Heparin neutralization of antiplatelet effect of aspirin and dipyridamole.
Heparin is used as an anticoagulant for treatment or prevention of thromboembolism. Heparin has been shown also to 1) stimulate platelet aggregation and platelet release reaction, 2) enhance thromboxane A2 production in platelets, and 3) neutralize prostacyclin, a potent inhibitor of platelet aggregation. In the light of these observations, the effect of heparin on two commonly used antiplatelet agents, aspirin and dipyridamole, was investigated. It was noted that heparin reversed the antiplatelet effect of both aspirin and dipyridamole although the effect was relatively more pronounced with aspirin. Presence of aspirin in blood in vitro as well as in vivo resulted in the inhibition of release reaction and the secondary wave of platelet aggregation. In the presence of heparin, platelets previously treated with aspirin showed nearly normal platelet aggregation as well as the release reaction. This reversal by heparin of the inhibitory effect of aspirin was dose dependent; the neutralization of inhibitory effect being more pronounced as the concentration of heparin was increased at a given concentration of aspirin. The neutralization of antiplatelet effect of aspirin was observed in vitro as well as in vivo and whether heparin was added before or after the addition of aspirin. These observations suggest the need for caution in the event heparin and antiplatelet agents are administered concurrently.
Mohammad
S F
SF
Division of Artificial Organs, University of Utah, Salt Lake City 84103.
Kim
S W
SW
Olsen
D B
DB
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000037:antagonists & inhibitors*; D001792:Blood Platelets / Q000378:metabolism; D002417:Cattle; D000242:Cyclic AMP / Q000097:blood; D004176:Dipyridamole / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006494:Heparin Antagonists; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000097:blood
D006494:Heparin Antagonists; D013928:Thromboxane A2; D004176:Dipyridamole; D006916:5-Hydroxytryptophan; D000242:Cyclic AMP; D001241:Aspirin