The Retention Index Test Homburg (RTH-II): Response to clopidogrel and comparison with aggregometry and CD62P-expression.
The Retention Index Test Homburg (RTH-II) is quoted to detect effects of shear stress on platelets, which involve ADP receptor signaling. RTH-II might be a tool for monitoring antiplatelet therapy for compounds that interfere with ADP induced platelet activation and secretion. In a series of investigations, we used an ADP (2 microM) triggered RTH-II in parallel with light-transmittance aggregometry and flow cytometry in subjects before and after clopidogrel. A loading dose of 225 mg clopidogrel leads to a significant reduction (p < 0.01) in the ADP-stimulated retention index (RI) from 69 +/- 15 to 48 +/- 21%, in the aggregation response to 5 microM ADP (from 50 +/- 20 to 29 +/- 21%) and the expression of CD62P (from 64 +/- 11 to 41 +/- 17%). Correlation analysis showed that the RI corresponds significantly to CD62P-expression (p < 0.01) but not to aggregation. We also found a strong correlation (p < 0.01) between the ADP-stimulated RI and the expression of CD62P after stimulation with 2 microM ADP, whereas no correlation was seen for RI vs. binding of PAC-1 or aggregation. Platelets not retained in the filter had lower CD62P expression than measured in the sample before the filter passage (54 vs. 35%). A direct interaction of CD62P with platelet ligands might lead to enhanced retention in RTH and explain the correlation of RI with CD62P expression. The RTH-II might be a simple and easy to handle platelet function assay for monitoring effects on P2Y(12)-inhibitors on platelet degranulation, perhaps in addition to aggregometry.
Klinkhardt
U
U
Pharmazentrum frankfurt, Institute for Clinical Pharmacology, University Hospital Frankfurt am Main, Frankfurt am Main, Germany.
Wenzel
E
E
Harder
S
S
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000096:biosynthesis* / Q000187:drug effects* / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010979:Platelet Function Tests / Q000379:methods*; D012016:Reference Values; D012044:Regression Analysis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D019007:P-Selectin; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine