Spontaneous omental bleeding in a 20-year old patient with hemophilia A

2016 ◽  
Vol 36 (S 02) ◽  
pp. S22-S24 ◽  
Author(s):  
F. Meyer ◽  
C. Wybranski ◽  
C. J. Bruns ◽  
O. Jannasch ◽  
V. Aumann ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Bleeding Event ◽  
Rare Event ◽  
Coagulation Factors ◽  
Emergency Laparotomy ◽  
Bleeding Disorders ◽  
Radiologic Imaging ◽  
Omentum Majus ◽  
Omental Bleeding ◽  
Intraabdominal Hemorrhage

SummarySpontaneous 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.

scholarly journals Parvovirus 4 in Individuals with Severe Hemophilia A and Matched Control Group

2021 ◽  
Author(s):  
Sanaz Asiyabi ◽  
Seyed Mahdi Marashi ◽  
Rouhollah Vahabpour ◽  
Ahmad Nejati ◽  
Alireza Azizi-Saraji ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Viral Infections ◽  
Coagulation Factors ◽  
Von Willebrand Disease ◽  
Control Group ◽  
Bleeding Disorders ◽  
Severe Hemophilia ◽  
Standard Regimen ◽  
Current Case ◽  
Worldwide Distribution

Background: Hemophilia is a well-known bleeding disorder with worldwide distribution. Replacement therapy, using plasma-derived or recombinant coagulation factors, comprises a gold standard regimen for the treatment. Regardless of the advancements made in viral inactivation methods in the production of plasma-derived coagulation factors, the possibility of transmission of new viral infections remained as a noticeable concern yet. The aim of the current study was to investigate the status of parvovirus 4 (PARV4) in severe hemophilia A, von Willebrand disease (vWD), and healthy control. Materials and Methods: In the current case-control study, 76 patients with hemophilia and vWD and 60 individuals from their family members entered the study. Nested PCR used to determine the presence of PARV4 in study subjects (76 cases). To characterize the PARV4 genotype, positive samples subjected to sequencing and phylogenetic analysis. Results: PARV4 genome detected in 11 (14.47%) patients with bleeding disorders. Among whom, nine patients (14.75%) were with severe hemophilia A and two (13.33%) patients with vWD. Only five healthy controls (8.33%) were positive for PARV4. All PARV4 sequences were found to be genotype 1. Conclusion: PARV4 infection in patients with hemophilia and vWD was higher than the control group. While detection of PARV4 DNA in patients with bleeding disorders may not necessarily reflect a clinical urgency, future investigations are needed to define the clinical significance of PARV4. It seems the detection of the virus immune signature of PARV4 infection, particularly in the context of acute and persistent infections, needs to focus on cellular and tissue targets.

Transient Ischemic Attack in a Hemophilia Patient with Severe Preeclampsia after Preoperative Administration of Tranexamic Acid and Factor VIII Replacement for Cesarean Section

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
D’Onofrio JD ◽  
◽  
Hoffman CR ◽  
Goldberg SF ◽  
◽  
...  
Keyword(s):  
Tranexamic Acid ◽  
Transient Ischemic Attack ◽  
Hemophilia A ◽  
Coagulation Factors ◽  
Background Information ◽  
Preoperative Administration ◽  
Increased Risk ◽  
Pharmacologic Prophylaxis ◽  
Ischemic Attack ◽  
Von Willebrand

Hemophilia A in females accounts for few cases due to hemophilia A and B having X-linked recessive inheritance patterns. Hemostatic changes in pregnancy include an increase in coagulation factors and von Willebrand activity, placing hemophilia patients at an increased risk for Postpartum Hemorrhage (PPH). General recommendations include considering pharmacologic prophylaxis, including tranexamic acid and factor replacement when necessary. The ultimate goal is to prevent uncontrolled bleeding during vaginal or operative delivery. Benefits of prophylactic therapies must be weighed with relevant risk profiles of each intervention. We present a case where a parturient with hemophilia prophylactically treated with TXA and FVIII experienced a transient ischemic attack. We discuss the background information known regarding tranexamic acid and factor replacement, and the subsequent recommendations for their use in this patient population. We consider recommendations to expand the multidisciplinary team incorporated in the assessment and planning for the peripartum care of such a patient.

