Predictive performance of adding platelet reactivity on top of CRUSADE score for 1-year bleeding risk in patients with acute coronary syndrome

CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines) risk score can independently predict major bleeding events in patients with non-ST elevation myocardial infarction whereas the discriminative capacity is moderate. Whether adding platelet reactivity on top of CRUSADE score improves the prognostic performance for bleeding remains unclear. 512 patients with acute coronary syndrome (ACS) underwent successful percutaneous coronary intervention were enrolled and 1-year data were available. CRUSADE risk score was calculated at hospital admission and P2Y₁₂ reaction unit (PRU) value was measured by VerifyNow P2Y₁₂ assay. Thirty-five (6.8 %) patients experienced major bleeding events within 1-year follow-up. Patients who developed bleeding complications had higher CRUSADE score (37.5 ± 9.4 vs. 29.0 ± 10.2, p < 0.001) and lower PRU value (149.7 ± 57.1 vs. 196.4 ± 51.4, p < 0.001) than those did not. Both CRUSADE score and platelet reactivity were independently associated with bleeding. Kaplan–Meier analysis showed that patients with high CRUSADE score plus low platelet reactivity had significantly elevated risk for bleeding (HR 7.905, 95 % CI 2.623–23.822, p < 0.001). Compared to CRUSADE score alone, adding platelet reactivity on top of CRUSADE score offered a discriminative increment which was demonstrated by c-statistic (0.827 vs. 0.732, p = 0.011), as well as net reclassification improvement (NRI = 0.258, p < 0.001) and integrated discrimination improvement (IDI = 0.022, p = 0.002). After successful coronary stent implantation in patients with ACS, combining CRUSADE score with platelet reactivity yielded more accurate predictive value for 1-year bleeding risk.     

Detection and quantification of circulating immature platelets: agreement between flow cytometric and automated detection

Immature platelets—also termed reticulated platelets (RP)—are platelets newly released into the circulation, and have been associated with a variety of pathological thrombotic events. They can be assessed by flow cytometry after staining with thiazole orange (TO) or by using a module added to a fully automated analyzer that is currently in wide clinical use and expressed as a fraction of the total platelet count (IPF). We sought to assess the correlation and agreement between these two methods. IPF was measured using Sysmex XE 2100—and at the same time point- we used TO staining and flow cytometry to measure RP levels. Two different gates were used for the flow cytometry method, 1 and 0.5 %. Measurements from the automated analyzer were then compared separately to measurements performed using each gate. Agreement between methods was assessed using Bland–Altman method. Pearson’s correlation coefficient was also calculated. 129 subjects were enrolled and stratified into 5 groups: (1) Healthy subjects, (2) End stage renal disease, (3) Chronic stable coronary artery disease, (4) Post Coronary artery bypass surgery, (5) Peripheral thrombocytopenia. Median IPF levels were increased for patients in groups 2, 3, 4 and 5 (4.0, 4.7, 4.3, and 8.3 % respectively) compared to healthy subjects (2.5 %) p = 0.0001. Although the observed correlation between the two methods tended to be good in patients with high IPF values (i.e., group 5), the overall observed correlation was poor (Pearson’s correlation coefficient r = 0.27). Furthermore, there was poor agreement between the two methods in all groups. Despite the good correlation that was observed between the two methods at higher IPF values, the lack of agreement was significant.     

Home management of INR in the public health system: feasibility of self-management of oral anticoagulation and long-term performance of individual POC devices in determining INR

