Greater Platelet Reactivity Research Articles

Platelet Reactivity with MACE in Acute Coronary Syndrome Patients Post-PCI under Dual Antiplatelet Therapy: A Meta-Analysis

Aim/Background Acute coronary syndrome (ACS), a condition characterized by acute cardiac ischemia, is among the major causes of death from cardiovascular diseases (CVD). However, whether there is a correlation between platelet reactivity and major adverse cardiovascular events (MACE) remains debatable, and whether platelet function tests should be tailored for ACS patients after percutaneous coronary intervention (PCI) is still under discussion. This study aims to investigate the relationship between platelet reactivity and the occurrence of MACE in ACS patients post-PCI and to discuss the implications of these findings. Methods Clinical studies on ‘PCI, ACS, dual antiplatelet therapy (DAPT), platelet reactivity, major adverse cardiovascular events (MACE)’ up to 31 October 2023, were systematically collected from Embase, PubMed, and the Cochrane Library. Twelve articles meeting predefined criteria were selected. Meta-analysis was performed using Review Manager 5.4 (Cochrane, London, UK) and Stata 15.0 (StataCorp LLC, College Station, TX, USA) to compute pooled effect sizes, assess heterogeneity, explore sources of heterogeneity, and evaluate publication bias. Results Twelve articles consisting of 9297 patients were included. The meta-analysis showed that ACS patients with high platelet reactivity (HPR) who received PCI and used DAPT for 1–2 years had a greater risk of MACE (risk ratio (RR) = 1.79, 95% confidence interval (CI): 1.30–2.46) compared to those with low platelet reactivity. Moreover, greater platelet reactivity was associated independently with all-cause mortality (RR = 2.26, 95% CI: 1.63–3.12), cardiac mortality (RR = 2.87, 95% CI: 2.16–3.8), myocardial infarction (RR = 1.98, 95% CI: 1.53–2.5), in-stent restenosis (RR = 1.87, 95% CI: 1.22–2.87), as well as stroke (RR = 1.62, 95% CI: 1.02–2.57), but not with coronary revascularization events (RR = 0.99, p = 0.96, 95% CI: 0.80–1.24). On the other hand, meta-regression revealed that region (p = 0.99), type of ACS patient (p = 0.16), drug regimen (p = 0.48), testing method (p = 0.51), sampling time (p = 0.70), follow-up time (p = 0.45), and PCI protocol (p = 0.27) were not sources of heterogeneity in the study. Conclusion The meta-analysis outcomes indicate that in ACS patients receiving PCI and using dual antiplatelet therapy for 1–2 years, HPR was independently positively correlated with major adverse cardiovascular events, all-cause (or cardiac) mortality, recurrent myocardial infarction, in-stent restenosis, and stroke. This suggests that platelet reactivity testing has clinical and translational significance in predicting patients’ risk of adverse cardiovascular events.

Impact of kidney function, ticagrelor and genetic polymorphism on high platelet reactivity

Abstract Background High platelet reactivity (HPR) is associated with worse clinical outcomes. Patients with chronic kidney disease (CKD) respond poorly to clopidogrel. The purpose was to investigate what is major determinant on HPR in CKD patients. Methods A total of 219 (139 normal kidney function, 80 CKD) patients who were treated with clopidogrel or ticagrlor were assessed platelet reactivity and genetic polymorphisms. Platelet function was evaluated by the VerifyNowTM P2Y12 assay. Genes tested were ABCB1, PON1, cytochrome P450 (CYP) 2C19, CYP2C9 and P2Y12. HPR was defined as P2Y12 reaction units ≥ 230. Results Platelet reactivity were significantly higher in patients with CKD compared to normal kidney function (288 ± 96 vs 223 ± 69, p < 0.01). But, there were no significant differences of genetic distribution between 2 groups. In patients with CKD and normal kidney function, CYP2C19 carriers had greater platelet reactivity during clopidogrel therapy but there were no differences during ticagrelor treatment regardless of CYP2C19 status (Figure). In multivariate analysis, CKD [hazard ratio (HR): 4.67 (2.27 – 9.78), p < 0.01], CYP2C19 carriers [HR: 2.81 (1.36 – 5.82), p < 0.01] and ticagrelor treatment [HR: 0.29 (0.18 – 0.48), p < 0.01] were significantly correlated with HPR. Conclusion Ticagrelor treatment achieved greater platelet inhibition in patients with CKD whereas CKD and CYP2C19 genotype were significantly correlated with HPR.

