Cancer and thrombosis: from Phlegmasia alba dolens to transgenic mice.
Thrombosis is the most frequent complication and the second cause of death in patients with overt malignant diseases. Increasing evidence suggests that thrombotic episodes may also precede the diagnosis of cancer by months or years thus representing a potential marker for occult malignancy. Recently, emphasis has been given to the potential risk of cancer therapy (both surgery and chemotherapy) in enhancing the risk for thromboembolic disease. Post-operative deep-vein thrombosis is indeed more frequent in patients operated for malignant diseases than for other disorders. On the other hand, both chemotherapy and hormone therapy are associated with an increased thrombotic risk, which can be prevented by low-dose oral anticoagulation. Possible contributory causes for thromboembolic disease in cancer include the capacity of tumor cells and their products to interact with platelets, clotting and fibrinolytic systems, as well as their interactions with endothelial cells and tumor-associated macrophages. In particular, procoagulant activities of tumor cells have been extensively studied; one of these, cancer procoagulant, could represent a novel marker of malignancy in both solid tumors and acute promyelocytic leukemia (APL). In solid tumors, CP, a vitamin K dependent enzyme could represent the selective target of the antimetastatic effects of warfarin treatment. In APL, CP may contribute to trigger the well known intravascular coagulation syndrome accompanying the early manifestations of the disease and is depressed by all-trans-retinoic acid, an agent capable to determine complete remission with a rapid amelioration of the bleeding syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Donati
M B
MB
Laboratory of Thrombosis Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D003546:Cysteine Endopeptidases / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D006728:Hormones / Q000009:adverse effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000150:complications; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000150:complications* / Q000628:therapy; D009374:Neoplasms, Experimental / Q000150:complications; D009382:Neoplasms, Unknown Primary / Q000150:complications; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D013924:Thrombophlebitis / Q000209:etiology* / Q000503:physiopathology; D013925:Thromboplastin / Q000502:physiology
D000970:Antineoplastic Agents; D006728:Hormones; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D013925:Thromboplastin; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant