Cumulative effects of quinidine and aspirin on bleeding time and platelet alpha 2-adrenoceptors: potential mechanism of bleeding diathesis in patients receiving this combination.
We observed quinidine-induced prolongation of bleeding time without thrombocytopenia in three subjects. In addition, we noticed a cumulative prolongation of bleeding time by a combination of quinidine and aspirin. We postulated that because both quinidine and aspirin inhibit epinephrine-induced platelet aggregation, a cumulative effect of the two drugs might be responsible for the hemostatic defect. In studies using normal human platelets, we confirmed a marked reduction in epinephrine-induced platelet aggregation by the combination of these two agents. To further study the potential mechanism of this cumulative effect, platelet lysates were incubated with the alpha 2-adrenoceptor antagonist tritiated yohimbine in the presence of quinidine and aspirin. On the basis of the radioligand binding data, the dissociation constant (KD) of alpha 2-adrenoceptors was observed to increase in the presence of quinidine as well as aspirin. The combination of these two agents caused a marked increase in the KD of platelet alpha 2-adrenoceptors without alteration in the number of receptor sites. These data suggest that the cumulative effects of quinidine and aspirin on platelet alpha 2-adrenoceptor KD may relate to the significant reduction in epinephrine-induced platelet aggregation. This phenomenon, coupled with other well-known effects of aspirin on the platelet release reaction and arachidonate metabolism, may lead to bleeding problems in some patients receiving this combination.
D001241:Aspirin / Q000494:pharmacology*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004198:Disease Susceptibility; D004347:Drug Interactions; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D011802:Quinidine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000097:blood*
D011942:Receptors, Adrenergic, alpha; D011802:Quinidine; D001241:Aspirin