged spleen. Growth failure, portal biliopathy and minimal hepatic encephalopathy are additional concerns in EHPVO. Long-term survival is reasonably good with endoscopic surveillance; however, parenchymal extinction leading to decompensation is seen in a minority of patients in both the disorders. Surgical shunts revert the complications secondary to PHT. Meso-Rex shunt has become the standard surgery in children with EHPVO. This review gives a detailed summary of these two vascular conditions of liver-IPH and EHPVO. Further research is needed to understand the pathogenesis and natural history of these disorders.

Predictors of Co-occurring Neurodevelopmental Disabilities in Children With Autism Spectrum Disorders.

PubMed

Zauche, Lauren Head; Darcy Mahoney, Ashley E; Higgins, Melinda K

Co-occurring neurodevelopmental disabilities (including cognitive and language delays and attention deficit hyperactivity disorder) affect over half of children with ASD and may affect later behavioral, language, and cognitive outcomes beyond the ASD diagnosis. However, no studies have examined predictors of co-occurring neurodevelopmental disabilities in children with ASD. This study investigated whether maternal sociodemographic, perinatal and neonatal factors are associated with co-occurring disabilities. This study involved a retrospective analysis of medical records for children diagnosed with ASD between 2009 and 2010 at an Autism Center in the southeast United States. Logistic regression was used to identify predictors of co-occurring neurodevelopmental disabilities. Of the 385 children in the sample, 61% had a co-occurring neurodevelopmental disability. Children whose mothers had less education (OR: 0.905), had never been married (OR: 1.803), or had bleeding during pregnancy (OR: 2.233) were more likely to have a co-occurring neurodevelopmental disability. Both preterm birth and African American race were associated with bleeding during pregnancy. Several maternal and perinatal risk factors for ASD were found to put children at risk for further diagnoses of co-occurring neurodevelopmental disabilities. While prematurity, a well-established risk factor for ASD, as well as maternal ethnicity was not found to increase the risk of a co-occurring disability, this study suggests that bleeding during pregnancy may moderate these relationships. Understanding maternal, perinatal, and neonatal risk factors may inform healthcare provider screening for ASD and co-occurring neurodevelopmental disabilities by helping providers recognize infants who present with multiple risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

[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.

Abnormal uterine bleeding: advantages of formal classification to patients, clinicians and researchers.

PubMed

Madhra, Mayank; Fraser, Ian S; Munro, Malcolm G; Critchley, Hilary O D

2014-07-01

To highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective. Review and recommendations for local implementation. In the past, research in the field of menstrual disorders has not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM-COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics). This commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation. The PALM-COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Acute Uterine Bleeding Unrelated to Pregnancy: A Southern California Permanente Medical Group Practice Guideline

PubMed Central

Munro, Malcolm G

2013-01-01

Acute uterine bleeding unrelated to pregnancy has been defined as bleeding “sufficient in volume as to, in the opinion of the treating clinician, require urgent or emergent intervention.” The Southern California Permanente Medical Group updated its guidelines for the management of this condition on the basis of the best available evidence, as identified in a systematic review of the available literature. Given the paucity of studies evaluating this condition, the guidelines, by necessity, include recommendations largely based on opinion or other sources such as case series that are, in general, categorized as low-quality evidence. Medical interventions with single or combined gonadal steroidal agents administered parenterally or orally show promise, but more high-quality studies are needed to better define the appropriate drugs, dose, and administrative scheduling. There is also some evidence that intrauterine tamponade may be useful in at least selected cases. Special attention must be paid to both diagnosing and treating inherited disorders of hemostasis, such as von Willebrand disease, that may otherwise be underdiagnosed in both adolescent and adult women. PMID:24355890

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

Intraoperative Conversion From Partial to Radical Nephrectomy: Incidence, Predictive Factors, and Outcomes.

PubMed

Petros, Firas G; Keskin, Sarp K; Yu, Kai-Jie; Li, Roger; Metcalfe, Michael J; Fellman, Bryan M; Chang, Courtney M; Gu, Cindy; Tamboli, Pheroze; Matin, Surena F; Karam, Jose A; Wood, Christopher G

2018-06-01

To evaluate preoperative and intraoperative predictors of conversion to radical nephrectomy (RN) in a cohort of patients undergoing a planned partial nephrectomy (PN) for renal cell carcinoma (RCC). A single-center, retrospective review was conducted using our PN database that includes patients who were scheduled to undergo PN (regardless of the approach) but were converted to RN between August 1990 and December 2016. Reasons for conversion were collected from the operative report. Patient demographics and perioperative variables were compared with the successful PN group. Univariate and multivariate logistic regression analyses were conducted to assess predictors of conversion. A total of 1857 patients were scheduled to undergo PN. Of these patients, 90 (5%) were converted to RN. The multivariate model showed that larger tumor size (odds ratio [OR] = 1.20, P = .040), higher RENAL nephrometry score (OR = 1.41, P = .001), hilar tumor or renal sinus invasion (OR = 2.80, P = .004), laparoscopic PN (OR = 7.34, P <.001), intraoperative bleeding (OR = 19.62, P <.001), positive surgical margin (OR = 31.85, P <.001), and advanced pathologic tumor-stage (T3 or T4) (OR = 7.29, P <.001) were associated with increased odds of intraoperative conversion to RN. The rate of conversion to RN was low in patients who were scheduled to undergo PN in this series. Larger tumor size with increasing complexity, hilar tumor location or renal sinus invasion, locally advanced tumors, laparoscopic PN but not robotic PN, bleeding complication, and positive surgical margin were associated with intraoperative conversion from scheduled PN to RN. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay.

PubMed

Lordkipanidzé, Marie; Lowe, Gillian C; Kirkby, Nicholas S; Chan, Melissa V; Lundberg, Martina H; Morgan, Neil V; Bem, Danai; Nisar, Shaista P; Leo, Vincenzo C; Jones, Matthew L; Mundell, Stuart J; Daly, Martina E; Mumford, Andrew D; Warner, Timothy D; Watson, Steve P

2014-02-20

Up to 1% of the population have mild bleeding disorders, but these remain poorly characterized, particularly with regard to the roles of platelets. We have compared the usefulness of Optimul, a 96-well plate-based assay of 7 distinct pathways of platelet activation to characterize inherited platelet defects in comparison with light transmission aggregometry (LTA). Using Optimul and LTA, concentration-response curves were generated for arachidonic acid, ADP, collagen, epinephrine, Thrombin receptor activating-peptide, U46619, and ristocetin in samples from (1) healthy volunteers (n = 50), (2) healthy volunteers treated with antiplatelet agents in vitro (n = 10), and (3) patients with bleeding of unknown origin (n = 65). The assays gave concordant results in 82% of cases (κ = 0.62, P < .0001). Normal platelet function results were particularly predictive (sensitivity, 94%; negative predictive value, 91%), whereas a positive result was not always substantiated by LTA (specificity, 67%; positive predictive value, 77%). The Optimul assay was significantly more sensitive at characterizing defects in the thromboxane pathway, which presented with normal responses with LTA. The Optimul assay is sensitive to mild platelet defects, could be used as a rapid screening assay in patients presenting with bleeding symptoms, and detects changes in platelet function more readily than LTA. This trial was registered at www.isrctn.org as #ISRCTN 77951167.

Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

PubMed

Favaloro, Emmanuel J

2016-05-01

von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

Clinical predictors and gender-wise variations in dyssynergic defecation disorders.

PubMed

Jain, Mayank; Baijal, Rajiv; Srinivas, Melpakkam; Venkataraman, Jayanthi

2018-06-12

There is insufficient data from India regarding clinical predictors of dyssynergic defecation. To identify demography, symptom, and colonoscopic parameters that can predict dyssynergic defecation (DD) among patients with chronic constipation (CC) and to compare the profile among male and female patients with DD. Data collected from three centers during June 2014 to May 2017 included age, gender, symptom duration, form and consistency of stools, digital examination, colonoscopy, and anorectal manometry (ARM). Patients were grouped based on ARM diagnosis: group I (normal study) and group II (DD). The two groups were compared for demography, symptom profile, and colonoscopy findings. Gender-wise subset analysis was done for those with the normal and abnormal ARM using chi-square and unpaired t tests. Of 236 patients with CC evaluated, 130 (55%) had normal ARM and 106 (45%) had DD. Male sex, straining during defecation, bleeding per rectum, and abnormal colonoscopic diagnosis were significantly more common in group II. While bleeding per rectum and absence of urge to defecate were more common in males (p < 0.02), straining, digital evacuation, and hard stools were commoner in females with DD. Straining during defecation, bleeding per rectum, and abnormal colonoscopy findings were more common in patients with DD. Symptoms of bleeding per rectum and absence of urge to defecate in men and straining during defecation in female patients were significantly associated with DD. Symptoms differ in males and females with DD.

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.

Prospective progression from high-prevalence disorders to bipolar disorder: Exploring characteristics of pre-illness stages.

PubMed

Ratheesh, Aswin; Cotton, Susan M; Betts, Jennifer K; Chanen, Andrew; Nelson, Barnaby; Davey, Christopher G; McGorry, Patrick D; Berk, Michael; Bechdolf, Andreas

2015-09-01

Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated. We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests. The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance. The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Molecular characterization of FXI deficiency.

PubMed

Berber, Ergul

2011-02-01

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

Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.

PubMed

MacLean, Joanna E; Cohen, Eyal; Weinstein, Michael

2002-06-01

Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.

Disseminated intravascular coagulation: pathophysiology and principles of management.

PubMed

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

1998-03-01

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

[Münchhausen syndrome by proxy].

PubMed

Le Heuzey, M-F; Mouren, M-C

2008-01-01

Münchhausen syndrome by proxy is a factitious disorder, a disease produced or simulated by a parent, the mother in most cases. Clinical presentation is miscellaneous (factitious bleeding, epilepsy, apnea are frequent) and unusual. Physicians participate in the abuse by their therapeutic and diagnostical measures. It is very important to think about this diagnostic in any ambiguous situation in order to evaluate and protect the child.

Acute Arthritis in Crimean-Congo Hemorrhagic Fever

PubMed Central

Ahmeti, Salih; Ajazaj-Berisha, Lindita; Halili, Bahrije; Shala, Anita

2014-01-01

Crimean-Congo hemorrhagic fever is a severe viral disease caused by a Nairovirus. An atypical manifestation in the form of acute arthritis was found in a confirmed Crimean-Congo hemorrhagic fever virus Kosova-Hoti strain positive patient. Acute arthritis in Crimean-Congo hemorrhagic fever (CCHF) may be as a result of immune mechanisms or the bleeding disorder underlying CCHF. PMID:24926169

Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

PubMed

Mast, Alan E

2016-01-01

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

Effects of platelet concentrate storage time reduction in patients after blood stem cell transplantation.

PubMed

Heuft, H-G; Goudeva, L; Krauter, J; Peest, D; Buchholz, S; Tiede, A

2013-07-01

To evaluate the clinical effect of platelet concentrate (PC) transfusions after PC storage time reduction to 4 days. This was a single-centre cohort study comparing two 3-month periods of time, before and after the reduction of PC storage time from 5 to 4 days. Seventy-seven consecutive patients with PC transfusions were enrolled after blood stem cell transplantation. Corrected platelet count increment (CCI) on the morning after transfusion, time to next platelet transfusion, need for red blood cell (RBC) transfusion and clinical bleeding symptoms were compared. Platelet concentrate storage time was reduced between period 1 (storage for up to 5 days, median storage time 78 h, range 11-136 h) and period 2 (storage for up to 4 days, median storage time 53 h, range 11-112 h). Patients were comparable for age, weight, body surface area, underlying disorder, type of transplantation and transfused platelet dose. The CCI increased from a median of 4 (range 0-20) to 8 (0-68) × 10(9) /l per 10(11) platelets/m(2) (P < 0·0001). Time to next PC transfusion increased from 1·1 to 2·0 days (P < 0·0001). Any bleeding symptom was noted in 20 of 36 patients (56%) vs. 9/41 patients (22%, P < 0·01). Nose bleeds, haematuria and bleeding at more than one site were significantly reduced. Frequency of RBC transfusion within 5 days after PC transfusion was reduced from 74 to 58% (P < 0·0001). Platelet concentrate storage time shortening was associated with highly significant CCI increase, reduced RC needs and lower patient numbers with bleeding events. © 2013 International Society of Blood Transfusion.

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States

PubMed Central

Christopherson, Pamela A.; Gill, Joan Cox; Friedman, Kenneth D.; Haberichter, Sandra L.; Bellissimo, Daniel B.; Udani, Rupa A.; Dasgupta, Mahua; Hoffmann, Raymond G.; Ragni, Margaret V.; Shapiro, Amy D.; Lusher, Jeanne M.; Lentz, Steven R.; Abshire, Thomas C.; Leissinger, Cindy; Hoots, W. Keith; Manco-Johnson, Marilyn J.; Gruppo, Ralph A.; Boggio, Lisa N.; Montgomery, Kate T.; Goodeve, Anne C.; James, Paula D.; Lillicrap, David; Peake, Ian R.; Montgomery, Robert R.

2016-01-01

von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population. PMID:26862110

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.

PubMed

Flood, Veronica H; Christopherson, Pamela A; Gill, Joan Cox; Friedman, Kenneth D; Haberichter, Sandra L; Bellissimo, Daniel B; Udani, Rupa A; Dasgupta, Mahua; Hoffmann, Raymond G; Ragni, Margaret V; Shapiro, Amy D; Lusher, Jeanne M; Lentz, Steven R; Abshire, Thomas C; Leissinger, Cindy; Hoots, W Keith; Manco-Johnson, Marilyn J; Gruppo, Ralph A; Boggio, Lisa N; Montgomery, Kate T; Goodeve, Anne C; James, Paula D; Lillicrap, David; Peake, Ian R; Montgomery, Robert R

2016-05-19

von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population. © 2016 by The American Society of Hematology.

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.

From CBCL to DSM: A Comparison of Two Methods to Screen for DSM-IV Diagnoses Using CBCL Data

ERIC Educational Resources Information Center

Krol, Nicole P. C. M.; De Bruyn, Eric E. J.; Coolen, Jolanda C.; van Aarle, Edward J. M.

2006-01-01

The screening efficiency of 2 methods to convert Child Behavior Checklist (CBCL) assessment data into Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) diagnoses was compared. The Machine-Aided Diagnosis (MAD) method converts CBCL input data directly into DSM-IV symptom criteria. The…

Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency.

PubMed

Jones, Kareen L; Greenberg, Robert S; Ahn, Edward S; Kudchadkar, Sapna R

2016-01-01

Congenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss. A two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa. Important considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period. A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Male gender, school attendance and sports participation are positively associated with health-related quality of life in children and adolescents with congenital bleeding disorders.

PubMed

Limperg, P F; Joosten, M M H; Fijnvandraat, K; Peters, M; Grootenhuis, M A; Haverman, L

2018-02-08

This study assesses health-related quality of life (HRQOL), and variables associated with HRQOL, in children and adolescents with haemophilia and congenital bleeding disorders (CBD) in the Netherlands. Patients <18 years with CBD under treatment at the Hemophilia Comprehensive Care Center of the Academic Medical Center were included. Participants completed generic HRQOL questionnaires (TAPQOL 0-5 years; PedsQL 6-18 years). Differences and effect sizes in HRQOL compared to healthy peers, and between hemophilia severity groups, were tested using Mann Whitney U-tests. Multivariate regression analyses were performed to assess variables associated with HRQOL. Data of 145 patients (81%) were analyzed (N = 32 with severe haemophilia). Children (0-12 years) show no significant impairments in HRQOL compared to healthy peers. Adolescent boys (13-18 years) with CBD report a slightly higher HRQOL on the total and emotional functioning scales than healthy peers (small-moderate effect sizes). In contrast, adolescent girls experience lower HRQOL on total, social functioning and psychosocial health scales compared to healthy peers (moderate effect sizes). No differences between severity groups were found in HRQOL, but more problem behaviour was found in young boys (0-5 years) with severe haemophilia. Male gender, participation in sports and school attendance are positively associated with HRQOL. Parental country of birth, type of treatment and number of bleeds are not associated with HRQOL. Continuing monitoring HRQOL in daily clinical practice for children with CBD is important, since possible influencing psychosocial factors can change over time, with special focus on adolescent girls, sports participation and school absence. © 2018 John Wiley & Sons Ltd.

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

PubMed

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

A French National Survey on Clotting Disorders in Mastocytosis.

PubMed

Carvalhosa, Ana B; Aouba, Achille; Damaj, Gandhi; Canioni, Danielle; Brouzes, Chantal; Gyan, Emmanuel; Durupt, Stéphane; Durieu, Isabelle; Cathebras, Pascal; Costédoat-Chalumeau, Nathalie; Launay, David; Pilmis, Benoit; Barete, Stephane; Frenzel, Laurent; Lortholary, Olivier; Hermine, Olivier; Hermans, Cedric; Chandesris, Marie-Olivia

2015-10-01

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids.

Unmasking an autosomal recessive disorder by a deletion in the DiGeorge/Velo-cardio-facial chromosome region (DGCR) in 22q11.2

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

Budarf, M.L.; Michaud, D.; Emanuel, B.

Unmasking an autosomal recessive disorder by constitutional hemizygosity is well documented for the embryonal tumors RB and WAGR, where the second hit is a somatic event. Few deletion-mediated recessive conditions have been reported in patients with germline mutations. The major platelet receptor for von Willebrand factor, Glycoprotein Ib (GpIb), is a complex of two plasma membrane glycoproteins, Ib{alpha} and Ib{beta}, covalently linked by disulfide bonds. Defects in this receptor have been associated with the rare congenital autosomal recessive bleeding disorder, Bernard-Soulier syndrome (BSS). BSS is characterized by prolonged bleeding times, thrombocytopenia and very large platelets. The GpIb{beta} gene has beenmore » cloned and we have mapped it within the DGCR. We have identified a patient with phenotypic features of both BSS and VCFS. The patient was referred for 22q11-deletion FISH studies because of a conventricular VSD and mild dysmorphia. FISH with the N25 DiGeorge cosmid demonstrated a deletion in 22q11.2. Western blot analysis of the patient`s platelet proteins demonstrates a complete absence of GpIb{beta}. We suggest that haploinsufficiency for the DGCR in this patient unmasks a mutation in the remaining GpIb{beta} allele, resulting in manifestations of BSS. This mechanism, haploinsufficiency coupled with a mutation of the {open_quotes}normal{close_quotes} chromosome, might explain some of the phenotypic variability seen amongst patients with 22q11.2 microdeletions. These results further suggest that patients with contiguous gene deletion syndromes are at increased risk for autosomal recessive disorders and that they provide the opportunity to {open_quotes}map{close_quotes}disease loci.« less

Bleeding disorders in pregnant patients with rheumatic diseases.

PubMed

Rick, M E

1989-05-01

Although the bleeding disorders that occur in patients with rheumatic diseases are not different during pregnancy than at other times, their diagnosis and management are often different during pregnancy. In idiopathic thrombocytopenic purpura, for instance, antiplatelet antibodies may cross the placenta and cause life-threatening thrombocytopenia in the fetus while the mother is asymptomatic. Management of this disease has changed significantly in the past 5 years with the use of intravenous gammaglobulin which appears to lessen the degree of fetal as well as maternal thrombocytopenia when administered during the peripartum period. The utilization of plasmapheresis and plasma infusions for patients with thrombotic thrombocytopenic purpura has salvaged both the mother and the fetus in a disease which was fatal in more than 60 per cent of patients prior to their use. The outcome of pregnancy in this patient population has markedly improved with this treatment. The stimulus for the production of factor VIII inhibitors in the postpartum period is still not understood, but guidelines for management have changed, with the increased likelihood of decreasing the antibody and inducing tolerance with regimens including factor VIII, immunosuppressive agents and intravenous gammaglobulin in those patients who require treatment. The diagnosis of von Willebrand's disease during pregnancy is difficult because of the physiologic increase in von Willebrand factor during pregnancy; in this instance family studies may help in the diagnosis of this relatively common, autosomal dominant inherited disorder. Management now includes treatment with desmopressin as well as cryoprecipitate replacement therapy.

Case report: a 70-year-old man with undiagnosed factor VII deficiency presented with acute ischemic stroke.

PubMed

Ip, Hing-Lung; Chan, Anne Yin-Yan; Ng, Kit-Chung; Soo, Yannie Oi-Yan; Wong, Lawrence Ka-Sing

2013-11-01

Factor VII deficiency is an uncommon coagulation disorder that patient usually presents with bleeding diathesis, but thrombotic event has been reported. We report a case of unusual clinical presentation in a patient with undiagnosed factor VII deficiency who presented with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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.

Pelvic packing with vaginal traction for the management of intractable hemorrhage.

PubMed

Naranjo-Gutiérrez, Leonardo A; Oliva-Cristerna, Joaquín; Ramírez-Montiel, Martha L; Ortiz, Mario I

2014-10-01

To present clinical cases examining the effectiveness and safety of pelvic packing with vaginal traction for inhibiting obstetric hemorrhage among women receiving treatment at a public obstetrics and gynecology tertiary care hospital in Mexico. In a retrospective observational descriptive study, eight cases of obstetric hemorrhage treated by pelvic packing with vaginal traction between January 2012 and December 2013 at Hospital de la Mujer, Mexico City, Mexico, were reviewed. The mean patient age was 28.8±6.8 years. The average blood loss was 4535±897 mL. Uterine atony was the cause of bleeding among six patients: histopathologic examination revealed two cases of placenta accreta, one case of placenta percreta, two cases of uteroplacental apoplexy, and one case of myomatosis. For two patients, placental separation was difficult and required surgical management. The packing technique was effective for all patients. No patients presented with infection or required re-operation for bleeding management. No deaths occurred. For management of bleeding among patients with underlying coagulation disorders, pelvic packing can be useful when standard techniques such as hysterectomy, tubal hypogastric ligation, and/or pharmacologic therapy are unsuccessful. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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

[Crisis management during obstetric surgery].

PubMed

Okutomi, Toshiyuki

2009-05-01

Obstetric crisis includes hemorrhagic shock, embolisms and difficult airway. Life will be rapidly threatened with disseminated intravascular coagulation, multiple organ failure or systemic inflammatory response syndrome in these crises. In the face of the crisis, repeated evaluation of parturients and differential diagnosis are necessary along with fetal heart monitoring. For evaluation of bleeding, one should notice that the visual estimation of vaginal bleeding does not reflect the extent of intravascular volume deficit. Treatments for hemorrhagic shock include fluid replacement, blood transfusion as well as fresh frozen plasma, platelet, anticoagulants, anti-thrombin III, and protease inhibitors. When bleeding is still uncontrollable, arterial embolization or hysterectomy will be considered. Embolic disorders are another cause of maternal mortality. The signs and symptoms are all similar (dyspnea, cyanosis and sudden cardiovascular collapse). Strategies against the embolism will be basically symptomatic therapy. The physiological change with pregnancy results in the need of careful pre-anesthetic airway evaluation for parturients. A difficult or failed intubation drill is also extremely important. Recently, laryngeal mask airway has been successfully used in these parturients. During resuscitation of a pregnant woman, left uterine displacement is essential. For a patient who has not responded after 4 to 5 minutes of ACLS, immediate cesarean delivery should be considered.

Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

PubMed

Al-Yahya, A M; Al-Masri, A A; El Eter, E A; Hersi, A; Lateef, R; Mawlana, O

2018-05-01

Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

Heavy menstrual bleeding: An update on management.

PubMed

Davies, Joanna; Kadir, Rezan A

2017-03-01

Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss (MBL) >80 mL per cycle, that interferes with a woman's physical, emotional, social wellbeing and quality of life. Aetiology is due to underlying uterine pathologies, coagulopathy, ovulation dysfunction, or iatrogenic. Up to 20% of women with HMB will have an underlying inherited bleeding disorder (IBD). Assessment of HMB should entail a menstrual and gynaecological history and a bleeding score to distinguish those women who require additional haematological investigations. A pelvic examination and ultrasound scan help to rule out presence of any underlying pathology. Management depends on the underlying cause and the woman's preference and her fertility wishes. Medical therapies include hormonal treatments; levonorgestrel-releasing intrauterine system (LNG-IUS) and combined hormonal contraceptives are most commonly used. Ulipristal acetate is an approved preoperative treatment for uterine fibroids, and has demonstrated efficacy in reducing MBL. Haemostatic therapies include tranexamic acid and DDAVP (1-deamino-8-D-arginine). DDAVP is used for HMB associated with certain IBDs. These therapies can be used in isolation or in combination with hormonal treatments. HMB associated with certain severe IBDs may require factor concentrate administration during menses to alleviate symptoms. Endometrial ablation is a minor surgical procedure that is associated with low operative morbidity and can be performed as an outpatient. Hysterectomy remains the definitive treatment of choice when medical therapies have failed and endometrial ablation is not suitable. Crown Copyright © 2017 Published by Elsevier Ltd. All rights reserved.

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.

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

PubMed

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

2013-06-01

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

IgMk paraprotein from gammopathy patient can bind to cardiolipin and interfere with coagulation assay: a case report.

PubMed

Wu, Xin-Yao; Yin, Yu-Feng; Teng, Jia-Lin; Zhang, Li-Wei; Yang, Cheng-de

2017-06-23

The monoclonal gammopathies are a group of plasma-cell proliferative disorders characterized by the secretion of monoclonal immunoglobulin (M protein or paraprotein). Some rare cases have revealed the specific affinity of paraprotein as autoantibody. Here we report a patient with monoclonal gammopathy of undetermined significance (MGUS) accompanied by a remarkable increase of anticardiolipin antibody (aCL) and an extensively decreased coagulation factor activity, however, without any clinical signs of antiphospholipid syndrome (APS) and bleeding. Our further investigation indicated that IgMκ paraprotein of this patient possessed an antibody activity against phospholipids so as to bind to cardiolipin and interfere with coagulation assay in vitro. This case might be indicative that an abnormality of coagulation tests, disturbed by IgMκ paraprotein, does not predict a risk of bleeding in this patient.

Prescribing Warfarin Appropriately to Meet Patient Safety Goals

PubMed Central

Dharmarajan, Lekshmi; Dharmarajan, T.S.

2008-01-01

The anticoagulant warfarin is increasingly used in a variety of disorders associated with risk of thromboembolism. The drug is undoubtedly effective but is linked to numerous nutrient, disease, and drug interactions; safe use of warfarin therefore necessitates close patient monitoring, using the international normalized ratio. The predominant adverse effect is bleeding, and individuals respond to warfarin in different ways. Both high and subtherapeutic international normalized ratios warrant attention, whereas a high international normalized ratio, with or without bleeding, mandates prompt patient evaluation. The 2008 National Patient Safety Goals require medical institutions to develop processes to ensure the safe use and monitoring of anticoagulant use. Last August, the US Food and Drug Administration revised the prescribing information for warfarin to include genetic testing before initiating therapy, although this is still not covered by most health plans. PMID:25126243

Networks of blood proteins in the neuroimmunology of schizophrenia.

PubMed

Jeffries, Clark D; Perkins, Diana O; Fournier, Margot; Do, Kim Q; Cuenod, Michel; Khadimallah, Ines; Domenici, Enrico; Addington, Jean; Bearden, Carrie E; Cadenhead, Kristin S; Cannon, Tyrone D; Cornblatt, Barbara A; Mathalon, Daniel H; McGlashan, Thomas H; Seidman, Larry J; Tsuang, Ming; Walker, Elaine F; Woods, Scott W

2018-06-06

Levels of certain circulating cytokines and related immune system molecules are consistently altered in schizophrenia and related disorders. In addition to absolute analyte levels, we sought analytes in correlation networks that could be prognostic. We analyzed baseline blood plasma samples with a Luminex platform from 72 subjects meeting criteria for a psychosis clinical high-risk syndrome; 32 subjects converted to a diagnosis of psychotic disorder within two years while 40 other subjects did not. Another comparison group included 35 unaffected subjects. Assays of 141 analytes passed early quality control. We then used an unweighted co-expression network analysis to identify highly correlated modules in each group. Overall, there was a striking loss of network complexity going from unaffected subjects to nonconverters and thence to converters (applying standard, graph-theoretic metrics). Graph differences were largely driven by proteins regulating tissue remodeling (e.g. blood-brain barrier). In more detail, certain sets of antithetical proteins were highly correlated in unaffected subjects (e.g. SERPINE1 vs MMP9), as expected in homeostasis. However, for particular protein pairs this trend was reversed in converters (e.g. SERPINE1 vs TIMP1, being synthetical inhibitors of remodeling of extracellular matrix and vasculature). Thus, some correlation signals strongly predict impending conversion to a psychotic disorder and directly suggest pharmaceutical targets.

The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism

PubMed Central

Sonsalla, Patricia K.; Coleman, Christal; Wong, Lai-Yoong; Harris, Suzan L.; Richardson, Jason R.; Gadad, Bharathi S.; Li, Wenhao; German, Dwight C.

2013-01-01

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin converting enzyme inhibitor captopril protects the striatum from acutely administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP), and that chronic captopril protects the nigral DA cell bodies from degeneration in a progressive rat model of parkinsonism created by the chronic intracerebral infusion of 1-methyl-4-phenylpyridinium (MPP+). The accompanying activation of microglia in the substantia nigra of MPP+-treated rats was reduced by the chronic captopril treatment. These findings indicate that captopril is neuroprotective for nigrostriatal DA neurons in both acute and chronic rodent PD models. Targeting the brain AngII pathway may be a feasible approach to slowing neurodegeneration in PD. PMID:24184050

External cephalic version of the term breech baboon (Papio sp.) fetus.

PubMed

Barrier, Breton F; Joiner, Laura Lee Rihl; Jimenez, Joe B; Leland, M Michelle

2007-06-01

Breech presentation in baboons may be associated with head entrapment and stillbirth during vaginal delivery. For this reason, pregnant dams at our institution typically undergo cesarean delivery for known breech presentation, leading to problems with maternal-infant bonding and increased nursery utilization. This paper describes a simple, non-invasive technique called external cephalic version (ECV) that effectively converts the baboon breech fetus into a cephalic presentation. ECV was successful in each of seven attempted cases, with the consistent development of contractions and vaginal bleeding leading to the delivery of a healthy liveborn infant within 72 hours. ECV may offer a safe and effective alternative to cesarean section for delivery of the breech baboon fetus.

Gynecologic disorders diagnosed during deployment to Southwest/Central Asia, active component females, U.S. Armed Forces, 2008-2013.

PubMed

2014-08-01

Service women in the U.S. Armed Forces face unique challenges that may lead to or exacerbate gynecologic disorders - particularly during deployment. This report documented that approximately one in 10 military women who served in Southwest/Central Asia were diagnosed with a gynecologic disorder at least once during deployment. In addition, gynecologic disorders accounted for approximately one of every 20 medical evacuations of female service members from the war zone. A majority of clinically significant gynecologic disorder cases were attributable to irregular menstruation/bleeding or unspecified inflammation or pain of the female genital organs. Incidence rates of gynecologic disorder diagnoses were higher among black, non-Hispanic service women, among younger women, and among those in the Army and in motor transport and communications/intelligence occupations. Approximately 50% of gynecologic disorder cases had received gynecologic care within 6 months prior to deployment and nearly 90% had received care within 2 years of deployment. Despite pre-deployment care, it is apparent from this report that service women need continuous access to gynecologic care during deployment, particularly if conditions during deployment lead to and exacerbate gynecologic disorders.

Traumatic Hemarthrosis of the Knee Secondary to Hemophilia A in a Collegiate Soccer Player: A Case Report

PubMed Central

Fiala, Kelly A.; Hoffmann, Sandra J.; Ritenour, Donna M.

2002-01-01

Objective: To present the case of a collegiate soccer player who suffered from a traumatic knee hemarthrosis secondary to hemophilia A. This case presents an opportunity to discuss the participation status of athletes with hemophilia. Background: Hemophilia is a hereditary blood disease characterized by impaired coagulability of the blood. Hemophilia A is the most common of the severe, inherited bleeding disorders. This type, also called classic hemophilia, is due to a deficiency of clotting factor VIII. The athlete with hemophilia A reported pain and loss of function of his knee during a soccer game despite the absence of injury. Differential Diagnosis: Anterior cruciate ligament tear, intra-articular fracture, meniscus tear, capsular tear, hemarthrosis. Treatment: After the injury, the athlete was admitted to the hospital, where his knee joint was aspirated and he was infused with factor VIII. Later, he participated in traditional knee rehabilitation and was returned to play at the discretion of the orthopaedist and the hematologist. Uniqueness: In past participation guidelines, individuals with bleeding disorders were disqualified from athletic participation; however, with advances in medical care, these individuals may be permitted to participate in accordance with the law. Conclusions: Individuals with hemophilia participate in athletics; therefore, team physicians and athletic trainers must be prepared to care for these individuals. PMID:12937588

Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene.

PubMed

Bisserbe, A; Tertian, G; Buffet, C; Turhan, A; Lambotte, O; Nasser, G; Alvin, P; Tardieu, M; Riant, F; Bergametti, F; Tournier-Lasserve, E; Denier, C

2015-05-01

Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The efficacy and safety of novel oral anticoagulants for the preventive treatment in atrial fibrillation patients: a systematic review and meta-analysis.

PubMed

Liu, Guang Jian; Wang, Yun Fu; Chen, Ping You; Chang, Wei; Tu, Ming Li; Chang, Li Ying; Cheng, Ping; Luo, Jie

2014-09-01

Novel oral anticoagulants, including direct factor Xa inhibitors and direct factor IIa inhibitors, have been used to prevent stroke in patients with atrial fibrillation (AF) for a decade. In this study, the efficacy and safety of the novel oral anticoagulants were assessed in AF patients. No language restrictions were applied. Study selection and data extraction were carried out by searching PubMed, EMBASE, OVID, the BIOSIS, the Web of Science, Clinical Trials Registers, Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. Each database was searched from its inception date to June 2013. Using odds ratio (OR) as an indicator, we systematically evaluated the primary efficacy endpoints and safety endpoints, as well as 10 secondary endpoints. Compared to the control drugs, the novel oral anticoagulants showed an OR decreased by 26% (OR: 0.74, 95% confidence interval (CI): 0.62-0.88) for stroke or systemic embolism, decreased by 24% (OR: 0.76, 95% CI: 0.64-0.90) for major bleeding, decreased by 10% (OR: 0.90, 95% CI: 0.84-0.95) for death from any cause, decreased by 27% for disabling or fatal stroke (OR: 0.73, 95% CI: 0.54-0.97), decreased by 31% (OR: 0.69, 95% CI: 0.60-0.8) for fatal bleeding, and decreased by 8% (OR: 0.92, 95% CI: 0.88-0.95) for serious adverse events. However, there was no significant difference in acute myocardial infarction, systemic embolism, major bleeding or clinically relevant non-major, all bleeding events, all adverse events and liver function disorder, between the novel oral anticoagulants and control drugs (p > 0.05). Compared to the control drugs, the novel oral anticoagulants showed higher efficiency and safety in patients with AF, as evidenced by their superior performance not only in reducing the risk of stroke or systemic embolism with a lower risk of major bleeding but also in decreasing the incidence of death from any cause, disabling or fatal stroke, serious adverse events and fatal bleeding.

Structural Modeling Insights into Human VKORC1 Phenotypes

PubMed Central

Czogalla, Katrin J.; Watzka, Matthias; Oldenburg, Johannes

2015-01-01

Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain γ-carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention and therapy of thromboembolism. Patients with these mutations require greater doses of VKA for stable anticoagulation than patients without mutations. The second phenotype, a very rare autosomal-recessive bleeding disorder caused by combined deficiency of vitamin K dependent clotting factors type 2 (VKCFD2) arises from a homozygous Arg98Trp mutation. The bleeding phenotype can be corrected by vitamin K administration. Here, we summarize published experimental data and in silico modeling results in order to rationalize the mechanisms of VKA resistance and VKCFD2. PMID:26287237

Ischemic stroke in a patient with moderate to severe inherited factor VII deficiency.

PubMed

Reddy, Manasa; Tawfik, Bernard; Gavva, Chakri; Yates, Sean; De Simone, Nicole; Hofmann, Sandra L; Rambally, Siayareh; Sarode, Ravi

2016-12-01

Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibitor development after liver transplantation in congenital factor VII deficiency.

PubMed

See, W-S Q; Chang, K-O; Cheuk, D K-L; Leung, Y-Y R; Chan, G C-F; Chan, S-C; Ha, S-Y

2016-09-01

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement. © 2016 John Wiley & Sons Ltd.

Cyclophosphamide Treatment for Acquired Factor VIII Inhibitor in a Patient with AIDS-Associated Progressive Multifocal Leukoencephalopathy.

PubMed

Malhotra, Uma; Aboulafia, David M

2016-01-01

Acquired hemophilia A (AHA) is a severe bleeding disorder with high mortality rates resulting from the development of autoantibodies to factor VIII (FVIII). Patients typically present with hemorrhages in the skin, subcutaneous tissues, and muscles, which are frequently severe. They can also develop life-threatening retroperitoneal hematomas and compartment syndromes. We describe the case of a man with a long history of AIDS complicated by progressive multifocal leukoencephalopathy (PML), who developed AHA while on stable antiretroviral therapy and then presented with new onset bleeding and hypotension. We treated our patient with incrementally increasing doses of cyclophosphamide resulting in resolution of coagulopathy. We review the medical literature for additional cases of HIV-associated AHA and discuss the challenges in the care of our patient, since the immunosuppression needed to eradicate the FVIII inhibitor had the potential to cause recrudescence of his PML. © The Author(s) 2015.

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

PubMed Central

Refaat, Marwan; Hotait, Mostafa; Winston, Brion

2014-01-01

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

Prothrombin complex concentrate and fatal thrombotic adverse events: A complication to keep in mind.

PubMed

Tabet, Rabih; Shammaa, Youssef; Karam, Boutros; Yacoub, Harout; Lafferty, James

2018-05-13

Thromboembolic events such as deep vein thrombosis and pulmonary embolism are well-known complications that can occur after prothrombin complex concentrate therapy. However, acute myocardial infarction is a very rare but potentially life-threatening complication that was exclusively described in patients with bleeding disorders who received chronic and recurrent concentrate infusions. We report the case of a 70 year-old male patient with cholangiocarcinoma who was admitted to our hospital with worsening fatigue and weakness. His stay was complicated by uncontrolled bleeding secondary to rivaroxaban use and advanced liver disease. By the end of the prothrombin complex concentrate infusion used to reverse his coagulopathy, patient developed ST-segment elevation myocardial infarction with cardiogenic shock and passed away. This is the first reported case of acute myocardial infarction that occurs in a patient without hemophilia and after the first prothrombin complex concentrate infusion.

[Anaesthetic implications in a pregnant patient with an extreme thrombocytopenia due to a May-Hegglin anomaly: general o regional anaesthesia?].

PubMed

García Vallejo, G; Cabellos, M; Kabiri, M; Fraile, J R; Cuesta, J

2014-10-01

The May-Hegglin anomaly is an inherited disorder, so uncommon that the incidence is still unknown. It is characterized by macro-thrombocytopenia with normal platelet function and cytoplasmic inclusion bodies in granulocytes. The case is reported of a 28-year-old primiparous patient who had an urgent caesarean section due to failed induction of labour. The patient had no history of abnormal bleeding. Other causes of thrombocytopenia or platelet dysfunction, such as preeclampsia, HELLP syndrome, or placental abruption, were ruled out. The platelet count prior to surgery was 20,900/mm(3) with normal platelet function. General anaesthesia was performed. No excessive bleeding occurred and a platelet transfusion was not needed. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Evaluation of a web-based registry of inherited bleeding disorders: a descriptive study of the Brazilian experience with HEMOVIDAweb Coagulopatias.

PubMed

Rezende, Suely Meireles; Rodrigues, Silvia Helena Lacerda; Brito, Kelly Neves Pinheiro; da Silva, Diego Lima Quintino; Santo, Marcos Lázaro; Simões, Bárbara de Jesus; Genovez, Guilherme; Melo, Helder Teixeira; Araújo, João Paulo Baccara; Barca, Danila Augusta Accioly Varella

2017-02-10

Inherited bleeding disorders (IBD) consist of a group of rare heterogeneous diseases, which require treatment for life. Management of these disorders is complex and costly. Therefore, good quality data of the affected population is crucial to guide policy planning. The aim of this manuscript is to describe the impact of a national, web-based registry - the Hemovidaweb Coagulopatias (HWC) - in the management of the IBD in Brazil. The system was developed in PHP 5.0 language and is available on the internet at http://coagulopatiasweb.datasus.gov.br . The system was validated in September 2008 and launched nationally with input from January 1, 2009. HWC collects variables related to socio-demographic, clinical, laboratory and treatment data of patients with IBD. Within 7 years, there was an increment of 90.8% on the diagnosis of IBD altogether, which increased from 11,040 in December 2007 to 21,066 in December 2014. This is now the fourth and third largest world population of patients with haemophilia and von Willebrand's disease (vWD), respectively, according to the most recent (2015) Annual Global Survey of the World Federation of Hemophilia. The data collected provided the basis for planning and implementing home therapy, prophylaxis and immune tolerance induction (ITI), recently initiated in Brazil. HWC was an effective tool in the increment of registration of patients with IBD in Brazil. Furthermore, it was essential to support policy planning, monitoring, evaluation and treatment. Future development should focus on surveillance, health outcomes and research. Every country should implement a national registry on IBD.

Immune Thrombocytopenia

PubMed Central

Kistanguri, Gaurav; McCrae, Keith R.

2013-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP, with the risk of bleeding and related morbidity increased in elderly patients. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Thrombocytopenia is caused by antibodies that react with glycoproteins expressed on platelets and megakaryocytes (glycoprotein IIb/IIIa, Ib/IX and others), causing shortened survival of circulating platelets and impairing platelet production. Diminished numbers and function of regulatory T cells, as well as the effects of cytotoxic T cells also contribute to the pathogenesis of ITP. Corticosteroids remain the most common first line therapy for ITP, occasionally in conjunction with intravenous immunoglobulin (IVIg) and anti-Rh(D). However, these agents do not lead to durable remissions in the majority of adults with ITP, and considerable heterogeneity exists in the use of second line approaches, which may include splenectomy, Rituximab, or thrombopoietin receptor agonists (TRAs). This review summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. Remarkable advances in the understanding and management of ITP have been achieved over the last decade, though many questions remain. PMID:23714309

Taste disturbance following tonsillectomy--a prospective study.

PubMed

Heiser, Clemens; Landis, Basile N; Giger, Roland; Cao Van, Helene; Guinand, Nils; Hörmann, Karl; Stuck, Boris A

2010-10-01

Persistent taste disturbance is a rare complication after tonsillectomy and mainly documented by case reports or a few retrospective and prospective trials with a limited number of patients. None could clarify frequency, time course, or prognosis of long-lasting dysgeusia after tonsillectomy. The aim of the study was to provide a symptom-based follow-up after tonsillectomy to assess postoperative taste disorders. Prospective clinical trial. From December 2007 to June 2009 adult patients undergoing tonsillectomy were asked to take part in the trial. Two hundred twenty-three patients (119 female, 104 male; mean age, 33 ± 13 years) were included. The day prior to surgery, and 2 weeks and 6 months after tonsillectomy a standardized questionnaire was completed by patients. The questionnaire focused on taste function, taste disorders, pain, foreign body sensation, and bleeding episodes after tonsillectomy. One hundred eighty-eight (2 weeks) and 181 (6 months) patients returned the questionnaires. Thirty-two percent (n = 60) of patients reported taste disorders after tonsillectomy 2 weeks postoperatively and 15 patients (8%) at 6-month follow-up. Metallic and bitter parageusia were most frequently reported. The mean ratings of gustatory function were significantly lower 2 weeks after surgery (P < .001) and reached preoperative values 6 months after surgery. Almost 30% of patients reported postoperative bleeding, 10% long-lasting postoperative pain, and 20% foreign body sensation. Long-lasting taste disturbance (metallic and bitter parageusia) after tonsillectomy is more frequent than previously reported. Long-lasting pain and foreign body sensation seem to be common symptoms. With regard to these results, a thorough preoperative explanation is mandatory.

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

Therapeutic Decision-Making in Endoscopically Unmanageable Nonvariceal Upper Gastrointestinal Hemorrhage

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

Defreyne, Luc, E-mail: Luc.Defreyne@UGent.b; Schrijver, Ignace De; Decruyenaere, Johan

2008-09-15

The purpose of this study was to identify endoscopic and clinical parameters influencing the decision-making in salvage of endoscopically unmanageable, nonvariceal upper gastrointestinal hemorrhage (UGIH) and to report the outcome of selected therapy. We retrospectively retrieved all cases of surgery and arteriography for arrest of endoscopically unmanageable UGIH. Only patients with overt bleeding on endoscopy within the previous 24 h were included. Patients with preceding nonendoscopic hemostatic interventions, portal hypertension, malignancy, and transpapillar bleeding were excluded. Potential clinical and endoscopic predictors of allocation to either surgery or arteriography were tested using statistical models. Outcome and survival were regressed on themore » choice of rescue and clinical variables. Forty-six arteriographed and 51 operated patients met the inclusion criteria. Univariate analysis revealed a higher number of patients with a coagulation disorder in the catheterization group (41.4%, versus 20.4% in the laparotomy group; p = 0.044). With multivariate analysis, the identification of a bleeding peptic ulcer at endoscopy significantly steered decision-making toward surgical rescue (OR = 5.2; p = 0.021). Taking into account reinterventions, hemostasis was achieved in nearly 90% of cases in both groups. Overall therapy failure (no survivors), rebleeding within 3 days (OR = 3.7; p = 0.042), and corticosteroid use (OR = 5.2; p = 0.017) had a significant negative impact on survival. The odds of dying were not different for embolotherapy or surgery. In conclusion, decision-making was endoscopy-based, with bleeding peptic ulcer significantly directing the choice of rescue toward surgery. Unsuccessful hemostasis and corticosteroid use, but not the choice of rescue, negatively affected outcome.« less

Platelets and hemophilia: A review of the literature.

PubMed

Riedl, Julia; Ay, Cihan; Pabinger, Ingrid

2017-07-01

Hemophilia A and B are inherited bleeding disorders due to deficiencies of the clotting factors VIII and IX, respectively. The severity of the disease correlates with remaining factor levels, although individual differences in bleeding tendency are seen despite similar factor levels. While thrombin generation is severely impaired in persons with hemophilia, primary hemostasis, i.e. platelet function, has been generally considered to be normal. However, some studies reported prolonged bleeding times in hemophilia, suggesting that also primary hemostasis is affected. In several other studies different aspects of platelet function in hemophilia have been investigated in more detail and various alterations were discovered, such as increased platelet P-selectin expression, a lower number of procoagulant, so-called 'coated' platelets, lower aggregation upon co-incubation with tissue factor, or reduced platelet contractile forces during clot formation in comparison to healthy individuals. An influence of platelet function on clinical phenotype was suggested, which might contribute in part to variations in bleeding tendency in hemophilic patients with similar factor levels. However, the available evidence is currently limited and no clear correlations between platelet function parameters and clinical phenotypes have been demonstrated. The impact of alterations of platelet function in hemophilia remains to be better defined. Another interesting role of platelets in hemophilia has been reported recently by establishing a novel gene-therapeutic strategy using platelets as a delivery system for FVIII, showing promising results in animal models. This review gives an overview on the currently published literature on platelet function and the potential roles of platelets in hemophilia. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-01-01

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

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

PubMed

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

2017-08-01

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

Did some 18th and 19th century treatments for mental disorders act on the brain?

PubMed

Leonard, Edward C

2004-01-01

Review of 18th and 19th century psychiatric therapies raises the possibility that several may have altered the activity of vasopressin or Na-K-ATPase. Bleeding, whirling, nausea created by medicines, and vagus nerve stimulation by application of electricity through the skin all perturb the hypothalamic hormone, arginine vasopressin, while helleborus and digitalis inhibit the sodium pump enzyme, Na-K-ATPase. These approaches were used with reported benefit many years ago, acting on the brain in ways ongoing research suggests may play a role in affective disorders. Study of long-abandoned treatments may clarify their mechanisms of action and the characteristics of responsive patients.

Immune Thrombocytopenic Purpura Detected with Oral Hemorrhage: a Case Report

PubMed Central

Sugiura, Tsutomu; Yamamoto, Kazuhiko; Murakami, Kazuhiro; Horita, Satoshi; Matsusue, Yumiko; Nakashima, Chie; Kirita, Tadaaki

2018-01-01

Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease found in both adults and children. It is characterized by transient or persistent decreases in the platelet count. We report a case of ITP detected based on oral hemorrhagic symptoms. The patient was a 79-year-old female with no significant past medical history. She presented with sudden onset of gingival bleeding and hemorrhagic bullae on the buccal mucosa. Gingival bleeding was difficult to control. Laboratory tests revealed severe thrombocytopenia with a platelet count as low as 2000/μL. Under a provisional diagnosis of a hematological disorder, she was referred to a hematologist. A peripheral smear showed normal-sized platelets. A bone marrow examination revealed increased numbers of megakaryocytes without morphologic abnormalities. The patient was diagnosed with ITP and treated with a combination of pulsed steroid therapy and high-dose immunoglobulin therapy. However, her severe thrombocytopenia was refractory to these treatments. Then, a thrombopoietin receptor agonist was begun as a second-line treatment. Her platelets rapidly increased, and no bleeding complications were reported. Because oral symptoms can be one of the initial manifestations of ITP, dentists should be familiar with the clinical appearance of ITP, and attention must be paid to detect and diagnose unidentified cases. PMID:29854891

Glanzmann Thrombasthenia: State of the Art and Future Directions

PubMed Central

Nurden, Alan T; Pillois, Xavier; Wilcox, David A.

2014-01-01

Glanzmann thrombasthenia (GT) is the principal inherited disease of platelets and the most commonly encountered disorder of an integrin. GT is characterized by spontaneous mucocutaneous bleeding and an exaggerated response to trauma due to platelets that fail to aggregate when stimulated by physiologic agonists. GT is caused by quantitative or qualitative deficiencies of αIIbβ3, an integrin coded by the ITGA2B and ITGB3 genes and which by binding fibrinogen and other adhesive proteins joins platelets together in the aggregate. Widespread genotyping has revealed mutations spread across both genes, yet the reason for the extensive variation in both the severity and intensity of bleeding between affected individuals remains poorly understood. Furthermore, while genetic defects of ITGB3 affect other tissues with β3 present as αvβ3 (the vitronectin receptor), the bleeding phenotype continues to dominate. Here, we look in detail at mutations that affect (i) the β-propeller region of the αIIb head domain and (ii) the membrane proximal disulfide-rich EGF domains of β3 and which often result in spontaneous integrin activation. We also examine deep vein thrombosis as an unexpected complication of GT and look at curative procedures for the disease including allogeneic stem cell transfer and the potential for gene therapy. PMID:23929305

Clinical characteristics and outcomes of acquired hemophilia A: experience at a single center in Japan.

PubMed

Ogawa, Yoshiyuki; Yanagisawa, Kunio; Uchiumi, Hideki; Ishizaki, Takuma; Mitsui, Takeki; Gouda, Fumito; Ieko, Masahiro; Ichinose, Akitada; Nojima, Yoshihisa; Handa, Hiroshi

2017-07-01

Acquired hemophilia A (AHA), which is caused by autoantibodies against coagulation factor VIII (FVIII) is a rare, life-threatening bleeding disorder, the incidence of which appears to be increasing in Japan as the population ages. However, the clinical characteristics, treatment, and outcomes of AHA remain difficult to establish due to the rarity of this disease. We retrospectively analyzed data from 25 patients (median age 73 years; range 24-92 years; male n = 15) diagnosed with AHA between 1999 and 2015 at Gunma University Hospital. We identified autoimmune diseases and malignancy as underlying conditions in four and three patients, respectively. Factor VIII activity was significantly decreased in all patients (median 2.0%; range <1.0-8.0) by FVIII inhibitor (median 47.0 BU/mL; range 2.0-1010). Among 71 bleeding events, subcutaneous or intramuscular hemorrhage was the most prevalent. Seventeen patients required bypassing agents. Twenty-two (91.7%) of 24 patients treated with immunosuppressive agents achieved complete response (CR) during a median of 57.5 days (range 19-714 days). Although three patients (12%) relapsed and seven (28%) died of infection, none of the deaths were related to bleeding. Although most of our patients achieved CR after immunosuppressive therapy, the rate of infection-related mortality was unsatisfactorily high.

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

PubMed

Hickman, DaShawn A; Pawlowski, Christa L; Sekhon, Ujjal D S; Marks, Joyann; Gupta, Anirban Sen

2018-01-01

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Factor XI as a target for antithrombotic therapy

PubMed Central

Bane, Charles E.; Gailani, David

2014-01-01

Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

Noonan syndrome

PubMed Central

Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

2014-01-01

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors.

PubMed

Chai-Adisaksopha, Chatree; Nevitt, Sarah J; Simpson, Mindy L; Janbain, Maissaa; Konkle, Barbara A

2017-09-25

People with hemophilia A or B with inhibitors are at high risk of bleeding complications. Infusion of bypassing agents, such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrate, are suggested as alternative therapies to factor VIII (haemophilia A) or IX (haemophilia B) for individuals who no longer respond to these treatments because they develop inhibitory antibodies. The ultimate goal of treatment is to preserve the individual's joints, otherwise destroyed by recurrent bleeds. To assess the effects of bypassing agent prophylaxis to prevent bleeding in people with hemophilia A or B and inhibitors. We searched for relevant studies from the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries (16 February 2017) and bibliographic references of retrieved studies were reviewed for potential articles to be included in the review.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register: 12 December 2016. We included randomized and quasi-randomized controlled studies (cross-over or parallel design) evaluating the effect of prophylaxis treatment with bypassing agents compared with on-demand treatment, or studies evaluating the effects of high-dose compared with low-dose prophylaxis in males of any age with hemophilia with inhibitors. Two authors independently selected studies and extracted data and assessed the risk of bias according to standard Cochrane criteria. They assessed the quality of the evidence using the GRADE criteria. We included four randomized studies (duration 7 to 15 months) involving 116 males. Risk of bias was judged to be high in two studies due to the open-label study design and in one study due to attrition bias.Two studies compared on-demand treatment to prophylaxis with bypassing agents. In one study (34 males) prophylaxis significantly reduced mean overall bleeding rates, MD - 7.27 (95% CI -9.92 to -4.62) (low quality evidence), mean number of overall bleeding events per month, MD -1.10 (95% CI -1.54 to -0.66), mean number of hemarthrosis, MD -6.60 (95% CI -9.32 to -3.88) (low quality evidence) and mean number of joints that had hemarthrosis, MD -0.90 (95% CI -1.36 to -0.44). The meta-analysis did not conclusively demonstrate significant benefit of prophylaxis on health-related quality of life as measured by Haem-A-QoL score, EQ-5D total score and utility score, EQ-5D VAS and SF-36 physical summary and mental summary score (low quality evidence for all health-related quality of life analyses).The remaining two studies compared dose regimens. The results from one study (22 males) did not conclusively demonstrate benefit or harm of high-dose versus low-dose recombinant activated factor VIIa (rFVIIa) as a prophylaxis for overall bleeding rate, MD -0.82 (95% CI -2.27 to 0.63) (moderate quality evidence), target joint bleeding rate, MD -3.20 (95% CI -7.23 to 0.83) (moderate quality evidence) and serious adverse events, RR 9.00 (95% CI, 0.54 to 149.50) (moderate quality evidence).The overall quality of evidence was moderate to low due to imprecision from limited information provided by studies with small sample sizes and incomplete outcome data in one study. The evidence suggests that prophylaxis with bypassing agents may be effective in reducing bleeding in males with hemophilia with inhibitors. However, there is a lack of evidence for the superiority of one agent over the other or for the optimum dosage regimen. Further studies are needed to evaluate the benefits and harms of prophylaxis treatment on health-related quality of life, as well as the effects of dose of bypassing agents on the outcomes.

Ventilatory Response to Hypercapnia Predicts Dementia with Lewy Bodies in Late-Onset Major Depressive Disorder.

PubMed

Takahashi, Sho; Mizukami, Katsuyoshi; Arai, Tetsuaki; Ogawa, Ryoko; Kikuchi, Norihiro; Hattori, Satoshi; Darby, David; Asada, Takashi

2016-01-01

Studies have shown that developing major depressive disorder (MDD) at 50 years of age or older can predict dementia. Depression is particularly common in dementia with Lewy bodies (DLB), and occasionally occurs before the onset of extrapyramidal symptoms. Moreover, systemic autonomic dysfunction, including an abnormal ventilatory response to hypercapnia (VRH), is common in patients with DLB. Here, we aimed to determine whether the VRH is useful for distinguishing depression that is predictive of DLB from other types of MDD. Participants were 35 consecutive patients with first onset MDD at 50 years or older with bradykinesia. After diagnosing the clinical subtype of MDD according to DSM-IV criteria, each subject underwent a battery of psychological tests, autonomic examinations including VRH, brain magnetic resonance imaging, and 123I-meta-iodobenzylguanidine scintigraphy. Longitudinal follow-up showed that all 18 patients with abnormal VRH results developed DLB, whereas none of the 17 patients with normal VRH results converted to DLB within the study period (sensitivity: 100% , specificity: 100%). Additionally, over half of the DLB converters showed abnormalities on other autonomic examinations. For converters, the most common MDD subtype had psychotic and melancholic features simultaneously. The frequency of hypersensitivity to psychotropics was higher in converters than it was in non-converters. In the present study, patients with abnormal VRH results were very likely to develop DLB. Thus, for patients with late-onset MDD accompanied by bradykinesia, the VRH in combination with the clinical subtype of MDD or hypersensitivity to psychotropics may be useful for diagnosing prodromal DLB.

Phenotypic Correction of Hemophilia A in Sheep by Postnatal Intraperitoneal Transplantation of FVIII-Expressing MSC

PubMed Central

Porada, Christopher D.; Sanada, Chad; Kuo, Chung-Jung; Colletti, Evan; Mandeville, Walter; Hasenau, John; Zanjani, Esmail D.; Moot, Robert; Doering, Christopher; Spencer, H. Trent; Almeida-Porada, Graça

2011-01-01

We recently re-established a line of sheep that accurately mimics the clinical symptoms and genetics of severe hemophilia A (HA). Herein, we tested a novel, non-ablative transplant therapy in 2 pediatric HA animals. Paternal mesenchymal stem cells (MSC) were transduced with a porcine FVIII-encoding lentivector, and transplanted via the intraperitoneal route, without preconditioning. At the time of transplantation, these animals had received multiple hFVIII treatments for various spontaneous bleeds, and had developed debilitating hemarthroses which produced severe defects in posture and gait. Transplantation of transduced MSC resolved all existent hemarthroses, and spontaneous bleeds ceased. Damaged joints recovered fully; the animals regained normal posture and gait and resumed normal activity. Despite achieving factor-independence, a sharp rise in pre-existent Bethesda titers occurred following transplantation, decreasing the effectiveness and duration of therapy. Post-mortem examination revealed widespread engraftment, with MSC present within the lung, liver, intestine, and thymus, but particularly within joints affected at the time of transplantation, suggesting MSC homed to sites of ongoing injury/inflammation to release FVIII, explaining the dramatic improvement in hemarthrotic joints. In summary, this novel, non-ablative MSC transplantation was straightforward, safe, and converted life-threatening, debilitating HA to a moderate phenotype in a large animal model. PMID:21906573

Polycystic Ovary Syndrome: An Under-recognized Cause of Abnormal Uterine Bleeding in Adolescents Admitted to a Children's Hospital.

PubMed

Maslyanskaya, Sofya; Talib, Hina J; Northridge, Jennifer L; Jacobs, Amanda M; Coble, Chanelle; Coupey, Susan M

2017-06-01

To evaluate whether ovulatory dysfunction due to polycystic ovary syndrome (PCOS) is a common underlying etiology of abnormal uterine bleeding (AUB) in adolescents who require hospitalization and to explore etiology, treatment, and complications of AUB with severe anemia in adolescents. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We identified female patients aged 8-20 years admitted to a children's hospital for treatment of AUB from January 2000 to December 2014. Our hospital protocol advises hormonal testing for PCOS and other disorders before treatment for AUB. We reviewed medical records and recorded laboratory evaluations, treatments, and final underlying diagnoses as well as recurrences of AUB and readmissions in the subsequent year. Of the 125 subjects, the mean age was 16.5 ± 2.9 years; mean hemoglobin level was 7.0 ± 1.8 g/dL; 54% were overweight/obese; and 41% sexually active. PCOS accounted for 33% of admissions; hypothalamic pituitary ovarian axis immaturity 31%; endometritis 13%; bleeding disorders 10%. Girls with PCOS were more likely to be overweight/obese (74% vs 46%; P < .01) and girls with hypothalamic pituitary ovarian axis immaturity had lower hemoglobin levels (6.4 g/dL vs 7.4 g/dL; P < .05), than girls with all other etiologies of AUB. Treating physicians failed to diagnose endometritis as the etiology for AUB in 4 of 8 girls with positive tests for sexually transmitted infection and no other etiology. PCOS was the most common underlying etiology in adolescents hospitalized with AUB. Screening for hyperandrogenemia is important for early diagnosis of PCOS to allow ongoing management and prevention of comorbidities. Endometritis was frequently underestimated as an etiology for AUB. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Risk Factors for Neurodegeneration in Idiopathic REM sleep Behavior Disorder: A Multicenter Study

PubMed Central

Postuma, RB; Iranzo, A; Hogl, B; Arnulf, I; Ferini-Strambi, L; Manni, R; Miyamoto, T.; Oertel, W; Dauvilliers, Y; Ju, Y; Puligheddu, M; Sonka, K; Pelletier, A; Santamaria, J; Frauscher, B; Leu-Semenescu, S; Zucconi, M; Terzaghi, M; Miyamoto, M.; Unger, MM; Carlander, B; Fantini, ML; Montplaisir, JY

2018-01-01

Objective To assess whether risk factors for Parkinson’s disease and Dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic REM sleep behavior disorder Methods 12 centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic REM sleep behavior disorder. Variables included demographics, lifestyle factors, pesticide exposures, occupation, co-morbid conditions, medication use, family history, and autonomic/motor symptoms. After 4-years follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression. Results Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years, and 41% after 5 years. Patients who converted were older (difference=4.5 years, p<0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide=2.3% vs. 9.0%). Convertors were more likely to report family history of dementia (OR=2.09), without significant differences in Parkinson’s disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR=2.6). Interpretation Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and non-convertors have both important commonalities and differences. PMID:25767079

Clinical applications of CO2 laser resurfacing in the treatment of various pathologic skin disorders

NASA Astrophysics Data System (ADS)

Giler, Shamai

1997-12-01

CO2 laser skin resurfacing devices are widely used in cosmetic surgery for the treatment of facial rhytides, acne scars and aging skin. This technique is also useful in the treatment of various benign and premalignant or multiple pathological skin conditions and disorders originating in the epidermal, dermal and skin appendages, vascular lesions, epidermal nevi, infected wounds and ulcers, and keloids. Various surgical techniques have been developed in our clinic using laser resurfacing in the treatment of more than 2,000 patients with various skin pathologic disorders. We describe our experience with the various techniques used. The precise depth control and ablation properties combined with the hemostatic and sterilizing effects of the CO2 laser beam, reduction of the possibility of bleeding, infection and damage to healthy tissues, make the CO2 laser resurfacing techniques the treatment of choice for cosmetic surgery and treatment of benign, premalignant and multiple pathologic skin conditions.

Christmas disease: diagnosis and management of a haemorrhagic diathesis following dentofacial trauma

PubMed Central

Tamagond, Sridevi B; Hugar, Santosh I; Patil, Anil; Huddar, SandhyaRani

2015-01-01

Haemorrhagic diathesis has been of much concern to health professionals including dentists. It is not infrequent that a dentist becomes the first person to diagnose a bleeding disorder while performing dental treatment. Haemophilia is an X linked disorder with a frequency of about 1:10 000 births. Haemophilia B is much less common than haemophilia A, and affects only 1:300 000 males born alive. The clinical features of haemophilia B are very similar to those of haemophilia A with a prolongation of activated partial thromboplastin time. This case report describes the dental management of a patient with an uncommon haematological disorder, namely, factor IX deficiency, which remained undiagnosed until the patient had to undergo dentofacial trauma with unexpected severe haemorrhage. Preventive dentistry remains vital to young haemophiliacs. Surgical dental procedures may be performed for haemophiliacs but they must be judiciously coordinated by dental and medical health professionals. PMID:25568261

Diagnostic findings in infants presenting to a pediatric emergency department for lethargy or feeding complaints.

PubMed

Webb, Tara; Nugent, Melodee; Simpson, Pippa; Melzer-Lange, Marlene

2014-03-01

Lethargy is a common complaint among infants in the pediatric emergency department (ED), yet there is little data to guide appropriate evaluation. The objectives of the study were (1) to determine the frequency of diagnoses requiring intervention/monitoring and (2) to identify predictors of these diagnoses. A retrospective chart review of patients aged 0 to 6 months with a chief complaint of lethargy or poor feeding from January 2004 to December 2009 was performed. Patients were excluded if they had a fever, hypothermia, a chronic medical condition, or a history of trauma. Charts were reviewed by a single investigator; 10% were reviewed by a second investigator for agreement. History, examination, laboratory and radiology results, ED and inpatient diagnoses, as well as return visits within 7 days were recorded. Frequencies of diagnoses and interventions were described, and history and examination findings associated with these categories were determined. Two hundred seventy-two patients were included; 34 patients (12.5%; 95% confidence interval [CI], 8.8%-17%) required intervention/monitoring. These patients were classified into 6 categories. Eighteen had hematologic disorders (6.6%; 95% CI, 4.0%-10.3%), 8 had dehydration (2.9%; 95% CI, 1.3%-5.7%), 2 had intracranial bleeds (0.7%; 95% CI, 0.09%-2.6%), 3 had serious bacterial infections (1%; 95% CI, 0.2%-3.2%), 1 had a cardiac disorder (0.4%; 95% CI, 0.009%-2%), and 2 had neurologic disorders (0.7%; 95% CI, 0.9%-2.6%). Of the patients, 76% had conditions that were clinically evident (dehydration and hyperbilirubinemia requiring phototherapy). The patients with cardiac disorders, neurologic disorders, and intracranial bleeds all had abnormal examination findings in the ED. The 3 patients with serious bacterial infections were younger than 2 months of age and ill appearing; all had urinary tract infections. Infants with lethargy or poor feeding who require an intervention are likely to have conditions that are clinically evident or focal examination findings that lead to the diagnosis. Well-appearing infants with normal findings in examinations are unlikely to have a condition requiring intervention and should receive minimal testing.

