No abstract

SummaryThe influence of Daunorubicin on some platelet functions in vitro was investigated, using different concentrations of the drug (0.01-0.02-0.04 μg/ml). Daunorubicin was shown to inhibit Collagen and Thrombin induced platelet aggregation and the intensity of inhibition depended on both drug concentration and the time of preincubation.Daunorubicin was also shown to inhibit the release reaction, the platelet prostaglandin pathway and the availability platelet factor 3; the drug at concentrations for clinical use does not damage the platelet membrane, as is the case with the freezing and thawing test, in platelet uptake of 14C-serotonin and as confirmed by the electron microscope. When very high doses (0.16 mg) of Daunorubicin are used, lysis of the platelets can be observed and this is confirmed under the electron microscope by the presence of empty platelets with fractures at the level of the cytoplasmic membrane.Finally, Daunorubicin causes irreversible inhibition of reptilase clot-retraction, even if this is less severe than with Vincristine. Working with gel-filtered platelets, it would appear that the inhibition exercised by the drug on platelet reactions is not caused through modifications in Ca++ metabolism.The authors suggest that Daunorubicin, at the dosages used clinically, induces in vitro thrombocytopathy without damaging the cellular membrane as confirmed by the electron microscope.This impairment of platelet functions could play a part in hemorrhagic diathesis observed during Daunorubicin therapy.

Platelet 14C-serotonin release induced by collagen, and platelet malondialdehyde (M.D.A.) generation induced by thrombin were assessed in twenty patients with stable angina, before and after exercise with a bicycle ergometer. The patients received a single oral 200 mg dose of indobufen or placebo according to a crossover design in double-blind conditions. The M.D.A. concentration increased when exercise was carried out after placebo, whereas indobufen markedly inhibited M.D.A. production and 14C-serotonin release. These results suggest that effort may be an important factor in activation of the platelet prostaglandin pathway and that the use of antithrombotic drugs may be appropriate in patients with angina.

Platelet aggregation induced by 3 concentrations of ADP and collagen was assessed in thirty patients with stable angina, before and after exercise with a bicycle ergometer. The patients received a single oral 200 mg dose of indobufen and placebo according to a crossover design in double-blind conditions. Platelet sensitivity to both aggregating agents increased when exercise was carried out after placebo, whereas indobufen markedly inhibited ADP- and collagen-induced aggregation. Circulating platelet aggregates increased in some patients during exercise after placebo but not after indobufen. These results suggest that effort may be an important factor in activation of platelet functions and that the use of drugs blocking the arachidonate pathway and the release reaction may be appropriate in patients with angina.

A platelet function study in a patient with megakaryoblastic leukaemia is reported. The abnormalities of the platelet function suggest a probable platelet membrane injury and a platelet release defect. The reduced platelet half-life and the non changing splenohepatic ratio confirm the clinical and histological features of the systemic disease.