INFLUENCE OF CYTOTOXIC DRUGS ON PLATELET FUNCTIONS AND COAGULATION INVITRO .4. MELPHALAN

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (1) , 53-61
Abstract
Influence of the antitumor agent melphalan on some human platelet functions, plasmatic coagulation and fibrinolysis in vitro was investigated, using different concentrations of the drug (25, 50 and 250 .mu.g/ml). The lowest concentration slightly inhibited adrenaline and/or collagen induced platelet aggregation. Following the highest concentration of the drug, strong inhibition of aggregation was recorded, regardless of the inducer used. Melphalan also inhibited release of aggregating activity and release of platelet factor 4, as well as availibility of platelet factor 3 and platelet acid phosphatase. The intensity of inhibition depended on melphalan concentration and the time of preincubation. In contrast to this, adhesion of platelets to glass slides was not influenced by melphalan. Melphalan did not induce (in any concentration) loss of LDH [lactate dehydrogenase] from platelet cytoplasm, while Triton X-100 or freezing and thawing of platelets caused a significant increase of LDH activity. From coagulation tests studied, only thrombin time and reptilase time was moderately prolonged in the presence of melphalan. Melphalan acts as a specific inhibitor of the release reaction and can induce acquired thrombocytopathy. The platelet membrane is not damaged by the drug, as was confirmed by the investigation of LDH activity. Influence on coagulation indicates some antithrombin effect of the drug. Although the presented results were obtained in vitro, analogous changes in vivo could be suspected. Impairment of platelet functions might play a part in hemorrhagic complications accompanying melphalan therapy.

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