Joint bleeding in von Willebrand disease

Abstract

Von Willebrand disease (VWD) is the most common inherited bleeding disorder occurring in approximately 1/100 people. Until now, joint bleeds did not get much attention in clinical research on VWD, since mucocutaneous bleeding is predominant. However, recurrent joint bleeds lead to arthropathy, the main cause of pain and functional limitations in patients with hemophilia, a severe bleeding disorder that affects 1/5000 men. Because of this potential big impact, the overall aim of this thesis was to provide more insight into the occurrence, predictors and consequences of joint bleeds and arthropathy in patients with VWD. We reviewed existing literature and analyzed joint bleed- and surgery data derived from the ‘Willebrand in the Netherlands’ (WiN) study database and medical files. Until May 2012, ten scientific reports contained information on arthropathy in VWD. The data indicated that arthropathy clearly exists in VWD and can be a substantial burden. However, the published studies were heterogeneous, mostly small and uniformly lacked a clear definition for arthropathy. Further research within the WiN study cohort revealed that joint bleeds, when strictly defined as ‘any joint symptom treated with clotting factor concentrate or desmopressin, as documented in the medical file’ occurs in approximately one in ten patients with moderate or severe VWD (VWF activity ≤30 IU/dL). Joint bleeds occur in over half of the patients with the most severe type 3 VWD. Large joint surgery, performed in 1/7 of the WiN patients, appeared to be related to joint damage after joint bleeds in a quarter of the procedures. Within the ‘Willebrand Arthropathy Study’, we compared joint outcome between VWD patients with and without a history of joint bleeds. We based joint outcome assessment on the International Classification of Functioning, Disability and Health (the ICF model) of the World Health Organization that incorporates body structure and functioning, activities and participation. For this purpose, we first showed that the hemophilia specific Hemophilia Joint Health Score (HJHS) and Hemophilia Activities List questionnaire are valid in VWD. Finally, we compared joint outcome after joint bleeds between adults with VWD and moderate and severe hemophilia A. Arthropathy, defined as a HJHS ≥10 or apparent joint damage on X-rays, occurs in almost half of VWD patients treated for joint bleeds compared to one in ten VWD patients without joint bleeds. The main predictor of arthropathy is the cumulative number of joint bleeds. In addition, a low FVIII level <10 IU/dL at VWD diagnosis and manifestation of the first joint bleed at young age are weaker predictors. Arthropathy has significant impact on daily life activities and quality of life in VWD, comparable to moderate and severe hemophilia A patients. Furthermore, arthropathy in VWD is strongly associated with chronic joint pain and related to less social participation. In summary, the results of this thesis emphasize the necessity of prevention of arthropathy in VWD patients. VWD patients and their physicians should be aware of joint bleeds and consider early treatment or even prophylaxis with clotting factor concentrates in VWD patients presenting with recurrent joint bleeds.