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Related Experiment Videos

Activation of factor VIII by factor IXa.

M E Rick

    Blood
    |September 1, 1982
    PubMed
    Summary

    Factor IXa, similar to thrombin, activates factor VIII coagulant (VIII:C) activity, causing a temporary increase followed by a decrease. This interaction, enhanced by phospholipid, may play a role in the intrinsic coagulation cascade.

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    Area of Science:

    • Biochemistry
    • Hematology
    • Molecular Biology

    Background:

    • Thrombin transiently increases factor VIII coagulant (VIII:C) activity before it declines.
    • This interaction is hypothesized as a prerequisite for factor VIII's role in coagulation.
    • Factor IXa shares structural similarities with thrombin.

    Purpose of the Study:

    • To investigate the effect of factor IXa on factor VIII coagulant (VIII:C) activity.
    • To compare the interaction of factor IXa with factor VIII to that of thrombin.
    • To elucidate the role of factor IXa in the coagulation cascade.

    Main Methods:

    • Incubation of factor VIII with factor IXa.
    • Assay of factor VIII coagulant (VIII:C) activity.
    • Analysis of factor-VIII-related protein (VIII:RP) using PAGE and radioimmunoassay.
    • Inhibition studies using a factor IX inhibitor, diisopropylfluorophosphate, and hirudin.
    • Investigation of phospholipid's effect on the reaction.

    Main Results:

    • Factor IXa caused a temporary increase and subsequent fall in VIII:C activity, similar to thrombin.
    • The reaction was inhibited by a factor IX inhibitor.
    • Only VIII:C was affected; VIII:RP levels remained unchanged.
    • Phospholipid enhanced factor VIII activation by factor IXa.
    • High concentrations of diisopropylfluorophosphate and hirudin inhibited the reaction.

    Conclusions:

    • Factor IXa can activate factor VIII coagulant (VIII:C) activity in a manner qualitatively similar to thrombin.
    • This interaction is specific to VIII:C and is influenced by phospholipid.
    • Factor IXa may act as an initial activator of factor VIII in the intrinsic coagulation cascade, especially at high local concentrations.

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