THE THROMBOSTAT SYSTEM - A USEFUL METHOD TO TEST ANTIPLATELET DRUGS AND DIETS

The use of platelet inhibitory drugs, like aspirin, has resulted in a significant reduction of thrombotic complications in primary and secon dary prevention of heart attacks. To find more effective substances or better drug combinations, inhibition of primary hemostasis in vitro ( Thrombostat system) was investigated, with different drugs and fish di et, using small samples (1 ml) of anticoagulated (Na- citrate 3.8%, 1/ 9) human blood. Results: 1. In the presence of 1 mM aspirin, which had no effect on bleeding volume, only 0.6 nM iloprost were necessary to show a 50% inhibition, in contrast to 2.5 nM without aspirin. 2. At as pirin concentrations of 1 mM, 50% inhibition of primary hemostasis cou ld be achieved with 20 mu M SIN-1, or with 7 mu M SIN-1 together with iloprost (500 pM). The same effect was seen only with very high doses of SIN-1 (1000 mu M) alone. 3. For 50% inhibition of primary hemostasi s in vitro, RGDS concentrations were reduced from 250 mu M to 160 mu M when blood was pretreated with 1 mM aspirin and to 75 mu M when 500 p M iloprost were added additionally. 4. Japanese fishermen (eating 270 g fish/day) demonstrated significantly longer in-vivo bleeding times a nd in-vitro bleeding volumes (6.49 min/224 mu l), respectively, as com pared to Japanese farmers (90g fish/day, 4.85 min/137 mu l). 5. In Jap anese subjects in-vivo bleeding times correlated with in-vitro bleedin g volumes (0.69). The Thrombostat system proved to be a sensitive meth od to detect synergistic effects of various antiplatelet drugs in vitr o and of a platelet inhibitory diet ex vivo.