Thromb Haemost 1969; 21(01): 181-195
DOI: 10.1055/s-0038-1653527
Originalarbeiten - Original Articles - Travaux Originaux
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Factor V and Thrombin in the Intrinsic Clotting System[*]

J. H Ferguson
1  Department of Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, U.S.A
,
Ella Gray W. Ennis
1  Department of Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, U.S.A
,
S Hitsumoto
1  Department of Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, U.S.A
,
Norma B. White
1  Department of Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, U.S.A
› Author Affiliations
Further Information

Publication History

Publication Date:
10 June 2018 (online)

Summary

Allegedly factor V 1-stage bioassays and an established mode of 2-stage thrombingeneration tests are performed with three alternative prime activators : (A) thrombokinase; (B) Russell’s viper venom (Stypven); (C) tissue thromboplastin (Simplastin), each with adequate cofactors. Study of effects of thrombin and factor V mixtures or preincubates shows a marked apparent potentiation in the 1-stage tests, but no real evidence of such in the 2-stage methods, although these are equally sensitive to changes in factor V activity. Cited (13) new observations in the 1-stage experiments record: (a) that no preincubation of thrombin and factor V is necessary; (b) that thrombin-treated factor V (= Vt) potentiates anew with a second thrombin addition ; and (c) that Vt + thrombin again shows a shift in the Sephadex G-200 elution pattern similar to the difference between the original V and Vt. These facts all constitute a convincing refutation of the theory that factor V is activated by thrombin to a postulated ‘Va’. What is obviously needed is a complete reinterpretation of the uniquely 1-stage results. A novel approach is based on testings of selective combinations of the 5 basic components (prothrombin, thrombokinase, Ca++, phospholipid, and factor V) required for thrombin generation by <1 ìg/ml thrombokinase. The results permit the conclusion that the true explanation is to be found in activities of the prime activator, especially thrombokinase, as controlled by availabilities of the 3 cofactors, namely, factor V, Ca++ions, and phospholipid. Factor V was previously shown to be a determinant of thrombokinase activity during thrombin generation. In no way should the evidence be misinterpreted as any V → Va activation. A new enzymic and colloidal clotting mechanism (12) is reaffirmed, in which factor V has a dual role.

* Supported by USPHS Research Grant No. HE-01510.