The Retention Index Test Homburg (RTH-II): Response to clopidogrel and comparison with aggregometry and CD62P-expression

Abstract

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 µM) 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 µM 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 µM 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 P2Y₁₂-inhibitors on platelet degranulation, perhaps in addition to aggregometry.

• Homburg Retention Test
• clopidogrel
• shear stress
• CD62p
• aggregation