Female Reproductive Effects of Exposure to Jet Fuel at U.S. Air Force Bases

DTIC Science & Technology

2001-05-01

amenorrhea and dys- strual characteristics of adult Afri- tors associated with menstrual disor- ,e r 4.6, 7 13 Prolonged bleed- can-Americans, and few...smokers than in non-smokers. Al- Stress (measured by life event or strual disorders.4󈧒 The major though vigorous exercise has been perceived stress...bases for both military and civilian the frequency of physical exercise .7 although personal gains (eg, starting women. Specifically, jet fuel, gaso

Invisible Bleeding: The Command Team’s Role in the Identification, Understanding, and Treatment of Traumatic Brain Injury and Post Traumatic Stress Disorder

DTIC Science & Technology

2013-04-11

of loss of or a decreased level of consciousness (LOC) -Any loss of memory for events immediately before or after the injury [post-traumatic amnesia ...diagnosis and is unlikely to change within the medical community. Symptoms of PTSD and TBI Symptom ASD and PTSD TBI Dissociation Emotional... Amnesia Present Present Reexperiencing Recurrent images Present Present Nightmares Present NA Distress on reminders

Hepatic manifestations of telomere biology disorders.

PubMed

Patnaik, Mrinal M; Kamath, Patrick S; Simonetto, Douglas A

2018-06-07

A 51-year-old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia with no significant fibrosis or necroinflammatory activity. Hepatic venous pressure gradient was elevated at 31 mmHg, consistent with clinically significant portal hypertension. The clinical course was complicated by refractory gastric variceal bleeding requiring a surgical portosystemic shunt. Approximately seven years after the initial presentation, the patient developed progressive dyspnoea and a diagnosis of idiopathic pulmonary fibrosis was made. Contrast-enhanced echocardiogram was not suggestive of hepatopulmonary syndrome or portopulmonary hypertension. Given this new diagnosis a telomere biology disorder was suspected. A flow-fluorescence in situ hybridisation analysis for telomere length assessment revealed telomere lengths below the first percentile in both lymphocytes and granulocytes. Next generation sequencing analysis identified a heterozygous mutation involving the hTERT gene (Histidine983Threonine). The lung disease unfortunately progressed in the subsequent two years, leading to the patient's death nine years after his initial presentation with portal hypertension. During those nine years two brothers also developed idiopathic pulmonary fibrosis. The questions that arise from this case include. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Revision Knee Arthroplasty in Patients with Inherited Bleeding Disorders: A Single-Center Experience

PubMed Central

Kotela, Andrzej; Wilk-Frańczuk, Magdalena; Żbikowski, Piotr; Łęgosz, Paweł; Ambroziak, Paweł; Kotela, Ireneusz

2017-01-01

Background The results of total knee arthroplasty (TKA) in patients with inherited bleeding disorders (IBDs) are poorer when compared with those in the general population, with a notably higher risk of complications and higher revision rates. Thus, revision procedures are becoming a growing concern in this group of patients. The aim of this study was to evaluate the results of revision TKA in patients with IBD. Material/Methods A retrospective cohort study with longitudinal assessment of hemophilia patients scheduled for revision TKA between January 2010 and September 2015 was performed. The clinical status of the patients was assessed based on the Knee Society Score, and the Numeric Rating Scale was used to assess knee pain severity and patient satisfaction with the surgery. Radiological examination, post-operative complications, and reinterventions were recorded and analyzed. Results Very good results were obtained in all patients treated for aseptic loosening of the implant. However, inferior results were found in cases with infection. All patients operated on for aseptic loosening required only single-stage TKA, whereas patients with infection underwent multiple interventions. Complications were observed only in cases with infection. Conclusions Our study clearly outlined the differences in results based on failure mode, with far inferior results obtained in cases with infection. Given the lack of data in this area as well as the high specificity of this population, further high-quality studies are needed. PMID:28068306

Recombinant Activated Factor VII (Eptacog Alfa Activated, NovoSeven®) in Patients with Rare Congenital Bleeding Disorders. A Systematic Review on its Use in Surgical Procedures.

PubMed

Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale; Myasoedova, Veronika; Amato, Manuela; Ventre, Itala; Tremoli, Elena; Minno, Alessandro Di

2017-01-01

In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann's thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann's Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Agreement of histopathological findings of uterine curettage and hysterectomy specimens in women with abnormal uterine bleeding.

PubMed

Moradan, Sanam; Ghorbani, Raheb; Lotfi, Azita

2017-05-01

To examined the diagnostic value of  dilatation and curettage (D and C) in patients with abnormal uterine bleeding (AUB) by conducting a histopathological examination of endometrial tissues by D and C and hysterectomy. Methods: In this retrospective study, the medical records of 163 women who had been hospitalized  in the Obstetrics and Gynecology Ward, Amir-al-Momenin Hospital, Semnan, Iran between 2010 and 2015 for diagnostic curettage due to  AUB and who had undergone hysterectomy were investigated. The patients' characteristics and histopathologic results of curettage and hysterectomy were extracted, and sensitivity and specificity and positive and negative predictive values of curettage were calculated. Results: The mean ± standard deviation age of the patients was 49.8±7.8 years. The sensitivity values of D and C in the diagnosis of endometrial pathologies was 49.1%, specificity 84.5%, positive 60.5%, and negative predictive 77.5%. The sensitivities of D and C in the diagnosis of various endometrial hyperplasia was 62.5%, disordered proliferative endometrium 36.8%, and endometrial cancer 83.3%. Of 6 patients with endometrial polyps on performing hysterectomy, no patient was diagnosed by curettage. Conclusions: Dilatation and curettage has acceptable sensitivity in the diagnosis of endometrial cancer, low sensitivity in the diagnosis of endometrial hyperplasia, and very low sensitivity in the diagnosis of disordered proliferative endometrium and endometrial polyps.

Agreement of histopathological findings of uterine curettage and hysterectomy specimens in women with abnormal uterine bleeding

PubMed Central

Moradan, Sanam; Ghorbani, Raheb; Lotfi, Azita

2017-01-01

Objectives: To examined the diagnostic value of dilatation and curettage (D&C) in patients with abnormal uterine bleeding (AUB) by conducting a histopathological examination of endometrial tissues by D&C and hysterectomy. Methods: In this retrospective study, the medical records of 163 women who had been hospitalized in the Obstetrics and Gynecology Ward, Amir-al-Momenin Hospital, Semnan, Iran between 2010 and 2015 for diagnostic curettage due to AUB and who had undergone hysterectomy were investigated. The patients’ characteristics and histopathologic results of curettage and hysterectomy were extracted, and sensitivity and specificity and positive and negative predictive values of curettage were calculated. Results: The mean ± standard deviation age of the patients was 49.8±7.8 years. The sensitivity values of D&C in the diagnosis of endometrial pathologies was 49.1%, specificity 84.5%, positive 60.5%, and negative predictive 77.5%. The sensitivities of D&C in the diagnosis of various endometrial hyperplasia was 62.5%, disordered proliferative endometrium 36.8%, and endometrial cancer 83.3%. Of 6 patients with endometrial polyps on performing hysterectomy, no patient was diagnosed by curettage. Conclusions: Dilatation and curettage has acceptable sensitivity in the diagnosis of endometrial cancer, low sensitivity in the diagnosis of endometrial hyperplasia, and very low sensitivity in the diagnosis of disordered proliferative endometrium and endometrial polyps. PMID:28439599

Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis

PubMed Central

Kyriakides, Themis R.; Zhu, Yu-Hong; Smith, Lynne T.; Bain, Steven D.; Yang, Zhantao; Lin, Ming T.; Danielson, Keith G.; Iozzo, Renato V.; LaMarca, Mary; McKinney, Cindy E.; Ginns, Edward I.; Bornstein, Paul

1998-01-01

Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2−/− mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration. PMID:9442117

Bowel habits and behaviors related to defecation in 10- to 16-year-olds: impact of socioeconomic characteristics and emotional stress.

PubMed

Devanarayana, Niranga Manjuri; Rajindrajith, Shaman

2011-05-01

Bowel habits vary depending on food consumption and genetic factors. The knowledge regarding this physiological phenomenon is limited. Thorough understanding of normal bowel habits is essential for correct diagnosis of defecation disorders. This study evaluated the normal bowel habits of Sri Lankan children. Children ages 10 to 16 years were randomly selected from 5 schools in 4 districts. Those without defecation disorders were recruited. Details regarding their bowel habits during previous 2 months were collected using a validated, self-administered questionnaire. A total of 2273 children were enrolled (mean age 13.2 years, SD 1.7 years, boys 49.7%). Of them, 1748 (76.9%) opened bowels once daily, whereas 149 (6.6%) and 11 (0.5%) had <3/week and >3/day defecations, respectively. Stool consistency was normal in 1997 (87.9%), hard in 86 (3.8%), and changing consistency in 163 (7.1%). Straining was present in 639 (28.1%), painful defecation in 241 (10.6%), and bleeding in 49 (2.2%). One hundred six (4.7%) children reported stool withholding. Bulky stool was present in 158 (7.0%). Straining, bulky stools, and withholding posture were more common in boys, whereas painful defecation and bleeding were reported more often in girls (P<0.05). Defecation frequency was lower in those from a poor socioeconomic background and war-affected areas (P < 0.05). Bowel frequency < 3/week, bulky stools, painful defecation, straining, and withholding posture were more common in those exposed to stressful life events (P < 0.05). The present study provides data on normal bowel habits of Sri Lankan schoolchildren and provides a firm platform to evaluate defecation disorders in them.

Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders.

PubMed

Westmoreland, D; Shaw, M; Grimes, W; Metcalf, D J; Burden, J J; Gomez, K; Knight, A E; Cutler, D F

2016-04-01

Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy. However, recently developed super-resolution microscopes provide sufficient spatial resolution to effectively image platelet granules. When combined with automated image analysis, these methods provide a quantitative, unbiased, rapidly acquired dataset that can readily and reliably reveal differences in platelet granules between individuals. To demonstrate the ability of structured illumination microscopy (SIM) to efficiently differentiate between healthy volunteers and three patients with Hermansky-Pudlak syndrome. Blood samples were taken from three patients with Hermansky-Pudlak syndrome and seven controls. Patients 1-3 have gene defects in HPS1, HPS6 and HPS5, respectively; all controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets fixed, stained for CD63 and processed for analysis by immunofluorescence microscopy, using a custom-built SIM microscope. SIM can successfully resolve CD63-positive structures in fixed platelets. A determination of the number of CD63-positive structures per platelet allowed us to conclude that each patient was significantly different from all of the controls with 99% confidence. A super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers. CD63 is a useful marker for predicting Hermansky-Pudlak syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

The haemtrack home therapy reporting system: Design, implementation, strengths and weaknesses: A report from UK Haemophilia Centre Doctors Organisation.

PubMed

Hay, C R M; Xiang, H; Scott, M; Collins, P W; Liesner, R; Dolan, G; Hollingsworth, R

2017-09-01

Haemtrack is an electronic home treatment diary for patients with inherited bleeding disorders, introduced in 2008. It aimed to improve the timeliness and completeness of patient-reported treatment records, to facilitate analysis of treatment and outcome trends. The system is easy to use, responsive and accessible. The software uses Microsoft technologies with a SQL Server database and an ASP.net website front-end, running on personal computers, android and I-phones. Haemtrack interfaces with the UK Haemophilia Centre Information System and the National Haemophilia Database (NHD). Data are validated locally by Haemophilia Centres and centrally by NHD. Data collected include as follows: treatment brand, dose and batch number, time/date of bleed onset and drug administration, reasons for treatment (prophylaxis, bleed, follow-up), bleed site, severity, pain-score and outcome. Haemtrack was used by 90% of haemophilia treatment centres (HTCs) in 2015, registering 2683 patients using home therapy of whom 1923 used Haemtrack, entering >17 000 treatments per month. This included 68% of all UK patients with severe haemophilia A. Reporting compliance varied and 55% of patients reported ≥75% of potential usage. Centres had a median 78% compliance overall. A strategy for progressively improving compliance is in place. Age distribution and treatment intensity were similar in Haemtrack users/non-users with severe haemophilia treated prophylactically. The Haemtrack system is a valuable tool that may improve treatment compliance and optimize treatment regimen. Analysis of national treatment trends and large-scale longitudinal, within-patient analysis of changes in regimen and/or product will provide valuable insights that will guide future clinical practice. © 2017 John Wiley & Sons Ltd.

Clinical feature and management of immune thrombocytopenic purpura in a tertiary hospital in Northwest Nigeria

PubMed Central

Hassan, Abdulaziz; Adebayo, Adeshola; Musa, Abubakar Umar; Suleiman, Aishatu Maude; Ibrahim, Ismaila Nda; Kusfa, Ibrahim Usman; Aminu, Mohammed Sirajo

2017-01-01

Background: Immune thrombocytopenic purpura (ITP) is a rare bleeding disorder that may remit spontaneously. Life-threatening bleeding may require transfusion support, steroids, and other immunosuppressive therapy or splenectomy. Objective: To review the clinical presentation and laboratory features of ITP at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. Subjects and Methods: A retrospective analytic study of case notes and bone marrow (BM) records of patients diagnosed with ITP at Haematology Department, ABUTH, Zaria, from January 1, 2004, to December 31, 2012. Results: There were nine cases (six females, three males), aged 6–20 (mean 11.11) years. The presentations were epistaxis 8 (88.9%), purpura 4 (44.4%), gum bleeding 4 (44.4%), menorrhagia 2 (22.2%), and intracranial hemorrhage (ICH) 1 (11.1%). Only 1 (11.1%) had clinical splenomegaly. Platelet count of <20 × 109/L was found in 4 (44.4%) while 6 (66.7%) had packed cell volume of <25%. All the nine cases had BM megakaryocytic hyperplasia. Six patients had blood transfusion support while 7 (77.8%) patients received oral prednisolone therapy with time to cessation of bleeding of 12–16 (mean of 8) weeks. One case had spontaneous remission while another had anti-D due to relapse after steroid therapy; this resulted in transient rise in platelet counts. None had other immunosuppressive therapy or splenectomy. Six (66.7%) cases were lost to follow-up after achieving remission and one died of ICH. Conclusion: ITP is not common in our center though its clinical presentations are varied. However, prednisolone and blood transfusion therapy are central to the management of these patients with favorable outcome. PMID:29269984

Discovery of glycyrrhetinic acid as an orally active, direct inhibitor of blood coagulation factor xa.

PubMed

Jiang, Lilong; Wang, Qiong; Shen, Shu; Xiao, Tongshu; Li, Youbin

2014-03-01

Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P<0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

Flavonoid mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) in the treatment of I-III degree hemorroidal disease: a double-blind multicenter prospective comparative study.

PubMed

Corsale, Italo; Carrieri, Paolo; Martellucci, Jacopo; Piccolomini, Alessandro; Verre, Luigi; Rigutini, Marco; Panicucci, Sonia

2018-06-22

We evaluated the efficacy of new flavonoids mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) to reduce bleeding from I-III degrees hemorrhoidal disease in the short and medium time. One hundred fifty-four consecutive patients with hemorrhoidal disease recruited in four colorectal units were enrolled to the study. Exclusion criteria were allergy to the flavonoids, inflammatory bowel disease, obstructed defecation syndrome, pregnancy and puerperium, associated anal disease or hemorrhoidal thrombosis, proctologic surgical procedures within 1 year before recruitment, contemporary cancer or HIV, previous pelvic radiotherapy, patients receiving oral anticoagulant therapy, or contemporary administration of other therapy for hemorrhoids. Patients with inability to understand the study or mental disorders were also excluded. Seventy-eight were randomized to receive the mixture of diosmin, troxerutin, rutin, hesperidin, and quercetin (study group, SG), and 76 a mixture of diosmin in combination with hesperidin, diosmetin, isoroifolin, and linarin in purified micronized fraction (control group, CG). Bleeding, number of pathological piles, and Golligher's grade were assessed at each scheduled visit and compared using the Chi-square test. During the study period, bleeding improved after 1 and 6 months both in the SG (79.5 and 70.5%) and in the CG (80.2 and 75%) without significant differences between two groups. Satisfaction degree after 6 months was greater in the patients of the SG (4.05) towards the CG (3.25): this result was statistical significant (p 0.003). Use of flavonoids mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) is a safe and effective mean of managing bleeding from hemorrhoidal disease and minimal adverse events are reported.

[Complications of tongue base reduction with radiofrequency tissue ablation on obstructive sleep apnea hypopnea syndrome].

PubMed

Chen, Jin-hui; Luo, Zhi-hong; Xu, Hong-xing; Yang, Xi-lin; Zhu, Ming-wan; Tao, Ze-zhang

2010-07-01

To investigate the complications of tongue base reduction with radiofrequency tissue ablation on patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and find out the effective prevention strategies. One hundred and ninety three OSAHS patients diagnosed by polysomnography were received tongue base reduction with radiofrequency tissue ablation between March 2008 and December 2009. The intraoperative and postoperative complications including bleeding, hematoma of tongue base, abscess of tongue base, altered taste, tongue numbness, deviation of tongue extension movement, dysfunctions of pronunciation and swallowing as well as the managements were analyzed retrospectively. No perioperative complications occurred. There were 186 cases with postoperative pain (96.4%), 155 cases with submandibular edema (80.3%). Nocturnal sudden cardiac death was encountered in 1 case and secondary bleeding in 1 case. There was no ulceration of tongue base mucose, hematoma or abscess of tongue base, altered taste, tongue numbness, tongue deviations, speech, swallowing and taste disorder after operation. The scale of postoperative pain claimed by patients was ranged between mild to moderate. Diclofenac suppository had analgesic effect for these patients. The quantity of bleeding in patient with secondary hemorrhage was so little that after proper treatment the bleeding was stopped and never happened again. Patient with nocturnal sudden cardiac death occurred at thirty-seven hours after operation, because of swelling and pain of tongue base aggravated sleep apnea and night hypoxemia inducing fatal arrhythmia. Postoperative pain and submandibular edema were 2 most common postoperative complications which can be easily controlled by antibiotics, Glucocorticoids and Diclofenac suppository. For those severe OSAHS patients accompanied by cardiopulmonary diseases, the tongue base reduction with radiofrequency tissue ablation can induce nocturnal sudden cardiac death. It is important to pay more attention on arrhythmias at night in severe OSAHS patients.

The High Price of Noise Exposure

MedlinePlus

... Current Issue Past Issues Hearing Disorders The High Price of Noise Exposure Past Issues / Fall 2008 Table ... These tiny structures convert sound waves into electrical energy. Our auditory nerve sends this energy to the ...

The Natural History of Antisocial Personality Disorder.

PubMed

Black, Donald W

2015-07-01

Antisocial personality disorder (ASPD) is characterized by a pattern of socially irresponsible, exploitative, and guiltless behaviour. ASPD is associated with co-occurring mental health and addictive disorders and medical comorbidity. Rates of natural and unnatural death (suicide, homicide, and accidents) are excessive. ASPD is a predictor of poor treatment response. ASPD begins early in life, usually by age 8 years. Diagnosed as conduct disorder in childhood, the diagnosis converts to ASPD at age 18 if antisocial behaviours have persisted. While chronic and lifelong for most people with ASPD, the disorder tends to improve with advancing age. Earlier onset is associated with a poorer prognosis. Other moderating factors include marriage, employment, early incarceration (or adjudication during childhood), and degree of socialization.

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

PubMed

Franchini, Massimo; Lippi, Giuseppe; Targher, Giovanni

2011-08-01

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

Local convertibility of the ground state of the perturbed toric code

NASA Astrophysics Data System (ADS)

Santra, Siddhartha; Hamma, Alioscia; Cincio, Lukasz; Subasi, Yigit; Zanardi, Paolo; Amico, Luigi

2014-12-01

We present analytical and numerical studies of the behavior of the α -Renyi entropies in the toric code in presence of several types of perturbations aimed at studying the simulability of these perturbations to the parent Hamiltonian using local operations and classical communications (LOCC)—a property called local convertibility. In particular, the derivatives, with respect to the perturbation parameter, present different signs for different values of α within the topological phase. From the information-theoretic point of view, this means that such ground states cannot be continuously deformed within the topological phase by means of catalyst assisted local operations and classical communications (LOCC). Such LOCC differential convertibility is on the other hand always possible in the trivial disordered phase. The non-LOCC convertibility is remarkable because it can be computed on a system whose size is independent of correlation length. This method can therefore constitute an experimentally feasible witness of topological order.

Inborn Errors of Metabolism with Hyperammonemia: Urea Cycle Defects and Related Disorders.

PubMed

Summar, Marshall L; Mew, Nicholas Ah

2018-04-01

The urea cycle disorders are a group of inherited biochemical diseases caused by a complete or partial deficiency of any one of the enzymes or transport proteins required to convert toxic ammonia into urea and to produce arginine and citrulline. The clinical manifestations of these disorders are mostly the result of acute or chronic hyperammonemia, which affects the central nervous system. Affected individuals can also develop hepatic dysfunction. These disorders can present at any age from the immediate newborn to later in life. Early diagnosis and treatment are key to improving outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

[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.

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

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

PubMed

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

2018-06-01

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

Gene Therapy for Hemophilia.

PubMed

Nienhuis, Arthur W; Nathwani, Amit C; Davidoff, Andrew M

2017-05-03

The X-linked bleeding disorder hemophilia causes frequent and exaggerated bleeding that can be life-threatening if untreated. Conventional therapy requires frequent intravenous infusions of the missing coagulation protein (factor VIII [FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a lasting cure through gene therapy has long been sought. After a series of successes in small and large animal models, this goal has finally been achieved in humans by in vivo gene transfer to the liver using adeno-associated viral (AAV) vectors. In fact, multiple recent clinical trials have shown therapeutic, and in some cases curative, expression. At the same time, cellular immune responses against the virus have emerged as an obstacle in humans, potentially resulting in loss of expression. Transient immune suppression protocols have been developed to blunt these responses. Here, we provide an overview of the clinical development of AAV gene transfer for hemophilia, as well as an outlook on future directions. Copyright © 2017. Published by Elsevier Inc.

