Increased platelet sensitivity among individuals with aspirin resistance – Platelet aggregation to submaximal concentration of arachidonic acid predicts response to antiplatelet therapy

Sasidhar Guthikonda; Kirankumar Mangalpally; Muthiah Vaduganathan; Rajnikant Patel; Timothy DeLao; Angela L. Bergeron; Jing-Fei Dong; Eli I. Lev; Neal S. Kleiman

doi:10.1160/TH07-10-0590

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2008; 100(01): 83-89
DOI: 10.1160/TH07-10-0590

Platelets and Blood Cells

Schattauer GmbH

Increased platelet sensitivity among individuals with aspirin resistance – Platelet aggregation to submaximal concentration of arachidonic acid predicts response to antiplatelet therapy

Authors

Sasidhar Guthikonda

¹The Methodist Hospital Research Institute and The Methodist DeBakey Heart andVascular Center, Houston, Texas, USA
Kirankumar Mangalpally

¹The Methodist Hospital Research Institute and The Methodist DeBakey Heart andVascular Center, Houston, Texas, USA
Muthiah Vaduganathan

¹The Methodist Hospital Research Institute and The Methodist DeBakey Heart andVascular Center, Houston, Texas, USA
Rajnikant Patel

²Department of Cardiology, Sun Health Boswell Hospital, Boswell, Arizona, USA
Timothy DeLao

¹The Methodist Hospital Research Institute and The Methodist DeBakey Heart andVascular Center, Houston, Texas, USA
Angela L. Bergeron

³Department of Thrombosis, Baylor College of Medicine, Houston, T e xas, USA
Jing-Fei Dong

³Department of Thrombosis, Baylor College of Medicine, Houston, T e xas, USA
Eli I. Lev

¹The Methodist Hospital Research Institute and The Methodist DeBakey Heart andVascular Center, Houston, Texas, USA
Neal S. Kleiman

¹The Methodist Hospital Research Institute and The Methodist DeBakey Heart andVascular Center, Houston, Texas, USA

Abstract

Summary

Aspirin ‘resistance’ (AR) is a phenomenon of uncertain etiology describing decreased platelet inhibition by aspirin. We studied whether (i) platelets inAR demonstrate increased basal sensitivity to a lower degree of stimulation and (ii) platelet aggregation with submaximal stimulation could predict responses to aspirin. Serum thromboxane B₂ (TxB₂) levels and platelet aggregation with light transmission aggregometry (LTA ) were measured at baseline and 24 hours after 325 mg aspirin administration in 58 healthy subjects. AR was defined as the upper sixth of LTA (≥ 12%) to 1.5 mM AA. Baseline platelet aggregation with sub-maximal concentrations of agonists [ADP 2 µM, arachidonic acid (AA) 0.75 mM, collagen 0.375 and 0.5 µg/ml] was greater in AR subjects compared with non-AR subjects, but not with higher concentrations (ADP 5 µM and 20 µM, AA 1.5 mM and collagen 1 µg/ml). Post-aspirin platelet aggregation was elevated in AR subjects with both submaximal and maximal stimulation. Baseline and post-aspirin serumTxB₂ were higher inAR subjects and decreased further with ex-vivo COX -1 inhibition, suggesting incompletely suppressed COX -1 activity. Pre-aspirin platelet aggregation to 0.75 AA demonstrated a dichotomous response with 29/58 subjects having aggregation ≤15% and 29/58 subjects having aggregation ≥75%. In the high aggregation group 28% had AR compared to 6% in the non-AR group (p=0.04). In conclusion, platelets in AR subjects demonstrate increased basal sensitivity to submaximal stimulation, which could predict responses to antiplatelet therapy.

Keywords

Platelets - aspirin resistance - thromboxane

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Referenzen

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