Increased procoagulant platelet levels are predictive of death in COVID-19.

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan-Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2-12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680-1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.

Clopidogrel use and smoking cessation result in lower coated-platelet levels after stroke.

Coated-platelets are a subset of highly procoagulant platelets elevated in patients with non-lacunar ischemic stroke and associated with stroke recurrence. Cross-sectional studies in controls have shown that smoking is associated with higher coated-platelet levels while chronic use of serotonin reuptake inhibitors (SSRIs), statins or aspirin is associated with lower coated-platelet levels. We now investigate if initiation of treatment with SSRIs, statins, clopidogrel, aspirin or oral anticoagulants and smoking cessation impacts coated-platelet levels at 90 days after ischemic stroke. Coated-platelet levels, reported as percent of cells converted to coated-platelets, were measured in 87 consecutive patients with stroke at baseline and repeated at 90 days. Repeated-measure ANOVA was used to determine if initiation of treatment with individual medications or smoking cessation impacted coated-platelet levels. Decreased coated-platelets levels at 90 days as compared to baseline were observed after initiation of treatment with clopidogrel (p = .0001, partial η2 = 0.17) and smoking cessation (p = .014, partial η2 = 0.10). Initiation of treatment with SSRIs, statins, aspirin or oral anticoagulants did not result in significant changes in coated-platelet potential. These novel longitudinal data suggest that clopidogrel therapy and smoking cessation attenuate coated-platelet potential at 90 days after ischemic stroke.

Increased platelet procoagulant potential predicts recurrent stroke and TIA after lacunar infarction.

BACKGROUND: Mean levels of coated-platelets, a subset of highly procoagulant platelets, are decreased in patients with lacunar as compared to those with non-lacunar stroke. Elevated coated-platelets are associated with increased risk for recurrent infarction in non-lacunar stroke and predict incident stroke after transient ischemic attack (TIA). OBJECTIVE: We investigated if coated-platelet levels are predictive of recurrent cerebral ischemia following lacunar stroke. METHODS: Coated-platelet levels were assayed in consecutive patients with acute lacunar stroke, who were followed for up to 12 months. Cox proportional hazards regression analysis was used to estimate the combined risk of stroke and TIA at 12 months according to initial coated-platelet levels. RESULTS: We enrolled a total of 109 lacunar stroke patients. Eight events were recorded over a mean follow-up period of 10.8 months. A cut-off of 42.6% for coated-platelet levels yielded a sensitivity of 0.75 (0.35-0.97; 95% confidence interval [CI]), specificity of 0.92 (0.85-0.97), positive predictive value of 0.43 (0.26-0.62), and a negative predictive value of 0.98 (0.93-0.99) for recurrent stroke/TIA. The adjusted hazard ratio for recurrent stroke/TIA in patients with coated-platelet levels ≥ 42.6% was 23.9 (95% CI: 4.26-134.4) when compared to those with levels < 42.6%. CONCLUSIONS: Identification of increased platelet procoagulant potential may improve our ability to identify patients at higher risk of recurrent stroke/TIA following a lacunar stroke. Further study of mechanisms involved is warranted and may yield novel targets for prevention and treatment.

Higher Coated-Platelet Levels in Acute Stroke are Associated with Lower Cognitive Scores at Three Months Post Infarction.