scholarly journals The Relationship between Hemophilia A Severity and Hemophilia Activities List

2021 ◽  
Author(s):  
Faizal Muhammad
Keyword(s):  
High Risk ◽  
Hemophilia A ◽  
Bleeding Event ◽  
Clinical Manifestations ◽  
Self Care ◽  
Daily Activities ◽  
Clotting Factors ◽  
Household Tasks ◽  
The Relationship ◽  
Lying Down

Hemophilia is a hereditary bleeding disorder due to clotting factors deficiency. Its clinical manifestations including spontaneous and recurrent joints and muscle bleeding. Thus, hemophilia can limit the patients’ daily activities. This study aims to assess the relationship of hemophilia A severity on daily activities and the Hemophilia Activities List (HAL). The research subjects were thirty men with hemophilia A aged 18 years old or older who went to the Hematology-Oncology Clinic of Dr. Moewardi General Hospital during February - September 2020. Standardized seven aspects of routine activities with high-risk for bleeding event were assessed using the HAL questionnaire including lying down/ sitting/ kneeling/ standing, functions of the legs, functions of the arms, use of transportation, self-care, household tasks, leisure activities and sports. Based on the frequency of activity difficulty due to hemophilia A, each average score of HAL aspect was categorized into never (100% - 76%); rarely (75% - 51%), sometimes (50% - 26%), and impossible (25% - 0%). Based on Factor VIII level, hemophilia A severity was categorized into mild, moderate, and severe. Spearman’s correlation test was used for statistical analysis. The result showed significant correlation (p < 0.05) on five aspects, including lying down/ sitting/ kneeling/ standing, functions of the legs, use of transportation, self-care, and household tasks. The aspects of arms functions and leisure sports activities were not significantly correlated (p > 0.05). Nevertheless, these two aspects showed positive sufficient (r = 0.330) and weak (r = 0.177) correlation respectively. Joint and muscle bleeding are an undeniable pathological event in hemophilia patients. Hemophilia A severity positively correlates with the bleeding event frequency in the essential routine musculoskeletal activities. According to the HAL questionnaire, it needs to be a concern for clinicians and patient education to prevent bleeding in any high-risk musculoskeletal activities.

scholarly journals In Hemophilia Α Plasma Treated with Emicizumab, Factor IXa in Activated Prothrombin Complex Concentrates Is the Dominant Contributor to Enhanced Thrombin Generation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Dougald Monroe ◽  
Mirella Ezban ◽  
Maureane Hoffman
Keyword(s):  
Thrombin Generation ◽  
Hemophilia A ◽  
State Level ◽  
Peak Level ◽  
Coagulation Factors ◽  
Major Effect ◽  
Factor Ix ◽  
Factor X ◽  
Factor Ixa ◽  
Activated Prothrombin Complex Concentrates

