Weight as an assay-independent predictor of poor response to enteric aspirin in cardiovascular patients.

Aspirin non-response is associated with poor outcome but there is no agreement between the different methods to asses it. Weight has been shown to be a predictor of poor response but only using one method. In this study, we determine the effects of weight on different assays of platelet function. The response to aspirin was determined in 138 cardiology patients using serum thromboxane, arachidonic acid-induced platelet aggregation and VerifyNow©. Twenty-five percent of patients showed an inadequate response to aspirin in at least one assay on the initial test. After ensuring patient compliance only 5% of patients were considered to be non-responders. Only 9% of non-responders were non-responsive in all three assays. When switched to plain aspirin, only 2% of patients were non-responsive. All patients responded adequately to 150 mg aspirin. The non-responders were significantly heavier than responders (78.5 kg ± 14.0 (SD); BMI: 28.4 kg/m2± 4.4 v's 102.6 kg ± 20.6, P = .0016; BMI: 38.3 kg/m2 ± 7.6, P= .0015). A rule-based approach of using plain aspirin in patients over 90 kg or BMI 32 along with patient education to ensure compliance will ensure that all patients respond to their aspirin without the need for testing.

Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy.

BACKGROUND: Current or recent use of abacavir for treating human immunodeficiency virus type 1 (HIV-1) infection has been associated with increased rates of myocardial infarction (MI). Given the role of platelet aggregation in thrombus formation in MI and the reversible nature of the abacavir association, we hypothesized that patients treated with abacavir would have increased platelet reactivity. METHODS: In a prospective study in adult HIV-infected patients, we determined associations between antiretrovirals (ARVs), and in particular the nucleoside reverse transcriptase inhibitor abacavir, and platelet reactivity by measuring time-dependent platelet aggregation in response to agonists: adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), collagen, and epinephrine. RESULTS: Of 120 subjects, 40 were ARV-naive and 80 ARV-treated, 40 of whom were receiving abacavir. No consistent differences in platelet reactivity were observed between the ARV-naive and ARV-treated groups. In contrast, within the ARV-treated group, abacavir-treated subjects had consistently higher percentages of platelet aggregation upon exposure to ADP, collagen, and epinephrine (P = .037, P = .022, and P = .032, respectively) and had platelets that were more sensitive to aggregation upon exposure to TRAP (P = .025). CONCLUSIONS: The consistent increases in platelet reactivity observed in response to a range of agonists provides a plausible underlying mechanism to explain the reversible increased rates of MI observed in abacavir-treated patients.

Platelet function and HIV: a case-control study.

OBJECTIVE: Cardiovascular disease and myocardial infarction are of increasing concern in HIV-infected populations. Although platelets mediate arterial thrombosis, central to myocardial infarction, data on platelet function in HIV infection are lacking. We hypothesized that HIV-infected patients would have altered platelet reactivity. DESIGN: A case-control study of platelet reactivity in 20 HIV-infected (HIVpos) and 20 age and sex-matched HIV-negative (HIVneg) individuals. METHODS: Time-dependent platelet aggregation was measured in response to increasing concentrations of platelet agonists: epinephrine, collagen, thrombin receptor-activating peptide and ADP using light absorbance. RESULTS: In both groups, mean age was 34 years, and 65% were men. Sixteen out of 20 (80%) of the HIVpos patients were on antiretroviral therapy with 12 out of 20 (60%) patients having HIV RNA less than 50 copies/ml. There were significant between-group differences in platelet reactivity across all four agonists. Platelets from HIVpos patients were more reactive to epinephrine [mean (SD) log concentration required to induce 50% maximal aggregation, 1.9 (1.2) versus 3.0 (1.7) mumol/l in HIVneg individuals, P = 0.028], whereas less platelet aggregation was observed in response to submaximal concentrations of the other agonists [thrombin receptor-activating peptide 72.5 (14.5)% versus 82.2 (7.6)% at 10 mumol/l, P = 0.011; ADP 67.3 (12.1)% versus 75.2 (8.8)% at 10 mumol/l, P = 0.035; collagen 16.6 (25.1)% versus 35.4 (31.5)% at 71.25 microg/ml, P = 0.007]. CONCLUSION: Between-group differences in platelet responses to all agonists suggest multiple underlying defects in platelet function in HIV infection. Further research is required to determine the contribution of antiretroviral therapy and relationships between platelet function and the increased cardiovascular disease observed in HIV-infected populations.

Platelet hyper-reactivity in active inflammatory arthritis is unique to the adenosine diphosphate pathway: a novel finding and potential therapeutic target.

OBJECTIVE: To assess the influence of disease activity on platelet function in patients with inflammatory arthritis (IA). METHODS: Ninety-six patients with an established diagnosis of IA (RA, PsA, seronegative SpA) were recruited. Patients with a history of cardiovascular disease (CVD), diabetes mellitus or receiving anti-platelet therapy were excluded. Demographic data, traditional CVD risk factors and medication use were recorded. Patients were characterized as active disease (n = 38) or control disease (n = 58) groups, respectively, based on internationally validated measures of disease activity [comprising serological markers (ESR, CRP, fibrinogen), patient measures (visual analogue scale of disease activity), evaluator global assessment and the 28-joint disease activity score]. Platelet function was assessed using a novel assay of platelet reactivity. Platelet aggregation to multiple concentrations of arachidonic acid, collagen, epinephrine, thrombin receptor activating peptide and adenosine diphosphate (ADP) were measured simultaneously using a modification of light transmission aggregometry. RESULTS: The two groups (active vs control) were similar in terms of demographics and CVD risk factors. Anti-TNF-alpha therapy use was higher in the control group (P = 0.004), whereas NSAID use was higher in the active group (P = 0.001). There was a significant difference between the two groups in platelet response to ADP (P < 0.001). Platelet aggregation, in response to submaximal concentrations of ADP, was increased in the active disease group compared with the control group. There was no difference in platelet reactivity between the groups in response to any of the other agonists. CONCLUSION: Patients with active IA demonstrate enhanced platelet reactivity, unique to the ADP pathway. This potential pro-thrombotic bias may contribute to their increased cardiovascular risk.