Analysis of Differences of Serum Thromboxane B2 Level after Taking Acetosal in Acute Thrombotic Stroke with Diabetes Mellitus and Non-Diabetes Mellitus

Endothelial dysfunction and vascular injuries are the early processes in thrombogenesis leading to thrombotic stroke. These processes trigger platelet activation characterized by synthesis of Thromboxane A2, potent agonist in platelet aggregation. Acetosal (ASA) 100 mg usually given to thrombotic stroke patients exerts its pharmacological effect by inhibition of TxA2 synthesis, thus could prevent thrombus formation. Diabetes mellitus (DM) as risk factor of thrombotic stroke exhibits an increase in TxA2 synthesis. It is not known whether ASA 100 mg could inhibit TxA2 adequately in diabetic patients. This study aimed to analyze the differences of serum TxA2 level, which was measured by serum TxB2 level as stabile metabolite of TxA2, after taking ASA 100 mg in diabetic and non-diabetic thrombotic stroke patients. This prospective observational study was held in Neurology Department of Dr. Soetomo Hospital, Surabaya. Total 27 patients, consisted of 15 patients with DM and 12 patients with non-DM were enrolled. Serum TxB2 was measured before and after 5-7 days 100 mg ASA 100 administration. Mean value of serum TxB2 level before and after taking ASA was 16.43 ± 16.08 ng/mL and 2.93 ± 1.83 ng/mL in diabetic and 27.36 ± 21.04 ng/mL and 5.36 ± 4.06 ng/mL in non-diabetic group. Mean reduction of serum TxB2 level in diabetic and non-diabetic group was 13.49 ± 15.9 ng/mL and 22.00 ± 21.65 ng/mL. There were significant differences in serum TxB2 level after taking ASA 100 mg in diabetic and non-diabetic group but the mean reduction of serum TxB2 level were not significantly different.

rs5911 and rs3842788 Genetic Polymorphism, Blood Stasis Syndrome, and Plasma TXB2 and hs-CRP Levels Are Associated with Aspirin Resistance in Chinese Chronic Stable Angina Patients

The identification of single nucleotide polymorphisms (SNPs) related to aspirin resistance (AR) is of great significance for the explanation why some individuals demonstrate an incomplete response to aspirin and for optimizing the antiplatelet therapy strategy. The study was designed to investigate the possible associated genetic markers and clinical factors of AR for Chinese patients with chronic stable angina after PCI and to analyze the association between TXA2, PGI2, hs-CRP level, AR, and gene polymorphisms. Totally 207 chronic stable angina patients who received 100 mg maintenance dose daily of aspirin for more than 7 days were enrolled. The inhibition of platelets was assessed using light transmittance aggregometry. TXB2, 6-keto-PGF1α, and hs-CRP were measured by radioimmunoassay. Genotyping was performed using Taqman probe technique (rs5787 and rs5911) and gene sequencing technology (rs3842788). By using binary logistic regression analysis, the impact of clinical and genetic determinants on AR was evaluated. The prevalence of AR and aspirin semiresistance (ASR) was 3.86% and 20.76%, respectively, in Chinese chronic stable angina patients. rs5911 A/C and C/C versus A/A genotype (OR = 5.546, 95% CI = 1.812–11.404), rs3842788 A/G versus G/G genotype (OR = 8.358, 95% CI = 2.470–28.286), and blood stasis syndrome (BSS, OR = 10.220, 95% CI = 4.242–24.621) were associated with AR, but rs5787 variants were all homozygous of G/G genotype. Plasma TXB2 and hs-CRP increased significantly in AR and ASR group, while 6-keto-PGF1αshowed no difference, and TXB2 level was significantly higher in carriers of the rs3842788 A/G genotype. According to our results, rs5911 and rs3842788 are proved to be specific genetic markers of AR in Chinese chronic stable angina patients for the first time, and BSS was also proved to be a remarkable determinant for AR. The AR and ASR patients were with increased plasma TXB2 and hs-CRP levels, and the TXB2 level was influenced by the variation of rs3842788 genotype.