Hypercoagulability, platelet function, inflammation and coronary artery disease acuity: Results of the Thrombotic RIsk Progression (TRIP) Study

Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA.
Platelets (Impact Factor: 2.98). 04/2010; 21(5):360-7. DOI: 10.3109/09537100903548903
Source: PubMed


The objective of the study was to determine the relation of platelet reactivity, hypercoagulability and inflammation in various stages of coronary artery disease acuity (CAD). Thrombin-induced platelet-fibrin clot strength (MA), time to initial platelet-fibrin clot formation (R), C-reactive protein (CRP), prothrombotic factors, activated GPIIb/IIIa receptor expression and other biomarkers were studied in patients with asymptomatic stable CAD (AS), in patients undergoing PCI for stable (SA) and unstable angina (UA). MA and R were measured by thrombelastography, GPIIb/IIIa expression by flow cytometry and all other markers by fluorokine multianalyte profiling assays. An overall increase in all measurements from a clinically stable to an unstable disease state was observed. There was a distinct stepwise increment in MA [AS vs. SA (p = 0.02), SA vs. UA (p = 0.02) and AS vs. UA (p < 0.001)]. MA exhibited the strongest correlation with other prothrombotic markers (p < or = 0.02), with CRP (p < 0.001) at all levels of CAD acuity. A distinct pathophysiological state of heightened platelet function, hypercoagulability and inflammation marks the presence of unstable cardiovascular disease requiring intervention. Further studies are required to investigate the primary mechanisms linking the above processes associated with a prothrombotic state resulting in clinical destabilization of the disease.

