Homocysteine levels and platelet reactivity in coronary artery disease patients treated with ticagrelor

Background and aimRecurrent atherothrombotic events have been reported in certain higher risk subsets of patients even with ticagrelor, a potent first-line antiplatelet agent for the management of patients with acute coronary syndrome (ACS). Hyperhomocysteinemia is a known determinant of platelet function abnormalities. Therefore, the aim of our study was to evaluate the impact of homocysteine (Hcy) levels on platelet reactivity in patients receiving Ticagrelor.Methods and resultsPatients with ACS undergoing percutaneous coronary revascularization and on dual antiplatelet therapy with ASA + Ticagrelor (90mg/twice a day) were scheduled for platelet function assessment 30–90 days post-discharge. Aggregation tests were performed by Multiple Electrode Aggregometry (MEA). Suboptimal platelet inhibition HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min).We included 432 patients, divided according to Hcy tertiles. Higher Hcy levels were associated with age, renal failure, creatinine levels and use diuretics (p < 0.001).Patients with higher Hcy levels displayed a higher platelet reactivity at COL test (p = 0.002), and ADP test (p = 0.04), with a linear relationship between Hcy and platelet aggregation after stimulation with collagen (r = 0.202, p < 0.001), thrombin receptor peptide (r = 0.104, p = 0.05) and ADP (r = 0.145, p = 0.006).However, Hcy levels did not significantly affect the rate of HRPR with Ticagrelor (9.9% vs 13.7% vs 10.7%, p = 0.89; adjusted OR [95% CI] = [0.616–1.51], p = 0.99).ConclusionsAmong patients with ACS, despite the elevated platelet reactivity associated to hyperhomocysteinemia, DAPT with ticagrelor could overcome such phenomenon, achieving an adequate platelet inhibition in the majority of the patients.     

Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration.

PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p < 0.001) and 1 month (43.4 ± 20.3% vs. 46.8 ± 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders (age, sex, diabetes, chronic kidney disease, Syntax score>15), the β coefficient of smoke on PRI was ?8.51 [?11.90 to ?5.11, p < 0.001] at baseline and ?3.41 [?6.30 to ?0.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p < 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80).

Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.     

Medium on-treatment platelet reactivity to ADP is favorable in patients with acute coronary syndromes undergoing coronary stenting

Bleeding in the setting of acute coronary syndromes (ACS) has negative prognostic implications. We sought to determine the impact of different levels of on-treatment platelet reactivity (PR) to ADP on both bleeding and ischemic events in ACS patients receiving coronary stenting. PR to ADP was measured with the VerifyNow P₂Y₁₂ assay (Accumetrics, San Diego, CA) in 374 patients with ACS receiving standard dual antiplatelet therapy. Patients were stratified into three tertiles according to the increasing values of P₂Y₁₂ reaction units with the first tertile defined as low, second as medium, and third as high PR. The end points were bleeding (TIMI major or minor), ischemic end point (cardiovascular death and non-fatal myocardial infarction), and combined end point (bleeding or ischemic end point). At 30 days: low PR was associated with increased risk of bleeding as compared to medium (adjusted hazard ratio [HR] 3.50, 95% confidence intervals (CI) 1.30–9.42, p?=?0.013) and high PR (HR 2.78, 95% CI 1.50–5.15, p?=?0.001); high PR posed increased risk of ischemic endpoint as compared with medium PR (HR 7.26, 95% CI 1.67–31.55, p?=?0.008) and a trend towards higher incidence of ischemic events was observed when compared with low PR (HR 1.51, 95% CI 0.96–2.36, p?=?0.074); patients with medium PR were at significantly lower risk of combined end point as compared to those with low (HR 0.30, 95% CI 0.12–0.75, p?=?0.01) and high PR (HR 0.31, 95% CI 0.12–0.77, p?=?0.012). In conclusion, low PR to ADP is associated with increased hazard of bleeding and poses similar combined risk of bleeding and ischemic events as high PR. Medium PR predicts favorable net outcome in ACS patients.     

