TY - JOUR
T1 - Presurgical pharmacokinetic analysis of a von Willebrand factor/factor VIII (VWF/FVIII) concentrate in patients with von Willebrand's disease (VWD) has limited value in dosing for surgery
AU - Di Paola, J.
AU - Lethagen, S.
AU - Gill, J.
AU - Mannucci, P.
AU - Manco-Johnson, M.
AU - Bernstein, J.
AU - Nichols, W. L.
AU - Bergman, G. E.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/9
Y1 - 2011/9
N2 - Optimal doses of von Willebrand Factor/Factor VIII (VWF/FVIII) concentrates for surgical procedures in patients with VWD need to be determined. A prospective, multicenter study was performed that included an initial pharmacokinetic (PK) assessment following a standard dose of VWF/FVIII concentrate (Humate-P ®) to determine individual PK parameters and guide therapeutic dosing during surgery. Forty one subjects received 60IU kg -1 VWF: RCo. Median plasma levels, half-life, mean change from baseline and in vivo recovery (IVR) values were determined for VWF:RCo, VWF:Ag, and FVIII: C, and area under the plasma time-concentration curve (AUC), mean residence time (MRT), clearance, volume of distribution and dose linearity were also assessed for VWF:RCo at various time points. Median baseline VWF:RCo level was 13IU dL -1 (range, 6-124); with a mean change from baseline >100IU dL -1 immediately after the infusion, decreasing to 10IU dL -1 at 48h postinfusion. The group median incremental in vivo recovery (IVR) for VWF:RCo was 2.4IU dL -1 per IU kg -1, for VWF:Ag 2.3IU dL -1kg -1 and for FVIII:C was 2.7IU dL -1 per IU kg -1. When analysing individual recovery values on repeated infusions, a very weak correlation was observed between presurgery IVR and IVR for both VWF:RCo and FVIII, measured at various times just prior to and after the surgical procedure. Although group median values were fairly consistent among repeated IVR measurements, the intra-individual IVR values for FVIII and VWF:RCo with repeated infusions showed a large degree of variability. IVR values obtained from pharmacokinetic analyses performed in advance of anticipated surgery do not reliably predict postinfusion circulating levels of VWF:RCo or FVIII attained preoperatively or with subsequent peri-operative infusions.
AB - Optimal doses of von Willebrand Factor/Factor VIII (VWF/FVIII) concentrates for surgical procedures in patients with VWD need to be determined. A prospective, multicenter study was performed that included an initial pharmacokinetic (PK) assessment following a standard dose of VWF/FVIII concentrate (Humate-P ®) to determine individual PK parameters and guide therapeutic dosing during surgery. Forty one subjects received 60IU kg -1 VWF: RCo. Median plasma levels, half-life, mean change from baseline and in vivo recovery (IVR) values were determined for VWF:RCo, VWF:Ag, and FVIII: C, and area under the plasma time-concentration curve (AUC), mean residence time (MRT), clearance, volume of distribution and dose linearity were also assessed for VWF:RCo at various time points. Median baseline VWF:RCo level was 13IU dL -1 (range, 6-124); with a mean change from baseline >100IU dL -1 immediately after the infusion, decreasing to 10IU dL -1 at 48h postinfusion. The group median incremental in vivo recovery (IVR) for VWF:RCo was 2.4IU dL -1 per IU kg -1, for VWF:Ag 2.3IU dL -1kg -1 and for FVIII:C was 2.7IU dL -1 per IU kg -1. When analysing individual recovery values on repeated infusions, a very weak correlation was observed between presurgery IVR and IVR for both VWF:RCo and FVIII, measured at various times just prior to and after the surgical procedure. Although group median values were fairly consistent among repeated IVR measurements, the intra-individual IVR values for FVIII and VWF:RCo with repeated infusions showed a large degree of variability. IVR values obtained from pharmacokinetic analyses performed in advance of anticipated surgery do not reliably predict postinfusion circulating levels of VWF:RCo or FVIII attained preoperatively or with subsequent peri-operative infusions.
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U2 - 10.1111/j.1365-2516.2011.02583.x
DO - 10.1111/j.1365-2516.2011.02583.x
M3 - Article
C2 - 21689209
AN - SCOPUS:80052038558
SN - 1351-8216
VL - 17
SP - 752
EP - 758
JO - Haemophilia
JF - Haemophilia
IS - 5
ER -