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von Willebrand factor/factor VIII concentrate (Haemate ® P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery
Author(s) -
LETHAGEN S.,
KYRLE P. A.,
CASTAMAN G.,
HAERTEL S.,
MANNUCCI P. M.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02588.x
Subject(s) - medicine , interquartile range , von willebrand factor , dosing , pharmacokinetics , von willebrand disease , hemostasis , prospective cohort study , gastroenterology , elective surgery , urology , surgery , anesthesia , platelet
Summary. 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%), 15.6 h (IQR, 9.0–28.4 h) and 3.26 mL kg −1 h −1 (IQR, 2.29–5.21 mL 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.