抄録
Hemorrhagic diathesis is often caused by antineoplastic drugs, especially the Anthracyclines used in the treatment of malignancy. In this respect, we investigated the effect of Anthracyclines, including Adriamycin (ADM), Daunomycin (DM), and Aclacinomycin (ACR) on platelet function and metabolism.
All these drugs inhibited ADP, collagen, and epinephrine-induced platelet aggregation in dose-dependent manner and the intensity of inhibition was DM, ADM, and ACR in order. ATP and 14C-5HT release reactions were also reduced by Anthracyclines in proportion to their inhibitory effects on the second phase of ADP-induced aggregation.
Coenzyme Q10 (Q10), known to alleviate such adverse action as cardiotoxicity and to increase the antineoplastic efficacy of ADM was shown to enhance the antiplatelet effects of ADM.
Thin layer radiochromatographic analysis of platelet arachidonate metabolism revealed that ADM at a high concentration cauced slight inhibition of thromboxane synthesis. Furthermore, the liberation of radioactivity from 14C-arachidonate-labeled platelets in response to collagen was reduced by ADM. Cyclic nucleotides levels in platelets incubated with ADM or Q10 did not show any significant change.
In conclusion, it is suggested that impairment of platelet functions by Anthracyclines is partially attributable to the decrease of phospholipase activity, but the precise mechanism remains unexplained.
