Management of Perioperative Anticoagulation in Patients with VWD

Objectives: von Willebrand disease (VWD) is the most common hereditary bleeding disorder. This study reviews the management of perioperative anticoagulation in patients with VWD undergoing surgical procedures. Risk factors for VTE with von Willebrand factor (VWF) concentrate use are older age, previous VTE, obesity, surgery, hormone replacement therapy use, antifibrinolytic therapy use and high post infusion FVIII levels. Currently, there are few data from randomized clinical trials assessing efficacy and possible complications of perioperative VTE prophylaxis in VWD patients.

Methods: A total number of 116 surgeries were performed (minor: n=64 and major: n=52) in this retrospective, single-centre study. They were divided into groups of perioperative non-anticoagulation (n=54) and perioperative anticoagulation (n=62), who all received coagulation factor concentrate (CFC). Sub-analyses were done according to the type of concentrate used. Anticoagulation was performed using different low molecular weight heparins (LMWH) according to standard protocols or body-weight adapted doses in patients with either elevated body-mass-index or additional thrombosis risk factors. Blood samples had been collected pre- and post-surgery (up to 21 days) to analyse PT, aPTT, PFA, and trough levels of FVIII coagulant activity (FVIII:C), VWF activity (VWF:GPIbM) and antigen (VWF:Ag), respectively. Furthermore, the median doses of CFC/kg and the median total number of infusions were calculated.The rates of clinically overt thrombosis as well as bleeding were assessed during the post-operative phase.

Results: The majority of patients suffered from VWD type 1 (104), 9 patients with type 2A, 2 with type 2M and 1 with type 3 VWD. Humate-P (H) was used in 55 patients and 61 patients received Wilate (W). Using W, we found parallel curves for FVIII:C, VWF-antigen and VWF:GPIbM, respectively. Using H, less concordance between VWF:Ag and VWF:GPIbM was visible and FVIII:C tends to increase between D3 to D10 in spite of decreasing VWF:Ag and VWF:GPIbM. This observation was visible in minor as well as major surgical procedures. LMWH (Enoxaparin, Nadroparin and Certaparin) were used in doses between 30 and 100 mg/injection (mean 46.0 ± 18.5 mg/injection) and a mean of 32.2 ± 24.6 injections in total (range: 8-112). In one patient a significant haematoma occurred (1/116; 0.9%), also one thrombotic event was documented in a different patient (1/116; 0.9%).

Conclusion: Using standard dose LMWH in patients with no overt increased thrombosis risk as well as body-weight-adapted LMWH in high risk patients seem to be safe and effective in VWD patients receiving coagulation factor concentrate perioperatively. However, prospective randomized comparative studies are required to determine the optimal indication as well as type of anticoagulation according to the CFC treatment regimen in this setting.