Effect of low concentrations of prostacyclin on platelet function in vitro.
The study was performed to determine the possible direct effects of low concentrations of prostacyclin that might spill over into the systemic circulation during the administration of inhaled aerosolized prostacyclin. Platelet aggregation in response to adenosine diphosphate and collagen, as well as measurement of the maximum amplitude of the thrombelastograph (TEG), was undertaken in vitro using venous blood exposed to low concentrations of prostacyclin (0, 10, 100 and 500 pg/ml) from eight healthy volunteers. There were statistically significant reductions in parameters of platelet aggregation in response to the agonists adenosine diphosphate (1 mumol/l and 8 mumol/l) and collagen (10 mumol/l) following exposure to as little as 10 pg/ml of prostacyclin. The maximum amplitude of the TEG was unchanged over the entire range of prostacyclin concentrations studied. The results indicate that low concentrations of prostacyclin or prostacyclin metabolite such as may be observed during inhaled aerosolized prostacyclin therapy are likely to be associated with a marked platelet aggregation defect. This defect was not detected by the TEG.
van Heerden
P V
PV
Department of Intensive Care, Sir Charles Gairdner Hospital, Perth, Western Australia.
Gibbs
N M
NM
Michalopoulos
N
N
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D003094:Collagen / Q000494:pharmacology; D011464:Epoprostenol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D013916:Thrombelastography
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003094:Collagen; D011464:Epoprostenol