scholarly journals How I treat patients with inherited bleeding disorders who need anticoagulant therapy

Blood ◽  
2016 ◽  
Vol 128 (2) ◽  
pp. 178-184 ◽  
Author(s):  
Karlyn Martin ◽  
Nigel S. Key
Keyword(s):  
Atrial Fibrillation ◽  
Hemophilia A ◽  
Thrombotic Event ◽  
Management Strategies ◽  
Von Willebrand Disease ◽  
Bleeding Disorders ◽  
Atherothrombotic Disease ◽  
Risk Of Hemorrhage ◽  
Evidence Based Guidelines ◽  
Von Willebrand

Abstract Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we review atherothrombotic disease, venous thrombotic disease, and atrial fibrillation in patients with inherited bleeding disorders, and discuss strategies for using anticoagulants in this population using cases to illustrate these considerations.

scholarly journals Novel therapeutics for hemophilia and other bleeding disorders

Blood ◽  
2018 ◽  
Vol 132 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Michael U. Callaghan ◽  
Robert Sidonio ◽  
Steven W. Pipe
Keyword(s):  
Factor Viii ◽  
New Technologies ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Bleeding Disorders ◽  
Routes Of Administration ◽  
New Approaches ◽  
Dosing Regimens ◽  
Von Willebrand

Abstract Hemophilia and von Willebrand disease are the most common congenital bleeding disorders. Treatment of these disorders has focused on replacement of the missing coagulation factor to prevent or treat bleeding. New technologies and insights into hemostasis have driven the development of many promising new therapies for hemophilia and von Willebrand disease. Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase 3 trial in people with hemophilia A and inhibitors. Tissue factor pathway inhibitor, the protein C/S system, and antithrombin are targets of novel compounds in development to alter the hemostatic balance and new approaches using modified factor VIII molecules are being tested for prevention and eradication of inhibitor antibodies in hemophilia A. The first recombinant von Willebrand factor (VWF) product has been approved and has unique VWF multimer content and does not contain factor VIII. These new approaches may offer better routes of administration, improved dosing regimens, and better efficacy for prevention and treatment of bleeding in congenital bleeding disorders.

Congenital Bleeding Disorders

Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 559-574 ◽  
Author(s):  
Margaret E. Rick ◽  
Christopher E. Walsh ◽  
Nigel S. Key
Keyword(s):  
Gene Transfer ◽  
Immune Tolerance ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Von Willebrand Disease ◽  
Bleeding Disorders ◽  
Immune Tolerance Induction ◽  
Inhibitor Development ◽  
History Of ◽  
Von Willebrand

Abstract Both clinical and basic problems related to the congenital bleeding disorders continue to confront hematologists. On the forefront are efforts to bring genetic correction of the more common bleeding disorders such as hemophilia A to the clinic in a safe and accessible manner. A second issue, particularly for patients with hemophilia, is the development of inhibitors—questions of how they arise and how to prevent and treat these problems that confound otherwise very successful replacement therapy and allow patients to maintain normal lifestyles. A third issue is the continuing question of diagnosis and management of von Willebrand disease, the most common congenital bleeding disorder, especially in individuals who have borderline laboratory values, but have a history of clinical bleeding. In Section I, Dr. Christopher Walsh discusses general principles of effective gene transfer for the hemophilias, specific information about viral vectors and non-viral gene transfer, and alternative target tissues for factor VIII and factor IX production. He highlights information about the immune response to gene transfer and reviews data from the hemophilia gene transfer trials to date. The future prospects for newer methods of therapy such as RNA repair and the use of gene-modified circulating endothelial progenitors are presented as possible alternatives to the more traditional gene therapy approaches. In Section II, Dr. Nigel Key focuses on inhibitor development in patients with hemophilia A. He reviews the progress in our understanding of the risk factors and presents newer information about the immunobiology of inhibitor development. He discusses the natural history of these inhibitors and the screening, laboratory diagnosis, and treatment, including the use of different modalities for the treatment of acute bleeding episodes. Dr. Key also presents information about the eradication of inhibitors by immune tolerance induction and reviews recent information from the international registries regarding the status and success of immune tolerance induction. In Section III, Dr. Margaret Rick discusses the diagnosis, classification, and management of von Willebrand disease. Attention is given to the difficulty of diagnosis in patients with mild bleeding histories and borderline laboratory test results for von Willebrand factor. She presents the value of different laboratory assays for both diagnosis and classification, and she relates the classification of von Willebrand disease to the choice of treatment and to the known genetic mutations. Practical issues of diagnosis and treatment, including clinical cases, will be presented.

