Comparison of in Vivo and in Vitro Effects of Platelet Function Suppressing Drugs

Comparison of in vivo and in vitro platelet function tests to assess the antithrombotic efficacy of drugs which suppress platelet function have been contradictory. For example, aspirin (ASA) has a potent effect in vitro but little effect when tested on platelet survival in prosthetic heart valve replacements whereas dipyridamole (DIP) has little or no effect in vitro but a marked effect on platelet survival. We have compared in parallel the in vivo and in vitro effects of a number of drugs which suppress platelet function in an animal model. Rabbits were infused with homologous ⁵¹Cr-labelled platelets and then given either ASA (10-200 mg/kg), DIP (1-20 mg/kg) or sulfinpyrazone (SUF) (30-200 mg/kg) intravenously. One hour later PRP from each rabbit was tested by ADP and collagen-induced aggregation. Then each rabbit was infused with an identical final concentration of collagen and the subsequent recovery of ⁵¹Cr platelet radioactivity was monitored. In untreated rabbits collagen infusion produced 30% reduction of ⁵¹Cr platelets which returned to within 85% of a procollagen level by 5 min. ASA (⪖ 10 mg/kg) inhibited in vitro collagen-induced aggregation while a dose of 100 mg/kg of ASA was necessary to achieve the same inhibitory effect in vivo. On the other hand, DIP (1-20 mg/kg) had no inhibitory effect on in vitro platelet aggregation whereas it inhibited aggregation in vivo. The results of SUF were similar in vitro and in vivo. These results suggest that the effectiveness of drugs on platelet function may be affected by centrifugation, addition of anticoagulant or removal of red cells. This may explain the discrepancies reported between the in vivo and in vitro effectiveness of such drugs.