The home prothrombin time/international normalized ratio (PT/INR) self-management could be convenient for patients, enhancing treatment compliance and improving the quality of the oral anticoagulation. However, patient self-management (PSM) of oral anticoagulation may not be feasible for up to half of the patients due to cognitive or educational issues. In the present study, we aimed to evaluate the feasibility of a PSM program in a public health medical center that provides care for low-income patients. We also aimed to determine the accuracy of individual point-of-care devices (CoaguChek XS^®) during long-term of home manipulation. Patients’ time-in-therapeutic range (TTR) and perception of quality of life, were evaluated at scheduled study-visits to the center. Additionally, the accuracy of individual CoaguChek XS^® was evaluated in comparison to the standard automated coagulometer at scheduled study-visits to the center. Twenty-five patients were included in the PSM program. The median TTR of patients was 75 % before inclusion, 72 % at 3 months, 75 % at 6 months and 100 % at 12 months after the beginning of self-management (P = 0.14).The median DASS scores were 64, 63, 61.5 and 71.5 before inclusion and at 3, 6 and 12 months, respectively (P = 0.09). One hundred paired INR values were obtained. Correlation between INR values delivered by individual CoaguChek XS^® and the automated coagulometer was 94 % and the mean result bias was 0.07 INR units. The coefficient of correlation and the mean bias between methods was stable during 24 months of follow-up. The present study suggests that PSM is feasible for patients treated in the public health system and that the results delivered by CoaguChek XS^® have long-term reliability.     

High residual platelet reactivity (HRPR) for adenosine diphosphate (ADP) stimuli is a determinant factor for long-term outcomes in acute ischemic stroke with anti-platelet agents: The meaning of HRPR after ADP might be more prominent in large atherosclerotic infarction than other subtypes of AIS

High residual platelet activation (HRPA) after ADP stimuli has associated with recurrent vascular events in acute atherothrombosis with the use of antiplatelet agents (APAs). However, there has been little evidence supporting this association in acute ischemic stroke (AIS). In this study, we evaluated the influences of HRPR after ADP stimuli on the 1-year incidence of recurrent cardiovascular events and mortality in AIS with APAs. We conducted an observational, referral center cohort study on 968 AIS patients with APAs from January 2010 to December 2013 who were evaluated using optical platelet aggregometry (OPA). All patients received the dual APA combination of aspirin and clopidogrel or aspirin alone. We evaluated their platelet function 5 days after hospital admission using OPA. HRPR after ADP stimuli was defined as platelet aggregation of 70 % or greater according to OPA after 10 µM ADP stimuli. The primary endpoint was a composite of all causes of death, myocardial infarction, and stroke at the 1-year follow-up. The secondary endpoints were each component of the primary endpoint. The event rate of primary endpoint was 11.3 % (109/968). Its rate was significantly higher in the patients with HRPR (16.7 %) than in those without (9.7 %). HPRP was independently associated with the primary endpoint (OR = 1.97, CI 1.22–3.18, p < 0.01). According to the AIS subtype, the presence of HRPR was independently significant for the occurrence of the primary endpoint in the large artery atherosclerosis (LAA) subtype only (OR = 2.26, CI 1.15–4.45, p = 0.02). In this study, the presence of HRPR after ADP stimuli is associated with a poor long-term outcome after acute ischemic stroke. In particular, the influence of this factor might be more prominent in LAA compared with other types of AIS.     

Thromboinflammatory response and predictors of outcomes in patients undergoing transcatheter aortic valve replacement

Transcatheter aortic valve replacement (TAVR) has been increasingly used to treat patients with symptomatic aortic stenosis. Despite improvements in valve deployment, patients that have undergone TAVR are at high risk for major adverse events following the procedure. Blood cell numbers, platelet function, and biomarkers of systemic inflammation were analyzed in 58 patients undergoing TAVR with the Edward’s SAPIEN valve. Following valve deployment, platelet count and agonist-induced platelet activity declined and plasma markers of systemic inflammation (interleukin-6 and S100A8/A9) increased. Baseline platelet activity prior to TAVR correlated with perioperative changes plasma interleukin-6 levels. Moreover, perioperative changes in plasma inflammatory markers predicted the decline in platelet count in the days following the TAVR procedure. Additionally, a significant effect of gender on platelet count following TAVR and was observed. Finally, post-procedural mortality was associated with sustained thrombocytopenia after TAVR. Our findings suggest that TAVR elicits a thromboinflammatory state that may contribute to post-procedural thrombocytopenia. Importantly, our results add to the growing body of literature that suggests the thromboinflammatory changes that occur early after TAVR may predict long-term outcomes.     