Spectrum of Inherited Bleeding Disorders in Indians

2005 ◽  
Vol 11 (3) ◽  
pp. 325-330 ◽  
Author(s):  
Meenal Gupta ◽  
Maitreyee Bhattacharyya ◽  
V. P. Choudhry ◽  
Renu Saxena
Keyword(s):  
Platelet Function ◽  
Indian Population ◽  
Hemophilia A ◽  
Ethnic Origin ◽  
Von Willebrand Disease ◽  
Hemorrhagic Disease ◽  
Bleeding Disorders ◽  
White Population ◽  
Hemorrhagic Disorders ◽  
Von Willebrand

The incidence of hereditary hemorrhagic disorders may vary according to the country and ethnic origin. Von Willebrand disease has emerged as the most common hereditary hemorrhagic disease in the industrialized world. In this series of 966 patients diagnosed to have inherited bleeding disorders, hemophilia A was the most common and was seen in 410 (42.4%) of the patients followed by platelet function defects seen in 380 (39.4%) of the patients. It is thus concluded that, similar to the white population, hemophilia A remains the most common bleeding disorder in the Indian population, although this is closely followed by platelet function defects in India, which are quite rare in whites. Von Willebrand disease is relatively rare in the Indian population.

Risk and Management of Intracerebral Hemorrhage in Patients with Bleeding Disorders

2022 ◽  
Author(s):  
Akbar Dorgalaleh ◽  
Yadolah Farshi ◽  
Kamand Haeri ◽  
Omid Baradarian Ghanbari ◽  
Abbas Ahmadi
Keyword(s):  
Risk Factors ◽  
Intracerebral Hemorrhage ◽  
Platelet Function ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Vacuum Extraction ◽  
Bleeding Disorders ◽  
Platelet Function Disorders ◽  
Von Willebrand

AbstractIntracerebral hemorrhage (ICH) is the most dreaded complication, and the main cause of death, in patients with congenital bleeding disorders. ICH can occur in all congenital bleeding disorders, ranging from mild, like some platelet function disorders, to severe disorders such as hemophilia A, which can cause catastrophic hemorrhage. While extremely rare in mild bleeding disorders, ICH is common in severe coagulation factor (F) XIII deficiency. ICH can be spontaneous or trauma-related. Spontaneous ICH occurs more often in adults, while trauma-related ICH is more prevalent in children. Risk factors that can affect the occurrence of ICH include the type of bleeding disorder and its severity, genotype and genetic polymorphisms, type of delivery, and sports and other activities. Patients with hemophilia A; afibrinogenemia; FXIII, FX, and FVII deficiencies; and type 3 von Willebrand disease are more susceptible than those with mild platelet function disorders, FV, FXI, combined FV–FVIII deficiencies, and type 1 von Willebrand disease. Generally, the more severe the disorder, the more likely the occurrence of ICH. Contact sports and activities can provoke ICH, while safe and noncontact sports present more benefit than danger. An important risk factor is stressful delivery, whether it is prolonged or by vacuum extraction. These should be avoided in patients with congenital bleeding disorders. Familiarity with all risk factors of ICH can help prevent occurrence of this diathesis and reduce related morbidity and mortality.

scholarly journals Catheter Ablation for Atrial Fibrillation in Patients with Hemophilia or von Willebrand Disease

TH Open ◽  
2019 ◽  
Vol 03 (04) ◽  
pp. e335-e339
Author(s):  
Paul R. van der Valk ◽  
Eveline P. Mauser-Bunschoten ◽  
Jeroen F. van der Heijden ◽  
Roger E. G. Schutgens
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Early Mobilization ◽  
Von Willebrand Disease ◽  
Treatment Center ◽  
Clotting Factor ◽  
Low Molecular Weight ◽  
Bleeding Disorders ◽  
Von Willebrand

