Key result
Pre-mixing ZK 36374 with heparin blunts ADP-induced platelet inhibition but markedly enhances thrombin-induced inhibition.
Why the study?
Prostacyclin and heparin are often administered concurrently to maximize anticoagulant effect, but their interaction on platelet function is unclear.
Does the combination of ZK 36374 and heparin alter platelet aggregation and calcium mobilization compared to either agent alone?
Population
Platelets loaded with fluorescent calcium indicator Quin 2 in vitro
Comparison
ZK 36374 alone, heparin alone, and their combination
Design
Preclinical study using standard aggregometry and calcium mobilization assays
Authors
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Agonist-specific ZK 36374-heparin interaction may modify antiplatelet effects; leaves open human relevance and mechanistic studies.
Does the combination of ZK 36374 and heparin alter platelet aggregation and calcium mobilization compared to either agent alone?
Heparin interacts with the prostacyclin analogue ZK 36374, antagonizing its anti-aggregatory effect against ADP but enhancing its effect against thrombin.
Yardumian et al. (1987) studied this question. ZK 36374 and heparin combination vs. ZK 36374 alone and heparin alone was evaluated on Platelet aggregation and intra-platelet calcium mobilization in response to ADP and thrombin. Pre-mixture of ZK 36374 with heparin interfered with its ability to inhibit ADP-induced platelet aggregation and calcium flux, but markedly enhanced inhibition when thrombin was the agonist.
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