11-dehydro-thromboxane-b2 and Cerebral-Infarction

Incomplete platelet inhibition by aspirin (aspirin resistance) may be a reason for stroke recurrence in some patients. 11-dehydrothromboxane B2 (11-DTB2) is a stable thromboxane A2 metabolite that reflects in vivo platelet activation. This pilot study was intended to evaluate the reproducibility of urinary 11-DTB2 over time and to look for evidence of aspirin resistance.. All subjects were screened for the African American Antiplatelet Stroke Prevention Study (AAASPS) 7 to 90 days after noncardioembolic cerebral infarction. Of 83 subjects with at least 1 urine sample, 52 were enrolled in AAASPS (randomized to blinded treatment with aspirin 650 mg/d or ticlopidine 500 mg/d), and 31 were enrolled in an open-label antiplatelet therapy cohort. Subjects were followed up for 2 years, with 11-DTB2 measurements scheduled at baseline and 6, 12, and 24 months. Vascular events were cerebral infarction, myocardial infarction, or vascular death.. Despite considerable individual up or down fluctuations, the median 11-DTB2 change did not significantly differ from zero in any of the subgroups. However, in 6 subjects with a 4-fold decrease in aspirin dose from 1300 to 325 or 81 mg/d, the 11-DTB2 level increased from 611 to 1881 pg/mg creatinine (P=0.06). Vascular events occurred in 7 of 61 aspirin-treated subjects, and 11-DTB2 levels did not correlate with the events.. Fluctuations in urinary 11-DTB2 after cerebral infarction in blacks do not correlate with changes in aspirin doses, except perhaps when the dose changes by a factor of 4 or more. A larger study is needed to look further for aspirin resistance.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Black People; Cerebral Infarction; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Predictive Value of Tests; Recurrence; Risk Factors; Thromboxane B2; Ticlopidine

Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with chronic cerebral infarction, patients under chronic aspirin treatment and patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in patients with cerebral infarction and distinct carotid-atherosclerotic lesions (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than 0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2 excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial fibrillation showed very high values. Our results indicated that platelet activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro-TXB2 is the appropriate analytic target for detecting platelet activation.

Topics: Adult; Aged; Arteriosclerosis; Aspirin; Atrial Fibrillation; Carotid Artery Diseases; Cerebral Infarction; Female; Humans; Male; Middle Aged; Platelet Activation; Thromboxane A2; Thromboxane B2

The plasma level of 11-dehydrothromboxane B2 (11-dehydroTXB2) is free from artifactual increase during blood sampling, and it can be reliable indicator of TXA2 production in vivo. We have estimated plasma 11-dehydroTXB2 in patients with ischemic stroke. Subjects studied were 29 patients with cerebral thrombosis (62 +/- 9 years old) and 41 healthy controls (61 +/- 7 years old). Plasma 11-dehydroTXB2 and TXB2 were determined by radioimmunoassay. Plasma 11-dehydroTXB2 levels in patients and controls were 5.4 +/- 2.5 and 1.8 +/- 0.9 pg ml, respectively, and the difference was significant (p less than 0.001). Plasma TXB2 also was higher in patients than in controls: 401 +/- 61 vs 311 +/- 51 pg/ml (p less than 0.05). However, the 11-dehydroTXB2 was found to be a more effective parameter to distinguish between stroke patients and controls. Estimation of plasma 11-dehydroTXB2 levels is a reliable method to detect platelet hyperfunction in stroke patients.

Topics: Aged; Blood Platelets; Cerebral Infarction; Humans; Intracranial Embolism and Thrombosis; Middle Aged; Platelet Function Tests; Thromboxane A2; Thromboxane B2