The effect of haemophilia and von Willebrand disease on arterial thrombosis: a systematic review

Abstract

Background: Patients with haemophilia and von Willebrand disease (VWD) may have a reduced cardiovascular mortality, due to a hypocoagulable state or decreased atherogenesis. We performed a systematic review to assess the association between haemophilia and VWD, and fatal and nonfatal arterial thrombosis and asymptomatic atherosclerosis. Methods: Medline and PubMed were searched to identify studies that assessed the incidence of cardiovascular mortality and morbidity in haemophilia and VWD, and that measured asymptomatic atherosclerosis with intima media thickness (IMT) of the carotid and femoral arteries, or flow-mediated dilatation (FMD) of the brachial artery. Weighted standardised mortality ratios (SMR) and mean differences (WMD) were calculated and pooled using a random effects model. Results: 15 longitudinal and cross-sectional studies consisting of 19,242 patients were included. Mortality due to arterial thrombosis was nonsignificantly reduced in patients with haemophilia compared with healthy controls (SMR 0.50, 95% CI 0.24 to 1.09). Haemophilia reduced nonfatal coronary events, and severe haemophilia offered better protection, but these results were based on a single study. No results were available for VWD. Although IMT of the carotid and femoral arteries was similar between VWD and haemophilia patients and healthy controls, atherosclerotic plaques of the large arteries were less prevalent in haemophilia patients. Only two studies assessed FMD and the results were inconsistent. Conclusion: Haemophilia may reduce arterial thrombosis, but this association should be further studied in haemophilia patients with a higher prevalence of cardiovascular risk factors.