The relative importance of the factors II, VII, IX and X for the prothrombinase activity in plasma of orally anticoagulated patients.
The individual importance of each of the four vitamin K-dependent clotting factors on the generation of prothrombinase activity in the plasma of orally anticoagulated patients has been investigated. Addition of purified factors VII, IX or X to plasma from deeply anticoagulated patients (International Normalized Ratio 2.8-4.8) did not influence the amount of prothrombinase activity or the amount of thrombin formed. Only the prothrombin level in the plasma determines the course of thrombin generation. Addition of increasing amounts of purified factor II, VII, IX or X to plasmas deficient in respectively factor II, VII, IX or X showed that the prothrombinase activity increases linearly with the concentration of factor II added and that the concentration below which the factors VII, IX and X start to have a measurable effect on prothrombinase activity are 5%, 20%, and 30%, respectively. Half maximal prothrombinase activity was found at about 1% factor VII, 5% factor IX and 8% factor X respectively. From these observations we conclude that primarily the variation in factor II level determines thrombin generation and hence presumably the antithrombotic effect of oral anticoagulant therapy. It therefore seems likely that, for the control of oral anticoagulant therapy, tests that reflect factor II activity would be suitable.
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Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
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D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000502:physiology*; D005164:Factor IX / Q000502:physiology; D005167:Factor VII / Q000502:physiology; D005170:Factor X / Q000502:physiology; D006801:Humans; D011516:Prothrombin / Q000502:physiology; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000302:isolation & purification / Q000378:metabolism*
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; D013925:Thromboplastin; D013917:Thrombin