Journal
THROMBOSIS RESEARCH
Volume 132, Issue 2, Pages 211-216Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2013.06.010
Keywords
Acute stroke; Aspirin; Thromboxane A(2); Cyclooxygenase-1; Platelet-erythrocyte interactions
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Funding
- Spanish Fondo de Investigaciones Sanitarias del Ministerio de Sanidad y Consumo (FIS) [PI07/0463, RENEVAS RD06/0026, FMM 2006]
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Introduction: The pharmacological target of aspirin is the inhibition of cyclooxygenase-1 (COX1) and thromboxane-A(2) (TX) synthesis. Very few data are available on TX assessment in patients with stroke. We studied platelet TX synthesis, COX1-independent platelet reactivity, the influence of platelet-erythrocyte interactions and the potential association between platelet responses and the severity of stroke, evaluated with a clinical score (NIHSS). Material and Methods: We examined 157 aspirin-treated patients with acute stroke or TIA, 128 aspirin-free and 15 aspirin-treated healthy subjects (HS). Collagen-induced TX, platelet recruitment in whole blood and platelets +/- erythrocytes (haematocrit 40%) were assessed in patients on daily-aspirin within three days from onset. Arachidonic-acid-, ADP-, thrombin-receptor activating peptide TRAP-, and collagen-induced aggregation were also evaluated. Results: Partial TX inhibition (<95% inhibition vs aspirin-free controls) was observed in 13% of patients. This was associated with marked increases in COX1-dependent responses (arachidonic-acid-and collagen-induced aggregation and platelet recruitment; P < 0.0001) but not with differences in ADP-or TRAP-induced aggregation. Partial TX inhibition was independently associated with severe stroke (NIHSS >= 12) at both admission (P < 0.05) and discharge (P < 0.05). Among patients with fully blocked TX, those with elevated COX1-independent platelet reactivity (mean + 2SD of aspirin-treated HS) were most likely to suffer severe stroke (P < 0.05). Platelet-erythrocyte interactions enhanced platelet reactivity in these patients by COX1-dependent and -independent mechanisms (P < 0.0001). Conclusions: TX inhibition by aspirin varied across patients. Partial TX inhibition and COX1-independent platelet hyperfunction were associated with more-severe stroke. (c) 2013 Published by Elsevier Ltd.
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