Medium on-treatment platelet reactivity to ADP is favorable in patients with acute coronary syndromes undergoing coronary stenting

Bleeding in the setting of acute coronary syndromes (ACS) has negative prognostic implications. We sought to determine the impact of different levels of on-treatment platelet reactivity (PR) to ADP on both bleeding and ischemic events in ACS patients receiving coronary stenting. PR to ADP was measured with the VerifyNow P?Y?? assay (Accumetrics, San Diego, CA) in 374 patients with ACS receiving standard dual antiplatelet therapy. Patients were stratified into three tertiles according to the increasing values of P?Y?? reaction units with the first tertile defined as low, second as medium, and third as high PR. The end points were bleeding (TIMI major or minor), ischemic end point (cardiovascular death and non-fatal myocardial infarction), and combined end point (bleeding or ischemic end point). At 30 days: low PR was associated with increased risk of bleeding as compared to medium (adjusted hazard ratio [HR] 3.50, 95% confidence intervals (CI) 1.30-9.42, p?=?0.013) and high PR (HR 2.78, 95% CI 1.50-5.15, p?=?0.001); high PR posed increased risk of ischemic endpoint as compared with medium PR (HR 7.26, 95% CI 1.67-31.55, p?=?0.008) and a trend towards higher incidence of ischemic events was observed when compared with low PR (HR 1.51, 95% CI 0.96-2.36, p?=?0.074); patients with medium PR were at significantly lower risk of combined end point as compared to those with low (HR 0.30, 95% CI 0.12-0.75, p?=?0.01) and high PR (HR 0.31, 95% CI 0.12-0.77, p?=?0.012). In conclusion, low PR to ADP is associated with increased hazard of bleeding and poses similar combined risk of bleeding and ischemic events as high PR. Medium PR predicts favorable net outcome in ACS patients.     

Intensified P2Y12 inhibition for high-on treatment platelet reactivity

High on treatment platelet reactivity (HPR) during treatment with clopidogrel has been consistently found to be strong risk factor for recurrent ischemic events after percutaneous coronary intervention (PCI). Insufficient P2Y12 receptor inhibition contributes to HPR measured by the VerifyNow (VN) assay. Prasugrel and ticagrelor are more potent P2Y12 inhibitors than clopidogrel and commonly substituted for clopidogrel when HPR is documented, however benefit of VN guided intensified antiplatelet therapy is uncertain. We identified patients who had undergone platelet reactivity testing after PCI with VN after pretreatment with clopidogrel (n?=?252) in a single center observational analysis. Patients who had HPR defined as PRU?>?208 were switched to alternate P2Y12 inhibitors. Primary clinical endpoint was 1-year post PCI combined cardiovascular death, myocardial infarction (MI), and stent thrombosis. One hundred and eight (43%) subjects had HPR and were switched to prasugrel (n?=?60) and ticagrelor (n?=?48). Risk of recurrent 1-year primary endpoint remained higher for HPR patients switched to either ticagrelor or prasugrel as compared to subjects who had low on treatment platelet reactivity (n?=?144) (LPR) on clopidogrel [Hazard Ratio: 3.5 (95% CI 1.1–11.1); p?=?0.036)]. Propensity score matched analysis demonstrated higher event rates in patients with HPR on alternate P2Y12 inhibitor as compared to patients with LPR (log-rank: p?=?0.044). The increased risk of recurrent events associated with HPR measured by VN is not completely attenuated by switching to more potent P2Y12 inhibitors. Non-P2Y12 mediated pathways likely contribute to increased incidence of thrombotic events after PCI in subjects with HPR.

     

Inter-patient variability of platelet reactivity in patients treated with prasugrel and ticagrelor

The aim of this study was to evaluate the distribution of platelet reactivity values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 200 patients treated with prasugrel or ticagrelor. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) in the maintenance phase of treatment with prasugrel or ticagrelor. Only 3% of patients in the prasugrel group and 2% of study participants in the ticagrelor group had high on treatment platelet reactivity (HTPR). The majority of patients displayed low on treatment platelet reactivity (LTPR; prasugrel: 69%; ticagrelor: 64%). The pharmacodynamic effect was similar in patients treated with prasugrel and ticagrelor: the median level of ADP-induced platelet aggregation was 15U (interquartile range IQR 9-21U) under prasugrel treatment and 17U (IQR 8–24U) under ticagrelor treatment (p=0.370). In conclusion, our study suggests that there is some degree of variability in ADP-induced platelet aggregation under treatment with prasugrel and ticagrelor.     

替格瑞洛对老年急性心肌梗死患者血小板功能及临床预后的影响

目的:探索替格瑞洛联合阿司匹林对老年急性心肌梗死(AMI)患者血小板功能及临床预后的影响。方法:纳入2013年10月至2014年10月期间在我院就诊的老年(≥65岁)AMI患者200例,随机分为氯吡格雷组(n=101)和替格瑞洛组(n=99),分别给予负荷量阿司匹林300 mg+氯吡格雷600 mg或阿司匹林300 mg+替格瑞洛180 mg,次日起改为维持剂量阿司匹林100 mg/d和氯吡格雷75 mg/d或替格瑞洛180 mg/d,用药前及用药后1、6和12个月分别检测血小板反应指数(PRI),观察主要不良心血管事件(MACE)和心肌梗死溶栓治疗(TIMI)出血事件。结果:共有196例患者完成随访,两组治疗前PRI无统计学差异;PCI术后6个月和12个月时两组PRI均较治疗前分别下降(P0.05);与氯吡格雷组比较,替格瑞洛组在6个月和12个月时PRI降低更加明显(P0.01);随访1年时,替格瑞洛组MACE发生率明显低于氯吡格雷组(9.2%对12.9%,P=0.01);两组TIMI出血事件发生率无差别(氯吡格雷组9.6%对替格瑞洛组10.3%,P0.05)。结论:与氯吡格雷相比,老年AMI患者服用替格瑞洛可进一步降低MACE事件,而不增加出血风险。     

血栓弹力图评价急性冠状动脉综合征患者介入术后血小板高反应性对不良预后影响分析

目的:探讨由血栓弹力图(TEG)测定二磷酸腺苷激活血小板形成最大血凝块强度(MAADP),评价急性冠状动脉综合征(ACS)经皮冠状动脉介入治疗术(PCI)后,与氯吡格雷治疗相关的血小板高反应性(HTPR)对预后的影响。方法:入选2011年1月至2012年9月,行PCI术的ACS患者360例。使用TEG检测其血小板的反应性,记录患者基线资料,并进行12个月随访,记录心脏不良事件的发生情况(全因性死亡、非致死性心肌梗死、再次血运重建及反复心绞痛导致再住院等)。结果:采用受试者工作特征(ROC)曲线分析TEG检测ACS患者HTPR的MA-ADP最佳界值47mm,并依此分组,HTPR组71例,NTPR组289例。与NTPR组相比,HTPR组女性(39.4%vs.23.9%,P0.05),非ST段抬高性心肌梗死(14.1%vs.5.5%,P0.05),糖尿病(45.1%vs.31.5%,P0.05),高敏C反应蛋白(3.2vs.1.4,P0.05),纤维蛋白原[(3.2±0.7)vs.(2.9±0.7),P0.05]较高。Logistic回归显示女性、纤维蛋白原升高是TEG测定的HTPR的独立危险因素(OR=2.011,95%CI:1.144~3.533;OR=1.624,95%CI:1.122~2.350,P0.05);COX回归分析MAADP47mm是缺血事件的危险因素(HR=4.863,95%CI:2.505~9.439,P0.05)。结论:TEG测定的MAADP评价HTPR可预测ACS患者PCI术后再发缺血事件。     

Impact of non-inhibited platelet supplementation on platelet reactivity in patients treated with prasugrel or ticagrelor for an acute coronary syndrome: An ex vivo study

