Von Willebrand factor predicts major bleeding and mortality during oral anticoagulant treatment

Abstract

Aims. Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC-treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all-cause mortality.Methods and results. A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow-up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41-4.56) for major bleeding and HR 2.19 (95% CI 1.38-3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40-2.01) and all-cause mortality (HR 1.77, 95% CI 1.52-2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high-sensitivity C-reactive protein and creatinine.Conclusions. Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all-cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.

von Willebrand activation factor as a marker of mortality, cardiovascular events, and bleeding complications in patients treated with oral anticoagulants

“…This result sets VWF activation factor apart from VWF antigen, which has been associated with bleeding complications as well as cardiovascular events [10]. It was also noted that in patients with high levels of VWF activation factor and antigen, the incidences of cardiovascular events and mortality were especially high, indicating that these patients are at a highest risk.…”

“…The study cohort was recruited from the OAC clinic at Skellefteå County Hospital, Skellefteå, Sweden, in June 1996 and has in part been described in an earlier paper [10] Patients with a planned treatment time greater than 3 months were considered to be on long term treatment and eligible for the study; thus, consent forms were sent to them. Blood samples were obtained at inclusion for the 356 patients included in the final study cohort.…”

“…High levels of VWF antigen are associated with both thrombotic events and bleeding complications in patients treated with oral anticoagulants (OACs) [9,10]. The mechanism for this dual association is not clear and different pathways could contribute to high levels of VWF antigen.…”

Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation

“…25 Paradoxically, high levels of vWF antigen are associated with both thrombotic events and bleeding complications in patients treated with OACs. 8,26 The mechanism for the dual association is not clear, and different pathways could contribute to high levels of vWF. It is also possible that vWF could be an effector in thrombotic events, possibly by increased binding to platelets.…”

High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment

“…However, several risk factors in these schemes are also associated with a higher risk of serious bleeding events [12][13][14]. In previous studies, we have shown that biomarkers in blood plasma are associated with bleeding complications during anticoagulant treatment, as well as with thromboembolic events [15]. To our knowledge the relationships between homocysteine and folate and risk of cardiovascular events or bleedings have not previously been investigated in patients with oral anticoagulant treatment.…”