BACKGROUND: Coated-platelets are a subset of highly procoagulant platelets observed after dual agonist stimulation with collagen and thrombin. Coated-platelet levels are increased in acute stroke compared to controls, and higher levels are associated with stroke recurrence. We examined whether coated-platelet levels measured at the time of the stroke correlate with cognitive scores at 3 months following the brain infarction. METHODS: Coated-platelets were assayed in consecutive patients with nonlacunar stroke. Cognitive screening was performed using the Mini-Mental State Examination (MMSE) at 3 months after discharge. Linear regression, with adjustment for individual covariates, was used to model the association between coated-platelet levels and MMSE scores. RESULTS: One hundred and twenty-eight patients with a mean MMSE score of 26 points (range 14-30, standard deviation [SD] 3.1) and mean coated-platelet levels of 40.9% (range 5.2-76.2, SD 13.3), completed cognitive screening. An inverse linear association was found between coated-platelet levels and MMSE score, with higher levels seen in patients with lower MMSE scores (r = -.34, R2 = .12, P < .0001). This association remained despite adjustment for potential confounding factors. In the final model, higher coated-platelet levels (coefficient -.078, 95% confidence interval [CI]: -.12 to -.041, P < .0001), presence of hypertension (coefficient -2.42, 95% CI: -3.90 to -.95, P = .0015), and anticoagulant use at discharge (coefficient -1.48, 95% CI: -2.56 to -.39, P = .0079) were predictive of lower MMSE. CONCLUSIONS: These findings support a link between increased platelet procoagulant potential at the time of the stroke and development of cognitive impairment following cerebral infarction.

Systemic response of coated-platelet and peripheral blood inflammatory cell indices after aneurysmal subarachnoid hemorrhage and long-term clinical outcome.

PURPOSE: Post-hemorrhage period after aneurysmal subarachnoid hemorrhage (aSAH) has several systemic manifestations including prothrombotic and pro-inflammatory states. Inter-relationship between these states using established/routine laboratory biomarkers and its long-term effect on clinical outcome is not well-defined. MATERIALS AND METHODS: Retrospective analysis of prospective cohort of 44 aSAH patients. Trend of procoagulant biomarkers [coated-platelets, mean platelet volume to platelet count (MPV:PLT)] and peripheral inflammatory biomarkers [platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NLR)] were analyzed using regression analysis. Occurrence of delayed cerebral ischemia (DCI), modified Rankin score (mRS) of 3-6 and Montreal cognitive assessment (MoCA) of <26 at 1-year defined adverse clinical outcome. RESULTS: Patients with worse mRS and MoCA score had higher rise in coated-platelet compared to those with better scores [20.4 (IQR: 15.6, 32.9) vs. 10.95 (IQR: 6.1, 18.9), p = 0.003] and [16.9 (IQR: 13.4, 28.1) vs. 10.95 (IQR: 6.35, 18.65), p = 0.02] respectively. NLR and PLR trends showed significant initial decline followed by a gradual rise in NLR among those without DCI as compared to persistent low levels in those developing DCI (0.13 units/day vs. -0.07 units/day, p = 0.06). CONCLUSIONS: Coated-platelet rise after aSAH is associated with adverse long-term clinical outcome. NLR and PLR trends show an early immune-depressed state after aSAH.

Coated-Platelet Trends Predict Short-Term Clinical OutcomeAfter Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high socio-economic burden. Prothrombotic states of early brain injury (EBI) and delayed cerebral ischemia (DCI) after aSAH determine morbidity and mortality. To understand how activated platelets might contribute to such prothrombotic states, we studied trends in coated-platelets during EBI and DCI periods. Serial blood samples from a prospective cohort of aSAH patients were collected and assayed for coated-platelet levels. Patient's coated-platelet level during post-hospital discharge follow-up served as an estimate of baseline. Occurrence of DCI, Montreal cognitive assessment (MOCA) score of < 26, and modified Rankin scale (mRS) of 3-6 were considered poor clinical outcomes. Non-linear regression analysis detected a transition between periods of rising and declining coated-platelet levels at day 4. Additional regression analyses of coated-platelet trends before day 4 showed differences among patients with modified Fisher 3-4 [4.2% per day (95% CI 2.4, 6.1) vs. - 0.8% per day (95% CI - 3.4, 1.8); p = 0.0023] and those developing DCI [4.6% per day (95% CI 2.8, 6.5) vs. - 1.9% per day (95% CI - 4.5, 0.5); p < 0.001]. Differences between peak coated-platelet levels and baseline levels were larger, on average for those with DCI [18.1 ± 9.6 vs. 10.6 ± 8.0; p = 0.03], MOCA < 26 [17.0 ± 7.8 vs. 10.7 ± 7.4; p = 0.05] and mRS 3-6 [24.8 ± 10.5 vs. 11.9 ± 7.6; p = 0.01]. Coated-platelet trends after aSAH predict DCI and short-term clinical outcomes. The degree of rise in coated-platelets is also associated with adverse clinical outcomes.

