The activation of coagulation by extracts of mucus: a possible pathway of intravascular coagulation accompanying adenocarcinomas.

Abstract

Abstract Intravascular coagulation (thrombosis or defibrination) is frequently associated with mucin-producing adenocarcinomas. Studies are reported which test the hypothesis that mucus entering the circulation might activate coagulation and determine the site of activation. Extracts of human mucus had procoagulant activity. Partial purification of the mucus extracts was achieved and the product had remarkable stability, the procoagulant activity being resistant to a variety of physicial conditions and chemical agents. The active material had a high carbohydrate-to-protein ratio and contained very little phospholipid material. The partial thromboplastin time of plasmas deficient in factors XI, IX, VIII, VII, and partially deficient in X was corrected by addition of the mucus extracts. In a two-stage factor X activation test the extract activated factor X in the presence of Ca ++ and had a potency comparable to Russell's viper venom at a concentration of 50 μg per milliliter. There were no effects on other coagulation factors or directly on platelets. In addition factor VII was not required for activity. Thus, the procoagulant activity of the mucus extract is markedly different from that of tissue thromboplastin. The intravenous infusion of partially purified mucin into rabbits which had received 131 I-fibrinogen lead to an increased rate of fibrinogen disappearance from the plasma, whereas fractions with no procoagulant effect had no comparable effect. These findings suggest that mucus, on entering the circulation, can activate coagulation and may explain the frequency of coagulation disorders in patients with mucin-producing adenocarcinoma.