[Synergistic inhibition of thrombocyte activation by drugs added in pairs]

Synergistic activity on human platelets can be observed between two platelet agonists administered in threshold doses ("threshold synergism"). We were therefore interested to learn whether certain drugs known to inhibit platelet activation at high concentrations also exert a synergistic inhibitory activity if added in pairs at threshold doses to the platelets prior to activation. Samples of platelet-rich plasma were preincubated with either single drugs or pairs of drugs or saline (control). Platelet activation was performed in an aggregometer. Activation was registered as aggregation; in addition, either release of serotonin or beta-thromboglobulin was measured. All six drugs tested (propranolol, diclofenac, dipyridamole, theophylline, verapamil, ceftriaxone) clearly exhibited--independently of their inhibitory mechanisms--an additive or even synergistic inhibition of platelet activation if given in pairs. This finding may explain the clinical observation that patients under treatment with two or more such drugs develop a functional defect of platelets as the only explanation for an acquired hemorrhagic diathesis.