11-dehydro-thromboxane-b2 and Thromboembolism

Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B(2) (11-dTXB(2)) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB(2) levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

Topics: Adolescent; Aspirin; Blood Platelets; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistance; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Infant; Male; Platelet Aggregation Inhibitors; Prevalence; Prognosis; Retrospective Studies; Risk Factors; Texas; Thromboembolism; Thromboxane B2

Aspirin (ASA) failure to inhibit in vitro platelet function had been termed ASA resistance. The prevalence of this phenomenon as measured with different platelet function tests varies widely among studies.. In this study, we propose to determine the prevalence of ASA non-responsiveness in stable coronary artery patients using three different tests.. One hundred ninety-one patients with a stable coronary artery disease and receiving secondary ASA prophylaxis (250 mg/day) were tested. For each patient the ASA-induced platelet inhibition was determined using three different tests: Ivy Bleeding time (BT), collagen/epinephrine closure time (CEPI-CT; PFA-100, Dade-Behring) and urinary 11-dehydrothromboxane B2 (uTxB2) excretion level. The agreement between these tests was evaluated by kappa statistics test.. The prevalence of biological ASA resistance was 15.7% (n=30), 20.4% (n=39) and 24.6% (n=47) by BT, PFA-100 and UTxB2, respectively. Only fourteen patients (7.3%) were non-responders for two tests: 6 (3.1%) BT/ PFA-100; 1 (0.5%) BT/UTxB2; 7 (3.7%) PFA-100/UTxB2). A poor agreement was found between these three methods and only 3 patients were resistant with all the tests (1.6%).. The lack of agreement supposed that different types of aspirin resistance exist. Thus, combination of two tests or more could be a primary solution for a better identification of ASA resistant patients. This hypothesis must be confirmed by a large-scale randomized study with clinically well-defined endpoints.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Bleeding Time; Blood Platelets; Coronary Artery Disease; Drug Evaluation, Preclinical; Drug Resistance; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Function Tests; Thromboembolism; Thromboxane B2