Effects of cytarabine and various anthracyclins on platelet activation: Characterization of in vitro effects and their possible clinical relevance inacute myelogenous leukemia

Previous in vitro studies have demonstrated that normal platelets and plate let-released mediators can alter in vitro characteristics of human acute my elogenous leukemia (AML) blasts. To further investigate whether platelets c an be expected to adhere to and thereby affect AML blasts through their rel ease of soluble mediators into a common microenvironment, we investigated ( i) the effects on platelet activation by cytotoxic drugs commonly used in A ML therapy; (ii) the occurrence of circulating activated platelets in acute leukemia patients; and (iii) the in vivo and in vitro adherence of platele ts to AML blasts. The anthracyclins daunorubicin and idarubicin increased t he expression of activation-associated membrane molecules (GPIIb/IIIa, CD62 P, CD63) by normal platelets, daunorubicin then having the strongest effect . In contrast, cytarabine, epirubicin, doxorubicin and mitoxantrone had no significant effects. Although AML patients did not show increased levels of activated platelets in the circulation, adhesion of platelets to AML blast s was demonstrated both in vivo and in vitro. These results suggest that pl atelets and AML blasts may locate to common in vivo microenvironments, and platelet-derived soluble mediators may thereby affect the functional charac teristics of the leukemia cells. (C) 2002 Wiley-Liss, Inc.