Impact of COVID-19 disease on platelet reactivity and association with inflammatory parameters

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Aside from the pulmonary manifestations, COVID-19 is associated with increased risk of venous and arterial thrombotic complications. The actual impact of SARS-CoV-2 infection on platelet reactivity and whether this is mediated by a hyperinflammatory status has not been fully elucidated to date.ObjectiveTo evaluate platelet reactivity in COVID-19 patients compared to healthy subjects and to assess the association between platelet reactivity and levels of inflammatory biomarkers among COVID-19 patients.MethodsThis prospective observational investigation included COVID-19 patients admitted into a tertiary care hospital and adult healthy volunteers, all of them not receiving any antiplatelet therapy. Subjects were classified in three groups: 1) Healthy subjects (HS group); 2) COVID-19 patients in a pulmonary phase (viral pneumonia and bilateral infiltrates) but without meeting criteria for systemic hyperinflammation (C19-Pulm group); and 3) COVID-19 patients in a hyperinflammation phase (C19-Infl group) meeting at least 2 of the following criteria: CRP>100mg/l, D-dimer >1000mcg/l, LDH>400U/l, ferritin>1000ng/ml, IL-6>70ng/l. Blood samples for platelet function testing and quantification of inflammatory parkers were collected at a single visit. Platelet function was measured with multiple electrode aggregometry using ADP (MEA-ADP, primary endpoint), arachidonic acid (AA) and thrombin receptor activating peptide (TRAP) as stimuli. Unadjusted analyses are presented.ResultsA total of 60 patients were included in the present investigation (20 in each group). A significantly greater platelet reactivity, measured with MEA-ADP, was observed in both groups of COVID-patients compared to healthy subjects (HS: 634,9±53,5, C19-Pulm: 919,9±53,5 and C19-Infl: 931,6±53,5 AU*min; p for C19-Pulm vs. HS <0,001, p for C19-Infl vs. HS <0,001, p for C19-Pulm vs. C19-Infl 0,878; Figure 1). Parallel findings were found when using AA as stimulus for platelet aggregation showing greater platelet aggregation in COVID-19 patients compared to healthy subjects, but numerical differences were not statistically significant when using TRAP. Among COVID-19 patients, when stratified by IL-6 levels splitted into tertiles, greater platelet reactivity was observed in patients with higher IL-6 concentrations (mid and upper tertile together) compared to those with values in the lower tertile, as assessed with MEA-ADP (lower tertile: 829,0±75,8, mid and upper tertile: 1028,7±56,2; p=0,043); a similar trend was observed with AA and TRAP as stimuli.ConclusionPatients with severe COVID-19 disease have greater platelet reactivity than healthy subjects. Increased IL-6 levels might be associated with the observed heightened platelet reactivity among COVID-19 patients.Funding AcknowledgementType of funding sources: None. Figure 1

