The Role of Factor VIII in the Activation of Human Blood Coagulation Factor X by Activated Factor IX

K Mertens; A van Wijngaarden; R M Bertina

doi:10.1055/s-0038-1660091

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1985; 54(03): 654-660
DOI: 10.1055/s-0038-1660091

Original Article

Schattauer GmbH Stuttgart

The Role of Factor VIII in the Activation of Human Blood Coagulation Factor X by Activated Factor IX

Authors

K Mertens

The Haemostasis and Thrombosis Research Unit, Leiden University Hospital, Leiden, The Netherlands
A van Wijngaarden

The Haemostasis and Thrombosis Research Unit, Leiden University Hospital, Leiden, The Netherlands
R M Bertina

The Haemostasis and Thrombosis Research Unit, Leiden University Hospital, Leiden, The Netherlands

Abstract

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Summary

The role of factor VIII in the activation of human factor X by factor IXa, Ca²⁺ and phospholipid has been investigated. Factor VIII stimulated the factor Xa formation after activation by factor Xa or thrombin; the activity of thrombin-activated factor VIII was about 4-fold that of factor Xa-activated factor VIII. The isolated procoagulant moiety of the factor VIII complex behaved identically to the complete complex, whereas the von Willebrand factor moiety did not participate in the factor Xa formation. Thrombin-activated factor VIII complex (factor Villa) was used to study the effect of factor Villa in kinetic experiments. The results revealed a complex kinetic behaviour, including substrate inhibition and non-linearity of the reaction rate with the enzyme concentration. Using previously obtained insight into the kinetics of factor X activation in the absence of factor VIII, the results were found to support the hypothesis that factor Villa participates in the factor Xa formation in a complex with phospholipid-bound factor IXa; the formation of the factor VUIa-factor IXa complex then increases the catalytic efficiency of the factor IXa by 500-fold.

Keywords

Factor VIII - Factor IX - Factor X - Intrinsic pathway Summary

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References

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