A phase 1 study of prasugrel in patients with sickle cell disease: Effects on biomarkers of platelet activation and coagulation
Autor: | Andrew L. Frelinger, Joseph A. Jakubowski, Stipo Jurcevic, Neehar Gupta, Chunmei Zhou, Jo Howard, Timothy Mant, Christopher D. Payne, D. Richard Lachno, Kenneth J. Winters |
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Rok vydání: | 2014 |
Předmět: |
Adult
Blood Platelets Male Prasugrel Anemia Sickle Cell Thiophenes Pharmacology Piperazines Young Adult Tissue factor P2Y12 hemic and lymphatic diseases medicine Humans Platelet Platelet activation Blood Coagulation Chemistry Hematology Middle Aged Platelet Activation Clopidogrel Adenosine Diphosphate Coagulation Immunology Purinergic P2Y Receptor Antagonists Female Glycoprotein IIb/IIIa Prasugrel Hydrochloride Biomarkers medicine.drug |
Zdroj: | Thrombosis Research. 133:190-195 |
ISSN: | 0049-3848 |
Popis: | Introduction Prasugrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist effectively inhibits ADP-mediated platelet activation and aggregation, and may be useful in reducing vaso-occlusive crises in sickle cell disease (SCD). In this study, we assess the effect of prasugrel on biomarkers of platelet activation and coagulation in patients with SCD. Materials and Methods Twelve adult patients with SCD and 13 healthy subjects were examined before and after 12 ± 2 days of 5.0 or 7.5 mg/day oral prasugrel. Assessed cellular biomarkers included monocyte- and neutrophil-platelet aggregates, activated glycoprotein IIb-IIIa (GPIIbIIIa), P-selectin, CD40 ligand (CD40L), tissue factor (TF) expression on circulating platelets and on monocyte-platelet aggregates, and platelet-erythrocyte aggregates. Soluble biomarkers included CD40L, prothrombin fragment 1.2 (F1.2), thromboxane B2 (TXB2), P-selectin, and TF. Results Patients with SCD had increased platelet baseline activation compared to healthy subjects, as measured by percentages of monocyte-platelet aggregates, neutrophil-platelet aggregates, and platelets expressing CD40L. Likewise, baseline levels of soluble F1.2 and TXB2 were elevated in patients with SCD compared to healthy subjects. After 12 days of prasugrel, patients with SCD had a significant reduction in platelet-monocyte aggregates that was not observed in healthy subjects. Following prasugrel administration, those with SCD maintained higher levels of monocyte-platelet aggregates and soluble F1.2, but had lower levels of platelet-erythrocyte aggregates and soluble TF compared to healthy subjects. Conclusions These results provide evidence for chronic platelet activation in the SCD steady state, activation that was in part attenuated by prasugrel, thereby suggesting that ADP may mediate platelet activation in SCD. |
Databáze: | OpenAIRE |
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