Coated-platelets predict stroke at 30 days following TIA.

OBJECTIVE: To examine the potential for coated-platelets, a subset of highly procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, for predicting stroke at 30 days in patients with TIA. METHODS: Consecutive patients with TIA were enrolled and followed up prospectively. ABCD2 scores were obtained for each patient. Coated-platelet levels, reported as percent of cells converted to coated-platelets, were determined at baseline. The primary endpoint was the occurrence of stroke at 30 days. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including coated-platelets to predict incident stroke at 30 days. RESULTS: A total of 171 patients with TIA were enrolled, and 10 strokes were observed at 30 days. A cutoff of 51.1% for coated-platelet levels yielded a sensitivity of 0.80 (95% confidence interval [CI] 0.55-1.0), specificity of 0.73 (95% CI 0.66-0.80), positive predictive value of 0.16 (95% CI 0.06-0.26), and negative predictive value of 0.98 (95% CI 0.96-1.0). The adjusted hazard ratio of incident stroke in patients with coated-platelet levels ≥51.1% was 10.72 compared to those with levels <51.1%. ROC analysis showed significant improvement in the predictive ability of the coated-platelet model compared to ABCD2 score (AUC 0.78 ± 0.07 vs 0.54 ± 0.07, p = 0.01). CONCLUSIONS: These findings suggest a role for coated-platelets in risk stratification for stroke at 30 days after TIA.

Coated-Platelet Levels Increase with Number of Injuries in Patients with Mild Traumatic Brain Injury.

Coated-platelets are procoagulant platelets that are elevated in stroke and are associated with stroke recurrence. In a previous study, prompted by data showing an increased risk for stroke following traumatic brain injury (TBI), we found that coated-platelet levels are elevated in patients with combat-related mild TBI (mTBI) several years after the injury, compared with controls. We now investigate in an expanded patient population whether parameters commonly recorded in mTBI are related to increased coated-platelet potential. Coated-platelet levels were assayed in 120 mTBI patients at intervals ranging from 6 months to 10 years from the last injury. Correlations were calculated between coated-platelet levels and age, gender, race/ethnicity, loss of consciousness, alteration in consciousness, post-traumatic amnesia, number of injuries, mechanism of injury, time since first and last injury, smoking, medications that may influence coated-platelet levels, and pertinent comorbid conditions. Significant correlations were detected between coated-platelet levels and number of injuries (p = 0.026), gender (p = 0.01), and time since last injury (p = 0.04). A multi-variable linear model analysis, including these three parameters and an additional three parameters (race/ethnicity, smoking, and mechanism of injury) that reached a p value of <0.2, showed that the number of injuries were predictive of coated-platelet levels (p = 0.004). These results support a mechanistic link between increased coated-platelet levels and repeated injuries in mTBI. Long-term studies will be required to determine the impact of increased prothrombotic potential in mTBI patients.

