Aspirin, other NSAIDs, inhibitors of the platelet P2Y12 ADP receptor (eg, clopidogrel, prasugrel, ticagrelor), and glycoprotein IIb/IIIa receptor inhibitors (eg, abciximab, eptifibatide, tirofiban) may induce platelet dysfunction. Sometimes this effect is incidental (eg, when the drugs are used to relieve pain and inflammation) and sometimes therapeutic (eg, when aspirin or the P2Y12 inhibitors are used for prevention of stroke or coronary thrombosis).

Aspirin and NSAIDs prevent cyclooxygenase-mediated production of thromboxane A₂. This effect can last 5 to 7 days. Aspirin modestly increases bleeding in healthy people but may markedly increase bleeding in patients with underlying platelet dysfunction or a severe coagulation disturbance (eg, patients receiving heparin, patients with severe hemophilia). Clopidogrel, prasugrel, and ticagrelor all can markedly reduce platelet function and increase bleeding.

A number of other drugs can also cause platelet dysfunction (1).

Many disorders (eg, myeloproliferative and myelodysplastic disorders, uremia, macroglobulinemia, multiple myeloma, cirrhosis, SLE) can impair platelet function.

Uremia prolongs bleeding via unknown mechanisms. If bleeding is observed clinically, bleeding may be reduced with vigorous dialysis, cryoprecipitate administration, or desmopressin infusion. If necessary, increasing the hemoglobin concentration to > 10 g/dL by transfusion or by giving erythropoietin also reduces bleeding.

As blood circulates through a pump oxygenator during cardiopulmonary bypass, platelets may become dysfunctional, prolonging bleeding. The mechanism appears to be activation of fibrinolysis on the platelet surface with resultant loss of the glycoprotein Ib/IX binding site for von Willebrand factor. Regardless of platelet count, patients who bleed excessively after cardiopulmonary bypass are often transfused with platelets. Giving aprotinin (a protease inhibitor) during bypass may preserve platelet function and reduce the need for transfusion.