Abstract

Managing bleeding in patients receiving P2Y₁₂ inhibitors is challenging. Few data are available regarding the efficacy of platelet transfusion in patients treated with prasugrel or ticagrelor. The aim of this study was to evaluate the minimal amount of platelet supplementation (in terms of ratio of non-inhibited platelets to inhibited platelets) necessary to restore platelet reactivity in platelet-rich plasma (PRP) of patients treated with aspirin and a prasugrel or ticagrelor loading dose for an acute coronary syndrome. PRP samples from patients were mixed ex vivo with increasing proportions of pooled PRP from healthy volunteers. Platelet reactivity was challenged with adenosine diphosphate (ADP), arachidonic acid, collagen or thrombin receptor activating peptide using light transmission aggregometry. The primary endpoint was the proportion of patient samples recovering an ADP-induced maximal aggregation (ADP-Agg_max) value above 40%. In patients treated with prasugrel (n?=?32), ADP-Agg_max increased progressively with supplements of pooled PRP, with an average increase of 7.9% (95% CI [7.1; 8.8], p?<?0.001) per each 20% increase in the ratio of non-inhibited platelets to inhibited platelets. A ratio of 60% was associated with 90% of patients reaching the primary endpoint. In patients treated with ticagrelor (n?=?15), ADP-Agg_max did not significantly increase with any level of supplements. In conclusions, ex vivo addition of non-inhibited platelets significantly improved ADP-Agg_max in patients treated with prasugrel with a dose-dependent effect. There was no evidence of such a reversal in patients treated with ticagrelor. These results suggest that platelet transfusion may be more effective in blunting bleeding in patients treated with prasugrel, than those treated with ticagrelor.     

Follow-up of hemorheological parameters and platelet aggregation in patients with acute coronary syndromes

Pathologic hemorheological parameters and increased platelet aggregation in association with other risk factors significantly increase the possibility of the development of myocardial ischemia. Hemorheological parameters and platelet aggregation were investigated in 157 patients (mean age: 65+/-12 years) with acute coronary syndromes and in 68 healthy subjects (mean age: 36+/-6 years). Plasma fibrinogen, plasma and whole blood viscosity, red blood cell aggregation and filterability and platelet aggregation were measured in the hospital phase (after admission, on 2nd and 6th days) and monitored after discharge (at 1, 6 and 12 months). After admission all these parameters were significantly higher in patients than in control subjects (p<0.01) and almost all of them remained in the pathologic range at discharge. Some of the rheologic parameters showed a slight improvement after 1 month, but hematocrit and whole blood viscosity were higher than those after admission and of control subjects (p<0.05). After 6 and 12 months these parameters showed a small, but significant increase. Pathologically altered hemorheological parameters could be observed in patients with classical cardiovascular risk factors and significant improvement was found after elimination of them. Antiplatelet therapy was efficient in about half of the treated patients after admission; and despite a significant improvement, the proportion of ineffectively treated patients was still considerable during the follow-up. Our results support the role of abnormal hemorheological parameters in the development of myocardial ischemia and draw attention to the rheologic risk of these patients. The results of platelet aggregation measurements show the insufficiency of antiplatelet therapy at some cases and confirm the importance of guided secondary prevention.     

Predictors of high on-clopidogrel platelet reactivity in patients with acute coronary syndrome

High on-clopidogrel platelet reactivity (HPR) is a predictor of ischemic events after percutaneous coronary intervention. We conducted a prospective cohort study to identify variables related to HPR in acute coronary syndrome patients who are at high thrombotic risk. We enrolled 463 patients undergoing urgent coronary angiography. Platelet reactivity was measured 12–36 hours after 600?mg clopidogrel loading with multiple electrode aggregometry (Multiplate® analyzer, Roche, Basel, Switzerland, 6.4?µM ADP). HPR was defined by the consensus cut-off area under the curve >46?U. The rate of HPR was 16.0%. We analyzed simple clinical and laboratory parameters with backward multivariate logistic regression and identified the following predictors of HPR: platelet count (per G/L, OR: 1.0073, 95% CI: 1.0035–1.0112, p?=?0.0002), CRP level (per mg/L, OR: 1.0077, 95% CI: 1.0016–1.01372, p?=?0.01), and active smoking (OR: 0.51, 95% CI: 0.29–0.89, p?=?0.02). We developed and internally validated a risk prediction model demonstrating moderate discriminative capacity (area-under-the-receiver operating characteristic curve?=?0.67). In conclusion, we found a relatively low rate of high on-clopidogrel platelet reactivity (16.0%) even in an acute patient cohort. HPR measured by Multiplate was associated with high platelet count and CRP level on admission and was inversely related to active smoking. The model with rapidly available simple parameters might help to identify individuals at risk for HPR in the acute setting.     

