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von Willebrand factor/factor VIII concentrate (Haemate P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery.
J Thromb Haemost 2007; 5(7):1420-30JT

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%), 15.6 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.

Authors+Show Affiliations

Department for Coagulation Disorders, University Hospital Malmö, Malmö, Sweden. stefan.lethagen@rh.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17439628

Citation

Lethagen, S, et al. "Von Willebrand Factor/factor VIII Concentrate (Haemate P) Dosing Based On Pharmacokinetics: a Prospective Multicenter Trial in Elective Surgery." Journal of Thrombosis and Haemostasis : JTH, vol. 5, no. 7, 2007, pp. 1420-30.
Lethagen S, Kyrle PA, Castaman G, et al. Von Willebrand factor/factor VIII concentrate (Haemate P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery. J Thromb Haemost. 2007;5(7):1420-30.
Lethagen, S., Kyrle, P. A., Castaman, G., Haertel, S., & Mannucci, P. M. (2007). Von Willebrand factor/factor VIII concentrate (Haemate P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery. Journal of Thrombosis and Haemostasis : JTH, 5(7), pp. 1420-30.
Lethagen S, et al. Von Willebrand Factor/factor VIII Concentrate (Haemate P) Dosing Based On Pharmacokinetics: a Prospective Multicenter Trial in Elective Surgery. J Thromb Haemost. 2007;5(7):1420-30. PubMed PMID: 17439628.
* Article titles in AMA citation format should be in sentence-case
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 -