Relation of multi-vessel coronary artery disease to response to aspirin

Abstract Background Multi-vessel coronary artery disease (MV-CAD) is correlated with worse outcomes compared with single-vessel CAD (SV-CAD), potentially attributed to more advanced atherosclerotic disease in other vascular beds, greater endothelial dysfunction, thrombin activation and possibly greater platelet reactivity. Objectives The aim of the current study was to evaluate the association between MV-CAD and high on-aspirin platelet reactivity (HAPR) in patients with stable CAD treated with aspirin. Methods Patients with known stable CAD, who were taking aspirin (75–100 mg qd) regularly for at least one month, and had undergone coronary angiography at least 3 months prior to the test, were enrolled. Blood was drawn from the participants and sent for platelet function testing. MV-CAD was defined as &amp;gt;50% stenosis in ≥2 separate major coronary territories per coronary angiography. HAPR was defined as aspirin reaction units (ARU) &amp;gt;550. Results Overall 507 patients were analyzed; age 66.7±11.2, 17.9% women, 223 (44%) had MV-CAD. Mean ARU was significantly higher among patients with MV-CAD vs. SV-CAD (460±68 vs. 440±55, p&amp;lt;0.001, respectively). Furthermore, the rate of HAPR was significantly higher among patients with MV-CAD (figure 1). In a multivariate analysis adjusted for potential confounders, MV-CAD was found to be a strong independent predictor of HAPR [OR=1.8 (95% CI1.05–4.7), p=0.014]. In a reverse analysis, HAPR was associated with a higher number of coronary vessels involved (1.95±0.65 vs. 1.45±0.57, p&amp;lt;0.01) and a strong independent predictor of MVD (OR-2.44, CI 1.83–25.6, p=0.015). Conclusions MV-CAD is significantly associated with HAPR. This could potentially explain, in part, the increased risk and/or worse outcomes in patients with MV-CAD and implies considering intensive anti-thrombotic therapy among these patients. Funding Acknowledgement Type of funding source: None

255Impact of the type of acute coronary syndrome on the pharmocodynamic response to P2Y12 inhibitors in the acute and maintenance phase of therapy

Abstract Background The presence of an acute coronary syndrome (ACS) is per se a predictor of reduced responsiveness to clopidogrel; in particular, patients with ST-elevation myocardial infarction (STEMI) have impaired clopidogrel-induced platelet inhibition than those with other forms of ACS. However, the impact of the type of ACS on the pharmocodynamic efficacy of more potent P2Y12 antagonists such as prasugrel or ticagrelor has not been fully elucidated to date. Purpose To assess the impact of the type of ACS on platelet inhibition mediated by P2Y12 receptor antagonists in the acute and the maintenance phase of therapy in a contemporary cohort of ACS patients undergoing percutaneous coronary intervention (PCI). Methods Substudy of a prospective, national, multicentre, pharmacodynamic registry conducted in a population of ACS patients undergoing PCI and treated with dual antiplatelet therapy including aspirin and a P2Y12 inhibitor as per clinical indication. Patients were classified according to the ACS diagnosis into groups: a) STEMI, b) non-ST-elevation ACS (NSTEACS), c) unstable angina (UA), and d) other (excluded from the present analysis). Platelet function tests (PFT) were performed at day 1 and day 30 (±5) after PCI and included: 1) VerifyNow P2Y12 assay, expressed as P2Y12 reaction units (PRUs); 2) Vasodilator-stimulated phosphoprotein (VASP) assay; and 3) Multiple electrode aggregometry (MEA). Results A total of 965 patients (372 with STEMI, 395 with NSTEACS and 198 with UA) were included in the present substudy. At day 1, the proportions of patients with each type of ACS according to the P2Y12 inhibitor received were: 1) clopidogrel (n=317): STEMI 35.0%, NSTEACS 34.4% and UA 30.6%; 2) prasugrel (n=192): STEMI 70.3%, NSTEACS 17.7% and UA 12.0%; 3) ticagrelor (n=456): STEMI 27.6%, NSTEACS 55.3% and UA 17.1%. A statistically significant reduced platelet inhibition, measured with the VerifyNow system, was observed in STEMI patients compared with the other forms of ACS in patients receiving clopidogrel (STEMI: 217.3±8.1, NSTEACS: 157.1±7.9 and UA: 164.9±8.6 PRUs; p for STEMI vs. NSTEACS &lt;0.001 and p for STEMI vs. UA &lt;0.001) and ticagrelor (STEMI: 57.7±3.8, NSTEACS: 45.2.1±2.6 and UA: 40.6±4.9 PRUs; p for STEMI vs. NSTEACS 0.008 and p for STEMI vs. UA 0.007), while a numerical trend towards greater platelet reactivity in STEMI compared to UA was observed in subjects receiving prasugrel (Figure). Remarkably, at day 30, no significant differences on platelet inhibition were observed according to the ACS type with any of the P2Y12 inhibitors. Similar results were observed with MEA and VASP assays. PD response according to the ACS type Conclusions Patients presenting with STEMI have impaired platelet inhibition mediated by P2Y12 antagonists compared to other types of ACS during the acute phase of therapy, whereas no difference is observed during the maintenance phase of treatment. Acknowledgement/Funding Funded by Instituto de Salud Carlos III through the project PI13/01012 (co-funded by European Regional Development Fund. ERDF, a way to build Europe)