Lower Coated-Platelet Levels Are Associated With Increased Mortality After Spontaneous Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Coated-platelets are highly procoagulant platelets observed on dual-agonist stimulation with collagen and thrombin. Coated-platelet levels are decreased in patients with spontaneous intracerebral hemorrhage when compared with controls and inversely correlated with bleed volume. We sought to investigate whether coated-platelets are associated with increased mortality at 30 days after spontaneous intracerebral hemorrhage. METHODS: Coated-platelet levels were assayed in 95 consecutive patients with spontaneous intracerebral hemorrhage. The main outcome was mortality at 30 days according to coated-platelet levels at enrollment. Subjects were grouped into tertiles of the observed coated-platelet level distribution. Groups defined by tertile of coated-platelet level were compared using either ANOVA or a Kruskal-Wallis test for small group size for continuous measures and an exact Cochrane-Armitage trend test for categorical measures. Logistic regression was used to estimate the adjusted odds of death within 30 days associated with coated-platelet levels. RESULTS: Cumulative mortality at 30 days was 23% (22 subjects). Mortality at 30 days differed among the coated-platelet tertiles: 44% for the first tertile (lowest coated-platelet levels), 19% for the second tertile, and 6% for the third tertile (trend test; P=0.0004). Logistic regression examining the association between mortality and coated-platelet levels showed that the odds of death at 30 days in those with levels <27% (n=47) were 6.83× the odds for patients with levels ≥27% (95% confidence interval, 2.10-22.23). CONCLUSIONS: These results support a link between impaired coated-platelet potential and outcome in intracerebral hemorrhage.

Coated-platelets improve prediction of stroke and transient ischemic attack in asymptomatic internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Coated-platelets, a subset of procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke, and higher levels are associated with early stroke recurrence, suggesting a potential role for risk stratification in asymptomatic patients with carotid artery stenosis. METHODS: Three-hundred twenty-nine consecutive patients with technically adequate carotid Doppler evaluation without stroke or transient ischemic attack (TIA) in the previous 6 months were enrolled as part of a prospective cohort study conducted during a 40-month period. The main outcome was occurrence of stroke or TIA according to coated-platelet levels and internal carotid stenosis severity at enrollment. The optimal cutoff value of coated-platelet levels was determined by recursive partitioning analysis. Event-free survival was estimated using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: A cutoff of ≥45% for coated-platelet levels in combination with stenosis≥50% yielded a sensitivity of 0.78 (95% confidence interval, 0.51-1.0), specificity of 0.92 (0.89-0.95), positive predictive value of 0.21 (0.07-0.34), and a negative predictive value of 0.99 (0.98-1.0) for ipsilateral stroke or TIA. The incidence rate of ipsilateral stroke or TIA for patients with ≥50% stenosis and ≥45% coated-platelets was 21.5 per 100 person-years versus 1.27 per 100 person-years for patients with ≥50% stenosis and <45% coated-platelets (P<0.0001). CONCLUSIONS: Coated-platelet levels identify asymptomatic carotid stenosis patients at high risk for stroke or TIA, which suggests a role for coated-platelets in risk stratification before revascularization.

Cerebral microbleeds in nonlacunar brain infarction are associated with lower coated-platelet levels.

BACKGROUND: Coated-platelets are a subset of platelets with high procoagulant potential observed on dual-agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with nonlacunar ischemic stroke compared with controls, although the presence of early hemorrhagic transformation is associated with lower coated-platelet levels. In contrast to infarction, patients with spontaneous intracerebral hemorrhage have lower coated-platelet levels, and these levels inversely correlate with bleed size. Cerebral microbleeds (CMBs) represent previous small hemorrhagic occurrences. We undertook a pilot study to investigate coated-platelet production and the presence of CMBs in patients with nonlacunar ischemic stroke. METHODS: Coated-platelet levels were determined in 110 consecutive patients with a diagnosis of nonlacunar stroke. Microbleeds were identified using the published criteria by an experienced stroke neurologist. Coated-platelet levels were compared statistically between patients with and without CMBs using the nonparametric Wilcoxon rank sum test. RESULTS: Coated-platelet levels (median [interquartile range]) for all patients were 44.1% [34%-51.2%]. CMBs were detected in 22 patients (20%); these patients had significantly lower coated-platelet levels compared with those without CMBs (35.6% [22.6%-47.2%] versus 45.1% [36.1%-51.5%]; P = .025), whereas other demographic and clinical factors did not differ significantly. CONCLUSIONS: The presence of CMBs in patients with nonlacunar ischemic stroke is associated with lower levels of coated-platelets. Larger prospective studies are needed to better establish the potential connection between altered coated-platelet synthesis, microbleeds, cerebral infarction, and possible hemorrhage-prone vascular changes.

