Effect of Prostacyclin (Epoprostenol) on the Aggregation of Human Platelets in Whole Blood in vitro

Abstract

Prostacyclin (PGI₂) is a potent endogenous inhibitor of platelet aggregation. The effect of PGI₂ on platelet aggregation and disaggregation in whole human blood was studied at 37 °C in vitro. Aggregation or disaggregation was quantified by counting single platelets using the recently developed Ultra Flo 100 Whole Blood Platelet Counter. Aggregation of platelets in whole blood was induced by arachidonic acid (AA, 400 μM), adenosine 5’-diphosphate (ADP, 10 μM), thrombin (0.1 U/ml) and collagen (1 μg/ml). At peak aggregation, each aggregating agent induced about a 90% fall in the number of single platelets counted. When whole blood was pre-incubated with PGI₂ (0.5–8 nM), it dose dependently inhibited aggregation of platelets induced by all four aggregating agents. Platelet aggregates induced by ADP or thrombin could rapidly be disaggregated by PGI₂ added to blood at peak aggregation. Disaggregation of collagen-induced platelet aggregation by PGI₂ was slow and minimal and it was completely ineffective in disaggregating AA-induced platelet aggregates. Unlike platelet-rich plasma, which is routinely used to study platelet aggregation, the present whole-blood method allows red and white blood cells to exert their influences on platelet function, and is an important step towards a physiological state for evaluating the effects of pharmacological agents on platelets in whole blood in vitro and ex vivo.

Platelet Function Studies during and after Infusions of ZK 36374, a Stable Prostacyclin Analogue, to Healthy Volunteers

“…We have confirmed previous reports that ZK 36374 inhibits platelet aggregation in a dose-dependent fashion after in vitro addi tion to PRP and whole blood [10,16]. There was variability in responsiveness to the drug within our study group as reflected by the widely differing percent inhibition of aggre gation observed in each of the volunteers.…”

Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity

“…Although our data show upregulated FAO in PH platelets, we did not observe a significant increase in platelet activation markers. This is potentially due to the majority of our cohort being treated with PC, which have been demonstrated to directly inhibit platelet activation (41)(42)(43). Further study is required to define the lipid profile of platelets from PH patients and to determine whether (in the absence of medication) altered platelet bioenergetics are linked to changes in platelet function in PH.…”

Effect of Iloprost (ZK 36 374), a Novel Prostacyclin Analogue, on ADP-induced Platelet Aggregation

“…Also, studies in which human platelets were incubated with ZK 36 374 de monstrated that the drug may be an even more power ful antiaggregating agent than PGI2 [8,10,11]. Fur ther, in human whole blood aggregation studies, ZK 36 374 caused disaggregation of preformed platelet aggregates [12].…”