Activated Coagulation Factors: In‐Vivo and in‐Vitro Studies

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Summary: In the course of serial coagulation studies on patients with acute leukaemia, defibrination was frequently encountered in the lymphoblastic, myeloblastic and promyelocytic varieties of the disease. Factor‐VIII levels were often high and varied very considerably, a particular phenomenon being the association at times of very high one‐stage levels with decreased two‐stage levels. In one patient heparin infusion was associated with a rise in the two‐stage Factor‐VIII level and cessation of the infusion with a prompt drop in level. Less frequently, gross elevation of one‐stage Factor‐XI activity occurred compared with two‐stage (eluate test) levels. In order to study possible mechanisms for the phenomena observed, the effect of adding various pro‐coagulants to normal plasma on the one‐ and two‐stage methods for measuring Factors VIII, IX and XI was studied. Thrombin caused a marked rise in one‐stage Factor‐VIII activity and a much smaller rise in one‐stage Factor IX and XI measurements. Two‐stage Factor‐VIII activity was reduced and Factors IX and XI little affected. These findings simulate some of the findings in vivo. The effect of activated Factors IX, X and XI on the one‐stage activity of Factors VIII, IX and XI may be explained by assuming that an activated product increases the one‐stage activity of any factor which participates in the clotting reaction sequence at a stage preceding the formation of the product. The actual findings were that an activated Factor‐X preparation increased one‐stage Factors VIII, IX and XI measurements; an activated Factor‐IX preparation considerably increased one‐stage Factor IX and XI measurements but affected Factor‐VIII activity only when used at very high concentrations; an activated Factor‐XI preparation did not affect Factor VIII, IX or XI one‐stage activity. None of these three activated products influenced the two‐stage measurements of Factors VIII, IX and XI. Tissue thromboplastin increased one‐stage Factor VIII, IX and XI activity to a similar extent, did not influence two‐stage Factor VIII and IX measurements and slightly increased two‐stage Factor‐XI activity.

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