High and low on-treatment platelet reactivity to P2Y12 inhibitors in a contemporary cohort of acute coronary syndrome patients undergoing percutaneous coronary intervention

IntroductionThere is compelling evidence supporting the association between high on-treatment platelet reactivity (HPR) and low on-treatment platelet reactivity (LPR) to clopidogrel with atherothrombotic and bleeding events, respectively. However, it is uncertain if current cutoff values should be used in prasugrel- or ticagrelor-treated subjects. The objective of this analysis was to evaluate the pharmacodynamic (PD) efficacy of P2Y12 antagonists in a contemporary real-world population. Materials and methodsThis PD study included 988 patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and receiving dual therapy with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor). Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y12 assay, multiple electrode aggregometry and vasodilator-stimulated phosphoprotein (VASP) assay. ResultsClopidogrel-treated patients (n = 324) had greater platelet reactivity than those receiving ticagrelor (n = 469) or prasugrel (n = 195) at both time points (p < 0.001 for all comparisons). No difference between ticagrelor and prasugrel was observed at day 1 with the VerifyNow P2Y12 assay (51.5 ± 2.8 vs. 42.7 ± 3.5 PRUs; p = 0.298), whereas ticagrelor achieved greater platelet inhibition at day 30 (48.1 ± 2.5 vs. 89.2 ± 4.2 PRUs; p < 0.001). Similar results were obtained with the VASP assay. Both prasugrel and ticagrelor had markedly lower HPR rates than clopidogrel and very high rates of LPR at both time points. ConclusionsPrasugrel and ticagrelor displayed more potent and consistent PD effects than clopidogrel in ACS patients undergoing PCI, with a trend towards greater platelet inhibition with ticagrelor during the maintenance phase of therapy compared to prasugrel.

Effect of amlodipine on platelet inhibition by clopidogrel in patients with ischaemic heart disease: a randomised, controlled trial

BackgroundAmlodipine inhibits cytochrome P450 (CYP) enzyme and has the potential to reduce clopidogrel bioactivation in vivo. Reports in previous retrospective studies described greater platelet reactivity in patients on amlodipine.ObjectiveTo evaluate...