Background. Recently a novel bifunctional antibody (emicizumab) that binds both factor IXa and factor X has been used to treat hemophilia A. Emicizumab has proven remarkably effective as a prophylactic treatment for hemophilia A; however there are patients that still experience bleeding. An approach to treating this bleeding in hemophilia A patients with inhibitors is to give an activated prothrombin complex concentrate (APCC; FEIBA) (disfavored in NHF MASAC #255). APCC contains a number of coaguation factors including prothrombin, factor X (FX), and factor IX (FIX). APCC also contains activated factor X (FXa) and factor IX (FIXa). Previous work has shown that when APCCs are added to hemophilia A plasma containing emicizumab there is a significant increase in thrombin generation [J Thromb Haemost 2018;16:1580-1591]. The goal of this work was to study thrombin generation in hemophilia A plasma with emicizumab and to examine the role of the zymogen and activated components of an APCC in the increased thrombin generation. Methods. In hemophilia A plasma, thrombin generation assays were done using 100 µM lipid and 420 µM Z-Gly-Gly-Arg-AMC with or without emicizumab at 55 µg/mL which is the clinical steady state level. The reactions were initiated with low (1 pM) tissue factor (TF). The components of APCC were studied at concentrations that should mimic the levels seen in the plasma of a patient given a dose of 50 U/kg: prothrombin 1800 nM; FX 130 nM; FIX 90 nM; and FIXa 0.4 nM. Results. When initiated with low TF, hemophilia A plasma alone had essentially no thrombin generation. As expected, adding emicizumab enhanced thrombin generation. The addition of zymogen coagulation factors, prothrombin, FIX, and FX, separately or together gave a small increase in thrombin generation. However, addition of FIXa to emicizumab gave a large increase in peak thrombin. In hemophilia A plasma with emicizumab and FIXa, addition of prothrombin further increased thrombin generation and specifically increased the peak level of thrombin. Further addition of FX or FIX, separately or together, only minimally increased thrombin generation. Discussion. The strong contribution of factor IXa to the effects of APCCs on thrombin generation in hemophilia A plasma depends on the presence of emicizumab. In the absence of emicizumab, a study of the individual components of APCC showed that a combination of FXa and prothrombin at levels found in APCCs had the major effect on thrombin generation [Haemophilia. 2016;22:615-24]. That study found that FIXa did not increase thrombin generation. However, in the presence of emicizumab, despite the weak solution phase affinity of the bifunctional antibody for FIXa, small amounts of FIXa were the most significant contributor to thrombin generation. Disclosures Monroe: Novo Nordisk:Research Funding.Ezban:Novo Nordisk:Current Employment.Hoffman:Novo Nordisk:Research Funding.

scholarly journals A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle

Blood ◽  
2020 ◽  
Vol 136 (7) ◽  
pp. 898-908
Author(s):  
Xuejie Chen ◽  
Caihong Li ◽  
Da-Yun Jin ◽  
Brian Ingram ◽  
Zhenyu Hao ◽  
...  
Keyword(s):  
Vitamin K ◽  
High Throughput ◽  
High Throughput Screening ◽  
Molecular Mechanisms ◽  
Coagulation Factors ◽  
Bleeding Complications ◽  
Bleeding Disorders ◽  
Drug Induced ◽  
Vitamin K Cycle ◽  
Established Cell

Abstract Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding of obvious cause are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood, which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that affect the biosynthesis of active vitamin K–dependent (VKD) coagulation factors with possible adverse off-target results. The National Institutes of Health (NIH) Clinical Collection (NCC) library containing 727 drugs was screened, and 9 drugs were identified, including the most commonly prescribed anticoagulant warfarin. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), whereas idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other 3 drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs that target VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based, high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.

Coagulation (Hemostasis and Thrombosis)

2012 ◽  
Author(s):  
Rajiv K. Pruthi
Keyword(s):  
Risk Factors ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Fibrin Clot ◽  
Coagulation System ◽  
Bleeding Disorders ◽  
Hemostatic System ◽  
Blood Clots ◽  
Anticoagulant System ◽  
Plug Formation

The coagulation system has 2 essential functions: to maintain hemostasis and to prevent and limit thrombosis. The procoagulant component of the hemostatic system prevents and controls hemorrhage. Vascular injury results in activation of hemostasis, which consists of vasospasm, platelet plug formation (platelet activation, adhesion, and aggregation), and fibrin clot formation (by activation of coagulation factors in the procoagulant system). The anticoagulant system prevents excessive formation of blood clots, and the fibrinolytic system breaks down and remodels blood clots. Quantitative abnormalities (deficiencies) and qualitative abnormalities of platelets and coagulation factors lead to bleeding disorders, whereas deficiencies of the anticoagulant system are risk factors for thrombosis. Common disorders of hemostasis and thrombosis are reviewed.