Rectus sheath haematoma following exercise testing: a case report

PubMed Central

2009-01-01

Introduction Exercise testing is a safe diagnostic procedure which is widely used in the evaluation of patients suspected of having coronary heart disease or for the assessment of the prognosis in patients with established disease. Its complications are mainly cardiac disorders. Here, we report a rectus sheath haematoma as a complication of this procedure in a patient with acute coronary syndrome. To our knowledge, this is the first case report of rectus sheath haematoma in association with exercise testing. Case presentation A 72-year-old Caucasian woman was admitted for acute coronary syndrome. She received conservative treatment including low molecular weight heparin and anti-platelet agents. On the fifth day of her hospital stay, she underwent an exercise test, where no ischaemic response occurred. Several hours later, she experienced pain in the left side of her abdomen. Subsequent investigations revealed a rectus sheath haematoma. The patient underwent surgical haematoma evacuation. A few days later, re-operation was performed for recurrent bleeding in the abdominal wall. The patient had several characteristics known to increase the risk of bleeding during treatment for acute coronary syndrome. Conclusion Awareness of this possible consequence of exercise testing is important for preventing and treating it correctly. For prevention, an assessment of the bleeding risk of the individual patient is necessary before the test, and excessive anticoagulation must be avoided. PMID:20338023

Study of endometrial tissue in dysfunctional uterine bleeding.

PubMed

Kayastha, S

2013-03-01

Dysfunctional uterine bleeding (DUB) is defined as heavy and or irregular menstruation in the absence of recognizable pelvic pathology, pregnancy or general bleeding disorder. Hyperplastic endometrium is abnormal histology finding found in DUB. Out of three type of hyperplasia, atypical type is associated with co-existent ca endometrium and the chance of progression to ca endometrium is very high. Thus this study was conducted to see the incidence of hyperplasia of endometrium in cases of DUB and to see the risk factors for endometrial hyperplasia. It was a prospective study carried out in span of two years (2010 JULY- 2013 Jan) in Nepal Medical College and Teaching Hospital. Hundred cases DUB who under went D&C or hysterectomy were included to study the age range, the relation of parity, patient symptom, contraceptive method and medical disease with the type of endometrial histology. It was found that DUB was common in perimenopusal age (49%) and the incidence increase with the increase of parity. Abnormal endometrial finding (hyperplasia) was found in 31% of the cases. Atypical and complex hyperplasia were associated with irregular menstruation and one third of the hyperplastic patient had hypertension (32.26%). Thus perimenopausal age, irregular menstruation and hypertension are risk factors for hyperplasia. So it is mandatory to do endometrial sampling in cases of perimenopausal age with irregular menstruation withor without hypertension.

Structured imaging technique in the gynecologic office for the diagnosis of abnormal uterine bleeding.

PubMed

Dueholm, Margit; Hjorth, Ina Marie D

2017-04-01

The aim in the diagnosis of abnormal uterine bleeding (AUB) is to identify the bleeding cause, which can be classified by the PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system. In a gynecologic setting, the first step is most often to identify structural abnormalities (PALM causes). Common diagnostic options for the identification of the PALM include ultrasonography, endometrial sampling, and hysteroscopy. These options alone or in combination are sufficient for the diagnosis of most women with AUB. Contrast sonography with saline or gel infusion, three-dimensional ultrasonography, and magnetic resonance imaging may be included. The aim of this article is to describe how a simple structured transvaginal ultrasound can be performed and implemented in the common gynecologic practice to simplify the diagnosis of AUB and determine when additional invasive investigations are required. Structured transvaginal ultrasound for the identification of the most common endometrial and myometrial abnormalities and the most common ultrasound features are described. Moreover, situations where magnetic resonance imaging may be included are described. This article proposes a diagnostic setup in premenopausal women for the classification of AUB according to the PALM-COEIN system. Moreover, a future diagnostic setup for fast-track identification of endometrial cancer in postmenopausal women based on a structured evaluation of the endometrium is described. Copyright © 2016. Published by Elsevier Ltd.

Inhibitors in Hemophilia B.

PubMed

Santoro, Cristina; Quintavalle, Gabriele; Castaman, Giancarlo; Baldacci, Erminia; Ferretti, Antonietta; Riccardi, Federica; Tagliaferri, Annarita

2018-06-20

Hemophilia B (HB) is an X-linked bleeding disorder caused by deficiency of factor IX (FIX). Patients with the severe form (FIX <1%) account approximately for 30 to 45% of persons with HB and usually suffer from recurrent joint, soft-tissue, and muscle bleeds. The availability of safe plasma-derived and recombinant products has virtually abolished the risk of viral infections and the adoption of prophylactic regimens has attenuated the impact of hemophilic arthropathy. Therefore, the development of an inhibitor against FIX is currently the most serious complication that can still occur in the new generations of HB patients. The development of an inhibitor in HB is a rare event (1.5-3% of all patients) but is associated with a significant morbidity, related not only to the bleeding risk but also to the frequent occurrence of allergic/anaphylactic reactions and nephrotic syndrome. Due to the relative rarity of this event, few data exist about risk factors, pathophysiology, and clinical aspects of inhibitors in HB. The induction of immune tolerance is often unsuccessful and can be otherwise affected by many complications in patients with history of allergy or anaphylaxis. Therefore, alternative therapeutic strategies and new approaches are developing. The aim of this narrative review is to discuss current knowledge about risk factors, pathophysiology, and clinical aspects of this rare but serious complication. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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.

[Oral complications of chemotherapy of malignant neoplasms].

PubMed

Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

1999-01-01

Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

[Factor V congenital deficiency: about a case].

PubMed

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

2017-01-01

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

Elevated left mid-frontal cortical activity prospectively predicts conversion to bipolar I disorder

PubMed Central

Nusslock, Robin; Harmon-Jones, Eddie; Alloy, Lauren B.; Urosevic, Snezana; Goldstein, Kim; Abramson, Lyn Y.

2013-01-01

Bipolar disorder is characterized by a hypersensitivity to reward-relevant cues and a propensity to experience an excessive increase in approach-related affect, which may be reflected in hypo/manic symptoms. The present study examined the relationship between relative left-frontal electroencephalographic (EEG) activity, a proposed neurophysiological index of approach-system sensitivity and approach/reward-related affect, and bipolar course and state-related variables. Fifty-eight individuals with cyclothymia or bipolar II disorder and 59 healthy control participants with no affective psychopathology completed resting EEG recordings. Alpha power was obtained and asymmetry indices computed for homologous electrodes. Bipolar spectrum participants were classified as being in a major/minor depressive episode, a hypomanic episode, or a euthymic/remitted state at EEG recording. Participants were then followed prospectively for an average 4.7 year follow-up period with diagnostic interview assessments every four-months. Sixteen bipolar spectrum participants converted to bipolar I disorder during follow-up. Consistent with hypotheses, elevated relative left-frontal EEG activity at baseline 1) prospectively predicted a greater likelihood of converting from cyclothymia or bipolar II disorder to bipolar I disorder over the 4.7 year follow-up period, 2) was associated with an earlier age-of-onset of first bipolar spectrum episode, and 3) was significantly elevated in bipolar spectrum individuals in a hypomanic episode at EEG recording. This is the first study to identify a neurophysiological marker that prospectively predicts conversion to bipolar I disorder. The fact that unipolar depression is characterized by decreased relative left-frontal EEG activity suggests that unipolar depression and vulnerability to hypo/mania may be characterized by different profiles of frontal EEG asymmetry. PMID:22775582

Assessment of an Electronic Intervention in Young Women with Heavy Menstrual Bleeding.

PubMed

Dietrich, Jennifer E; Yee, Donald L; Santos, Xiomara M; Bercaw-Pratt, Jennifer L; Kurkowski, Jennifer; Soni, Heather; Lee-Kim, Youngna J; Shah, Mona D; Mahoney, Donald; Srivaths, Lakshmi V

2017-04-01

STUDY OBJECTIVE, DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Bleeding disorders (BD) occur in up to 50% of adolescents with heavy menstrual bleeding (HMB). This presents unique challenges to health care providers because of the complexity of treating the condition and such complexity can result in difficulty with patients understanding basic information about their condition, limit communication with medical providers, and patient compliance. The aim of the study was to use an electronic approach to enhance patient compliance with medications used to treat their HMB, and to provide educational access to adolescents with BD. This was a prospective cohort study involving patients in a Young Women's Bleeding Disorder Clinic at a single children's hospital. Subjects were given an iPod Touch (Apple Inc, Cupertino, CA) device (ITD), preloaded with the iPeriod (Winkpass Creations) application. Participants recorded information about their BD that they learned about on BD Web sites, and menses, and medications. Electronic and charted data were collected to monitor compliance with prescribed treatment regimens. All ITD allowed Wi-Fi access to allow teens to explore BD Web sites and knowledge was assessed. Twenty-three of 45 subjects completed the study. The mean age was 14.1 ± 1.9 years. Subjects who were compliant with the ITD (group 1), charted on baseline symptoms, menstrual flow (83.3%), cramps (100%, 23/23), breakthrough bleeding (95.6%, 22/23), mood (95.6%, 22/23), and medication use (91.7%) for a mean of 9.3 ± 3.1 months. Subjects who were nonusers (group 2) did not report on symptoms, their condition, or medication use in the device (n = 22). More than 75% (17/23) of subjects in group 1 used hormones alone or hormones with antifibrinolytic agents to control HMB. No subjects stopped or missed medications who were in group 1 intentionally, and also there were 9 enrollees within this same group who missed a medication related to awaiting the prescription to be filled from pharmacy. In group 2, 17 enrollees missed medications, resulting in 19% (4/22) of these enrollees being admitted to hospital for 1-2 days. In addition, enrollees in group 2 missed more medications on average compared with group 1. No subjects in group 1 required admission for HMB treatment failure during the study period, compared with those in group 2 (P = .006). All subjects in group 1 reported accessing Web sites using their ITD to learn about their BD. Groups 1 and 2 did not differ in the number of medications that were prescribed during the time frame (P = .77) or the number of follow-up clinic visits (P = .49). Furthermore, those in group 1 reported fewer breakthrough bleeding episodes than those in group 2 according to clinic notes (P = .03). Users of the ITD were given a set of knowledge questions. Group 2 subjects were not consistent users of the ITD use and did not complete the knowledge questions. Group 1 and 2 could not be compared with regard to knowledge as a result. ITD is an excellent tool for adolescents with HMB and BD to allow self-monitoring, provider monitoring, and improve educational access through engaging technology; compliance with device use was associated with several parameters suggestive of improved clinical outcomes. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-05-01

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

The Natural History of Antisocial Personality Disorder

PubMed Central

Black, Donald W

2015-01-01

Antisocial personality disorder (ASPD) is characterized by a pattern of socially irresponsible, exploitative, and guiltless behaviour. ASPD is associated with co-occurring mental health and addictive disorders and medical comorbidity. Rates of natural and unnatural death (suicide, homicide, and accidents) are excessive. ASPD is a predictor of poor treatment response. ASPD begins early in life, usually by age 8 years. Diagnosed as conduct disorder in childhood, the diagnosis converts to ASPD at age 18 if antisocial behaviours have persisted. While chronic and lifelong for most people with ASPD, the disorder tends to improve with advancing age. Earlier onset is associated with a poorer prognosis. Other moderating factors include marriage, employment, early incarceration (or adjudication during childhood), and degree of socialization. PMID:26175389

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

PubMed Central

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

2018-01-01

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

Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding.

PubMed

Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C

2018-01-01

Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is one of four residues that are important for receptor functional integrity, maintaining the binding pocket conformation and allowing rotation following ligand binding. Conclusion This novel dominant negative variant confirms the important role of R265 in EL3 in the functional integrity of P2Y12R, and suggests that pathologic heterodimer formation may underlie this family bleeding phenotype. © 2017 International Society on Thrombosis and Haemostasis.

Abnormal Uterine Bleeding

MedlinePlus

... abnormal uterine bleeding? Abnormal uterine bleeding is any heavy or unusual bleeding from the uterus (through your ... one symptom of abnormal uterine bleeding. Having extremely heavy bleeding during your period can also be considered ...

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

PubMed Central

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

2012-01-01

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

Acute on chronic gastrointestinal bleeding: a unique clinical entity.

PubMed

Rockey, Don C; Hafemeister, Adam C; Reisch, Joan S

2017-06-01

Gastrointestinal bleeding is defined in temporal-spatial terms-as acute or chronic, and/or by its location in the gastrointestinal tract. Here, we define a distinct type of bleeding, which we have coined 'acute on chronic' gastrointestinal bleeding. We prospectively identified all patients who underwent endoscopic evaluation for any form of gastrointestinal bleeding at a University Hospital. Acute on chronic bleeding was defined as the presence of new symptoms or signs of acute bleeding in the setting of chronic bleeding, documented as iron deficiency anemia. Bleeding lesions were categorized using previously established criteria. We identified a total of 776, 254, and 430 patients with acute, chronic, or acute on chronic bleeding, respectively. In patients with acute on chronic gastrointestinal bleeding, lesions were most commonly identified in esophagus (28%), colon and rectum (27%), and stomach (21%) (p<0.0001 vs locations for acute or chronic bleeding). In those specifically with acute on chronic upper gastrointestinal bleeding (n=260), bleeding was most commonly due to portal hypertensive lesions, identified in 47% of subjects compared with 29% of acute and 25% of chronic bleeders, (p<0.001). In all patients with acute on chronic bleeding, 30-day mortality was less than that after acute bleeding alone (2% (10/430) vs 7% (54/776), respectively, p<0.001). Acute on chronic gastrointestinal bleeding is common, and in patients with upper gastrointestinal bleeding was most often a result of portal hypertensive upper gastrointestinal tract pathology. Reduced mortality in patients with acute on chronic gastrointestinal bleeding compared with those with acute bleeding raises the possibility of an adaptive response. Copyright © 2017 American Federation for Medical Research.

Primary Systemic Amyloidosis and High Levels of Angiotensin-Converting Enzyme: Two Case Reports

PubMed Central

Praena-Segovia, J.; Sanchez-Gastaldo, A.; Bernabeu-Wittel, M.; Ocete-Pérez, R.; Ávila-Polo, R.; Martino, M. L.

2013-01-01

Infiltrative heart diseases are caused by a heterogeneous group of disorders; amyloidosis and sarcoidosis are two frequent causes of myocardial infiltration, which differ in clinical and biological outcome and treatment issues. The presence of high levels of angiotensin-converting enzyme (ACE) in a patient with infiltrative heart disease may increase suspicion of sarcoidosis. Nevertheless, no mention about increased ACE levels in extracerebral primary systemic amyloidosis is available. We present two cases of primary systemic amyloidosis, which are cardiac involvement and elevated ACE levels. PMID:24826302

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

PubMed

Aziz, Fahad

2014-02-01

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

What Is a Urea Cycle Disorder?

MedlinePlus

... in which nitrogen, a waste product of protein metabolism, is removed from the blood and converted to a compound called urea in the blood. Normally, the urea is transferred into the urine and removed from the body. In urea cycle ...

[A patient with Noonan syndrome].

PubMed

Bins, A; Gortzak, R A Th

2013-12-01

Noonan syndrome is a relatively common autosomal dominant genetic disorder which is characterised by typical facial features, congenital heart diseases and small stature. In 50% of the cases the syndrome is caused by a mutation on the PTPN11-gen. The expression of symptoms associated with Noonan syndrome can be very mild in nature and facial features usually become less pronounced with age, which can sometimes make a correct diagnosis more difficult. Despite a wide range of associated symptoms most adults with Noonan syndrome can be self-sustaining, with a good quality of life. It is important that the dentist is well-informed about this syndrome due to the heart diseases and bleeding disorders which can be present with these patients and may influence a dentist's choice of therapy when invasive treatment is indicated.

Perioperative Physiotherapy for Total Ankle Replacement in Patients with Inherited Bleeding Disorders: Outline of an Algorithm.

PubMed

Kotela, Andrzej; Wilk-Frańczuk, Magdalena; Jaczewska, Joanna; Żbikowski, Piotr; Łęgosz, Paweł; Ambroziak, Paweł; Kotela, Ireneusz

2017-01-27

The treatment of end-stage hemophilic arthropathy of the ankle joint remains a controversial problem, and total ankle replacement (TAR) is considered to be a valuable management option. Physiotherapy continues to be an extremely important part of TAR and has a tremendous impact on the outcomes of this procedure. Given the lack of data on the latter, this study details a protocol of perioperative physiotherapy in TAR in patients with inherited bleeding disorders (IBD). The protocol outlined in this paper was devised via consultations within an interdisciplinary group, the authors' own experiences with TAR in hemophilic and non-hemophilic patients, previous reports on this issue in the literature, and patient opinions. Our working group followed the criteria of the International Classification of Functioning, Disability and Health. The algorithm includes 4 physiotherapy phases with specified time frames, aims, interventions, and examples of exercises for each phase. We emphasize the importance of preoperative rehabilitation, and recommend introducing intensive physiotherapy immediately after the surgery, with regard to the wound protection and avoiding full weight-bearing in the first weeks. The intensity of physiotherapy should be adjusted individually depending on individual patient progress. This study details a rehabilitation protocol for TAR in patients with IBDs, which can be equally applicable to clinicians and researchers. Further scientific studies are required to investigate the beneficial effect of different protocols as well as to clarify the effectiveness of various frequencies, durations, and intensities of selected interventions.

Psychosocial correlates of physical activity in adolescents with haemophilia.

PubMed

Buxbaum, N P; Ponce, M; Saidi, P; Michaels, L A

2010-07-01

Boys with haemophilia are now encouraged to exercise and take part in physical activities, but actual measures of time spent in active participation is lacking. The aim of this study was to obtain an objective measure of daily physical activity in boys with haemophilia as compared with healthy controls. The study also aimed to ascertain the social and cognitive factors associated with exercise in this population. Seventeen patients (aged 11-18 years) with haemophilia were studied and compared with 44 healthy controls (aged 10-16.5 years). Physical activity was measured by accelerometry. Psychosocial correlates were assessed using validated questionnaires. Measured physical activity levels in subjects with haemophilia were slightly higher than for the control group. Both groups spent 70% of the day inactive, with similar proportions of time in moderate and vigorous activity. Subjects with haemophilia had a favourable self-image and similar levels of anxiety as peers without a bleeding disorder. Self-efficacy scores were lower than for controls suggesting increased sensitivity to barriers and lack of acceptance of alternatives. Health beliefs did not influence physical activity, but a negative correlation of time spent in high or vigorous activity with scores for support-seeking was observed. The data demonstrate that in the appropriate social environment and with medical support, patients with haemophilia may be as physically active as their peers without a bleeding disorder. Further investigation into the psychosocial barriers of physical activity in patients with haemophilia is needed to more effectively encourage healthy behaviours.

Noncirrhotic Portal Hypertension

PubMed Central

Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K

2011-01-01

Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension. PMID:25755321

Aortic Replacement with Sutureless Intraluminal Grafts

PubMed Central

Lemole, Gerald M.

1990-01-01

To avoid the anastomotic complications and long cross-clamp times associated with standard suture repair of aortic lesions, we have implanted sutureless intraluminal grafts in 122 patients since 1976. Forty-nine patients had disorders of the ascending aorta, aortic arch, or both: their operative mortality was 14% (7 patients), and the group's 5-year actuarial survival rate has been 64%. There have been no instances of graft dislodgment, graft infection, aortic bleeding, or pseudoaneurysm formation. Forty-two patients had disorders of the descending aorta and thoracoabdominal aorta: their early mortality was 10% (4 patients), and the group's 5-year actuarial survival rate has been 56%. There was 1 early instance of graft dislodgment, but no pseudoaneurysm formation, graft erosion, aortic bleeding, intravascular hemolysis, or permanent deficits in neurologic, renal, or vascular function. Thirty-one patients had the sutureless intraluminal graft implanted in the abdominal aortic position: their early mortality was 6% (2 patients), and the 5-year actuarial survival rate for this group has been 79%. There were no instances of renal failure, ischemic complication, postoperative paraplegia, pseudoaneurysm, or anastomotic true aneurysm. Our recent efforts have been directed toward developing an adjustable spool that can adapt to the widest aorta or the narrowest aortic arch vessel; but in the meanwhile, the present sutureless graft yields shorter cross-clamp times, fewer intraoperative complications, and both early and late results as satisfactory as those afforded by traditional methods of aortic repair. (Texas Heart Institute Journal 1990; 17:302-9) Images PMID:15227522

[Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 µg in the treatment of premenstrual dysphoric disorder: a randomized, double blind placebo-controlled study].

PubMed

Fu, Yi; Mi, Weifeng; Li, Lingzhi; Zhang, Hongyan; Wang, Jia; Cheng, Wenjun; Sun, Lizhou; Li, Lingjiang; Xie, Shiping; Zhang, Jinbei

2014-07-01

To compare the efficacy and safety of a new low-dose oral contraceptive pill (YAZ) containing drospirenone 3 mg and ethinylestradiol 20 µg with placebo in reducing symptoms of premenstrual dysphoric disorder (PMDD). This multicenter, double- blind, randomized clinical trial consisted of 2 run- in and 3 treatment cycles (84 days) with daily symptom charting; 187 women with symptoms of PMDD were randomized to either placebo group (n = 94) or YAZ group (n = 93), and assessed with daily record of severity of problems scale (DRSP) and clinical global impressions scale (CGI) before, during and after the treatments. Hormones were administered for 24 days, followed by 4 days of inactive pills. Compared with baseline level of DRSP, both groups got improvement after treatment; the YAZ group (median -28.7, range: -82.5 to 2.3) had greater improvement than that in the placebo group (median -23.7, range: -86.0 to 11.8), while there was not significant difference (P > 0.05). The main adverse effects of YAZ included intermenstrual bleeding [13% (12/93) versus 3% (3/94)], menorrhagia [9% (8/93) versus 1% (1/94)], nausea [5% (5/93) versus 4% (4/94)] and skin rash [4% (4/93) versus 2% (2/94)]. YAZ could improve symptoms of PMDD better than placebo, while without statistic significance in this study. The most common adverse effects are intermenstrual bleeding, menorrhagia, nausea and rash.

Frequency and prognostic significance of access site and non-access site bleeding and impact of choice of antithrombin therapy in patients undergoing primary percutaneous coronary intervention. The EUROMAX trial.