Clopidogrel Efficacy and Cigarette Smoking Status

RECENT ANALYSES OF LARGE-SCALE TRIALS SUGGEST either a reduced or complete lack of clinical benefit from clopidogrel therapy in nonsmokers. Importantly, this observation is not explained by an enhanced prothrombotic state (a condition in which P2Y12 inhibitor therapy may be expected to be most effective) in smokers relative to nonsmokers as evidenced by variable event rates in smokers and nonsmokers treated with placebo. Cigarette smoking induces the activity of cytochrome P450 (CYP) 1A2, an isoenzyme involved in the metabolic activation of clopidogrel but less recognized in importance than CYP2C19. Nonsmokers have greater platelet reactivity than smokers during clopidogrel treatment. A recent additional important analysis of the CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial revealed a significant interaction based on smoking status (P=.01 for interaction). Specifically, patients in the clopidogrel-treated nonsmoker group (a combination of the neversmoker group and former-smoker group) had no reduction in the incidence of the primary outcome of ischemic stroke, myocardial infarction (MI), or vascular death compared with the aspirin-treated nonsmoker group (10.4% vs 10.6%, respectively; hazard ratio [HR], 0.98 [95% CI, 0.88-1.09]), whereas patients in the clopidogrel-treated currentsmoker group had a significantly lower incidence of the primary outcome compared with the aspirin-treated currentsmoker group (8.3% vs 10.8%, respectively; HR, 0.76 [95% CI, 0.64-0.90]). To our knowledge, the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events [N=12 562]) trial investigators have not presented a similar adjusted analysis of nonsmokers and smokers. However, an abstract based on CURE trial data reported that in the largest smoking status subgroup—never smokers—clopidogrel treatment was not associated with a significant reduction in the primary outcome (a composite of death from cardiovascular causes, nonfatal MI, or stroke) compared with never smokers treated with placebo (10.2% vs 10.9%, respectively; HR, 0.93 [95% CI, 0.79-1.11]), whereas current smokers treated with clopidogrel had a significantly lower incidence of the primary outcome compared with placebo (6.1% vs 9.4%, respectively; HR, 0.63 [95% CI, 0.48-0.83]). In the CREDO (Clopidogrel for the Reduction of Events During Observation) trial, there was no difference in the occurrence of the primary composite end point (1-year death, MI, and stroke) in clopidogrel-treated nonsmokers relative to placebo-treated nonsmokers, whereas a significant benefit was observed in clopidogrel-treated smokers compared with placebo-treated smokers (6.3% vs 13.8%, respectively; HR, 0.44 [95% CI, 0.23-0.83]). Desai et al attempted to refine the relation between smoking status and clinical outcomes based on previous pharmacodynamic findings. These investigators conducted a post hoc analysis of patients with ST-segment elevation MI, based on the quantification of the number of cigarettes smoked at baseline, in the Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28) trial. They reported an adjusted analysis based on smoking status for both the primary end point (angiographic outcome) and the secondary end point (30-day clinical outcome), revealing a significant smoking status interaction for both end points (P=.04 and P=.006, respectively, for interaction in patients who smoked at least 10 cigarettes/d). In that trial, clopidogrel therapy was associated with an overall 36% and 20% reduction in the rate of the primary and secondary end points, respectively, relative to placebo. The reduction in the primary end point was enhanced among clopidogrel-treated patients who smoked 10 or more cigarettes per day relative to placebo (adjusted odds ratio [OR], 0.49; P .0001). In addition, clopidogreltreated patients who smoked zero cigarettes per day or less than one-half pack per day had no significant benefit in 30-day clinical end point occurrence compared with patients treated with placebo (13.7% vs 14.3%, respectively; OR, 0.98 [95% CI, 0.75-1.28]), whereas clopidogrel-treated patients who smoked 10 or more cigarettes per day exhibited a 46% reduction in the 30-day clinical end point relative to the placebo group (8.0% vs 14.3%, respectively; OR, 0.54 [95% CI, 0.38-0.76]).

Comparison of Platelet Reactivity and Clopidogrel Response in Patients ≤75 Years Versus >75 Years Undergoing Percutaneous Coronary Intervention for Non–ST-Segment Elevation Acute Coronary Syndrome

