Paeds · haematology-oncology-and-transfusion
Von Willebrand disease
Also known as Von Willebrand disease · VWD · Von Willebrand factor deficiency · Vascular haemophilia
Fellowship guide to von Willebrand disease, the most common inherited bleeding disorder, caused by a quantitative or qualitative defect of von Willebrand factor. Covers the Sadler 1994 classification into type 1 (partial deficiency, about 75 to 80 percent), the type 2 qualitative subtypes (2A loss of high-molecular-weight multimers, 2B gain-of-function with thrombocytopenia, 2M normal multimers but reduced function, 2N reduced factor VIII binding), and type 3 (virtual absence, severe, autosomal recessive, about 1 in a million); the two functions of von Willebrand factor as platelet adhesion via glycoprotein Ib and as the carrier and stabiliser of factor VIII; the diagnostic panel of von Willebrand factor antigen, ristocetin cofactor activity, factor VIII, ristocetin-induced platelet aggregation and multimer analysis; the desmopressin trial at 0.3 micrograms per kg intravenously over 30 minutes; and VWF concentrate, tranexamic acid and the special care of the adolescent with heavy menstrual bleeding, the neonate and the pregnant carrier.
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- Type 2B von Willebrand disease causes thrombocytopenia that worsens with desmopressin, so desmopressin is generally avoided in type 2B and VWF concentrate is used instead
- Type 3 von Willebrand disease has virtually absent von Willebrand factor and does not respond to desmopressin at all, so any bleed in type 3 needs VWF concentrate from the outset
- A normal von Willebrand factor level on a single sample never excludes the disease, because blood group O lowers the level by about 25 to 30 percent and stress, inflammation and oestrogen raise it, so repeat testing is required when the bleeding phenotype fits
- Heavy menstrual bleeding in an adolescent female may be the first presentation of von Willebrand disease, and any adolescent with menorrhagia severe enough to cause iron deficiency or disrupt daily life should be screened
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- Haematology
- Coagulation disorders
- Von Willebrand disease
- Paediatric Haematology — von Willebrand disease
- General Paediatrics learning goal — recognise and manage inherited bleeding disorder
- Desmopressin response, VWF concentrate and the adolescent with heavy menstrual bleeding
- Clinical Applications
- Coagulation and bleeding disorders
- Long Cases
- Short Cases
- Communication scenarios
- Haematology and oncology: recognises and manages von Willebrand disease
- Inherited bleeding disorders and desmopressin
- Heavy menstrual bleeding and the bleeding adolescent
- Foundation of Practice (FOP)
- Applied Knowledge in Practice (AKP)
- Clinical
- History
- Communication
- Adolescent gynaecology
- General Pediatrics Content Outline — Domain: Haematology
- Subspecialty: Pediatric Hematology — inherited bleeding disorder
- Patient Care 1: History and Physical Examination
- Patient Care 4: Clinical Reasoning
- Medical Knowledge 1: Clinical Knowledge of von Willebrand disease
- Systems-Based Practice 1: comprehensive bleeding-disorder centre care
- Medical Expert
- Collaborator
- Pediatrics: Core EPA — recognise and manage inherited bleeding disorder
Overview & Definition
Picture the thirteen-year-old girl sent to the paediatric clinic because her periods have been so heavy she has needed iron tablets and missed school, and you also learn she has always bruised easily and had nose-bleeds that lasted an hour. Her full blood count shows a mild microcytic anaemia, her platelet count is normal, and her coagulation screen is normal. That girl most likely has von Willebrand disease, and the heavy menstrual bleeding is its signature presentation in adolescence. The easy bruising and prolonged epistaxis are the mucocutaneous pattern that points to a primary-haemostasis defect rather than a clotting-factor deficiency. [1] [10]
Von Willebrand disease is an inherited bleeding disorder caused by a quantitative or qualitative defect of von Willebrand factor, a large multimeric glycoprotein that does two distinct jobs in haemostasis. It is the most common inherited bleeding disorder: the population prevalence of symptomatic disease is about 1 in 1000, though many cases are mild and never diagnosed, and the severe type 3 form affects about 1 in a million. Erik von Willebrand described the disease in 1926 in families on the Aland Islands, and it is now understood as a single disease with a spectrum of types rather than one uniform condition. [6] [1]
The defining principle is that VWF sits at the interface between primary and secondary haemostasis. It carries factor VIII in the circulation, protecting it from breakdown, and it mediates the adhesion of platelets to the injured vessel wall. So a shortage or malfunction of VWF can produce both the platelet-type bleeding of mucocutaneous surfaces and, in the severe forms, a low factor VIII that allows deeper joint and muscle bleeding. This dual role is the key to understanding why the disease looks the way it does and why the laboratory pattern varies so much between types. [4] [1]
References12ShowHide
- [1]Leebeek FW, Eikenboom JC Von Willebrand's Disease. N Engl J Med, 2016.PMID 27959741
- [2]Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) expert panel report. Haemophilia, 2008.PMID 18315614
- [3]Castaman G, Goodeve A, Eikenboom J Principles of care for the diagnosis and treatment of von Willebrand disease. Haematologica, 2013.PMID 23633542
- [4]Mannucci PM Treatment of von Willebrand's Disease. N Engl J Med, 2004.PMID 15306670
- [5]Sadler JE A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost, 1994.PMID 8052974
- [6]Rodeghiero F, Castaman G, Dini E Epidemiological investigation of the prevalence of von Willebrand's disease. Blood, 1987.PMID 3492222
- [7]Sadler JE Von Willebrand disease type 1: a diagnosis in search of a disease. Blood, 2003.PMID 12411289
- [8]Rodeghiero F, Tosetto A, Abshire T, Arnold DM, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost, 2010.PMID 20626619
- [9]Tosetto A, Castaman G, Rodeghiero F Assessing bleeding in von Willebrand disease with bleeding score. Blood Rev, 2007.PMID 16774804
- [10]Mannucci PM, Federici AB, James AH, Kessler CM von Willebrand disease in the 21st century: current approaches and new challenges. Haemophilia, 2009.PMID 19624761
- [11]Abshire TC, Federici AB, Alvárez MT, et al. Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN). Haemophilia, 2013.PMID 22823000
- [12]Leebeek FWG, Peyvandi F, Escobar M, Tiede A, et al. Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 trial results. Blood, 2022.PMID 35439298