Inhibitor of Blood Clotting Derived from Prothrombin

Abstract

SummaryPurified prothrombin was dissociated with thrombin and one of the three main degradation products was separated as a protein and found to be a competitive inhibitor of autoprothrombin C. Relatively large amounts were needed to inhibit the generation of thrombin activity. This slowing of thrombin generation occurred whether prothrombin or prethrombin was the source of thrombin. The main evidence is consistent with the view that the inhibitor originates from the prethrombin portion of prothrombin.

The localization of a vitamin K-induced modification in an N-terminal fragment of human prothrombin

“…The appearance of fragment PF-I during coagulation may therefore contribute to the limitation of the conversion of prothrombin into thrombin in vivo. The inhibitor observed in bovine prothrombin preparations treated with thrombin (Marciniak et al, 1967), and the corresponding activity obtained from human blood (Marciniak, 1972), might well be similar to or identical with fragment PF-I.…”

Protein C and S Deficiency

“…1 Seven years later, this protein factor, termed autoprothrombin-IIA, was purified by Marciniak and colleagues who, like Mammen, demonstrated prolonged plasma clotting times in the presence of autoprothombin-IIA. 2 In 1976, Stenflo characterized the vitamin K-dependent proteins and separated them by ion-exchange chromatography into four peaks, designated A through D. 3 The protein in the third of Stenflo's four peaks (peak C) was found by Seegers to be immunologically identical to autoprothrombin-IIA, thus the designation protein C (PC). 4 De spite this early work it was not until 1981 that Griffin et al described the first known heterozygous protein C defi ciency state in a 21-year-old male with a protein C level of 41% and recurrent thrombophlebitis.…”

VIII. Protein C and Autoprothrombin II-A

“…At the threshold of the surge in the development of protein fractionation and analytical techniques a nice separation (Fig. 1) of prethrombin 1, autopro thrombin II-A, and β-Factor X was made (Seegers and Marciniak 1965;Marciniak, Murano and Seegers 1967). This was done by chromatography on a DEAE-cellulose column.…”

“…In competitive inhibition (Marciniak, Murano and Seegers 1967;Murano, Seegers and Zolton 1974), it was possible to override the inhibition by adding more Factor V. Factor VIII and V were thus likely susceptible components. Activation of prethrombin 1 with trypsin was also retarded.…”