PubMed

Kilic, Sinem; Van't Hof, Arnoud W J; Ten Berg, Jurrien; Lopez, Ana Ayesta; Zeymer, Uwe; Hamon, Martial; Soulat, Louis; Bernstein, Debra; Deliargyris, Efthymios N; Steg, Phillippe Gabriel

2016-05-15

The overall impact of post percutaneous coronary intervention (PCI) bleeding on long term prognosis after acute coronary syndromes (ACS) has been established, but it may differ between access and non-access related bleeding events. The impact of antithrombin choice on bleeding may also differ according to the origin of the bleed. We sought to determine the origin of bleeding relative to the access site, its prognostic significance and the respective impact of antithrombin therapy in the EUROMAX trial. We performed a blinded review of the case records of all TIMI major or minor bleeds in the EUROMAX trial and assigned them in one of 2 categories: access site bleeds (ASB), or rest of bleeds (ROB). Incidence of bleeding for each category was assessed according to randomization to antithrombotic treatment. A total of 231 out of 2198 patients suffered a TIMI major/minor bleed (10.5%) and ASB accounted for 48.5%, while ROB for 51.5% of the bleeds. Thirty day mortality was 2.5% (50/1967) for patients without a bleed, 2.7% (3/112, p=0.76 vs. no bleed) for patients with ASB, and 10.9% (13/119, p<0.0001 vs. no bleed) for ROB patients. The use of bivalirudin reduced both ASB and ROB with relative risk reductions of 34% and 46% respectively. In contemporary primary PCI, bleeding originates with equal frequency either at or away from the access site. Access site bleeds were not associated with an excess in 30day mortality, but the rest of the bleeds were. Bivalirudin is associated with a lower risk of bleeding irrespective of origin. ClinicalTrials.gov identifier NCT01087723. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mortality in high-risk patients with bleeding Mallory-Weiss syndrome is similar to that of peptic ulcer bleeding. Results of a prospective database study.

PubMed

Ljubičić, Neven; Budimir, Ivan; Pavić, Tajana; Bišćanin, Alen; Puljiz, Zeljko; Bratanić, Andre; Troskot, Branko; Zekanović, Dražen

2014-04-01

The aim of this study was to identify the predictive factors influencing mortality in patients with bleeding Mallory-Weiss syndrome in comparison with peptic ulcer bleeding. Between January 2005 and December 2009, 281 patients with endoscopically confirmed Mallory-Weiss syndrome and 1530 patients with peptic ulcer bleeding were consecutively evaluated. The 30-day mortality and clinical outcome were related to the patients' demographic data, endoscopic, and clinical characteristics. The one-year cumulative incidence for bleeding Mallory-Weiss syndrome was 7.3 cases/100,000 people and for peptic ulcer bleeding 40.4 cases/100,000 people. The age-standardized incidence for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding remained unchanged during the observational five-year period. The majority of patients with bleeding Mallory-Weiss syndrome were male patients with significant overall comorbidities (ASA class 3-4). Overall 30-day mortality rate was 5.3% for patients with bleeding Mallory-Weiss syndrome and 4.6% for patients with peptic ulcer bleeding (p = 0.578). In both patients with bleeding Mallory-Weiss syndrome and peptic ulcer bleeding, mortality was significantly higher in patients over 65 years of age and those with significant overall comorbidities (ASA class 3-4). The incidence of bleeding Mallory-Weiss syndrome and peptic ulcer bleeding has not changed over a five-year observational period. The overall 30-day mortality was almost equal for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding and was positively correlated to older age and underlying comorbid illnesses.

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

Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease.

PubMed

Bunevicius, Robertas; Velickiene, Dzilda; Prange, Arthur J

2005-01-01

To evaluate the prevalence of mood and anxiety disorders in women with treated hyperthyroidism caused by Graves' disease and to compare them with the prevalence of such findings in women without past or present thyroid disease. Thirty inpatient women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease and 45 women hospitalized for treatment of gynecologic disorders such as abnormal vaginal bleeding, benign tumors or infertility were evaluated for the prevalence of mood and anxiety diagnoses using a standard Mini-International Neuropsychiatric Interview and for mood and anxiety ratings using the Profile of Mood States (POMS). At the time of assessment, it was discovered that 14 of 30 women with treated hyperthyroidism caused by Graves' disease were still hyperthyroid, while 16 women were euthyroid. Significantly greater prevalence of social anxiety disorder, generalized anxiety disorder, major depression and total mood and anxiety disorders, as well as higher symptom scores on the POMS, was found in hyperthyroid women with Graves' disease in comparison with the control group. A prevalence of total anxiety disorder, as well as history of mania or hypomania and lifetime bipolar disorder, but not lifetime unipolar depression, was more frequent in both the euthyroid and the hyperthyroid subgroups of study women in comparison with the control group. These results confirm a high prevalence of mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease. Hyperthyroidism plays a major role in psychiatric morbidity in Graves' disease.

Antidiabetic Polypill Improves Central Pathology and Cognitive Impairment in a Mixed Model of Alzheimer's Disease and Type 2 Diabetes.

PubMed

Infante-Garcia, Carmen; Ramos-Rodriguez, Juan Jose; Hierro-Bujalance, Carmen; Ortegon, Esperanza; Pickett, Eleanor; Jackson, Rosemary; Hernandez-Pacho, Fernando; Spires-Jones, Tara; Garcia-Alloza, Monica

2018-07-01

Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor. In order to test the effects of PP at the central level, we have long-term treated a new mixed model of AD-T2D, the APP/PS1xdb/db mouse. We have analyzed AD pathological features and the underlying specific characteristics that relate AD and T2D. As expected, metabolic alterations were ameliorated after PP treatment in diabetic mice, supporting a role for PP in maintaining pancreatic activity. At central level, PP reduced T2D-associated brain atrophy, showing both neuronal and synaptic preservation. Tau and amyloid pathologies were also reduced after PP treatment. Furthermore, we observed a reduction of spontaneous central bleeding and inflammation after PP treatment in diabetic mice. As consequence, learning and memory processes were improved after PP treatment in AD, T2D, and AD-T2D mice. Our data provide the basis to further analyze the role of PP, as an alternative or adjuvant, to slow down or delay the central complications associated with T2D and AD.

Laparoscopic myomectomy focusing on the myoma pseudocapsule: technical and outcome reports.

PubMed

Tinelli, Andrea; Hurst, Brad S; Hudelist, Gernot; Tsin, Daniel Alberto; Stark, Michael; Mettler, Liselotte; Guido, Marcello; Malvasi, Antonio

2012-02-01

Our aim was to assess surgical complaints and reproductive outcomes of laparoscopic intracapsular myomectomies by a prospective observational study run in University affiliated hospitals. Between 2005 and 2010, 235 women underwent subserous and intramural laparoscopic myomectomy of fibroids (4-10 cm in diameter) for indications of pelvic pain, menstrual disorders, a large growing myoma or infertility. The main outcome measures were post-surgical parameters, including complications, the need for subsequent surgery or symptomatic relief, resumption of normal life and reproductive outcome. Pelvic pain occurred in 27%, menorrhagia or metorrhagia in 21%, a large growing myoma in 10% and infertility in 42% of women. Single fibroids occurred in 51.9% of patients while 48.1% had multiple myomas. Of all patients, 58.2% had subserosal and 41.8% had intramural myomas. No laparoscopies were converted to laparotomy. In 3 years, 1.2% of patients had a second laparoscopic myomectomy for recurrent fibroids. The mean total operative laparoscopic time was 84 min (range 25-126 min), with mean blood loss of 118 ± 27.9 ml. By 48 h after surgery, 86.3% were discharged with no major post-operative complications. No late complications, such as bleeding, urinary tract infections or bowel lesions, occurred. Of the women who underwent myomectomy for infertility, 74% finally conceived. At term, 32.9% of patients underwent Caesarean section, 24.8% delivered by vacuum extractor and 42.2% had spontaneous deliveries. No case of uterine rupture occurred. Intracapsular subserous and intramural myomectomy saving the fibroid pseudocapsule showed few early and no late surgical complications, enhanced healing by preserving myometrial integrity and allowed a good fertility rate and delivery outcome. In young patients suffering fibroids, laparoscopic intracapsular myomectomy is a potential recommended surgical treatment.

Deletion of RUNX1 exons 1 and 2 associated with familial platelet disorder with propensity to acute myeloid leukemia.

PubMed

Cavalcante de Andrade Silva, Marcela; Krepischi, Ana Cristina Victorino; Kulikowski, Leslie Domenici; Zanardo, Evelin Aline; Nardinelli, Luciana; Leal, Aline Medeiros; Costa, Silvia Souza; Muto, Nair Hideki; Rocha, Vanderson; Velloso, Elvira Deolinda Rodrigues Pereira

2018-04-01

Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) associated with RUNX1 mutations is an autosomal dominant disorder included in the group of the myeloid neoplasms with germ line predisposition. We describe two brothers who were diagnosed with hematological malignancies (one with AML and the other with T-cell lymphoblastic lymphoma). There was a history of leukemia in the paternal family and two of their siblings presented with low platelet counts and no history of significant bleeding. A microdeletion encompassing exons 1-2 of RUNX1 (outside the cluster region of the Runt Homology domain and the transactivation domain) was detected in six family members using array-CGH and MLPA validation. A low platelet count was not present in all deletion carriers and, therefore, it should not be used as an indication for screening in suspected families and family members. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

Zhao, Juan; Yang, Dejuan; Zheng, Dongyou

2017-03-01

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

External Validation of Risk Scores for Major Bleeding in a Population-Based Cohort of Transient Ischemic Attack and Ischemic Stroke Patients.

PubMed

Hilkens, Nina A; Li, Linxin; Rothwell, Peter M; Algra, Ale; Greving, Jacoba P

2018-03-01

The S 2 TOP-BLEED score may help to identify patients at high risk of bleeding on antiplatelet drugs after a transient ischemic attack or ischemic stroke. The score was derived on trial populations, and its performance in a real-world setting is unknown. We aimed to externally validate the S 2 TOP-BLEED score for major bleeding in a population-based cohort and to compare its performance with other risk scores for bleeding. We studied risk of bleeding in 2072 patients with a transient ischemic attack or ischemic stroke on antiplatelet agents in the population-based OXVASC (Oxford Vascular Study) according to 3 scores: S 2 TOP-BLEED, REACH, and Intracranial-B 2 LEED 3 S. Performance was assessed with C statistics and calibration plots. During 8302 patient-years of follow-up, 117 patients had a major bleed. The S 2 TOP-BLEED score showed a C statistic of 0.69 (95% confidence interval [CI], 0.64-0.73) and accurate calibration for 3-year risk of major bleeding. The S 2 TOP-BLEED score was much more predictive of fatal bleeding than nonmajor bleeding (C statistics 0.77; 95% CI, 0.69-0.85 and 0.50; 95% CI, 0.44-0.58). The REACH score had a C statistic of 0.63 (95% CI, 0.58-0.69) for major bleeding and the Intracranial-B 2 LEED 3 S score a C statistic of 0.60 (95% CI, 0.51-0.70) for intracranial bleeding. The ratio of ischemic events versus bleeds decreased across risk groups of bleeding from 6.6:1 in the low-risk group to 1.8:1 in the high-risk group. The S 2 TOP-BLEED score shows modest performance in a population-based cohort of patients with a transient ischemic attack or ischemic stroke. Although bleeding risks were associated with risks of ischemic events, risk stratification may still be useful to identify a subgroup of patients at particularly high risk of bleeding, in whom preventive measures are indicated. © 2018 The Authors.

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.

Correlation Between Findings of Multislice Helical Computed Tomography (CT), Endoscopic Examinations, Endovascular Procedures, and Surgery in Patients with Symptoms of Acute Gastrointestinal Bleeding.

PubMed

Konecki, Dariusz; Grabowska-Derlatka, Laretta; Pacho, Ryszard; Rowiński, Olgierd

2017-01-01

Endoscopic methods (gastroscopy and colonoscopy) are considered fundamental for the diagnosis of gastrointestinal bleeding. In recent years, multidetector computed tomography (MDCT) has also gained importance in diagnosing gastrointestinal bleeding, particularly in hemodynamically unstable patients and in cases with suspected lower gastrointestinal tract bleeding. CT can detect both the source and the cause of active gastrointestinal bleeding, thereby expediting treatment initiation. The study group consisted of 16 patients with clinical symptoms of gastrointestinal bleeding in whom features of active bleeding were observed on CT. In all patients, bleeding was verified by means of other methods such as endoscopic examinations, endovascular procedures, or surgery. The bleeding source was identified on CT in all 16 patients. In 14 cases (87.5%), bleeding was confirmed by other methods. CT is an efficient, fast, and readily available tool for detecting the location of acute gastrointestinal bleeding.

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

PubMed

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

2014-10-09

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

Prospective analysis of delayed colorectal post-polypectomy bleeding.

PubMed

Park, Soo-Kyung; Seo, Jeong Yeon; Lee, Min-Gu; Yang, Hyo-Joon; Jung, Yoon Suk; Choi, Kyu Yong; Kim, Hungdai; Kim, Hyung Ook; Jung, Kyung Uk; Chun, Ho-Kyung; Park, Dong Il

2018-01-17

Although post-polypectomy bleeding is the most frequent complication after colonoscopic polypectomy, only few studies have investigated the incidence of bleeding prospectively. The aim of this study was to investigate the incidence of delayed post-polypectomy bleeding and its associated risk factors prospectively. Patients who underwent colonoscopic polypectomy at Kangbuk Samsung Hospital from January 2013 to December 2014 were prospectively enrolled in this study. Trained nurses contacted patients via telephone 7 and 30 days after polypectomy and completed a standardized questionnaire regarding the development of bleeding. Delayed post-polypectomy bleeding was categorized as minor or major and early or late bleeding. Major delayed bleeding was defined as a > 2-g/dL drop in the hemoglobin level, requiring hospitalization for control of bleeding or blood transfusion; late delayed bleeding was defined as bleeding occurring later than 24 h after polypectomy. A total of 8175 colonoscopic polypectomies were performed in 3887 patients. Overall, 133 (3.4%) patients developed delayed post-polypectomy bleeding. Among them, 90 (2.3%) and 43 (1.1%) patients developed minor and major delayed bleeding, respectively, and 39 (1.0%) patients developed late delayed bleeding. In the polyp-based multivariate analysis, young age (< 50 years; odds ratio [OR] 2.10; 95% confidence interval [CI] 1.18-3.68), aspirin use (OR 2.78; 95% CI 1.23-6.31), and polyp size of > 10 mm (OR 2.45; 95% CI 1.38-4.36) were significant risk factors for major delayed bleeding, while young age (< 50 years; OR 2.6; 95% CI 1.35-5.12) and immediate bleeding (OR 3.3; 95% CI 1.49-7.30) were significant risk factors for late delayed bleeding. Young age, aspirin use, polyp size, and immediate bleeding were found to be independent risk factors for delayed post-polypectomy bleeding.

Factor XIII deficiency in Iran: a comprehensive review of the literature.

PubMed

Dorgalaleh, Akbar; Naderi, Majid; Hosseini, Maryam Sadat; Alizadeh, Shaban; Hosseini, Soudabeh; Tabibian, Shadi; Eshghi, Peyman

2015-04-01

Factor XIII deficiency (FXIIID) is a rare bleeding disorder with an estimated prevalence of 1 in 2-million population worldwide. In Iran, a Middle Eastern country with a high rate of consanguineous marriages, there are approximately 473 patients afflicted with FXIIID. An approximately 12-fold higher prevalence of FXIIID is estimated in Iran in comparison with overall worldwide frequency. In this study, we have undertaken a comprehensive review on different aspects of FXIIID in the Iranian population. The distribution of this disease in different regions of Iran reveals that Sistan and Baluchestan Province has not only the highest number of patients with FXIIID in Iran but the highest global incidence of this condition. Among Iranian patients, umbilical cord bleeding, hematoma, and prolonged wound bleeding are the most frequent clinical manifestations. There are several disease causing mutations in Iranian patients with FXIIID, with Trp187Arg being the most common mutation in FXIIID in Iran. Traditionally, the management of FXIIID in Iran was only based on administration of fresh frozen plasma or cryoprecipitate, until 2009 when FXIII concentrate became available for patient management. Various studies have evaluated the efficacy and safety of prophylactic regimens in different situations with valuable findings. Although the focus of this study is on Iran, it offers considerable insight into FXIIID, which can be applied more extensively to improve the management and quality of life in all affected patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Laboratory hemostasis: from biology to the bench.

PubMed

Lippi, Giuseppe; Favaloro, Emmanuel J

2018-06-27

Physiological hemostasis is an intricate biological system, where procoagulant and anticoagulant forces interplay and preserves blood fluidity when blood vessels are intact, or trigger clot formation to prevent excessive bleeding when blood vessels are injured. The modern model of hemostasis is divided into two principal phases. The first, defined as primary hemostasis, involves the platelet-vessel interplay, whilst the second, defined as secondary hemostasis, mainly involves coagulation factors, damaged cells and platelet surfaces, where the so-called coagulation cascade rapidly develops. The activation and amplification of the coagulation cascade is finely modulated by the activity of several physiological inhibitors. Once bleeding has been efficiently stopped by blood clot formation, dissolution of the thrombus is essential to restore vessel permeability. This process, known as fibrinolysis, also develops through coordinate action of a vast array of proteins and enzymes. An accurate diagnosis of hemostasis disturbance entails a multifaceted approach, encompassing family and personal history of hemostatic disorders, accurate collection of clinical signs and symptoms, integrated with laboratory hemostasis testing. Regarding laboratory testing, a reasonable approach entails classifying hemostasis testing according to cost, complexity and available clinical information. Laboratory workout may hence initiate with some rapid and inexpensive "screening" tests, characterized by high negative predictive value, then followed by second- or third-line analyses, specifically aimed to clarify the nature and severity of bleeding or thrombotic phenotype. This article aims to provide a general overview of the hemostatic process, and to provide some general suggestions to optimally facilitate laboratory hemostasis testing.

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

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

2018-01-01

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

[Evaluation of a new polyvalent antivenom against snakebite envenomation (Inoserp® Panafricain) in two different epidemiological settings: Northern Benin and Maritime Guinea].

PubMed

Chippaux, J-P; Baldé, M C; Sessinou, É; Yéro Boiro, M; Massougbodji, A

2015-01-01

The authors evaluated the safety and efficacy of Inoserp(®) Pan Africa, a new polyvalent antivenom composed of highly purified and lyophilized fragments of F(ab')2 immunoglobulins, recently registered in Benin and Guinea. We treated 100 patients in northern Benin (Atacora) and 109 in Maritime Guinea (Kindia) with confirmed envenomation. Treatment consisted of intravenous administration of 1 vial for uncomplicated envenomation, and 2 vials for hemorrhagic or neurotoxic envenomation. The dose was repeated when bleeding or signs of neurotoxicity persisted or appeared. In Atacora, on arrival at the hospital, 90% of patients had incoagulable blood, and 50% were bleeding. The resolution of these bleeding disorders was obtained in less than 3 hours for 50% of the patients and in less than 24 hours for 98%. Four patients died. In Kindia, 96 patients (88%) presented viper bites with pain + edema and 13 (12 %) others showed elapid (ptosis, dyspnea) envenomation. One patient bitten by a member of the Elapidae family, died despite early treatment. In Benin, protocol deviations for 60% of patients led to significant underdosing of the antivenom; the proportion was much lower (2%) in Guinea. Signs of intolerance after Inoserp(®) Pan Africa administration were reported in 8% of patients. All these symptoms were mild and disappeared rapidly after an antihistamine or corticosteroid treatment. Treatment using intravenous Inoserp(®) Pan Africa appeared to be well tolerated and effective against snakebite envenomation in both epidemiological settings.

Comprehensive elements of a physiotherapy exercise programme in haemophilia--a global perspective.

PubMed

Blamey, G; Forsyth, A; Zourikian, N; Short, L; Jankovic, N; De Kleijn, P; Flannery, T

2010-07-01

Exercise programmes for people with haemophilia are usually designed and implemented to help manage the recovery after a haemarthrosis or a muscle bleed, or as a tool to help prevent bleeding episodes from occurring. In this article, we have identified individual components of exercise that are often applied as separate entities, but may also need to be implemented in concert for optimized impact. Although it may be necessary on occasion to bias an exercise programme towards one component over the others, it is important to recognize that the various elements of exercise are not mutually exclusive. Decreased flexibility, strength and proprioception, will result in an impairment of balance and a loss of function. Programme design should whenever possible be guided by proven methodology in terms of how each component is incorporated, and more specifically how long to perform the exercise for and how many repetitions should be performed. We recognize, however, that this is not always possible and that there is significant value in drawing from the experience of clinicians with specialized training in the management of haemophilia. In this study, both perspectives are presented, providing reference-based reviews of the mechanics of the various elements of exercise as well as the expert opinions of the authors. Research that has been completed using patients with conditions other than haemophilia may or may not have a direct application with the bleeding disorders population, but the programme design based on principles of tissue healing in addition to disease specific knowledge should be encouraged.

The Relationship Between Serum Neuron-Specific Enolase Levels and Severity of Bleeding and Functional Outcomes in Patients With Nontraumatic Subarachnoid Hemorrhage.

PubMed

Tawk, Rabih G; Grewal, Sanjeet S; Heckman, Michael G; Rawal, Bhupendra; Miller, David A; Edmonston, Drucilla; Ferguson, Jennifer L; Navarro, Ramon; Ng, Lauren; Brown, Benjamin L; Meschia, James F; Freeman, William D

2016-04-01

The value of neuron-specific enolase (NSE) in predicting clinical outcomes has been investigated in a variety of neurological disorders. To investigate the associations of serum NSE with severity of bleeding and functional outcomes in patients with subarachnoid hemorrhage (SAH). We retrospectively reviewed the records of patients with SAH from June 2008 to June 2012. The severity of SAH bleeding at admission was measured radiographically with the Fisher scale and clinically with the Glasgow Coma Scale, Hunt and Hess grade, and World Federation of Neurologic Surgeons scale. Outcomes were assessed with the modified Rankin Scale at discharge. We identified 309 patients with nontraumatic SAH, and 71 had NSE testing. Median age was 54 years (range, 23-87 years), and 44% were male. In multivariable analysis, increased NSE was associated with a poorer Hunt and Hess grade (P = .003), World Federation of Neurologic Surgeons scale score (P < .001), and Glasgow Coma Scale score (P = .003) and worse outcomes (modified Rankin Scale at discharge; P = .001). There was no significant association between NSE level and Fisher grade (P = .81) in multivariable analysis. We found a significant association between higher NSE levels and poorer clinical presentations and worse outcomes. Although it is still early for any relevant clinical conclusions, our results suggest that NSE holds promise as a tool for screening patients at increased risk of poor outcomes after SAH.