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    • "Calcium plays a critical role in osteogenic function, signalling function [22] and enzymatic function. An increasing level of intracellular calcium in platelet is one of the most important links in atherosclerotic plaques formation or thrombogenesis process in CHD [23], thus calcium is consumed, which induces hypocalcaemia in these patients [24]. Since the emergency revascularization rate and TIMI risk score for STEMI in this study was significantly associated with serum calcium level, the assumption was that low calcium level might partially reflect worsened vascular condition in patients. "
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    ABSTRACT: Objective The relationship between admission serum calcium levels and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) has not been well definitively explored. The objective was to assess the predictive value of serum calcium levels on in-hospital mortality in STEMI patients. Methods From 2003 to 2010, 1431 consecutive STEMI patients admitted to the First Affiliated Hospital of Nanjing Medical University were enrolled in the present study. Patients were stratified according to quartiles of serum calcium from the blood samples collected in the emergency room after admission. Between the aforementioned groups,the baseline characteristics, in-hospital management, and in-hospital mortality were analyzed. The association of serum calcium level with in-hospital mortality was calculated by a multivariable Cox regression analysis. Results Among 1431 included patients, 79% were male and the median age was 65 years (range, 55–74). Patients in the lower quartiles of serum calcium, as compared to the upper quartiles of serum calcium, were older, had more cardiovascular risk factors, lower rate of emergency revascularization,and higher in-hospital mortality. According to univariate Cox proportional analysis, patients with lower serum calcium level (hazard ratio 0.267, 95% confidence interval 0.164–0.433, p<0.001) was associated with higher in-hospital mortality. The result of multivariable Cox proportional hazard regression analyses showed that the Killip's class≥3 (HR = 2.192, p = 0.026), aspartate aminotransferase (HR = 1.001, p<0.001), neutrophil count (HR = 1.123, p<0.001), serum calcium level (HR = 0.255, p = 0.001), and emergency revascularization (HR = 0.122, p<0.001) were significantly and independently associated with in-hospital mortality in STEMI patients. Conclusions Serum calcium was an independent predictor for in-hospital mortality in patients with STEMI. This widely available serum biochemical index may be incorporated into the current established risk stratification model of STEMI patients. Further studies are required to determine the actual mechanism and whether patients with hypocalcaemia could benefit from calcium supplement.
    PLoS ONE 06/2014; 9(6):e99895. DOI:10.1371/journal.pone.0099895 · 3.23 Impact Factor
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    • "It is difficult to explain the apparent contradiction between the high prevalence of HTPR and the low incidence of thrombotic events after stent implantation among Asians. One possible explanation is that Asians have a favorable endogenous thrombolytic profile, whereas Westerners are in a prothrombotic state [40], induced by heightened platelet reactivity, hypercoagulability, endothelial dysfunction, and inflammation [41]. Modest platelet inhibition may be enough to avoid thrombotic events in Japanese patients. "
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    ABSTRACT: It remains unknown whether the time course of the antiplatelet effects of clopidogrel differs according to cytochrome P450 (CYP) 2C19 phenotype in Japanese patients with acute coronary syndromes (ACS). Platelet reactivity was serially assessed by VerifyNow-P2Y12 assay (Accumetrics, San Diego, CA, USA). Results were expressed as P2Y12-reaction-units (PRU) in 177 patients with ACS who underwent stent implantation and received aspirin plus a 300-mg loading dose of clopidogrel followed by 75mg/day. High on-clopidogrel treatment platelet reactivity (HTPR) was defined as PRU>235. On the basis of the CYP2C19*2 and *3 alleles, 46 patients (26.0%) were classified as extensive metabolizers (EM), 103 (58.2%) as intermediate metabolizers (IM), and 28 (15.8%) as poor metabolizers (PM). At <7 days, the PRU level (232±102 vs. 279±70, 308±67, p<0.001) and the incidence of HTPR (49% vs. 74%, 86%, p=0.001) was lower in EM than in IM and PM. At 14-28 days the effects of CYP2C19 polymorphisms on PRU levels increased in a stepwise fashion (168±99 vs. 213±77 vs. 278±69, p<0.001), and EM and IM had lower percentages of HTPR than PM (28%, 37% vs. 73%, p<0.001). There was no significant difference in the cumulative frequency of 12-month adverse cardiovascular events among 3 phenotypes (16.5%, 14.1%, 9.2%; p=0.67). About three quarters of Japanese patients with ACS carried CYP2C19 variant alleles. The majority of IM and PM had increased platelet reactivity during the early phase of ACS. Although HTPR was frequently observed even 14-28 days after standard maintenance doses of clopidogrel in PM, the incidence of adverse outcomes did not differ, irrespective of CYP2C19 genotype.
    Journal of Cardiology 07/2013; 62(3-4). DOI:10.1016/j.jjcc.2013.03.006 · 2.78 Impact Factor
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    • "In some other studies, increased level of circulating PLAs also was considered as a predictive marker of acute myocardial infarction and acute re-occlusion following percutaneous coronary interventions [97] [98] [99] [100] [101] [102]. Apart from Mac-1 induced activation of Factor X, growing body of evidence also propose an important role for recruited leukocytes and/or PLAs in propagation of blood coagulation cascade via the activation of tissue factor (TF) pathway during thrombus formation. "
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    ABSTRACT: Platelet activation is known to be associated with the release of a vast array of chemokines and proinflammatory lipids which induce pleiotropic effects on a wide variety of tissues and cells, including leukocytes. During thrombosis, the recruitment of leukocytes to activated platelets is considered an important step which not only links thrombosis to inflammatory responses but may also enhance procoagulant state. This phenomenon is highly regulated and influenced by precise mutual interactions between the cells at site of vascular injury and thrombi formation. Platelet-leukocyte interaction involves a variety of mediators including adhesion molecules, chemokines and chemoattractant molecules, shed proteins, various proinflammatory lipids and other materials. The current review addresses the detailed mechanisms underlying platelet-leukocyte crosstalk. This includes their adhesive interactions, transcellular metabolisms, induced tissue factor activity and neutrophil extracellular traps formation as well as the impacts of these phenomena in modulation of the proinflammatory and procoagulant functions in a reciprocal manner that enhances the physiological responses.
    Thrombosis Research 12/2012; 131(3). DOI:10.1016/j.thromres.2012.11.028 · 2.45 Impact Factor
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