von Willebrand factor/factor VIII concentrate (Haemate® P) dosing based on pharmacokinetics: A prospective multicenter trial in elective surgery

Abstract

Background: While plasma-derived concentrates containing large amounts of von Willebrand factor (VWF) are effective in treating von Willebrand disease (VWD), optimal dosing remains to be fully characterized. Objectives: To determine the feasibility of dosing Haemate P® VWF/factor VIII (FVIII) concentrate based on pharmacokinetics (PK) in the management of surgical subjects with VWD. Methods: VWD subjects scheduled for elective surgery were enrolled in a prospective multicenter open-label cohort study. A pre-operative loading dose of VWF/FVIII concentrate based upon prior individual subject PK analysis was administered followed by postoperative therapeutic/ maintenance infusions. Results: Twenty-eight subjects with types 1, 2A or 3 VWD and one with type 2 M were enrolled. Median in vivo recovery of VWF ristocetin cofactor (VWF:RCo) was 1.9 IU dL-1 (IU kg-1) -1 with an interquartile range (IQR) of 1.6-2.5 IU dL-1 (IU kg-1)-1. Median response, half-life and clearance were 74.0% (IQR, 55.5-100%), 15.6h (IQR, 9.0-28.4h) and 3.26 mL kg-1 h-1 (IQR, 2.29-5.21mL kg-1 h-1), respectively. A PK-guided median VWF:RCo loading dose of 62.4 IU kg-1 (IQR, 50.1-87.0 IU kg-1) was administered. Postoperative mean trough VWF:RCo levels of 62-73 IU dL-1 were sufficient to prevent bleeding. Investigators rated hemostasis excellent or good in 96.3% of subjects on the day of surgery and 100% on the next day and on day 14. A subject with multiple risk factors developed pulmonary embolism, which resolved without sequelae. Conclusions: Haemate P® provided effective and safe hemostasis in VWD subjects undergoing elective surgery. Selection of Haemate® P loading dose on the basis of VWF PK proved feasible. © 2007 International Society on Thrombosis and Haemostasis.