TY - JOUR T1 - von Willebrand factor/factor VIII concentrate (Haemate P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery. AU - Lethagen,S, AU - Kyrle,P A, AU - Castaman,G, AU - Haertel,S, AU - Mannucci,P M, AU - ,, Y1 - 2007/04/16/ PY - 2007/4/19/pubmed PY - 2007/10/12/medline PY - 2007/4/19/entrez SP - 1420 EP - 30 JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. VL - 5 IS - 7 N2 - 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. SN - 1538-7933 UR - https://www.unboundmedicine.com/medline/citation/17439628/von_Willebrand_factor/factor_VIII_concentrate__Haemate_P__dosing_based_on_pharmacokinetics:_a_prospective_multicenter_trial_in_elective_surgery_ L2 - https://doi.org/10.1111/j.1538-7836.2007.02588.x DB - PRIME DP - Unbound Medicine ER -