thromboxane-b2 and Acute-Coronary-Syndrome

Topics: Acute Coronary Syndrome; Administration, Intravenous; Administration, Oral; Adult; Aged; Aspirin; Biomarkers; Blood Platelets; Drug Monitoring; Female; Germany; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Risk Factors; Thromboxane B2; Time Factors; Treatment Outcome

The prescription of aspirin (acetylsalicylic acid (ASA)) to patients with a history of hypersensitivity to this drug could prove harmful. The aim of the study was to assess the antiplatelet activity and safety of a combined antiplatelet treatment with indobufen and clopidogrel in acute coronary syndrome (ACS) patients with hypersensitivity to aspirin, undergoing coronary stenting. Forty-two consecutive ACS patients treated with stent implantation were randomly assigned to receive clopidogrel 75 mg daily (loading dose 300 mg) plus indobufen 100 mg twice a day (group A), or clopidogrel 75 mg daily, after 300 mg of loading dose (group B). Platelet activity and safety were monitored in both groups at 1, 3, 6, 12, and 18 months with laboratory and clinical evaluation. A lower value of max % platelet aggregation to arachidonic acid and collagen was found in group A compared to group B (31.79 ± 27.33 vs. 73.67 ± 19.92; p < 0.0001 and 28.53 ± 21.32 vs. 73.58 ± 17.71; p < 0.0001, respectively). There was no difference in max % of platelet inhibition to adenosine diphosphate between the two groups (14.23 ± 18.92 vs. 10.30 ± 18.97; p = 0.23). In the population that was under indobufen treatment, the serum thromboxane B2 (TXB2) production at 1 week and 1 month was very low (2.6 ± 1.6 ng/ml and 3.0 ± 2.7 ng/ml, respectively; p = 0.82). The combined treatment was well tolerated in group A patients. This study suggests that the combined antiplatelet treatment with clopidogrel and indobufen could be a good option in ACS patients with hypersensitivity to aspirin undergoing coronary stenting.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Clopidogrel; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Isoindoles; Male; Middle Aged; Percutaneous Coronary Intervention; Phenylbutyrates; Platelet Aggregation Inhibitors; Risk Factors; Thromboxane B2; Ticlopidine; Treatment Outcome

A substantial proportion of patients have recurrence of vascular events despite daily intake of low-dose aspirin therapy. Therefore, different patients may require different aspirin dosages to achieve complete inhibition of platelet function.. The aim of this work was to measure the response to low-dose aspirin therapy (150 mg/day) among patients with unstable angina or non-ST-segment elevation myocardial infarction and to find out whether titrating aspirin dosage to 300 mg/day, would provide a better therapeutic response in the resistant cases. Moreover, we also aimed to study any association between aspirin non-responsiveness and atherothrombotic risk factors.. The antiplatelet effect of 150 mg/day aspirin was studied prospectively in 50 consecutive patients with unstable angina or non-ST-segment elevation myocardial infarction. Platelet aggregation was measured using optical platelet aggregometry and serum thromboxane B(2) level. Aspirin resistance was defined as collagen (1 μg/mL) and adenosine diphosphate (ADP) (5 μmol/L)-induced platelet aggregation of ≥ 40% when compared with control values. Twenty healthy age- and sex-matched individuals were taken as a control group. All patients were subjected to complete medical history (risk factors, medications), thorough clinical examination, ECG, coronary angiography and laboratory investigations including: complete haemogram, coagulation, kidney, liver and lipid profiles, fasting blood glucose and glycated haemoglobin (HbA(1C) ).. Eleven of 50 patients (22%) were found to be aspirin resistant. A highly significant difference was found between the mean values of ADP, collagen-induced platelet aggregation percentage and thromboxane B(2) level after aspirin 150 mg/day when compared with the corresponding mean values after aspirin 300 mg/day among the resistant patients (66 ± 7.01%, 62 ± 4.34% and 620 ± 64.58 pg/mL, respectively, vs. 26.87 ± 2.85%, 16.5 ± 3.8% and 77 ± 11.3 pg/mL) indicating enhanced response to aspirin after escalating the dose. The presence of atherothrombotic risk factors (hypertension, smoking, family history of ischaemic heart disease and previous MI) were not statistically different between aspirin-resistant and aspirin-sensitive patients. However, there was a highly significant difference between the aspirin sensitive and the resistant patients regarding the other risk factors (diabetes mellitus and dyslipidaemia) (P < 0.01).. There is inter-individual variability in response to the antiplatelet effect of standard doses of aspirin (150, 300 mg/day). The response to aspirin 300 mg/day is enhanced in resistant patients when compared to 150 mg/day. There was a significant association between aspirin resistance and atherothrombotic risk factors (diabetes, hyperlipidaemia and obesity).

