Simplification of the Concept of Coagulation by Revival of the Inhibitor Theory

Summary

It is proposed that there are only two factors essential for the conversion of prothrombin to thrombin : vitamin K dependent factor (KDF) and antihemophilic factor (AHF). In order to form the reaction complex for the conversion of prothrombin to thrombin, a KDF – calcium molecule and an AHF molecule, each bearing an active site, become bound on the surface of a lipid thromboplastin particle and the inhibitor initially associated with the KDF and AHF shifts to KDF and AHF molecules which are directly adjacent on the thromboplastic surface and which have inhibitor receptor sites free. In different abnormalities of coagulation KDF and AHF exist in multiple molecular forms varying with respect to presence or absence and steric location of active sites, inhibitor receptor sites and inhibitor. Thus in different abnormahties of coagulation KDF or AHF may be inactive for different reasons and mixed populations of abnormal KDF and AHF can supplement each other to form the reaction complex which requires only two molecules. This is a simpler concept than one requiring a separate essential factor and a separate reaction step to explain each different abnormality. Evidence is presented for this point of view.

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