Treatment of von Willebrand disease

Summary. von Willebrand disease is the most frequent of inherited bleeding disorders (1:100 affected individuals in the general population). The aim of treatment is to correct the dual defects of haemostasis, i.e., abnormal coagulation expressed by low levels of factor VIII and abnormal platelet adhesion expressed by a prolonged bleeding time. There are two main options available for the management of von Willebrand disease: desmopressin and transfusion therapy with blood products. Desmopressin is the treatment of choice in patients with type 1 von Willebrand disease, who account for approximately 80% of cases. This pharmacological compound raises endogenous factor VIII and von Willebrand factors and thereby corrects the intrinsic coagulation defect and the prolonged bleeding time in most type 1 patients. In type 3 and in the majority of type 2 patients desmopressin is not effective, and it is necessary to resort to plasma concentrates containing factor VIII and von Willebrand factor. Treated with virucidal methods, these concentrates are effective and currently safe, but the bleeding time defect is not always corrected by them. Platelet concentrates or desmopressin can be used as adjunctive treatments when poor correction of the bleeding time after concentrates is associated with continued bleeding

von Willebrand Disease (vWD)

This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of von Willebrand Disease

Individualizing treatment in Von Willebrand disease:One size does not fit all

The focus of this thesis was on individualizing dosing of treatment in von Willebrand disease (VWD), the most common inherited bleeding disorder. First, current treatment strategies were evaluated and reviewed to identify where improvements can be made. Secondly, several population pharmacokinetic (PK) models were developed, which can be applied for individualized PK-guided dosing of the currently available treatment. Thirdly, a study protocol on implementation of PK-guided dosing of desmopressin and VWF-containing concentrates in clinical practice was presented, as well as new covariates that can be useful for further research

Acquired bleeding disorders

Acquired bleeding disorders can develop in previously healthy people irrespective of age or gender but are particularly common in patients with certain underlying conditions. Here, we review recent advances in the management of acquired haemophilia A (AHA), acquired von Willebrand syndrome (AVWS), and patients with hemostatic abnormalities due to chronic liver disease (CLD). Patients with AHA can now benefit from prophylaxis with emicizumab, a therapeutic antibody that mimics the function of activated coagulation factor VIII. The treatment of AVWS remains challenging in many situations and requires careful consideration of the underlying condition. Haemostatic abnormalities in CLD are often compensated by proportional reduction in pro and anti-haemostatic factors resulting in sustained or even increased thrombin generation. Consequently, bleeding in CLD is rarely caused by haemostatic failure and infusion of plasma or coagulation factor concentrates may not be effective.</p

von Willebrand's disease: a report from a meeting in the Åland islands

von Willebrand's disease (VWD) is probably the most common bleeding disorder, with some studies indicating that up to 1% of the population may have the condition. Over recent years interest in VWD has fallen compared to that of haemophilia, partly the result of focus on blood-borne diseases such as HIV and hepatitis. Now the time has come to revisit VWD, and in view of this some 60 international physicians with clinical and scientific interest in VWD met over 4 days in 2010 in the Åland islands to discuss state-of-the-art issues in the disease. The Åland islands are where Erik von Willebrand had first observed a bleeding disorder in a number of members of a family from Föglö, and 2010 was also the 140th anniversary of his birth. This report summarizes the main papers presented at the symposium; topics ranged from genetics and biochemistry through to classification of VWD, pharmacokinetics and laboratory assays used in the diagnosis of the disease, inhibitors, treatment guidelines in different age groups including the elderly who often have comorbid conditions that present challenges, and prophylaxis. Other topics included managing surgeries in patients with VWD and the role of FVIII in VWF replacement, a controversial subject

Hemostatic complications associated with ventricular assist devices.

