Von Willebrand factor/factor VIII concentrate (Haemate(R) P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery.
(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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https://lup.lub.lu.se/record/167574
- author
- Lethagen, Stefan LU ; Kyrle, P A ; Castaman, G ; Haertel, S and Mannucci, P M
- organization
- publishing date
- 2007
- 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
- Wiley-Blackwell
- external identifiers
-
- wos:000247980000015
- scopus:34250691461
- pmid:17439628
- ISSN
- 1538-7933
- DOI
- 10.1111/j.1538-7836.2007.02588.x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Clinical Coagulation Research Unit (013242510)
- 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
- 2016-04-01 12:17:17
- date last changed
- 2022-03-28 22:51:32
@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}},
keywords = {{surgical hemostasis; factor VIII; studies; prospective; von Willebrand factor; postoperative hemorrhage; hereditary diseases}},
language = {{eng}},
number = {{Apr 16}},
pages = {{1420--1430}},
publisher = {{Wiley-Blackwell}},
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}},
doi = {{10.1111/j.1538-7836.2007.02588.x}},
volume = {{5}},
year = {{2007}},
}