PARTIAL INHIBITION OF PLATELET-AGGREGATION BY NEBULIZED PENTAMIDINE IN SEVERE HEMOPHILIACS

The antiparasite agent pentamidine has been shown to inhibit human pla telet aggregation in vitro at concentrations that (potentially) may be attained in patient plasma after the administration of the drug by ne bulizer. We measured platelet aggregation in platelet-rich plasma (PRP ) before and after the administration of 300 mg nebulized pentamidine to 10 HIV-positive patients with severe haemophilia on prophylaxis aga inst Pneumocystis carinii pneumonia. All patients had normal platelet counts. PAF-acether, U46619, collagen and ADP at different concentrati ons were used as agonists. Platelet aggregation was lower in PRP sampl es taken at the end of pentamidine administration and Ih thereafter th an in samples taken at the same time points in control experiments (wi thout the administration of pentamidine). The inhibition of platelet a ggregation was mild and tended to be overcome by higher concentrations of platelet agonists. The bleeding time was prolonged from 5 to 15 mi n in one patient but did not change in the remaining nine patients. In conclusion, this controlled study shows that nebulized pentamidine in hibits platelet aggregation in HN-positive haemophiliacs without signi ficantly affecting their bleeding times. Although this mild inhibitory effect may not be clinically relevant in haemophiliacs with normal pl atelet counts despite their defect in intrinsic coagulation, patients with HIV-related thrombocytopenia should be monitored to detect any ex cessive prolongation of their bleeding times after nebulized pentamidi ne.