Vaginal Bleeding

MedlinePlus

... bleeding is any vaginal bleeding unrelated to normal menstruation. This type of bleeding may include spotting of ... two or more hours. Normal vaginal bleeding, or menstruation, occurs every 21 to 35 days when the ...

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 ...

Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study.

PubMed

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

2018-03-01

While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (p<0.001) and MBR factors score (p=0.013) but not ATRIA and ORBIT scores. When HAS-BLED was compared to other bleeding scores, c-indexes were significantly higher compared to MBR factors (p<0.001) and ORBIT (p=0.05) scores for major bleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all p<0.001). When NRI was performed, HAS-BLED outperformed all other bleeding risk scores for major bleeding (all p<0.001). C-indexes for ATRIA and ORBIT scores suggested no significant prediction for ICH. All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major bleeding in AF patients, when compared to the HAS-BLED score. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Improving the management of chronic diseases using web-based technologies: an application in hemophilia care.

PubMed

Teixeira, Leonor; Saavedra, Vasco; Ferreira, Carlos; Sousa Santos, Beatriz

2010-01-01

Modern methods of information and communication that use web technologies provide an opportunity to facilitate closer communication between patients and healthcare providers, allowing a joint management of chronic diseases. This paper describes a web-based technological solution to support the management of inherited bleeding disorders integrating, diffusing and archiving large sets of data relating to the clinical practice of hemophilia care, more specifically the clinical practice at the Hematology Service of Coimbra Hospital Center (a Hemophilia Treatment Center located in Portugal).

Cerebral Venous Sinus Thrombosis in a Patient with Undiagnosed Factor VII Deficiency.

PubMed

Qadir, Hira; Rashid, Anila; Adil, Salman Naseem

2017-09-01

Factor VII (FVII) deficiency is one of the rare inherited bleeding disorders. Thrombosis has been occasionally described in inherited FVII deficiency. Here, we report a young female with undiagnosed FVII deficiency who presented with cerebral venous sinus thrombosis (CVST). Oral contraceptive pill was found to be prothrombotic risk factor. The CVSToccurred in spite of the congenital FVII deficiency indicating that no definitive antithrombotic protection is assured by this defect. Low molecular weight heparin and anti-Xa assay were found to be safe choice of anticoagulation and monitoring, respectively, in this patient.

Evolving Complexity in Hemophilia Management.

PubMed

Croteau, Stacy E

2018-06-01

Rapid expansion of therapeutic options have increased the complexity of hemophilia care. Previously, on-demand therapy aimed to reduce morbidity and early mortality; however, now aggressive prophylaxis, particularly in children, encourages an active lifestyle. Accurate diagnosis, recognition of early threats to musculoskeletal health, and optimization of therapy are critical for both males and females affected by hemophilia. The diversity of emerging hemophilia therapies, from modified factor protein concentrates, to gene therapy, to nonfactor hemostatic strategies, provide an exciting opportunity to target unmet needs in the bleeding disorder community. Copyright © 2018 Elsevier Inc. All rights reserved.

Guidelines for pubertal suspension and gender reassignment for transgender adolescents.

PubMed

Hembree, Wylie C

2011-10-01

Pubertal suppression at Tanner stage 2 should be considered in adolescents with persistent gender identity disorder (GID). Issues related to achievement of adult height, timing of initiating sex steroid treatment, future fertility options, preventing uterine bleeding, and required modifications of genital surgery remain concerns. Concerns have been raised about altering neuropsychological development during cessation of puberty and reinitiation of puberty by the sex steroid opposite those determined by genetic sex. Collaborative assessment and treatment of dysphoric adolescents with persistent GID resolves these concerns and deepens our understanding of gender development.

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

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.

Outcomes of Propofol Sedation During Emergency Endoscopy Performed for Upper Gastrointestinal Bleeding.

PubMed

Park, Chan Hyuk; Han, Dong Soo; Jeong, Jae Yoon; Eun, Chang Soo; Yoo, Kyo-Sang; Jeon, Yong Cheol; Sohn, Joo Hyun

2016-03-01

Although propofol-based sedation can be used during emergency endoscopy for upper gastrointestinal bleeding (UGIB), there is a potential risk of sedation-related adverse events, especially in patients with variceal bleeding. We compared adverse events related to propofol-based sedation during emergency endoscopy between patients with non-variceal and variceal bleeding. Clinical records of patients who underwent emergency endoscopy for UGIB under sedation were reviewed. Adverse events, including shock, hypoxia, and paradoxical reaction, were compared between the non-variceal and variceal bleeding groups. Of 703 endoscopies, 539 and 164 were performed for non-variceal and variceal bleeding, respectively. Shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding (12.2 vs. 3.5%, P < 0.001). All patients except one recovered from shock after normal saline hydration, and emergency endoscopy could be finished without interruption in most cases. The incidence of hypoxia and paradoxical reaction did not differ based on the source of bleeding (non-variceal bleeding vs. variceal bleeding: hypoxia, 3.5 vs. 1.8%, P = 0.275; paradoxical reaction interfering with the procedure, 4.1 vs. 5.5%, P = 0.442). Although shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding, most cases could be controlled without procedure interruption. Paradoxical reaction, rather than shock or hypoxia, was the most common cause of procedure interruption in patients with variceal bleeding, but the rate did not differ between patients with non-variceal and variceal bleeding.

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.

Histological Pattern Of Endometrial Samples In Postmenopausal Women With Abnormal Uterine Bleeding.

PubMed

Deeba, Farhat; Shaista; Khan, Bushra

2016-01-01

Abnormal uterine bleeding is one of the most common clinical problems in gynaecological practice and is an indicator of various underlying disorders. An endometrial biopsy should be done in all women over 35 years with AUB to rule out endometrial cancer or pre-malignant lesion and to initiate treatment. However, wide range of histological patterns on endometrial biopsy offer a diagnostic challenge to practicing pathologists. The objective of this study was to determine histological patterns of endometrium in postmenopausal women with abnormal uterine bleeding. This cross-sectional study was conducted in the department of obstetrics and gynaecology, Benazir Bhutto Shaheed women and children teaching hospital, Abbottabad from 15/11/2014 to 14/05/2015. This study involved 110 postmenopausal women presenting with abnormal uterine bleeding. A written informed consent was obtained from every patient. The mean age of the patients was 61.60±6.17 years and the mean duration of AUB was 5.20±2.80 years. Most of the patients were para 6 (28.2%) and para 5 (28.2%) followed by para 4 (18.2%) and para 3 (17.3%) while only 8.2% were para 1. The most common histological pattern observed was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%). When stratified the data, there was no significant difference of histological patterns across various age groups (p=.673), duration of AUB (p=.064) and parity (p=.242). The most common histological pattern observed in postmenopausal women with AUB was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%).

Correlation Between Findings of Multislice Helical Computed Tomography (CT), Endoscopic Examinations, Endovascular Procedures, and Surgery in Patients with Symptoms of Acute Gastrointestinal Bleeding

PubMed Central

Konecki, Dariusz; Pacho, Ryszard; Rowiński, Olgierd

2017-01-01

Summary Background Endoscopic methods (gastroscopy and colonoscopy) are considered fundamental for the diagnosis of gastrointestinal bleeding. In recent years, multidetector computed tomography (MDCT) has also gained importance in diagnosing gastrointestinal bleeding, particularly in hemodynamically unstable patients and in cases with suspected lower gastrointestinal tract bleeding. CT can detect both the source and the cause of active gastrointestinal bleeding, thereby expediting treatment initiation. Material/Methods The study group consisted of 16 patients with clinical symptoms of gastrointestinal bleeding in whom features of active bleeding were observed on CT. In all patients, bleeding was verified by means of other methods such as endoscopic examinations, endovascular procedures, or surgery. Results The bleeding source was identified on CT in all 16 patients. In 14 cases (87.5%), bleeding was confirmed by other methods. Conclusions CT is an efficient, fast, and readily available tool for detecting the location of acute gastrointestinal bleeding. PMID:29662594

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

PubMed

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

2017-04-01

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

Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model.

PubMed Central

O'Brien, D P; Giles, A R; Tate, K M; Vehar, G A

1988-01-01

The bleeding disorder of hemophilia A currently treated by replacement therapy of the missing coagulation factor, factor VIII, is frequently complicated by the development of neutralizing antibodies. The therapeutic potential of attenuated forms of the lipid-associated glycoprotein tissue factor, a known initiator of coagulation, was investigated as a factor VIII-by-passing activity. The protein moiety of tissue factor (Apo-TF) was partially purified and exhibited minimal procoagulant activity before relipidation in vitro. In pilot studies, Apo-TF injection into rabbits previously anticoagulated with an antibody to factor VIII was found to have a procoagulant effect. The efficacy of the material was further demonstrated when injection of Apo-TF in hemophilic dogs resulted in a normalization of the cuticle bleeding time. Little or no change in the blood parameters associated with disseminated intravascular coagulation was observed at lower doses, although mild to moderate effects were seen at higher doses. These data suggest a novel role for Apo-TF preparations as a potential therapeutic agent for hemophiliacs with antibodies to factor VIII once the potential thrombogenicity of such materials is evaluated. Images PMID:3134399

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.

Endoscopic Ultrasound-Guided Vascular Therapy: The Present and the Future

PubMed Central

Hall, Philip S.J.; Teshima, Christopher; May, Gary R.; Mosko, Jeffrey D.

2017-01-01

Endoscopic ultrasound (EUS) offers access to many intra-abdominal vessels that until now have only been accessible to the surgeon and interventional radiologist. In addition to assisting with diagnostics, this unique access offers the potential for therapeutic intervention for a host of indications. To date, this has had the most clinical impact in the treatment of gastroesophageal varices, with EUS-guided coil and glue application growing in use worldwide. Although randomised controlled trial data is lacking, we discuss the growing body of literature behind EUS-guided therapy in the management of varices. EUS has also been used in specialized centres to assist in non-variceal gastrointestinal bleeding. The treatment of bleeding from Dieulafoy lesions, tumours and pancreatic pseudoaneurysms has all been described. The potential applications of EUS have also extended to the placement of portal vein stents and porto-systemic shunts in animal models. As medicine continues to move to increasingly less invasive interventions, EUS-guided therapies offer substantial promise for the safe and effective delivery of targeted treatment for a widening array of vascular disorders. PMID:28391673

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.

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.

Animal Models of Hemophilia

PubMed Central

Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.

2013-01-01

The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432

Low-level light treatment ameliorates immune thrombocytopenia

PubMed Central

Yang, Jingke; Zhang, Qi; Li, Peiyu; Dong, Tingting; Wu, Mei X.

2016-01-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP. PMID:27901126

Low-level light treatment ameliorates immune thrombocytopenia

NASA Astrophysics Data System (ADS)

Yang, Jingke; Zhang, Qi; Wu, Mei X.

2017-02-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

Endodontic management of a haemophilic patient- a clinical perspective.

PubMed

Dudeja, Pooja Gupta; Dudeja, Krishan Kumar; Lakhanpal, Manisha; Ali, Sartaj

2014-07-01

Haemophilia and other bleeding disorders remain an enigma to the dentists world over. They not only challenge the skills of dental specialists but also raise the question of how these individuals should be managed emotionally as well as psychologically. The high incidence of dental problems in haemophiliacs is most likely caused by the fear and apprehension not only on the part of the patients but also dentists of inducing bleeding during treatment which can even be life threatening in certain cases. With proper care, diligence and meticulous treatment planning, there is no dental treatment that cannot be performed in such patients. Mild haemophiliacs can be easily managed and can effectively undergo even surgical endodontics without factor replacement therapies. However, severe haemophilia can pose significant health hazard and needs thorough preparation to meet any exigencies arising during the treatment. This case report describes how one such severely haemophilic patient with pain and swelling in the left submandibular region was managed with nonsurgical endodontic treatment in mandibular molar teeth and also discusses the importance of correct methods of diagnosis and various treatment considerations in such patients.

Physical activity and risk of bleeding in elderly patients taking anticoagulants.

PubMed

Frey, P M; Méan, M; Limacher, A; Jaeger, K; Beer, H-J; Frauchiger, B; Aschwanden, M; Rodondi, N; Righini, M; Egloff, M; Osterwalder, J; Kucher, N; Angelillo-Scherrer, A; Husmann, M; Banyai, M; Matter, C M; Aujesky, D

2015-02-01

Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy. © 2014 International Society on Thrombosis and Haemostasis.

Clinicopathological and Prognostic Analysis of Primary Gastrointestinal Stromal Tumor Presenting with Gastrointestinal Bleeding: a 10-Year Retrospective Study.

PubMed

Yin, Zhijie; Gao, Jinbo; Liu, Weizhen; Huang, Cheng; Shuai, Xiaoming; Wang, Guobin; Tao, Kaixiong; Zhang, Peng

2017-05-01

The objectives of this paper were to investigate the clinicopathological characteristics and prognostic factors of GI-bleeding GIST patients and explore whether GI bleeding is a risk factor for GIST relapse. Primary GIST patients with initial symptoms of GI bleeding or no GI bleeding were retrospectively studied. Up to 178 GI-bleeding GIST patients including 108 (60.7%) males and 70 (39.3%) females were evaluated for the clinicopathological characteristics. The stomach, small bowel, and colorectum were the tumor sites in 82 (46.1%), 85 (47.8%), and 11 (6.2%) patients. Of the 178 patients, 163 GI-bleeding patients had follow-up while another 363 patients from the total population presented without GI bleeding were followed up. Up to 526 patients who received postoperative follow-up were included in the survival analysis. Compared with the 363 non-GI-bleeding patients, GI-bleeding patients developed smaller tumors (P = 0.015) and had a longer relapse-free survival (RFS; P = 0.014). For the 163 GI-bleeding patients, a Cox regression analysis showed that the mitotic count and the platelet-lymphocyte ratio before surgery were independent prognostic predictors for poor outcome regarding RFS. For all 526 patients, a Cox regression analysis indicated that tumor location, mitotic index, platelet-lymphocyte ratio, and GI bleeding were independent prognosis predictors. Compared to non-GI-bleeding GIST patients, patients with GI bleeding were more likely to be male and to have more small intestine GISTs, smaller tumors, and a longer RFS. For GI-bleeding patients, mitotic count and platelet-lymphocyte ratio were independent prognostic indicators. GI bleeding served as a surrogate for smaller GIST and was a protective factor for GIST recurrence.

The Role of Therapeutic Endoscopy in Patients With Cirrhosis-Related Causes of Gastrointestinal Bleeding.

PubMed

Kezer, Camille A; Gupta, Neil

2018-06-09

This article aims to review current therapeutic endoscopic treatments available for the management of gastrointestinal bleeding related to cirrhosis. Endoscopic band ligation is an effective treatment for primary prophylaxis, acute bleeding, and secondary prophylaxis of esophageal varices as well as for acute bleeding and secondary prophylaxis of select gastric varices. Sclerotherapy is a treatment option for acute bleeding and secondary prophylaxis of esophageal varices when band ligation is technically difficult. Cyanoacrylate glue injection is an effective treatment for acute bleeding of gastric and ectopic varices. Argon plasma coagulation is first-line and radiofrequency ablation is second-line treatment for chronic bleeding secondary to gastric antral vascular ectasia. There are a variety of endoscopic treatment modalities for cirrhosis-related gastrointestinal bleeding, and the appropriate therapy depends on the location of the bleed, history or presence of acute bleeding, and risk factors for intervention-related adverse events.

Premature extravasation. A bleeding site identified during the dynamic phase of Tc-99m red blood cell bleeding scintigraphy.

PubMed

el-Shirbiny, A; Fernandez, R; Zuckier, L S

1995-08-01

Tc-99m RBC scintigraphy is favored by many investigators because it provides the ability to image the abdomen over a prolonged period of time, thereby allowing identification of delayed bleeding sites that are frequently encountered due to the intermittent nature of gastrointestinal bleeding. The authors describe a case of bleeding scintigraphy with labeled red blood cells in which the bleeding site was identifiable only on the dynamic blood-flow and first static images. On later images, the labeled blood cells had spread throughout the colon, rendering localization of the actual bleeding site impossible. Two previous red blood cell scintigraphies and a subsequent contrast angiogram did not reveal sites of active bleeding. As illustrated by this unusual case, factors governing timing and visualization of abnormal bleeding sites are discussed, as is a differential diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding scintigraphy.

Gastrointestinal bleeding after intracerebral hemorrhage: a retrospective review of 808 cases.

PubMed

Yang, Tie-Cheng; Li, Jian-Guo; Shi, Hong-Mei; Yu, Dong-Ming; Shan, Kai; Li, Li-Xia; Dong, Xiao-Yan; Ren, Tian-Hua

2013-10-01

This study examined the incidence and risk factors for gastrointestinal (GI) bleeding after spontaneous intracerebral hemorrhage (ICH). The available medical records of patients with ICH admitted from June 2008 to December 2009 for any episode of GI bleeding, possible precipitating factors and administration of ulcer prophylaxis were reviewed. The prevalence of GI bleeding was 26.7%, including 3 cases of severe GI bleeding (0.35%). Patients with GI bleeding had significantly longer hospital stay and higher in-hospital mortality compared with patients without GI bleeding. Multivariate logistic regression analyses showed that age, Glasgow Coma Scale scores, sepsis and ICH volume were independent predictors of GI bleeding. About 63.4% of patients with ICH received stress ulcer prophylaxis. GI bleeding occurred frequently after ICH, but severe events were rare. Age, Glasgow Coma Scale score, sepsis and ICH volume were independent predictors of GI bleeding occurring after ICH.

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.

Highlighted Steps of the Management Algorithm in Acute Lower Gastrointestinal Bleeding - Case Reports and Literature Review.

PubMed

Andrei, Gabriel Nicolae; Popa, Bogdan; Gulie, Laurentiu; Diaconescu, Bogdan Ionut; Martian, Bogdan Valeriu; Bejenaru, Mircea; Beuran, Mircea

2016-01-01

Acute lower gastrointestinal bleeding is a major problem worldwide, being a rare and life threatening condition, with a mortality rate situated between 2 and 4%. Acute lower gastrointestinal bleeding is solvent for 1 - 2% of the entire hospital emergencies, 15% presenting as massive bleeding and up to 5% requiring surgery. Lower gastrointestinal bleeding can be classified depending on their location in the small or large intestine. The small bowel is the rarest site of lower gastrointestinal bleeding, at the same time being the commonest cause of obscure bleeding. 5% of total lower GI bleeding appears in the small bowel. When endoscopic therapy associated with medical treatment are insufficient, endovascular intervention can be lifesaving. Unfortunately in some rare cases of acute lower gastrointestinal bleeding with hemo-dynamic instability and the angiography performed being unable to locate the source of bleeding, the last therapeutic resource remains surgery. In the following we exemplify two cases of acute lower gastrointestinal bleeding which were resolved in different ways, followed by a thorough description of the different types of available treatment and finally, in the conclusions, we systematize the most important stages of the management algorithm in acute lower gastrointestinal bleeding. Celsius.

Harnessing the natural inhibitory domain to control TNFα Converting Enzyme (TACE) activity in vivo.

PubMed

Wong, Eitan; Cohen, Tal; Romi, Erez; Levin, Maxim; Peleg, Yoav; Arad, Uri; Yaron, Avraham; Milla, Marcos E; Sagi, Irit

2016-12-16

Dysregulated activity of A Disintegrin And Metalloproteinase 17 (ADAM17)/TNFα Converting Enzyme (TACE) is associated with inflammatory disorders and cancer progression by releasing regulatory membrane-tethered proteins like TNFα, IL6R and EGFR ligands. Although specific inhibition of TACE is thought to be a viable strategy for inflammatory disorders and for malignancies treatment, the generation of effective inhibitors in vivo has been proven to be challenging. Here we report on the development of a protein inhibitor that leverages the endogenous modulator of TACE. We have generated a stable form of the auto-inhibitory TACE prodomain (TPD), which specifically inhibits in vitro and cell-surface TACE, but not the related ADAM10, and effectively modulated TNFα secretion in cells. TPD significantly attenuated TACE-mediated disease models of sepsis, rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), and reduced TNFα in synovial fluids from RA patients. Our results demonstrate that intervening with endogenous ADAM sheddase modulatory mechanisms holds potential as a general strategy for the design of ADAM inhibitors.

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

PubMed

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

2017-12-01

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

Anatomy and embryology of umbilicus in newborns: a review and clinical correlations.

PubMed

Hegazy, Abdelmonem A

2016-09-01

Umbilicus is considered a mirror of the abdomen in newborns. Despite its importance, the umbilicus has been stated in literature and textbooks as discrete subjects with many body systems, such as the urinary, digestive, and cardiovascular ones. This article aimed to address the basic knowledge of the umbilicus in relation to clinical disorders under one integrated topic to aid physicians and surgeons in assessing newborns and infants. The umbilicus appears as early as the fourth week of fetal life when the folding of the embryonic plate occurs. The umbilicus appears initially as a primitive umbilical ring on the ventral aspect of the body. The primitive umbilicus contains the connecting stalk, umbilical vessels, vitelline duct and vessels, allantois, and loop of the intestine. Changes occur to form the definitive cord, which contains three umbilical vessels, namely, "one vein and two arteries," embedded in Wharton's jelly. After birth, the umbilical vessels inside the body obliterate and gradually form ligaments. Congenital disorders at the umbilicus include herniation, bleeding, and discharge of mucous, urine, or feces. Some of these disorders necessitate emergent surgical interference, whereas others may be managed conservatively. The umbilicus has many embryological remnants. Thus, the umbilicus is prone to various clinical disorders. Detecting these disorders as early as possible is essential to prevent or minimize possible complications.

