Consequences of joint bleeds in von Willebrand disease patients: A retrospective patient control study

Abstract

Introduction: Joint bleeds (JB) have been reported to occur in 8-45% of von Willebrand disease (VWD) patients, depending on VWD severity. The consequences of JB in VWD are largely unknown. Therefore, we started a patient control study based on retrospective medical files (MF) examination in all Dutch haemophilia treatment centres to analyse the nature and consequences of self-reported JB. Methods: All moderate and severe VWD patients who participated in the Willebrand in The Netherlands (WiN) study, a large nationwide cross-sectional study on VWD (defined as VWF ≤ 30 U dL-1), completed a comprehensive self-reported questionnaire including JB and treatment questions. To select for patients most likely to have developed arthropathy due to JB, MF were studied from all participants who selfreported that they recieved JB treatment with desmopressin or clotting factor concentrate (plasma FVIII/VWF; CFC). For comparison 2:1 controls were selected from the same WiN database, matched for gender, age, FVIII and VWF activity. Results: Treated JB were reported by 81/804 WiN participants (10%), MF were available in 98% (79 patients, 156 controls). Mean age was 37 years (range 1- 75), mean FVIII level 42 U dL-1 ± 32 and mean VWF activity 22 U dL-1 ± 28. JB treatment was found in MF in 70% (55/79) of patients and 9% (14/156) controls. A larger proportion of the patients with treated JB had type 3 VWD (21/79, 27% vs. 17/156, 11%, P = 0.002). Compared to the controls, JB patients were more likely to have spontaneous JB (20/79 vs. 2/155, P <0.001), used higher mean CFC dose (178 vs. 38 IE FVIII kg-1 year-1, P = 0.003), had CFC prophylaxis more often (17/79, 22% vs. 7/155, 5%, P <0.001) and more joint surgery (20/79, 25% vs. 13/155, 8%, P = 0.001). Joint damage on X-rays was found in35%of JB patients (28/79), and in 11% (17/155) of the controls (P <0.001). Furthermore, joint pain was documented in a larger proportion of JB patients (33/79, 42% vs. 26/155, 17%, P <0.001). However, MF documented use of pain medication for joint pain was only found in 10% of JB patients (8/79) compared to7%of the controls (11/155,P = 0.45). Discussion/Conclusion: Compared to matched controls who did not self-report treatment for joint bleeds, VWD patients experiencing joint bleeds more often had joint damage on X-rays and joint pain, but did not use more pain medication, according to their medical files. The results of this study indicate that treatment of joint bleeds in VWD can be improved.