Calcium entry blockers and human platelet aggregation

It has been hypothesized that calcium entry blocking agents inhibit platelet aggregation by decreasing calcium flux across the thrombocyte membrane. Previous studies have given equivocal results, demonstrating decreased platelet aggregation in vitro, but only at concentrations of calcium blockers far above the therapeutic range. Nevertheless, bleeding time is mildly prolonged in patients taking these drugs. We have attempted to resolve this paradox by determining the effect of diltiazem and verapamil, in therapeutic concentrations, on collagen and adenosine diphosphate (ADP)-induced platelet aggregation in vitro. Both diltiazem (180 ng/mL and 360 ng/mL) and verapamil (300 ng/mL, 500 ng/mL, and 1,000 ng/mL) produced significant decreases in collagen-induced platelet aggregation. While this effect was statistically significant, its absolute magnitude was unlikely to have clinical significance. Neither drug produced a significant decrease in ADP-induced platelet aggregation. These results suggest that the effect of calcium entry blockers on platelet aggregation should not be a serious concern for surgical patients whose platelet function is not otherwise compromised.