Activation of blood coagulation in cancer: Trousseau's syndrome revisited.

T HREE TYPES of evidence exist that support an important relationship between blood coagulation and tumor homeostasis: clinical, histologic, and pharmacologic. Clinical and laboratory evidence focuses on the well known propensity of patients with certain forms of cancer to develop thromboembolic disease (TED) and/or disseminated intravascular coagulation (DIC), commonly observed following rapid tumor lysis or surgical manipulation. The postmortem observations of platelet and fibrin thrombi in vessels draining tumors and the immunochemical demonstration of fibrin surrounding tumor cells have provided incontrovertible histologic evidence for an association between growing tumors and the end-products of blood coagulation, e.g., platelet aggregates and fibrin. The specificity of these reactions, however, remains uncertain. The positive results of pharmaco-. logic intervention with anticoagulant drugs and/or antiplatelet agents in animal tumor models and in human cancer have also supported the notion that a “hypercoagulable” state associated with cancer is disadvantageous to the host. Thus, local or systemic activation of blood coagulation can be produced by tumor products and favors tumor spread, while interruption of blood coagulation reactions, in general, favors the host and impairs tumor metastasis. The effect of blood coagulation on the growth of the primary tumor is less well defined, with some studies suggesting a beneficial effect and others demonstrating an inhibitory effect on the tumor growth. We will summarize briefly the studies that have provided the three types of evidence described, and we will detail the concepts regarding the pathogenesis of these abnormalities of blood coagulation. We will then assess the potential pathways for activation of blood