Von Willebrand Diseases

In parallel with the growth of ATHN's clinical studies, the number of new therapies for all blood disorders is increasing significantly. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have not yet demonstrated long-term safety and effectiveness beyond the pivotal trials that led to their approval. In addition, results from well controlled, pivotal studies often cannot be replicated once a therapy has been approved for general use.2,3,4,5 In 2019 alone, the FDA has issued approvals for 24 new therapies for congenital and acquired hematologic conditions.6 In addition, almost 10,000 new studies for hematologic diseases are currently registered on www.clinicaltrials.gov.7 With this increase in potential new therapies possible, it is imperative that clinicians and clinical researchers in the field of non-neoplastic hematology have a uniform, secure, unbiased, and enduring method to collect long-term safety and efficacy data. As emphasized in a recently published review, accurate, uniform and quality national data collection is critical in clinical research, particularly for longitudinal cohort studies covering a lifetime of biologic risk.8

In Willebrand disease, there is currently no test available to identify non-invasively patients with a high risk of bleeding from angiodysplasias The study propose to use a sublingual capillary bed analysis by video-microscopy, a sensitive, reproducible and non-invasive technique, to assess whether sublingual capillary density is predictive of hemorrhagic risk for patients with von Willebrand disease.

The Hemophilia Treatment Center (HTC) where you receive care is working with The American Thrombosis and Hemostasis Network (ATHN) to look at the quality of life of people with blood disorders and problems. Doctors, scientists, policymakers, and other health care providers need a large amount of information from a lot of people to answer scientific, public health, and policy questions about better ways to treat blood disorders. They will use the information from the ATHNdataset to answer these questions.

Currently, the exploration of primary hemostasis (a physiological phenomenon used to stop bleeding) is imperfect because it is based on targeted tests for platelets or von Willebrand factor, without taking into account blood flow and other blood cells (red and white blood cells). Tests for whole blood and flow conditions exist, but there is currently no test that comes close to actual physiological conditions. An exploration of whole blood haemostasis in a device that is similar to a blood vessel and at different flow conditions (venous and arterial) could help to better identify the risk of bleeding in predisposed patients (von Willebrand factor deficiency, antiplatelet therapy). The objective of the study is to evaluate the performance of this new hemostasis test in whole blood and under flow conditions. Participation in the study is ad hoc and is limited to adding a maximum of 4 citrated tubes (20 mL or the equivalent of 4 teaspoons) and 1 EDTA tube (5mL) to a routine blood sample (for patients) or during blood donation (for controls).

In parallel with the growth of ATHN's clinical studies, the number of new therapies for all blood disorders is increasing significantly. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have not yet demonstrated long-term safety and effectiveness beyond the pivotal trials that led to their approval. In addition, results from well controlled, pivotal studies often cannot be replicated once a therapy has been approved for general use.2,3,4,5 In 2019 alone, the FDA has issued approvals for 24 new therapies for congenital and acquired hematologic conditions.6 In addition, almost 10,000 new studies for hematologic diseases are currently registered on www.clinicaltrials.gov.7 With this increase in potential new therapies possible, it is imperative that clinicians and clinical researchers in the field of non-neoplastic hematology have a uniform, secure, unbiased, and enduring method to collect long-term safety and efficacy data. As emphasized in a recently published review, accurate, uniform and quality national data collection is critical in clinical research, particularly for longitudinal cohort studies covering a lifetime of biologic risk.8

In pregnant women with von Willebrand disease (VWD) who by the third trimester do not have von Willebrand factor (VWF) or factor VIII (FVIII) levels greater than 50-100%, specific guidance is lacking for delivery planning in terms of how high of a VWF level should be achieved to reduce bleeding. This is a prospective, open-label, cohort study in women with VWD using Wilate VWF replacement therapy to maintain trough or minimum VWF levels of 100-150% for delivery and the immediate postpartum period, followed by levels of 50-100% for 5-10 days after delivery, depending upon the route of delivery. The primary objective is to document the rate of primary postpartum hemorrhage (PPH). The secondary objective is to document further effectiveness outcomes and safety.

The goal of this multicenter prospective observational study and registry of U.S. adolescents and young adults with heritable bleeding disorders is to determine the bleeding outcomes, satisfaction, hemostatic parameter changes, and patient reported quality of life after 6 months of use of either of two commonly used hormonal treatments for menstrual suppression - levonorgestrel intrauterine device (LNG-IUD) and norethindrone acetate (NETA). Under this application the study will compare the two treatments and compare outcomes after LNG-IUD treatment results to a control group without a bleeding disorder, with the goal of determining the benefits and expected outcomes of these treatment options for this population.

The VIVID study is structured in a master protocol format comprised of multiple parts that evaluate intravenous (IV) and subcutaneous (SC) VGA039 in healthy volunteers and subjects with von Willebrand Disease (VWD) and other bleeding disorders.

Due to increasing of life expectancy, patients with von Willebrand disease are exposed to age-related pathologies such as cancer or cardiovascular diseases. Management of thrombotic events is challenging given the inherent bleeding risk in von Willebrand disease. Few data are currently available in the literature. The aim of the study is to describe the frequency and nature of arterial and venous thromboembolic events and atrial fibrillation in patients with von Willebrand disease in the West of France. The investigators will perform a retrospective multicenter study conducted in the von Willebrand population of the French West. Von Willebrand adult patients followed in one of the French West medical centers participating in the study, who presented deep vein thrombosis, pulmonary embolism, ischemic stroke, transient ischemic attack, acute coronary syndrome, acute limb ischemia, atrial fibrillation, arteriopathy of the lower limbs, angina will be eligible.

The EMPOWER trial is a pilot multi-center, placebo-controlled (normal saline), double-blind (patient and outcome assessor), crossover, 2-year randomized trial in female outpatients with von Willebrand disease (VWD) and heavy menstrual bleeding to determine trial feasibility and viability, and to explore assay sensitivity of the proposed efficacy clinical outcomes for a definitive randomized controlled trial

The WBDR is an international observational disease registry of patients with hemophilia. It will provide a platform for a network of hemophilia treatment centres (HTCs) around the world to collect uniform and standardized patient data and guide clinical practice. With informed consent from the patient, the WBDR stores anonymous data about the person's disease, such as hemophilia type and severity, symptoms, and treatment.