Utility of a high VWF: FVIII ratio in preventing FVIII accumulation: a study in VWF-deficient mice.
Blood Coagul Fibrinolysis
; 26(5): 515-21, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25767894
ABSTRACT
Treatment of von Willebrand disease typically requires multiple infusions of von Willebrand factor (VWF)/factor VIII (FVIII) concentrate. Accumulation of FVIII is a clinical concern due to potential risk for thromboembolism. This study sought to determine whether VWF/FVIII concentrate of high VWFFVIII ratio can prevent FVIII accumulation. VWF-deficient knockout mice received four 150âIU/kg VWFristocetin cofactor (RCo) infusions at 3-h intervals, with VWF/FVIII concentrates of a high (Haemate P/Humate-P) or low (Wilate) VWFFVIII ratio. After each infusion, trough FVIII and VWF levels in plasma were determined. Separately, pharmacokinetic analysis was performed after single 250-IU/kg VWFRCo infusions of each concentrate. Over the course of the four infusions, trough FVIII increased significantly in the group receiving Wilate (Pâ<â0.001), but not Haemate P/Humate P (Pâ=â0.058). After the first infusion, mean trough FVIII level in the Wilate group (31.7âIU/dl) was greater by 82% (Pâ=â0.017) than that in the Haemate P/Humate P group (17.4âIU/dl). After the final infusion, mean trough FVIII of animals receiving Wilate (55.1âIU/dl) continued to exceed that of Haemate P/Humate P recipients (30.2âIU/dl) significantly (Pâ<â0.001). Trough VWF levels were similar in the two groups. The VWF pharmacokinetics of the two concentrates coincided closely; however, the FVIII peak concentration and area under the curve were approximately twice as great in the mice treated with Wilate. In a murine model of severe von Willebrand disease, a VWF/FVIII concentrate with a high VWFFVIII ratio prevented persistent exposure to elevated trough FVIII levels.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator VIII
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Blood Coagul Fibrinolysis
Ano de publicação:
2015
Tipo de documento:
Article