Coated-platelet levels are persistently elevated in patients with mild traumatic brain injury.

OBJECTIVE: Coated-platelets are procoagulant platelets that are elevated in patients with large-vessel ischemic stroke and are associated with stroke recurrence. Because of recent reports showing an increased risk for stroke following traumatic brain injury (TBI), we undertook a pilot study to investigate coated-platelet synthesis in veterans with TBI. DESIGN: Cross-sectional study. PARTICIPANTS: Forty patients with a diagnosis of mild TBI (mTBI) and 40 controls without a history of TBI and matched for age, gender, and ethnicity/race were enrolled in the study. MAIN MEASURE: Coated-platelet levels were determined in patients with mTBI and controls. The time period since most recent injury ranged from 6 months to 9 years. RESULTS: Coated-platelet levels were significantly higher for mTBI patients than for controls (mean ± SD = 52.0% ± 14.0% vs 35.4% ± 13.0%; P < .0001). No relationship between these levels and the length of time since the last injury was found (P = .5). CONCLUSIONS: Coated-platelet levels are markedly and persistently elevated in individuals with mTBI. These data suggest a link to previous findings of increased stroke risk and chronic inflammation among individuals who sustained a TBI.

Elevated coated-platelets in symptomatic large-artery stenosis patients are associated with early stroke recurrence.

Coated-platelets are a subset of platelets with increased procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. These prothrombotic platelets are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage compared to controls. We now investigated coated-platelet synthesis in patients with symptomatic large-artery stenosis and explored the association between coated-platelet levels and stroke recurrence at 3 months in this population. Coated-platelet levels were determined in 60 patients with either acute stroke or transient ischemic attack due to large-artery stenosis and 60 controls. Recurrent stroke incidence at 3 months was stratified by tertiles of coated-platelet levels and compared among groups using a log-rank test. Large-artery stenosis patients had significantly higher coated-platelet levels than controls (mean ± SD, 42.0 ± 15.5% vs. 29.4 ± 13.5%, p < 0.0001). The 3-month cumulative incidence of recurrent stroke was 41% for the highest, 6% for the middle, and 5% for the lowest tertile of coated-platelet levels (p = 0.0045). These results show that elevated coated-platelet levels in patients with symptomatic large-artery stenosis are associated with early stroke recurrence.

Higher levels of coated-platelets are observed in patients with subarachnoid hemorrhage but lower levels are associated with increased mortality at 30 days.

BACKGROUND: Coated-platelets are procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in non-lacunar ischemic stroke compared to either lacunar stroke or controls. In contrast, coated-platelet levels are decreased in spontaneous intracerebral hemorrhage (ICH) and inversely correlated with bleed size. We now report the first investigation of coated-platelets in patients with subarachnoid hemorrhage (SAH). METHODS: Coated-platelet levels were determined in 40 consecutive patients with spontaneous SAH and in 40 controls. Results are reported as percent of cells converted to coated-platelets. Mortality at one month was recorded for all patients. RESULTS: Coated-platelet levels (mean ± SD) were significantly higher in SAH patients compared to controls (41.8 ± 11.4% vs. 30.7 ± 12.2%, p<0.0001). Among all patients, mortality at 1 month was 20% (8 deaths). Patients were analyzed according to tertiles of coated-platelet levels (split at <36.7%, 36.7-46.2%, >46.2%). The 1-month mortality differed significantly between the coated-platelet tertiles (p=0.01) with 46% mortality (6/13) among patients in the lowest tertile (lowest levels) compared to 14.3% (2/14) among those in the middle tertile and 0% in the highest tertile. CONCLUSIONS: Coated-platelet levels are higher in SAH patients compared to controls. However, lower coated-platelet levels are associated with increased 1-month mortality in SAH patients, a finding compatible with prior observations of an inverse relationship between coated-platelet levels and bleed volume in ICH. The current data support the role played by these prothrombotic platelets in thrombosis or hemorrhage and suggest a potential place for coated-platelet levels in predicting prognosis after SAH.

