The Emergence of Prophylaxis as the Standard of Care to Treat Joint Bleeding Associated with Von Willebrand Disease

US Hematology, 2007;1(1):6-10 DOI:
Citation US Hematology, 2007;1(1):6-10 DOI:

Von Willebrand disease (VWD)—a disorder due to dysfunctional or deficient von Willebrand factor (VWF)—is the most common inherited disorder of hemostasis and is prevalent in approximately 1% of the total worldwide population,1,2 although the prevalence of symptomatic VWD is about 10 times lower.3
The International Society on Thrombosis and Haemostasis (ISTH)4 classified VWD into three primary categories: type 1, type 2, and type 3. Type 2 is further divided into four sub-categories: type 2A, type 2B, type 2M, and type 2N. Type 1 is the mildest form of VWD and accounts for approximately 75% of VWD.5 It is defined by a partial quantitative deficiency in VWF and it is estimated that 56.3 and 30.7% of type 1 patients suffer from epistaxis and menorrhagia, respectively (see Table 1). Combined, type 2 accounts for an estimated 25% of VWD patients, and is caused by qualitative abnormalities in VWF. The most common bleeding symptoms in type 2 VWD are epistaxis (63%) and bleeding after dental extraction (39%) (see Table 1). Type 3 is the most severe form of the disease and the least common, with an incidence of 0.55–3.2 per million in Western countries.6 Type 3 is characterized by low or no detectable VWF in plasma and is associated with the most severe bleeding symptoms. Epistaxis occurs in 74% of type 3 patients, 52% suffer bleeding after dental extraction, and joint bleeding occurs in 42% of type 3 cases (see Table 1).2
Joint Bleeding Associated with Von Willebrand Disease
Joint disease is one of the most severe complications of inherited bleeding disorders in general; however, the exact prevalence of this complication in VWD is still unclear. Lak et al. reported that 37% of 385 Iranian children with type 3 VWD had at least one episode of joint bleeding.7 In the US, a Universal Data Collection Program (UDCP) has been established to collect clinical data from Hemophilia Treatment Centers (HTCs). To date, the UDCP has reported that 14% of type 3 VWD patients suffered from target joint complications and 28.4% had limitations to movement because of joint complications.8 Target joint bleeds are less common in VWD patients with type 1 and 2 disease, at rates of 1.4 and 1.1%, respectively.
  1. Werner EJ, Broxson EH, Tucker EL, et al., Prevalence of von Willebrand disease in children: a multiethnic study, J Pediatr, 1993;123:893–8.
  2. Federici AB, Mannucci PM, Diagnosis and management of von Willebrand disease, Haemophilia, 1999;5:28–37.
  3. Castaman G, Eikenboom JC, Bertina RM, Rodeghiero F, Inconsistency of association between type 1 von Willebrand disease phenotype and genotype in families identified in an epidemiological investigation, Thromb Haemost, 1999;82(3): 1065–70.
  4. Sadler JE, Budde U, Eikenboom JC, et al., the Working Party on von Willebrand Disease Classification, Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor, J Thromb Haemost, 2006;4:2103–14.
  5. Mannucci PM, Treatment of von Willebrand’s Disease, N Engl J Med, 2004;351:683–95.
  6. Mannucci PM, Bloom A, Larrieu MJ, et al., Atherosclerosis and von Willebrand factor I. Prevalence of severe von Willebrand disease in Western Europe and Israel, Br J Haematol, 1984;57:166–72.
  7. Lak M, Peyvandi F, Mannucci PM, Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von Willebrand disease, Br J Haematol, 2000;111:1236–9.
  8. Centers for Disease Control and Prevention, Report on the Universal Data Collection Program, 2005;7(1).
  9. Berntorp E, Petrini P, Long-term prophylaxis in von Willebrand disease, Blood Coagul Fibrinolysis, 2005;16(Suppl. 1):S23–6.
  10. Nilsson IM, Management of haemophilia in Sweden, Thromb Haemost, 1976;35:510–21.
  11. Berntorp E, Lethagen S, Ljung R, et al., Centralized care is the basis of care programs for hemophilia patients, Lakartidningen, 1999;96(15):1849–52.
  12. Federici AB, Gianniello F, Canciani MT, et al., Secondary long-term prophylaxis in severe patients with von Willebrand’s disease: an Italian cohort study, Blood, 2005;106:507a, abstract 1782.
  13. Lethagen S, Clinical experience of prophylactic treatment in von Willebrand disease, Thromb Res, 2006;118S1:S9–S11.
  14. Traivaree C, Blanchette V, Hilliard P, et al., Type 3 VWD: clinical manifestations and the need for prophylaxis, Haemophilia, 2006; 12(Suppl. 2):Abstract 918.
  15. Federici AB, Castaman G, Franchini M, et al., Clinical use of Haemate P in inherited von Willebrand disease: a cohort study on 100 Italian patients, Haematologica, 2007;92:944–51.
  16. Berntorp E, Abshire T, for the von Willibrand Disease Prophylaxis Network Steering Committee, The von Willebrand disease prophylaxis network: exploring a treatment concept, J Thromb Haemost, 2006;4:2511–12.
  17. Feldman BM, Aledort L, Bullinger M, et al., Second International Prophylaxis Study Group, The economics of haemophilia prophylaxis: governmental and insurer perspectives. Proceedings of the Second International Prophylaxis Study Group (IPSG) symposium, Haemophilia, 2007;13(6):745–9.