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Residual platelet thromboxane A 2 and prothrombotic effects of erythrocytes are important determinants of aspirin resistance in patients with vascular disease
Author(s) -
SANTOS M. T.,
VALLES J.,
LAGO A.,
TEMBL J.,
SÁNCHEZ E.,
MOSCARDO A.,
COSIN J.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.02915.x
Subject(s) - aspirin , platelet , thromboxane a2 , medicine , platelet aggregation , cardiology
Summary. Background: Permanent inactivation of cyclooxygenase‐1 and inhibition of platelet thromboxane A 2 (TxA 2 ) constitute the main mechanisms underlying the prevention of vascular disease by aspirin. Methods and Results: We studied platelet TxA 2 synthesis and its impact on platelet reactivity and platelet–erythrocyte [platelet‐rich plasma (PRP)–RBC] interactions in 533 aspirin‐treated patients with vascular disease. Seventy aspirin‐free and 16 aspirin‐treated normal subjects were evaluated as controls. Collagen (1 μg mL −1 )‐induced platelet activation ( 14 C‐5HT release) and recruitment (proaggregatory activity of cell‐free releasates from activated platelets) were assessed in PRP, PRP + RBC, and whole blood (WB). TxA 2 was quantified in releasates from WB. Aspirin inhibited TxA 2 synthesis and platelet function in all patients, but to different degrees. Forty‐two patients (8%) displayed partial (<95%) inhibition of TxA 2 relative to that of aspirin‐free controls. They produced >3.5 ng mL −1 TxA 2 and had higher platelet reactivity than 491 patients who had undetectable TxA 2 or produced residual TxA 2 (R‐TxA 2 ; ≤3.5 ng mL −1 ). Patients with R‐TxA 2 were distributed into TxA 2 quartiles. Patients in the third and fourth quartiles had significantly elevated 14 C‐5HT release in PRP, which was markedly amplified in PRP + RBC and WB. TxA 2 in the fourth quartile translated into increased platelet aggregation and recruitment. Significant correlations were found between R‐TxA 2 and platelet hyperfunction. Conclusion: Biochemical markers (TxA 2 synthesis, 14 C‐5HT release) and biological assays (platelet aggregation and recruitment) used to monitor the aspirin effect in a large population of patients presenting with vascular disease have evidenced the importance of R‐TxA 2 and the prothrombotic effects of RBC in aspirin resistance.