Platelet interaction with a pancreatic ascites tumor.
The mechanism leading to the hypercoagulability in pancreatic carcinoma is unclear. The rapid progress of the disease after its diagnosis and the inaccessibility of the tumor make studies on the mechanism difficult in man. With the successful induction of this malignancy and conversion of it into an ascites tumor in Syrian golden hamsters, interactions between isolated tumor cells and individual hemostatic components can be investigated. In this paper, studies on in vitro tumor cell-platelet interactions and some hemostatic changes in hamsters following intravenous injection of isolated tumor cells are described. Freshly isolated tumor cells and tumor-cell sonicates, but not those that had been kept at 4 or -70 C overnight, induced comparable aggregation of human platelets in both heparinized and citrated platelet-rich plasmas (hPRP and cPRP). The aggregation was not followed by clot formation; a specific synthetic thrombin inhibitor had no effect on the aggregation in either hPRP or cPRP. Washed and gel-filtered platelets, even in the presence of 5% of citrated or heparinized platelet-poor plasma (cPPP or hPPP) failed to be aggregated by tumor cells. Tumor-cell-induced platelet aggregation was accompanied by thromboxane formation and serotonin release, both of which were several orders of magnitude greater in cPPP than in hPRP. Aspirin, apyrase, and PGI2 all inhibited tumor-cell-induced platelet aggregation in both PRPs, but the inhibition by aspirin was minimal. Intravenous infusion of isolated tumor cells into normal hamsters resulted in a 50% reduction of platelet count and a 20-30% decline in antithrombin III and fibrinogen. Platelet aggregates and fibrin strands were seen in the lungs of these animals.
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001081:Apyrase / Q000494:pharmacology; D001201:Ascites; D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D011464:Epoprostenol / Q000494:pharmacology; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008647:Mesocricetus; D008854:Microscopy, Electron; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000648:ultrastructure; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D012701:Serotonin / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D012701:Serotonin; D013929:Thromboxane B2; D000990:Antithrombin III; D005340:Fibrinogen; D011464:Epoprostenol; D001081:Apyrase; D001241:Aspirin