Daunomycin and Platelet Function

Daunomycin, an antimetabolite antibiotic used in the treatment of acute leukemia, is highly cytotoxic to both normal and malignant cells. Thrombocytopenia occasionally noted with its use, has usually been attributed to its toxic effect on the bone marrow. Citrated platelet-rich plasma (PRP) from normal volunteers was tested in vitro in the aggregometer after addition of either aggregating agent, collagen, (0.083 mg/ml PRP), or varying concentrations of daunomycin, or both. Other aliquots were exposed to daunomycin or saline for 90 seconds before fixing in glutaraldehyde. The remainder, labelled with 0.5 μM 2⁻¹⁴C-5-hydroxytryptamine binoxalate (¹⁴C-5-HT), 27.5 c/mole for 15 minutes, was tested for ¹⁴C-5-HT release before and after exposure (90 sees. 37° C) to collagen of final concentration 0.04 mg/ml.

At a concentration 0.001 mg/ml PRP, daunomycin was associated with decreased response of platelets to collagen with decreased ¹⁴C-5-HT release. At 0.02–0.04 mg/ml daunomycin was associated with vacuole formation, loss of dense bodies as well as platelet lysis as well as liberation of newly absorbed ¹⁴C-5-HT. Electron micrographs of platelets exposed to higher doses of daunomycin showed platelet swelling, vacuole formation, swollen mitochondria and granules and interruption of the trilaminar membrane.