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

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

NASA Technical Reports Server (NTRS)

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

1971-01-01

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

Health-Related Quality of Life in Children and Adolescents with Hereditary Bleeding Disorders and in Children and Adolescents with Stroke: Cross-Sectional Comparison to Siblings and Peers

PubMed Central

Neuner, Bruno; von Mackensen, Sylvia; Holzhauer, Susanne; Funk, Stephanie; Klamroth, Robert; Kurnik, Karin; Krümpel, Anne; Halimeh, Susan; Reinke, Sarah; Frühwald, Michael; Nowak-Göttl, Ulrike

2016-01-01

Objectives. To investigate self-reported health-related quality of life (HrQoL) in children and adolescents with chronic medical conditions compared with siblings/peers. Methods. Group 1 (6 treatment centers) consisted of 74 children/adolescents aged 8–16 years with hereditary bleeding disorders (HBD), 12 siblings, and 34 peers. Group 2 (one treatment center) consisted of 70 children/adolescents with stroke/transient ischemic attack, 14 siblings, and 72 peers. HrQoL was assessed with the “revised KINDer Lebensqualitätsfragebogen” (KINDL-R) questionnaire. Multivariate analyses within groups were done by one-way ANOVA and post hoc pairwise single comparisons by Student's t-tests. Adjusted pairwise comparisons were done by hierarchical linear regressions with individuals nested within treatment centers (group 1) and by linear regressions (group 2), respectively. Results. No differences were found in multivariate analyses of self-reported HrQoL in group 1, while in group 2 differences occurred in overall wellbeing and all subdimensions. These differences were due to differences between patients and peers. After adjusting for age, gender, number of siblings, and treatment center these differences persisted regarding self-worth (p = .0040) and friend-related wellbeing (p < .001). Conclusions. In children with HBD, HrQoL was comparable to siblings and peers. In children with stroke/TIA HrQoL was comparable to siblings while peers, independently of relevant confounder, showed better self-worth and friend-related wellbeing. PMID:27294108

[Disorders of libido from the gynecological view point].

PubMed

Eicher, W

1976-12-02

Sexual dysfunctions are differentiated according to the following symptoms: libido dysfunction, orgasmic dysfunction, vaginism, algopareunia and polysymptomatic dysfunction. In the out-patient service for sexual and other psychosomatic disorders of the University of Heidelberg's Women's Hospital 90 women with libido dysfunction were treated with conflict-centered psychotherapy after exclusion of organic diseases which could explain the reduction of libido and after exclusion of a depression where the loss of libido is a regular symptom. The success-rate was 63%. It was attempted to reinforce the ego of the patient which enables him to experience his surroundings with less conflicts. Neurotic anxieties and symptoms are decreased and loos their importance so that the patient is able to handle his sexual disturbance. Among the psychosocial factors, i.e. focal causes, responsible for the libido dysfunction we found: In 48% of the cases the relationship between parents and children had been disturbed, which caused difficulties in the identification process (lack of father or mother, cool mother, divorce, borken home). Problems with the partners were found in 42%. 2/3 of these women had not grown up in intact families, which seems to predestinate difficulties in communication later on. Psychodynamically the loss of libido means sexual resistance which can lead to aversion or disgust. When there is no excitement the vasocongestion and lubrication do not take place: cohabitation pain (algopareunia) results. On the other hand the reduction of libido can also be a result of chronic algopareunia, i.e. secondary. Psychogenic bleedings ("aversion-bleeding") during or after intercourse occasionally occur in combination with algopareunia and lack of libido.

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.

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

PubMed Central

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

2016-01-01

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

Nonintubated thoracoscopic lung resection: a 3-year experience with 285 cases in a single institution

PubMed Central

Chen, Ke-Cheng; Cheng, Ya-Jung; Hung, Ming-Hui; Tseng, Yu-Ding

2012-01-01

Objective Tracheal intubation with one-lung ventilation is considered mandatory for thoracoscopic surgery. This study reported the experience of thoracoscopic lung resection without endotracheal intubation in a single institution. Methods From August 2009 through July 2012, 285 consecutive patients were treated by nonintubated thoracoscopic surgery using epidural anesthesia, intrathoracic vagal blockade, and sedation for lobectomy, segmentectomy, or wedge resection in a tertiary medical center. The feasibility and safety of this technique were evaluated. Results The final diagnosis for surgery were primary lung cancer in 159 patients (55.8%), metastatic lung cancer in 17 (6.0%), benign lung tumor in 104 (36.5%), and pneumothorax in 5 (1.8%). The operative methods consisted of conventional (83.2%) and needlescopic (16.8%) thoracoscopic surgery. The operative procedures included lobectomy in 137 patients (48.1%), wedge resection in 132 (46.3%), and segmentectomy in 16 (5.6%). Collapse of the operative lung and inhibition of coughing were satisfactory in most of the patients. Fourteen (4.9%) patients required conversion to tracheal intubation because of significant mediastinal movement [5], persistent hypoxemia [2], dense pleural adhesions [2], ineffective epidural anesthesia [2], bleeding [2], and tachypnea [1]. One patient (0.4%) was converted to thoracotomy because of bleeding. No mortality was noted in our patients. Conclusions Nonintubated thoracoscopic lung resection is technically feasible and safe in selected patients. It can be a valid alternative in managing patients with pulmonary lesions. PMID:22934136

Laparoscopic cholecystectomy: a report of 409 consecutive cases and its future outlook.

PubMed

Kano, N; Yamakawa, T; Ishikawa, Y; Sakai, S; Honda, H; Kasugai, H; Tachibana, A

1994-01-01

A retrospective study was conducted on 409 patients who underwent laparoscopic cholecystectomy at Teikyo University Hospital between May, 1990 and October, 1992. The operation had to be converted to an open cholecystectomy in ten of these patients because of uncontrollable bleeding from the cystic artery in one, venous bleeding due to portal hypertension in one, extensive adhesions of the omentum and the duodenum to the gallbladder in two, extensive adhesions around the gallbladder in four, and extensive adhesions between the gallbladder and the common bile duct (CBD) in two. The time taken to complete the procedure ranged from 30 to 235 min, the average time being 81 min, and the postoperative hospital stay ranged from 3 to 56 days, the average stay being 6.5 days. Eleven patients developed complications intra- or postoperatively: bile duct injury which became manifest after the operation and required laparotomy in three patients; injury to the right hemidiaphragm resulting in a right pneumothorax in one; periumbilical subcutaneous emphysema in one; mild bile leaks which resolved in a few days in two; and a severe bile leak which resolved after 6 days in one. The indications for laparoscopic cholecystectomy have widened with experience and now, CBD stones and a history of previous gastrectomy are no longer contraindications for laparoscopic cholecystectomy. Thus, it seems that laparoscopic cholecystectomy can be performed as safely as a standard cholecystectomy, provided the patients are selected properly and appropriate caution is exercised.

Questioning our Questions: Do frequently asked questions adequately cover the aspects of women's lives most affected by abnormal uterine bleeding? Opinions of women with abnormal uterine bleeding participating in focus group discussions

PubMed Central

Matteson, Kristen A.; Clark, Melissa A.

2010-01-01

Objectives: (1) To explore the effects on women's lives by heavy or irregular menstrual bleeding; (2) To examine whether aspects of women's lives most affected by heavy or irregular menstrual bleeding were adequately addressed by questions that are frequently used in clinical encounters and available questionnaires. Methods: We conducted four focus group sessions with a total of 25 English-speaking women who had reported abnormal uterine bleeding. Discussions included open-ended questions that pertained to bleeding, aspects of life affected by bleeding, and questions frequently used in clinical settings about bleeding and quality of life. Results: We identified five themes that reflected how women's lives were affected by heavy or irregular menstrual bleeding: irritation/inconvenience, bleeding-associated pain, self-consciousness about odor, social embarrassment, and ritual like behavior. Although women responded that the frequently used questions about bleeding and quality of life were important, they felt that the questions failed to go into enough depth to adequately characterize their experiences. Conclusions: Based on the themes identified in our focus group sessions, clinicians and researchers may need to change the questions used to capture “patient experience” with abnormal uterine bleeding more accurately. PMID:20437305

Implications of bleeding in acute coronary syndrome and percutaneous coronary intervention

PubMed Central

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

2011-01-01

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

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 endoscopy in pediatric gastrointestinal bleeding

PubMed Central

Franke, Markus; Geiß, Andrea; Greiner, Peter; Wellner, Ulrich; Richter-Schrag, Hans-Jürgen; Bausch, Dirk; Fischer, Andreas

2016-01-01

Background and study aims: Gastrointestinal bleeding in children and adolescents accounts for up to 20 % of referrals to gastroenterologists. Detailed management guidelines exist for gastrointestinal bleeding in adults, but they do not encompass children and adolescents. The aim of this study was to assess gastrointestinal bleeding in pediatric patients and to determine an investigative management algorithm accounting for the specifics of children and adolescents. Patients and methods: Pediatric patients with gastrointestinal bleeding admitted to our endoscopy unit from 2001 to 2009 (n = 154) were identified. Retrospective statistical and neural network analysis was used to assess outcome and to determine an investigative management algorithm. Results: The source of bleeding could be identified in 81 % (n = 124/154). Gastrointestinal bleeding was predominantly lower gastrointestinal bleeding (66 %, n = 101); upper gastrointestinal bleeding was much less common (14 %, n = 21). Hematochezia was observed in 94 % of the patients with lower gastrointestinal bleeding (n = 95 of 101). Hematemesis (67 %, n = 14 of 21) and melena (48 %, n = 10 of 21) were associated with upper gastrointestinal bleeding. The sensitivity and specificity of a neural network to predict lower gastrointestinal bleeding were 98 % and 63.6 %, respectively and to predict upper gastrointestinal bleeding were 75 % and 96 % respectively. The sensitivity and specifity of hematochezia alone to predict lower gastrointestinal bleeding were 94.2 % and 85.7 %, respectively. The sensitivity and specificity for hematemesis and melena to predict upper gastrointestinal bleeding were 82.6 % and 94 %, respectively. We then developed an investigative management algorithm based on the presence of hematochezia and hematemesis or melena. Conclusions: Hematochezia should prompt colonoscopy and hematemesis or melena should prompt esophagogastroduodenoscopy. If no source of bleeding is found, additional procedures are often non-diagnostic. PMID:27652293

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.

Acute bleeding after bone marrow transplantation (BMT)- incidence and effect on survival. A quantitative analysis in 1,402 patients.

PubMed

Nevo, S; Swan, V; Enger, C; Wojno, K J; Bitton, R; Shabooti, M; Fuller, A K; Jones, R J; Braine, H G; Vogelsang, G B

1998-02-15

Acute bleeding after bone marrow transplantation (BMT) was investigated in 1,402 patients receiving transplants at Johns Hopkins Hospital between January 1, 1986 and June 30, 1995. Bleeding categorization was based on daily scores of intensity used by the blood transfusion service. Moderate and severe episodes were analyzed for bleeding sites. Analysis of the cause of death and the interval of the bleeding episode to outcome endpoints was recorded. Survival estimates were computed for 1,353 BMT patients. The overall incidence was 34%. Minor bleeding was seen in 10.6%, moderate bleeding was seen in 11.3%, and severe bleeding was seen in 12% of all patients. Fourteen percent of patients had moderate or severe gastrointestinal hemorrhage, 6.4% had moderate or severe hemorrhagic cystitis, 2.8% had pulmonary hemorrhage, and 2% had intracranial hemorrhage. Sixty-one percent had 1 bleeding site and 34.4% had more than 1 site. Moderate and severe bleeding was more prevalent in allogeneic (31%) and unrelated patients (62.5%) compared with autologous patients (18.5%). Significant distribution of incidence was found among the different diagnoses, but not by disease status in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma. Bleeding was associated with significantly reduced survival in allogeneic, autologous, and unrelated BMT and in each disease category except multiple myeloma. Survival was correlated with the bleeding intensity, bleeding site, and the number of sites. Although close temporal association was evident to mortality, bleeding was recorded as the cause of death in only the minority of cases compared with other toxicities after BMT (graft-versus-host disease, infections, and preparative regimen toxicity). Acute bleeding is a common complication after BMT that is profoundly associated with morbidity and mortality. Although bleeding was not a direct cause of death in the majority of cases, it has a potential prognostic implication as a predictor of poor outcome in clinical assessment of patients after BMT.

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.

Symptom characteristics of depressive episodes prior to the onset of mania or hypomania.

PubMed

Pfennig, A; Ritter, P S; Höfler, M; Lieb, R; Bauer, M; Wittchen, H-U; Beesdo-Baum, K

2016-03-01

Depressive episodes are typically the initial presentation of bipolar disorder. The evidence as to whether depressive episodes occurring in persons who later convert to bipolar disorder are symptomatically distinct from episodes of unipolar depression remains controversial. As there are crucial differences in the therapeutic management, symptom profiles indicating subsequent bipolar conversion may aid in appropriate treatment. A representative community sample of originally N = 3021 adolescents and young adults aged 14-24 years at baseline was assessed up to four times over 10 years. Assessment of symptoms was conducted by clinically trained interviewers using the standardized M-CIDI. Symptom profiles of depressive episodes were compared via logistic regression between subjects that subsequently developed (hypo-)manic episodes (n = 35) or remained unipolar depressive (n = 659). Initial depression amongst prospective converters was characterized by significantly increased suicidality (odds ratio, OR = 2.31), higher rates of feelings of worthlessness and excessive guilt (OR = 2.52), complete loss of pleasure (OR = 2.53) and diurnal variation (OR = 4.30). No differences were found for hyperphagia, hypersomnia and psychomotor alterations. Findings suggest that the symptom profile of initial depressive episodes may be useful in the identification of subjects with an elevated risk for the subsequent conversion to bipolar disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Control of shock-wave boundary-layer interactions by bleed in supersonic mixed compression inlets

NASA Technical Reports Server (NTRS)

Fukuda, M. K.; Reshotko, E.; Hingst, W. R.

1975-01-01

An experimental investigation has been conducted to determine the effect of bleed region geometry and bleed rate on shock wave-boundary layer interactions in an axisymmetric, mixed-compression inlet at a Mach number of 2.5. The full realizable reduction in transformed form factor is obtained by bleeding off about half the incident boundary layer mass flow. Bleeding upstream or downstream of the shock-induced pressure rise is preferable to bleeding across the shock-induced pressure rise. Slanted holes are more effective than normal holes. Two different bleed hole sizes were tested without detectable difference in performance.

[Gastrointestinal bleeding in the elderly].

PubMed

Glaser, J

2014-08-01

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

Aminocaproic acid for the management of bleeding in patients on extracorporeal membrane oxygenation: Four adult case reports and a review of the literature.

PubMed

Buckley, Leo F; Reardon, David P; Camp, Phillip C; Weinhouse, Gerald L; Silver, David A; Couper, Gregory S; Connors, Jean M

2016-01-01

Extracorporeal membrane oxygenation (ECMO) is associated with a significant risk of bleeding and thrombosis. Despite high rates of bleeding and bleeding-related mortality in patients on ECMO, there is little evidence available to guide clinicians in the management of ECMO-associated bleeding. We report the use of aminocaproic acid in four patients with bleeding on ECMO and a review of the literature. High D-dimer levels and low fibrinogen levels suggested that an antifibrinolytic agent may be effective as an adjunct to control bleeding. After aminocaproic acid administration, bleeding was controlled in each patient as evidenced by clinical and laboratory parameters. One patient suffered a cardiac arrest and care was withdrawn. In patients on ECMO with evidence of fibrinolysis, aminocaproic acid may be an effective option to control bleeding and to stabilize clot formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of bleed-hole geometry and plenum pressure on three-dimensional shock-wave/boundary-layer/bleed interactions

NASA Technical Reports Server (NTRS)

Chyu, Wei J.; Rimlinger, Mark J.; Shih, Tom I.-P.

1993-01-01

A numerical study was performed to investigate 3D shock-wave/boundary-layer interactions on a flat plate with bleed through one or more circular holes that vent into a plenum. This study was focused on how bleed-hole geometry and pressure ratio across bleed holes affect the bleed rate and the physics of the flow in the vicinity of the holes. The aspects of the bleed-hole geometry investigated include angle of bleed hole and the number of bleed holes. The plenum/freestream pressure ratios investigated range from 0.3 to 1.7. This study is based on the ensemble-averaged, 'full compressible' Navier-Stokes (N-S) equations closed by the Baldwin-Lomax algebraic turbulence model. Solutions to the ensemble-averaged N-S equations were obtained by an implicit finite-volume method using the partially-split, two-factored algorithm of Steger on an overlapping Chimera grid.

Control of shock wave-boundary layer interactions by bleed in supersonic mixed compression inlets

NASA Technical Reports Server (NTRS)

Fukuda, M. K.; Hingst, W. G.; Reshotko, E.

1975-01-01

An experimental investigation was conducted to determine the effect of bleed on a shock wave-boundary layer interaction in an axisymmetric mixed-compression supersonic inlet. The inlet was designed for a free-stream Mach number of 2.50 with 60-percent supersonic internal area contraction. The experiment was conducted in the NASA Lewis Research Center 10-Foot Supersonic Wind Tunnel. The effects of bleed amount and bleed geometry on the boundary layer after a shock wave-boundary layer interaction were studied. The effect of bleed on the transformed form factor is such that the full realizable reduction is obtained by bleeding of a mass flow equal to about one-half of the incident boundary layer mass flow. More bleeding does not yield further reduction. Bleeding upstream or downstream of the shock-induced pressure rise is preferable to bleeding across the shock-induced pressure rise.

Effect of nabumetone and aspirin on colonic mucosal bleeding time.

PubMed

Basson, M D; Panzini, L; Palmer, R H

2001-04-01

The management of patients taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) who require colonoscopy remains controversial because of concerns over bleeding after biopsy or polypectomy. To determine whether patients using the NSAID nabumetone, a non-acidic prodrug with mixed activity against cyclooxygenase-1 (COX-1) and COX-2, exhibited prolonged mucosal bleeding times and how this might compare with mucosal bleeding times in patients using aspirin. We assessed triplicate mucosal bleeding times in patients undergoing screening flexible sigmoidoscopy. We compared 90 patients who had taken no aspirin or NSAIDs within the previous 2 weeks, to 60 patients who had received nabumetone 1 g b.d. by mouth for the previous 2 weeks, and 30 patients who had taken 325 mg aspirin daily for the previous 2 weeks. In each case, the investigator performing the study was blinded to the patient's medication. Mucosal bleeding times did not differ significantly among control or nabumetone-using patients. However, the patients receiving aspirin exhibited significant prolongation. Mucosal bleeding time correlated statistically significantly, but weakly, with skin bleeding time. Nabumetone does not appear to prolong mucosal bleeding time after mucosal pinch biopsy, and skin bleeding time does not reliably screen for prolonged mucosal bleeding time.

Endoscopic treatment and risk factors of postoperative anastomotic bleeding after gastrectomy for gastric cancer.

PubMed

Kim, Ki-Han; Kim, Min-Chan; Jung, Ghap-Joong; Jang, Jin-Seok; Choi, Seok-Ryeol

2012-01-01

Anastomotic leakage, bleeding, and stricture are major complications after gastrectomy. Of these complications, postoperative anastomotic bleeding is relatively rare, but lethal if not treated immediately. Of 2031 patients with gastric cancer who underwent radical gastrectomy (R0 resection) between January 2002 and December 2010, postoperative anastomotic bleeding was observed in 7 patients. The clinicopathological features, postoperative outcomes such as surgical procedures, bleeding sites and, methods used to achieve hemostasis, and the risk factors of anastomotic bleeding of these 7 patients were analyzed. Of the 2031 patients, 1613 and 418 underwent distal and total gastrectomy, respectively. The bleeding sites were as follows: Billroth-I anastomosis using a circular stapler (n = 1), Billroth-II anastomosis by manual suture (n = 5), and esophagojejunostomy using a circular stapler (n = 1). All patients were treated with endoscopic clipping or epinephrine injection. There was no further endoscopic intervention or reoperation for anastomotic bleeding. Postoperative anastomotic bleeding is an infrequent but potentially life-threatening complication. Scrupulous surgical procedures are essential for the prevention of postoperative bleeding, and endoscopy was useful for both the confirmation of bleeding and therapeutic intervention. Copyright © 2012 Surgical Associates Ltd. All rights reserved.

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

PubMed

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

2016-04-01

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

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.

Long-term bleeding risk prediction in 'real world' patients with atrial fibrillation: Comparison of the HAS-BLED and ABC-Bleeding risk scores. The Murcia Atrial Fibrillation Project.

PubMed

Esteve-Pastor, María Asunción; Rivera-Caravaca, José Miguel; Roldan, Vanessa; Vicente, Vicente; Valdés, Mariano; Marín, Francisco; Lip, Gregory Y H

2017-10-05

Risk scores in patients with atrial fibrillation (AF) based on clinical factors alone generally have only modest predictive value for predicting high risk patients that sustain events. Biomarkers might be an attractive prognostic tool to improve bleeding risk prediction. The new ABC-Bleeding score performed better than HAS-BLED score in a clinical trial cohort but has not been externally validated. The aim of this study was to analyze the predictive performance of the ABC-Bleeding score compared to HAS-BLED score in an independent "real-world" anticoagulated AF patients with long-term follow-up. We enrolled 1,120 patients stable on vitamin K antagonist treatment. The HAS-BLED and ABC-Bleeding scores were quantified. Predictive values were compared by c-indexes, IDI, NRI, as well as decision curve analysis (DCA). Median HAS-BLED score was 2 (IQR 2-3) and median ABC-Bleeding was 16.5 (IQR 14.3-18.6). After 6.5 years of follow-up, 207 (2.84 %/year) patients had major bleeding events, of which 65 (0.89 %/year) had intracranial haemorrhage (ICH) and 85 (1.17 %/year) had gastrointestinal bleeding events (GIB). The c-index of HAS-BLED was significantly higher than ABC-Bleeding for major bleeding (0.583 vs 0.518; p=0.025), GIB (0.596 vs 0.519; p=0.017) and for the composite of ICH-GIB (0.593 vs 0.527; p=0.030). NRI showed a significant negative reclassification for major bleeding and for the composite of ICH-GIB with the ABC-Bleeding score compared to HAS-BLED. Using DCAs, the use of HAS-BLED score gave an approximate net benefit of 4 % over the ABC-Bleeding score. In conclusion, in the first "real-world" validation of the ABC-Bleeding score, HAS-BLED performed significantly better than the ABC-Bleeding score in predicting major bleeding, GIB and the composite of GIB and ICH.

How to describe disordered structures

PubMed Central

Nishio, Kengo; Miyazaki, Takehide

2016-01-01

Disordered structures such as liquids and glasses, grains and foams, galaxies, etc. are often represented as polyhedral tilings. Characterizing the associated polyhedral tiling is a promising strategy to understand the disordered structure. However, since a variety of polyhedra are arranged in complex ways, it is challenging to describe what polyhedra are tiled in what way. Here, to solve this problem, we create the theory of how the polyhedra are tiled. We first formulate an algorithm to convert a polyhedron into a codeword that instructs how to construct the polyhedron from its building-block polygons. By generalizing the method to polyhedral tilings, we describe the arrangements of polyhedra. Our theory allows us to characterize polyhedral tilings, and thereby paves the way to study from short- to long-range order of disordered structures in a systematic way. PMID:27064833