The relation between mean platelet volume and coronary collateral vessels in patients with acute coronary syndromes

ObjectiveElevated mean platelet volume (MPV) has been proposed as a risk factor for coronary artery disease (CAD) and is associated with poor clinical outcome in acute coronary syndrome (ACS). We aimed to evaluate the association of MPV with presence of coronary collateral vessel (CCV) in patients with ACS.MethodsA total of 417 patients with ACS were included in the study. All patients underwent coronary angiography on the first day after admission and patients with a greater than or equal to 80% obstruction in at least one epicardial coronary artery were included in the study. The CCVs are graded according to the Rentrop scoring system and a Rentrop grade 0 was accepted as no CCV development (Group 1), Rentrop Grade 1–2–3 were accepted as presence of CCV development (Group 2).ResultsThe median of MPV was 9.1 ± 1.4 fl. Mean age was 60 ± 12 year. Group 1 consisted of 233 (55.9%) patients and Group 2 consisted of 184 (44.1%) patients. Presence of CCV was significantly associated with high levels of MPV (p = 0.005). Presence of CCV was also associated with presence of diabetes and systolic blood pressure.ConclusionHigh MPV on admission was associated with presence of CCV in patients with ACS.     

Immature platelet fraction in hypertensive pregnancy

Background: Imbalance in hemostatic mechanisms can occur during pregnancy with a tendency for hypercoagulability and increased thrombosis risk. Pregnant women with hypertensive disorder, especially preeclampsia, show alterations in platelet indexes. Immature platelet fraction (IPF) has been suggested as a sensitive index for monitoring changes in platelet production and destruction. Objectives: To evaluate the IPF in patients diagnosed with a gestational hypertensive disorder (GHD). Patients and methods: A cross-sectional study was conducted at an University Hospital to estimate maternal blood IPF index in 99 pregnant women, divided into three groups: normotensive pregnancy (NP), preeclampsia syndrome (PES), and non-proteinuric hypertensive pregnancy (nPHP). Following ethical approval and written informed consent, samples were collected from 33 NP, 34 PES, and 32 nPHP women. Platelet indexes were measured by fluorescent flow cytometry. Results: IPF and mean platelet volume (MPV) counts in GHD were significantly higher than in NP (IPF: 3.8, 2.4–5.1%; 8.6, 5.8–10.6%; 7.3, 4.2–10.2%; p < 0.001 and MPV: 10.6 ± 0.9 fL; 12.1 ± 1.0 fL; 11.6 ± 1.0 fL; p < 0.001 for NP, PES, and nPHP, respectively). No difference was detected between PES and nPHP groups. The distribution of patients with an IPF above 6.1%for NP, PES, and nPHP was 9%, 65%, and 43.8%, respectively (p < 0.001). IPF as a test to differentiate GHD from the controls achieved an area under the curve of 0.83 on a receiver operating characteristics curve. Conclusion: A distinct profile in platelet indexes was detected in hypertensive pregnancies. It suggests that these markers could be used in daily routine as an additional tool in the management of pregnant women.     