Bacillus anthracis peptidoglycan activates human platelets through FcγRII and complement.

Platelet activation frequently accompanies sepsis and contributes to the sepsis-associated vascular leakage and coagulation dysfunction. Our previous work has implicated peptidoglycan (PGN) as an agent causing systemic inflammation in gram-positive sepsis. We used flow cytometry and fluorescent microscopy to define the effects of PGN on the activation of human platelets. PGN induced platelet aggregation, expression of the activated form of integrin αIIbß3, and exposure of phosphatidylserine (PS). These changes were dependent on immunoglobulin G and were attenuated by the Fcγ receptor IIa-blocking antibody IV.3, suggesting they are mediated by PGN-anti-PGN immune complexes signaling through Fcγ receptor IIa. PS exposure was not blocked by IV.3 but was sensitive to inhibitors of complement activation. PGN was a potent activator of the complement cascade in human plasma and caused deposition of C5b-9 on the platelet surface. Platelets with exposed PS had greatly accelerated prothrombinase activity. We conclude that PGN derived from gram-positive bacteria is a potent platelet agonist when complexed with anti-PGN antibody and could contribute to the coagulation dysfunction accompanying gram-positive infections.

Higher coated-platelet levels are associated with chronic hypertension in patients with transient ischemic attack.

Coated-platelets are procoagulant platelets observed upon dual stimulation with collagen and thrombin. We previously reported that coated-platelet levels are elevated in patients with transient ischemic attack (TIA) compared to controls and that these levels correlate with ABCD2 scores, a validated tool for identifying the short-term risk for stroke occurrence in TIA patients. We now investigate the effect of individual elements of the ABCD2 score on coated-platelet levels in TIA. Coated-platelet levels were measured in 124 TIA patients. A nine-way ANOVA evaluated the impact of components of the ABCD2 score (age, blood pressure (BP), clinical features, symptom duration, and diabetes), smoking, pertinent medications, race, and gender on coated-platelet levels. In the initial model, the only significant main effect was for BP; patients with BP ≥ 140/90 had higher coated-platelet levels than those without (mean ± SEM; 44.0 ± 2.1% vs. 35.4 ± 2.3%, p = 0.0007). Because the diagnosis of hypertension (HTN) requires multiple readings of elevated BP, we re-analyzed the data by replacing BP with HTN. In the second model, there were two significant main effects: HTN - with higher coated-platelet levels in patients with vs. those without HTN (46.3 ± 2.1% vs. 33.6 ± 2.1%, p < 0.0001), and symptom duration - with higher coated-platelet levels in patients with duration ≥60 minutes vs. those with duration <60 minutes (42.5 ± 2.0% vs. 37.4 ± 2.1%, p = 0.031). These data suggest a link between chronic HTN and platelet thrombotic potential.

Higher coated-platelet levels are associated with stroke recurrence following nonlacunar brain infarction.

Coated-platelets are procoagulant platelets observed upon dual-agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with nonlacunar (large-vessel) ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage as compared with controls. The purpose of this study was to investigate a possible relationship between coated-platelet levels and stroke recurrence in patients with nonlacunar ischemic stroke. We assayed coated-platelet levels in 190 consecutive patients with nonlacunar stroke who were followed for up to 12 months; 20 subjects experienced recurrent stroke. Subjects were categorized into tertiles of coated-platelet levels. The distributions of time-to-recurrent stroke were estimated for each tertile using cumulative incidence curves and compared statistically using a log-rank test. The cumulative incidence of recurrent stroke at 12 months differed among the coated-platelet tertiles: 2% for the first tertile (lowest coated-platelet levels), 18% for the second tertile, and 17% for the third tertile (overall log-rank test, P=0.019). These data suggest that higher levels of coated-platelets, measured shortly after a nonlacunar stroke, are associated with an increased incidence of stroke recurrence. This observation offers an additional tool for identifying patients at highest risk for stroke recurrence following a nonlacunar (large-vessel) infarct.