Specific data about the clopidogrel response in elderly patients are lacking. The present study was performed to compare the platelet reactivity and clopidogrel response between patients aged > 75 years and < 75 years undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome. A total of 689 patients were enrolled, including 162 patients aged > 75 years and 527 younger patients. All patients received a loading dose of 600 mg clopidogrel followed by 150 mg/day. Post-treatment platelet reactivity was assessed by adenosine diphosphate 10 μmol/L-induced platelet aggregation and the specific pharmacologic response to clopidogrel by the platelet reactivity index vasoactive stimulated phosphoprotein. High post-treatment platelet reactivity was defined as adenosine diphosphate 10 μmol/L-induced platelet aggregation >70%. Clinical events were recorded during 1 month of follow-up. The patients > 75 years old had a greater rate of both ischemic and bleeding complications (p = 0.04 and p = 0.03, respectively). The post-treatment platelet reactivity in response to both the loading and the maintenance clopidogrel dose was greater in patients > 75 years old than in the younger patients: 50 ± 17% versus 45 ± 17% (p = 0.002) and 57 ± 15% versus 53 ± 16% (p = 0.0005), respectively. The rate of high post-treatment platelet reactivity was significantly greater in patients aged > 75 years after 600 mg and 150 mg clopidogrel: 14% versus 9% (p = 0.04) and 23% versus 15% (p = 0.02), respectively. In contrast, the pharmacologic response to clopidogrel was not impaired in patients > 75 years after loading and maintenance doses: 43 ± 21% versus 46 ± 21% (p = 0.17) and 38 ± 18% versus 39 ± 18% (p = 0.55), respectively. In conclusion, patients aged > 75 years have an impaired prognosis after acute coronary syndrome. They display greater post-treatment platelet reactivity. However, this greater platelet reactivity does not seem to be related to an impaired specific response to clopidogrel.

First Analysis of the Relation Between CYP2C19 Genotype and Pharmacodynamics in Patients Treated With Ticagrelor Versus Clopidogrel

Background— The influence of cytochrome P450 (CYP) 2C19 genotype on platelet function in patients treated with ticagrelor versus clopidogrel is unknown. Methods and Results— CYP2C19 (*1, *2, *3, *4, *5, *6, *7, *8, *17) genotyping was performed in patients with coronary artery disease treated with ticagrelor (180-mg load, 90 mg BID) (n=92) or clopidogrel (600-mg load, 75 mg/d) (n=82). All patients received 75 to 100 mg/d aspirin. Platelet function was measured by aggregometry, VerifyNow P2Y12 assay, and vasodilator-stimulated phosphoprotein-phosphorylation assay at predose, 8 hours postloading, and maintenance. In each treatment group, patients were categorized according to 2C19 genotype carrier status (loss-of-function, gain-of-function) and metabolizer status. Kruskal-Wallis test was used to compare platelet function among these categories for each treatment, and Wilcoxon rank sum test was used to compare platelet function between the clopidogrel and ticagrelor groups for each category. There was no statistically significant influence of genotype on platelet function during aspirin therapy alone. Ticagrelor exhibited lower platelet reactivity than clopidogrel by all assays irrespective of 2C19 genotype or metabolizer status ( P &lt;0.01). Loss-of-function carriers had greater platelet reactivity during clopidogrel therapy. The influence of genotype on platelet reactivity was greatest during clopidogrel maintenance and best demonstrated by the VerifyNow P2Y12 assay. Conclusions— This report is the first to demonstrate the superior pharmacodynamic effect of ticagrelor compared with clopidogrel irrespective of CYP2C19 genotype. Whereas CYP2C19 genotype influenced the antiplatelet effect of clopidogrel, there was no effect of CYP2C19 genotype during ticagrelor therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00642811 and NCT00528411.

Abstract 3477: Platelet Hyper-responsiveness in Aspirin-Treated Patients with Clinical Cardiovascular Disease Compared to Matched High Risk Controls

Background: Platelet hyper-responsiveness to activating stimuli during aspirin (ASA) therapy may discriminate between high risk subjects who have developed acute thrombotic cardiovascular disease (CVD) events (coronary disease and stroke) and those who are at increased risk but are disease free. We hypothesized that subjects with documented CVD would have greater platelet reactivity on ASA therapy compared to matched high risk non-CVD subjects. Methods: Subjects (N=228; 61 +/− 8 yrs, 69% male, 60% white) were selected from families with known CVD; 114 had prevalent CVD and were matched on age, sex, and race to 114 apparently healthy controls with risk factors but without clinical CVD. CVD risk factors were measured and therapy adherence was determined by questionnaires. Platelet reactivity on 81 mg ASA/day was determined by whole blood (WB) aggregometry, platelet function analyzer (PFA) closure time, thromboxane B2 (TxB2) release ex vivo , and urinary excretion of 11-dehyrothromboxane B2 (Tx-M) in vivo . Results. CVD cases had greater platelet reactivity by all measures, both unadjusted, and adjusted for age, sex, race and adherence (Table ). Multivariable adjustment for cardiac risk factors and statin therapy eliminated case-control differences for Tx-M, but not for the ex vivo measures of platelet activation. ASA therapy duration in CVD subjects (8.8 +/− 6.2 yrs) was not related to platelet function. Conclusions: Greater residual platelet reactivity exists during ASA therapy in CVD subjects compared to matched high risk controls, even controlling for CVD risk factors and adherence to therapy. The data suggest that platelet hyper-responsiveness during ASA chemoprophylaxis may differentiate patients with CVD from those who are at risk for CVD, but have not developed it. Platelet hyper-responsiveness may be an intrinsic property of CVD, related to as yet unidentified environmental or genetic factors.