Abstract Background Management of atrial fibrillation (AF) is complex in patients with bleeding disorders. Catheter ablation such as pulmonary vein isolation (PVI) has been suggested in cases with bleeding disorders. However, data on safety are missing. This report describes the outcome of PVI in patients with bleeding disorders. Methods A retrospective study in our hemophilia treatment center of patients who underwent a PVI in 2014 to 2018. PVI was done according to local protocol. Clotting factor was given periprocedural. Postprocedural anticoagulation was given for at least 4 weeks, with clotting factor suppletion if needed to maintain factor VIII (FVIII) levels >0.20 IU/mL. Results and Discussion Five patients with hemophilia and one with von Willebrand disease were included. Eight PVIs were performed. Target FVIII levels (>0.80 IU/mL) were met before the procedure. Postprocedural anticoagulation was given: vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC) dabigatran. All patients obtained long-term sinus rhythm, in two patients after a second PVI. However, late recurrent AF occurred in one patient after 42 months. A notable incidence of groin bleeds was observed: two of eight interventions (25%) compared with 0.9% in the general population. Bleeding seemed to be related to agitation, early mobilization, and bridging of VKA with low molecular weight heparin (LMWH). No relevant bleeding was observed when on DOAC therapy. Conclusion PVI seems to be effective in the case of bleeding disorders. To reduce the groin bleeds agitation and early mobilization should be avoided and DOAC is preferred over bridging VKA with LMWH.

scholarly journals Resolving Differential Diagnostic Problems in von Willebrand Disease, in Fibrinogen Disorders, in Prekallikrein Deficiency and in Hereditary Hemorrhagic Telangiectasia by Next-Generation Sequencing

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 202
Author(s):  
Réka Gindele ◽  
Adrienne Kerényi ◽  
Judit Kállai ◽  
György Pfliegler ◽  
Ágota Schlammadinger ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Von Willebrand Disease ◽  
Differential Diagnostics ◽  
Bleeding Disorders ◽  
Next Generation ◽  
Illumina Platform ◽  
Clinical Patient ◽  
Von Willebrand ◽  
Generation Sequencing

Diagnosis of rare bleeding disorders is challenging and there are several differential diagnostics issues. Next-generation sequencing (NGS) is a useful tool to overcome these problems. The aim of this study was to demonstrate the usefulness of molecular genetic investigations by summarizing the diagnostic work on cases with certain bleeding disorders. Here we report only those, in whom NGS was indicated due to uncertainty of diagnosis or if genetic confirmation of initial diagnosis was required. Based on clinical and/or laboratory suspicion of von Willebrand disease (vWD, n = 63), hypo-or dysfibrinogenemia (n = 27), hereditary hemorrhagic telangiectasia (HHT, n = 10) and unexplained activated partial thromboplastin time (APTT) prolongation (n = 1), NGS using Illumina platform was performed. Gene panel covered 14 genes (ACVRL1, ENG, MADH4, GDF2, RASA1, F5, F8, FGA, FGB, FGG, KLKB1, ADAMTS13, GP1BA and VWF) selected on the basis of laboratory results. We identified forty-seven mutations, n = 29 (6 novel) in vWD, n = 4 mutations leading to hemophilia A, n = 10 (2 novel) in fibrinogen disorders, n = 2 novel mutations in HHT phenotype and two mutations (1 novel) leading to prekallikrein deficiency. By reporting well-characterized cases using standardized, advanced laboratory methods we add new pieces of data to the continuously developing “bleeding disorders databases”, which are excellent supports for clinical patient management.

Coagulopathies

2020 ◽  
Author(s):  
Michael Levine
Keyword(s):  
Key Words ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Coagulation Cascade ◽  
Bleeding Disorders ◽  
Platelet Disorders ◽  
Von Willebrand

Coagulopathy can be caused by numerous hereditary or acquired etiologies. Although some of these conditions are known and the patient is aware of the bleeding disorder, other bleeding disorders are diagnosed only after the onset of excessive hemorrhage. This review discusses both hereditary and acquired disorders of coagulopathy. Platelet disorders are discussed elsewhere. This review contains 2 figures, 7 tables, and 72 references. Key words: Coagulopathies; Coagulopathy; Bleeding disorder; Hereditary bleeding disorder; Acquired bleeding disorder; von Willebrand disease; Hemophilia; Coagulation cascade; Hemorrhage; Anticoagulant-associated hemorrhage

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