Significance of Factor VIII Inhibitors by ELISA in Patients with Hemophilia A.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3398-3398
Author(s):  
Jamie R Brewer ◽  
Sandra Harris ◽  
David Green ◽  
Anaadriana Zakarija
Keyword(s):  
Factor Viii ◽  
Functional Status ◽  
Hemophilia A ◽  
Statistical Significance ◽  
Bleeding Event ◽  
Clinical Information ◽  
Prior History ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viii Inhibitor

Abstract Background: The Bethesda assay traditionally has been used to detect Factor VIII inhibitors in patients with Hemophilia A, but recent evidence suggests that it is not sensitive to all inhibitors, particularly non-inhibitory or low-titer antibodies. Methods: Patients with Hemophilia A without prior history of inhibitor were recruited. Study questionnaire collected demographic and clinical information, bleeding history and factor usage over the preceding 6 months. Functional status was assessed by the Hemophilia Activities List (HAL). Factor VIII inhibitor was assessed by both the Bethesda assay and Factor VIII inhibitor ELISA (GTI Diagnostics). T-test was performed to assess statistical significance. Results: Data is available for 26 patients, 19 severe, 2 moderate and 7 mild. All subjects had a negative Bethesda assay, but 10 (39%) had a detectable inhibitor by ELISA. 9/10 inhibitor patients had severe hemophilia, while one had mild hemophilia. In severe hemophiliacs, there were no differences in age, HIV status, CD4 count, Hepatitis C positivity or viral load between those with and those without inhibitors. Inhibitors were more frequent in those using plasma-derived concentrates 4/5 (80%), than in those using recombinant products 6/14 (43%), p=0.15. There was no difference in bleeding frequency or functional status in patients with or without inhibitors, although those with inhibitors had more frequent infusions.(Table). In patients on prophylaxis, those with inhibitors had a higher bleeding frequency compared to those without an inhibitor, (p =0.2). 11 patients were not on prophylaxis and had a higher bleeding frequency (p = 0.02) than patients on prophylaxis irrespective of inhibitor presence. However those with inhibitors required more factor doses per bleed compared to those without an inhibitor (4.4 vs. 1.5, p=0.16) even though the mean factor dose was the same (25.3 units/kg vs 25.2 units/kg). Conclusions: The Factor VIII ELISA assay detected inhibitors in 39 % of Hemophilia A patients who had undetectable inhibitors by standard Bethesda assay. This data suggests that these inhibitors may be clinically relevant, given that inhibitor patients who are not on prophylaxis require more doses of factor per bleeding event. Further study is necessary to determine mechanism and clinical significance of these Factor VIII inhibitors. Table. Characteristics of severe hemophilia patients with and without ELISA Factor VIII inhibitor All severe (n=19) Inhibitor (n=9) No inhibitor (n=10) Age 43.4 40.8 45.7 Plasma-derived factor 5 (26.3%) 4 (44.4%) 1 (10%) Total bleeds/6 months 8.6 8.1 9.0 Muscle bleeds/6 months 1.3 0.8 1.7 Joint bleeds/6 months 7.3 7.3 7.3 Factor infusions/6 months 50.9 57.2 45.2 On prophylaxis 8 (42%) 4 (44.4%) 4 (40%) Total bleeds/6 months 4.3 5.8 2.8 Not on prophylaxis 11 (58%) 5 (55.6%) 6 (60%) Total bleeds/6 months 11.7 10 13.2 Factor doses/bleed 2.9 4.4 1.5

scholarly journals Tolerogenic properties of the Fc portion of IgG and its relevance to the treatment and management of hemophilia

Blood ◽  
2018 ◽  
Vol 131 (20) ◽  
pp. 2205-2214 ◽  
Author(s):  
Richard S. Blumberg ◽  
David Lillicrap ◽  
Keyword(s):  
Immune Responses ◽  
Recombinant Proteins ◽  
Fusion Proteins ◽  
Hemophilia A ◽  
Coagulation Factors ◽  
Therapeutic Agents ◽  
On Demand ◽  
Genetic Deficiency ◽  
The Impact ◽  
Uncontrolled Bleeding