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Aspirin; Collagen; Dose-Response Relationship, Drug; Drug Resistance; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Risk Factors; Thromboxane B2

Currently 162-325 mg aspirin is recommended for the treatment of acute coronary syndrome. We tested the effect of an additional loading dose of 250 mg aspirin at the onset of acute coronary syndrome in patients who were already on chronic therapy with 100 mg aspirin.. This was a prospective trial in patients presenting with symptoms suggestive of acute coronary syndrome that included a randomized, double-blind, placebo-controlled trial subgroup.. An emergency department in a tertiary care center.. Consecutive patients with symptoms suggestive of acute coronary syndrome were enrolled, including a cohort already on chronic aspirin therapy.. Patients received an intravenous infusion of 250 mg aspirin.. Platelet function was measured with a platelet function analyzer in 234 patients before and after aspirin infusion. Aspirin infusion prolonged collagen epinephrine closure times in almost all patients. Aspirin infusion further lowered thromboxane B(2) levels in patients with acute coronary syndrome who were on chronic aspirin therapy before admission. Concomitantly, collagen epinephrine closure times increased by 22% from 223 secs (95% confidence interval, 192-255 secs) before to 273 secs (95% confidence interval, 252-294 secs) after aspirin infusion (p < .01). Eleven patients with ST-elevation myocardial infarction on daily aspirin therapy (53%) displayed platelet hyperfunction (collagen epinephrine closure times <193 secs). Additional aspirin infusion further decreased platelet function in these patients with ST-elevation myocardial infarction (30% prolongation of collagen epinephrine closure times; p < .01), and only two patients with ST-elevation myocardial infarction still displayed platelet hyperfunction (p = .02).. Aspirin loading in the emergency room further reduced thromboxane B(2) levels and further inhibited platelet function in many patients with acute coronary syndrome already on 100 mg aspirin.

Topics: Acute Coronary Syndrome; Aspirin; Cohort Studies; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Emergency Service, Hospital; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Thromboxane B2

Dual antiplatelet therapy with aspirin and a P2Y12 antagonist is widely prescribed for the prevention of thrombotic events in patients with an acute coronary syndrome or undergoing percutaneous coronary intervention (PCI). It is recognised that there is inter-individual variation in the antiplatelet effects of both drugs. Recent data also suggest that P2Y12 antagonists can affect the response to aspirin. A direct indicator of the effect of aspirin on platelets is their ability to generate thromboxane, which if measured as the difference between the level of thromboxane B2 in serum and plasma ([TxB2]S-P) avoids the confounding effect of endogenous TxB2 production from other cells. We therefore analysed [TxB2]S-P as a measure of aspirin response in a group of 123 patients undergoing elective PCI before and after the introduction of clopidogrel. In a subgroup of 40 patients taking aspirin alone, we compared [TxB2]S-P and VerifyNow Aspirin for the assessment of aspirin response. There was a wide variation in plasma and serum TxB2 concentrations both before and after clopidogrel therapy but only 3.5% of patients had residual serum concentration of TxB2 > 10 ng/ml. There was a strong correlation between the pre and post clopidogrel levels of TxB2 (r ≥ 0.78; p = 0.001) and no significant difference in [TxB2]S-P. There was no correlation between the magnitude of response to clopidogrel response and the generation of thromboxane B2. Correlation between [TxB2]S-P and VerifyNow Aspirin was poor. We conclude that the use of a P2Y12 antagonist does not influence the effect of aspirin on the ability of platelets to generate thromboxane. Therefore, measurement of TxB2 levels in serum, after subtracting the contribution from plasma, provides a measure of the response to aspirin in patients taking dual antiplatelet therapy.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Clopidogrel; Cross-Sectional Studies; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Thromboxane B2; Ticlopidine; Treatment Outcome

Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low-dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11-dehydro-TXB2) is predictive of vascular events in high-risk patients. Myeloid-related protein (MRP)-8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP-14 has emerged as a powerful predictor of ACS.. We enrolled 68 stable ischemic heart disease (IHD) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP-8/14 release in the circulation is related to TX-dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low-dose aspirin-treated ACS patients. In ACS patients, plasma MRP-8/14 and urinary 11-dehydro-TXB2 levels were linearly correlated (r=0.651, P<0.001) but significantly higher than those in IHD patients (P=0.012, P=0.044) only among subjects not receiving aspirin. In aspirin-treated ACS patients, MRP-8/14 and 11-dehydro-TXB2 were lower versus those not receiving aspirin (P<0.001) and still significantly correlated (r=0.528, P<0.001). Higher 11-dehydro-TXB2 significantly predicted higher MRP-8/14 in both all ACS patients and ACS receiving aspirin (P<0.001, adj R(2)=0.463 and adj R(2)=0.497) after multivariable adjustment. Conversely, plasma MRP-8/14 (P<0.001) and higher urinary 8-iso-prostaglandin F2α (P=0.050) levels were significant predictors of residual, on-aspirin, TX biosynthesis in ACS (adjusted R(2)=0.384).. Circulating MRP-8/14 is associated with TX-dependent platelet activation in ACS, even during low-dose aspirin treatment, suggesting a contribution of residual TX to MRP-8/14 shedding, which may further amplify platelet activation. Circulating MRP-8/14 may be a target to test different antiplatelet strategies in ACS.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Calgranulin A; Calgranulin B; Chronic Disease; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Platelet Activation; Platelet Aggregation Inhibitors; Thromboxane B2

Topics: Acute Coronary Syndrome; Aspirin; Humans; Thromboxane B2

Despite the clinical benefit associated with the combined use of aspirin and clopidogrel in patients with acute coronary syndrome or those undergoing percutaneous coronary intervention, a considerable interindividual variability in response to these drugs have been consistently reported. There is a growing interest on applying platelet functional tests with the goal of identifying patients at increased risk of recurrent ischaemic events and potentially tailoring antiplatelet treatment regimens. This manuscript will review the state of the art on the most commonly available platelet functional tests, describing their advantages and disadvantages and exploring their applicability in clinical practice.

Topics: Acute Coronary Syndrome; Aspirin; Blood Platelets; Clopidogrel; Electric Impedance; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Prognosis; Thromboxane B2; Ticlopidine