Systemic inflammatory status is associated with increased platelet reactivity in the early period after acute coronary syndromes

Systemic inflammation measured by high-sensitivity C reactive protein (CPR) is associated with increased risk of major adverse cardiovascular events (MACE). Recent clinical trials targeting CPR showed a reduction in MACE after an acute coronary syndrome (ACS). Inflammation could be linked to high platelet reactivity (HPR), which is an independent predictor of MACE in patients with ACS. We aimed to evaluate the impact of 1-month C-reactive Protein (CRP) levels on HPR in patients enrolled in the GEPRESS study. We measured CRP and platelet reactivity index (PRI) at 30 days follow-up. PRI was assessed with vasodilator stimulated phosphoprotein (VASP) phosphorylation assay at the same timepoint. HPR was defined as PRI >50%. Of the 1042 patients included in the GEPRESS study, 756 (75%) had both VASP and CRP data at 30 days follow-up. HPR was found in 61 (49.1%) patients with CRP >1 mg/L and 233 (36.4%) patients with CRP ≤1 mg/L, p = 0.012. After adjustment for covariates, we found a direct gradient of effect between CRP and HPR; the inclusion of CRP significantly increased the discrimination of HPR regression model. This is the first study showing that residual HPR is more likely to occur in patients with CRP >1 mg/L at 1 month after non-ST elevation-ACS and this may contribute to the unfavorable outcome observed in such patients.     

Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes

OBJECTIVES: The study was done to determine the role of partial agonist activity in the lack of effectiveness of the oral GPIIb/IIIa antagonist orbofiban. BACKGROUND: Orbofiban, an oral GPIIb/IIIa antagonist, was found to increase the mortality of patients with acute coronary syndromes (ACS) in the OPUS-TIMI-16 trial, despite the fact that it is a very potent anti-platelet agent and that IV agents have proven very effective. METHODS: Patients (n = 520) with ACS were randomized to orbofiban 30 mg, 40 mg or 50 mg twice daily or 50 mg once daily or placebo. Platelet activity was assessed in 175 patients by examining GPIIb/IIIa receptor conformation, expression of CD63 antigen, and platelet aggregation. RESULTS: Plasma concentrations of orbofiban at the highest dose (74 +/- 6 ng/ml peak, 61 +/- 5 ng/ml trough) exceeded the IC50 for platelet aggregation to adenosine diphosphate (ADP) (29 +/- 6 ng/ml) and thrombin-activating peptide (61 +/- 18 ng/ml). Orbofiban induced a conformational change in GPIIb/IIIa detected as the displacement of the monoclonal antibody mAb2; such conformational changes have been linked to partial agonist activity. Consistent with this, platelet expression of CD63 ex vivo was significantly increased at five time points during the study. In vitro, orbofiban increased platelet aggregation to a submaximal concentration of epinephrine (67 +/- 19% vs. 27 +/- 9%, n = 5) and increased thromboxane formation when the platelet GPIIb/IIIa were clustered using monoclonal antibodies to the receptor. CONCLUSIONS: Orbofiban is both an antagonist and a partial agonist of platelet GPIIb/IIIa. At low concentrations of the drug, this partial agonist activity may enhance platelet aggregation. Along with suboptimal plasma drug levels, these findings may help explain the lack of efficacy seen with orbofiban in patients with ACS.     

Increased rate of formation of small-sized platelet aggregates in patients with acute coronary syndromes

Coronary thrombosis has been implicated in the pathogenesis of acute coronary syndromes, and platelet activation plays a pivotal role in the pathogenesis of coronary thrombus. A new platelet aggregometer using a laserlight scattering beam was trialled for assessment of platelet aggregation. Platelet aggregability, especially small-sized platelet aggregates, was investigated on admission using the laser-light scattering method and again after treatment in 23 patients with acute coronary syndromes. The platelet aggregability in 14 patients with stable exertional angina and in 14 control subjects was also examined. On admission, the number of small- and medium-sized platelet aggregates in the acute coronary syndromes group was significantly greater than in the stable exertional angina group or control group. However, the number of large-sized platelet aggregates on admission was not increased in the acute coronary syndromes group. Furthermore, the number of small- and medium-sized platelet aggregates decreased significantly after treatment in the acute coronary syndromes group. The increased number of small-sized platelet aggregates may sensitively reflect attacks of thrombosis in patients suffering acute coronary syndromes.