Relation of augmented platelet reactivity to the magnitude of distribution of atherosclerosis

The extent of luminal involvement of atherosclerotic vascular disease and platelet reactivity portend subsequent cardiovascular events. This study was designed to determine whether platelet reactivity correlates with the extent of the territorial distribution of vascular disease. Blood was obtained from 130 patients who had known atherosclerotic vascular disease categorized as being in > or =1 of the following territories: coronary artery disease (CAD; n = 89), cerebrovascular disease (n = 36), and peripheral arterial disease (n = 61). Platelet reactivity, i.e., the activation of platelets in response to a low concentration of adenosine diphosphate (0.2 micromol/L), was measured using flow cytometry. Patients with vascular disease in >1 territory compared with those with disease in only 1 territory had greater platelet reactivity with respect to P-selectin expression (p = 0.01). The percentages of platelets expressing P-selectin (mean +/- SD) were 6.4 +/- 4.2 in patients who had involvement of 1 territory (n = 88), 10.0 +/- 6.8 in those who had involvement of 2 territories (n = 28), and 10.1 +/- 9.9 in those who had involvement of 3 territories (n = 14). Patients who had CAD and diabetes mellitus had greater P-selectin expression than did those who had CAD without diabetes (p <0.02 for interaction). Thus, platelet reactivity is greater in patients who have more extensive territorial distribution of atherosclerotic vascular disease and in those who have CAD and diabetes mellitus. Accordingly, patients who have more widely distributed vascular disease are likely to derive particular benefit from antiplatelet regimens that suppress platelet function to a greater extent.

Comparative evaluation of antepartum and postpartum platelet function in smokers and nonsmokers

Platelet aggregation was analyzed during normal pregnancy by evaluation of the same patient cohort (n = 19) on two separate prenatal visits and at 4 weeks post partum. To analyze platelet aggregation five different parameters were evaluated in platelet-rich plasma and whole blood (by impedance aggregometry) with the use of four different aggregating agents: adenosine diphosphate, collagen, sodium arachidonate, and epinephrine. Plasma levels of β-thromboglobulin, thromboxane B2, and 1,6-keto-prostaglandin F1α were also analyzed. Platelet counts rose 19% after delivery. Plasma levels of β-thromboglobulin and thromboxane B2 were not significantly changed during the two antepartum visits, but B-thromboglobulin levels were modestly elevated post partum. Levels of 1,6-keto-prostaglandin F1α decreased significantly from a mean of 125 pg/ml before delivery to 50 pg/ml post partum. All antepartum parameters on whole blood aggregation that were significantly different from postpartum values showed enhanced antepartum reactivity. In platelet-rich plasma, pregnancy was associated with greater platelet reactivity except for two variables, time to half-maximal aggregation for epinephrine and the extent of aggregation by collagen, both noted during the first antepartum evaluation. When the patient cohort of 19 was subdivided according to smoking status, all aggregation parameters of significance (p < 0.05) demonstrated increased platelet reactivity during pregnancy compared with postpartum values. Smoking women accounted for a disproportionate number of significantly enhanced reactivity (seven variables versus three).