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Date of Award

3-1988

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Professor Morris A. Blajchman

Abstract

A method for the preparation of human prothrombin fragment 1.2 (F1.2) from freshly clotted plasma was developed. Addition of exogenous F1.2 to citrated nonnal human plasma prolonged prothrombin time and activated partial thromboplastin time by 0.9 and 2.4 s/μM Fl.2, respectively. Delayed thrombin generation was not attributed to inhibition of tissue factor activity nor inhibition of factor X activation but to interference with phospholipid interactions in the prothrombinase complex. In mice, 500 μg (14 μM) of F1.2 gave 100% protection from tissue factor lethality, whereas 6 units (3 μM) of heparin was required for 100% protection. Either dose of F1.2 or heparin protected mice from thrombin-induced death. However, 500 μg of F1.2 was not effective in protecting mice from lethal effect of factor Xa and cephalin, while 0.75 units of heparin prevented such lethality. These findings demonstrate that human prothrombin F1.2 has anticoagulant and antithrombotic properties.

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