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Von Willebrand factor/factor VIII concentrate (Haemate(R) P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery.

Lethagen, Stefan LU ; Kyrle, P A; Castaman, G; Haertel, S and Mannucci, P M (2007) In Journal of Thrombosis and Haemostasis 5(Apr 16). p.1420-1430
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-(R) 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... (More)
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-(R) 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-(R) provided effective and safe hemostasis in VWD subjects undergoing elective surgery. Selection of Haemate((R)) P loading dose on the basis of VWF PK proved feasible. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
surgical hemostasis, factor VIII, studies, prospective, von Willebrand factor, postoperative hemorrhage, hereditary diseases
in
Journal of Thrombosis and Haemostasis
volume
5
issue
Apr 16
pages
1420 - 1430
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000247980000015
  • scopus:34250691461
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2007.02588.x
language
English
LU publication?
yes
id
05b1e483-aa10-405d-973a-4f6fc772c02b (old id 167574)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17439628&dopt=Abstract
date added to LUP
2007-07-25 11:00:01
date last changed
2017-10-01 03:51:41
@article{05b1e483-aa10-405d-973a-4f6fc772c02b,
  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-(R) 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-(R) provided effective and safe hemostasis in VWD subjects undergoing elective surgery. Selection of Haemate((R)) P loading dose on the basis of VWF PK proved feasible.},
  author       = {Lethagen, Stefan and Kyrle, P A and Castaman, G and Haertel, S and Mannucci, P M},
  issn         = {1538-7933},
  keyword      = {surgical hemostasis,factor VIII,studies,prospective,von Willebrand factor,postoperative hemorrhage,hereditary diseases},
  language     = {eng},
  number       = {Apr 16},
  pages        = {1420--1430},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Von Willebrand factor/factor VIII concentrate (Haemate(R) P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery.},
  url          = {http://dx.doi.org/10.1111/j.1538-7836.2007.02588.x},
  volume       = {5},
  year         = {2007},
}