Alterations of the thrombin generation profile in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder resulting in the erosion of the cartilage and bone. Systemic involvement including the cardiovascular system with the risk of atherosclerosis may also occur. Calibrated automated thrombogram (CAT), a commercially available thrombin generation assay is suitable for the general assessment of the functionality of coagulation system. In this study we performed CAT assay in RA patients and in non-affected control subjects (matched for age, sex and comorbidities). Among the CAT parameters Velocity Index increased (from 60 to 83 nM/min), Lag Time and Time to Peak decreased (from 3.47 to 2.83 min and from 6.98 to 5.58 min respectively) in RA. On the other hand, Endogenous Thrombin Potential values decreased (from 1242 to 1108 nM min). The observed alterations were not associated with the applied therapy. These results indicate that the velocity of thrombin formation is increased, while the thrombin generating capability is reduced in RA.     

Clinical predictors and outcomes of patients with left ventricular thrombus following ST-segment elevation myocardial infarction

We aimed to characterize the independent predictors of LVT following STEMI and the association with outcomes. The clinical predictors of left ventricular thrombus (LVT) formation after ST-segment elevation myocardial infarction (STEMI) are not well-defined in the contemporary era. We performed a retrospective analysis of STEMI patients at Duke from 2000 to 2011 who had a transthoracic echocardiogram within 90 days post-STEMI and compared patients with and without LVT (LVT+ vs. LVT?). Univariate Cox proportional hazards regression models of baseline characteristics were examined and significant variables were used in a multivariable model to assess adjusted relationships with LVT. A multivariable Cox PH survival model with covariate adjustments was used for assessment of LVT and long-term mortality. Of all eligible patients, 1734 patients met inclusion criteria and 4.3 % (N = 74) had a LVT. LVT+ patients tended to have a history of heart failure (HF) and higher initial troponin compared to LVT- patients. After adjustment, higher heart rate, non-white race, HF severity, and presence of left anterior descending artery (LAD) disease were independent predictors of LVT. There was a trend toward an association between LVT and increased all-cause mortality (HR 1.36; 95 % CI 0.84–2.21, P = 0.22), however this was not statistically significant. LVT was seen in over 4 % of this contemporary post-STEMI population. Several baseline characteristics were independently associated with LVT: Heart rate, HF severity, LAD disease, and non-white race. Prospective studies are warranted to determine whether anticoagulation in patients at increased risk for LVT improves outcomes.     

Pharmacology of anticoagulants used in the treatment of venous thromboembolism

Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE.     

Antibradykarde Therapie

Pacemaker therapy (PMT) in grown-up congenital heart disease (GUCH) must meet the demands of a young, dynamic and heterogeneous group of patients. The duration of the therapy has to be planned for several decades and should be accompanied by an invasive procedure at the very least. Most of the patients enter adulthood with their pacemaker (PM) already implanted; for others the indications can be derived from the published guidelines for GUCH and PMT, but need to be adjusted to the individual situation of the patient. Depending on the underlying heart disease the decision on the use of either an epimyocardial or a transvenous PM system has to be made. Both electrodes and PM should correspond to the latest technical developments to optimally adapt to the patients’ multiple requirements. In the case of PM system revisions abandoned leads should be removed and vascular stenosis or occlusions cleared to be prepared for later revisions. During any cardiac surgery epimyocardial PM systems should be checked against the patient’s needs and expanded or revised accordingly. Epimyocardial resynchronization systems in particular offer more opportunities for compensating for cardiac dysfunction with greater reliability using a second ventricular lead. The PMT is an essential part of the medical treatment for many patients with GUCH and contributes significantly to the well-being and quality of life. Against this background, a competent and consequent follow-up regime requires experienced physicians. An integrated telemetric monitoring system for the PM has proven valuable and supports the early recognition of cardiac arrhythmia.