Abstract Hemophilia, or inherited genetic deficiencies in coagulation factors, results in uncontrolled bleeding requiring replacement therapy with recombinant proteins given preventively or on demand. However, a major problem with these approaches is the potential for development of immune responses to the administered proteins due to the underlying genetic deficiency of the factor(s) throughout life. As such, there is great interest in developing strategies that avoid immunogenicity and induce immune tolerance. Recently, recombinant factor VIII (rFVIII) and rFIX fused to the crystallizable fragment (Fc) domain of immunoglobulin G (IgG) have been developed as therapeutic agents for hemophilia A and B, respectively. Although it is well known that the possession of an Fc domain confers IgG’s longer-lasting circulating half-life, it is not generally appreciated that the Fc domain also confers immunoregulatory properties that are associated with the induction of tolerance. Here, we review some of the latest advances in our understanding of the tolerogenic abilities of IgG Fc and the impact of Fc-fusion proteins of rFVIII on the treatment of hemophilia.

scholarly journals CIRCUMCISION IN MALES WITH BLEEDING DISORDERS

2013 ◽  
Vol 5 (1) ◽  
pp. e2013004 ◽  
Author(s):  
Hassan Mansouritorghabeh ◽  
Abdollah Banihashem ◽  
Alireza Modaresi ◽  
Lida Manavifar
Keyword(s):  
Medical Center ◽  
Invasive Procedure ◽  
Normal Subjects ◽  
Coagulation Factors ◽  
Bleeding Disorders ◽  
Coagulation Therapy ◽  
North Eastern ◽  
Bleeding Episodes ◽  
Question Form ◽  
North Eastern Part

Introduction: Male circumcision practice is an invasive procedure that is using worldwide. It makes challenges to haemostatic system and its possible haemorrhagic side effects are more serious in bleeding individuals than normal subjects. In most cases, it can be complete controlled using infusion of appropriate amount of coagulation factors before and post circumcision.Aim: We aim to documentation type of coagulation therapy and post circumcision practice haemorrhagic presentation among 463 bleeder males of both common and rare bleeding disorders in north eastern part of country.Methods: We retrospectively gathered information using evaluation medical records in 3 major hospitals during last 15 years and list of patients with bleeding disorders that obtained from haemophilia center. Also a call phone established for each bleeder person to complete data and updating of them. The survey took time from Sep 2009- Mar 2011. The designed question form included data on doing circumcision or not? types of treatment before and post the procedure and occurrence of bleeding episodes after the surgery.Results: Overall among 424 cases with various common and rare bleeding disorders who had circumcised, 239 cases (56.3%) had passed the procedure with bleeding experience, while 185 cases (43.7%) had passed it successfully and without noticeable bleeding experience. The types of coagulation therapy in each group have been cited.Conclusion: The circumcision practice in unequipped medical center for bleeder ones may make challenges for them and medical services. Also it needed supervision of expert haematologist for adjusting treatment to ensure control of unwanted bleeding. 

scholarly journals How we choose factor VIII to treat hemophilia

Blood ◽  
2012 ◽  
Vol 119 (18) ◽  
pp. 4108-4114 ◽  
Author(s):  
Pier Mannuccio Mannucci ◽  
Maria Elisa Mancuso ◽  
Elena Santagostino
Keyword(s):  
Factor Viii ◽  
Replacement Therapy ◽  
Hemophilia A ◽  
Recombinant Dna ◽  
Tolerance Induction ◽  
Coagulation Factors ◽  
Pathogen Transmission ◽  
Recombinant Dna Technology ◽  
Mammalian Cell Cultures ◽  
Main Determinants

AbstractIn high-income countries, the large availability of coagulation factors for replacement therapy of patients with hemophilia A has raised the life expectancy of these lifelong bleeders to that of males from the general population. The practicing clinician is offered a multitude of choices among several commercial brands of factor VIII extracted from human plasma or engineered from mammalian cell cultures by means of recombinant DNA technology. This article has the goal to offer our opinions on how to choose among the different products, that we consider interchangeable relevant to their clinical efficacy in the control of bleeding and safety from pathogen transmission. Hence, the main determinants of our choices are price and the risk of occurrence of factor VIII inhibitory alloantibodies. With this as background, we present the rationale underlying the choices for different categories of patients with severe hemophilia A: previously untreated patients, multiply treated patients, and patients undergoing immune tolerance induction with large doses of factor VIII to eradicate inhibitors. Mention is also made to the possible strategies that should be implemented to make available coagulation factors for replacement therapy in developing countries.

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