Hemostatic complications are common in patients with ventricular assist devices. The pathophysiologic mechanisms that lead to dysregulated hemostasis involve complex interactions between device surface, sheer stress, and blood flow. These factors lead to various manifestations that require a thorough understanding of the interplay among platelets, coagulation factors, and red cells. In this article, we review the pathophysiology of hematologic complications (bleeding, acquired von Willebrand disease, heparin-induced thrombocytopenia, hemolysis, stroke and pump thrombosis), the clinical manifestations, and the management of each. We summarize the evidence available for management of these entities and provide a pragmatic clinical review

Intravenous immunoglobulin treatment in a type 3 von Willebrand disease patient with alloantibodies and a life-threatening gastrointestinal bleed

Non peer reviewe

Sixth Åland Island Conference on von Willebrand disease

Introduction The sixth angstrom land Islands Conference on von Willebrand disease (VWD) on the angstrom land Islands, Finland, was held from 20 to 22 September 2018. Aim The meeting brought together experts in the field of VWD from around the world to share the latest advances and knowledge in VWD. Results and discussion The topics covered both clinical aspects of disease management, and biochemical and laboratory insights into the disease. The clinical topics discussed included epidemiology, diagnosis and treatment of VWD in different countries, management of children with VWD, bleeding control during surgery, specific considerations for the management of type 3 VWD and bleeding control in women with VWD. Current approaches to the management of acquired von Willebrand syndrome were also discussed. Despite significant advances in the understanding and therapeutic options for VWD, there remain many challenges to be overcome in order to optimise patient care. In comparison with haemophilia A, there are very few registries of VWD patients, which would be a valuable source of data on the condition and its management. VWD is still underdiagnosed, and many patients suffer recurrent or severe bleeding that could be prevented. Awareness of VWD among healthcare practitioners, including non-haematologists, should be improved to allow timely diagnosis and intervention. Diagnosis remains challenging, and the development of fast, simple assays may help to facilitate accurate and rapid diagnosis of VWD.Peer reviewe

Inherited bleeding disorders in obstetrics and gynaecology

The aim of this thesis is to investigate the obstetric and gynaecological problems and their management in women with inherited bleeding disorders, as well as the role of such disorders in obstetric and gynaecological haemorrhage. The uptake of prenatal diagnosis and termination of an affected pregnancy is low in carriers of haemophilia. Fetal gender determination has important implications in the management of labour in carriers who do not wish to have specific prenatal diagnosis. The attitude of women towards reproductive choices is influenced by ethnic and cultural issues and family experience with the disease. Haemostatic response to pregnancy is variable in different types and subtypes of inherited bleeding disorders and in the same patient in different pregnancies. Haemorrhagic complications are confined to post-abortal and post-partum period. The incidence of primary and secondary post-partum haemorrhage was 22% and 11% in carriers of haemophilia, 18.5% and 20% in vWD and 16% and 24% in FXI deficient women, respectively. Women with low factor levels (<50 iu/dl) and no prophylactic treatment for labour and puerperium are especially at risk. There are great inter- and intra-individual variations in coagulation markers in women due to different physiological conditions including age, ethnicity, blood group and hormonal changes during different phases of the menstrual cycle. Women with inherited bleeding disorders suffer from heavy and prolonged menstruation which adversely affects their quality of life. Objectively confirmed menorrhagia is significantly higher in these women (67%) compared with the control group (29%). On the other hand, undiagnosed inherited bleeding disorders can be the underlying cause in a significant proportion (17%) of women presenting with unexplained menorrhagia. The DDAVP nasal spray was shown not to be superior to placebo in the treatment of menorrhagia. Increased awareness among clinicians responsible for women's health of these disorders and their morbidity and the availability of management guidelines are essential for optimal care and improvement of the quality of life of these patients

How I manage severe von Willebrand disease

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Most patients with mild and moderate VWD can be treated effectively with desmopressin. The management of severe VWD patients, mostly affected by type 2 and type 3 disease, can be challenging. In this article we review the current diagnosis and treatment of severe VWD patients. We will also discuss the management of severe VWD patients in specific situations, such as pregnancy, delivery, patients developing alloantibodies against von Willebrand factor and VWD patients with recurrent gastrointestinal bleeding. Moreover, we review emerging treatments that may be applied in future management of patients with severe VWD