Direct oral anticoagulants in oncology in clinical praxis.

Relation between oncological diseases and venous thrombo-embolism (VTE) is well known for almost 2 centuries. In 1823 Bouillaud assumed by three patients with tumor and recent deep vein thrombosis (DVT), that peripheral edema of lower limbs emerges as a result of „obturation“ of veins by „fibrinous coagulum“ (caillot fibrineux), which was induced by oncological disease. French physician Armand Trousseau wrote about this relation in his book „Phlegmasia alba dolens” again in the year 1865. Many studies were developed in times of Bouillaud a Trousseau, which just confirmed existence of relation between tumor and VTE. Oncological disease presents a significant risk factor of formation of VTE. Recent references favorising the use of light molecular weight heparin (LMWH) in long-term anticoagulation therapy of patients with cancer. Recently we have just few clinical data about efficiency and safety of direct oral anticoagulants (DOACs) in oncological patients, however many meta-analysis of clinical studies has shown benefit of therapy with DOACs towards conventional therapy. Key words: direct oral anticoagulants (DOACs) - oncology - venous thromboembolism.

Trimeresurus albolabris (white-lipped green pit viper) - bite report: case report.

Toxicology is a specialized scientific discipline, focusing on microbiological, botanical and animal venoms, poisons and toxins. This discipline includes more than just the chemistry and mode of action of a toxin, but also with the biology of venom or poison producing organism, the structure and function of the venom apparatus, as well as the use of the venom or poison. The discipline of toxicology involves the study of the poison on living organisms and the therapy of the intoxication. A genus Trimeresurus, to which belongs Green Pit Viper, is large and includes around 36 types. Snake venoms have various composition and they can effect cardiovascular and nervous system, kidneys, hemocoagulation, vessel wall and muscle cells. In this article, we are presenting a rare case report about Trimeresurus albolabris, review of literature and general treatment after intoxication with snake venom. Prompt assessment, observation and early specific management are the keys to treat intoxication with snake venom. Key words: hemotoxin - intoxication - snake venom - treatment - Trimeresurus albolabris.

Role of Thromboelastography and Rotational Thromboelastometry in the Management of Cardiovascular Diseases.

The monitoring of coagulation by viscoelastometric methods-thromboelastography and rotational thromboelastometry-may detect the contributions of cellular and plasma components of hemostasis. These methods might overcome some of the serious limitations of conventional laboratory tests. Viscoelastic testing can be repeatedly performed during and after surgery and thus provides a dynamic picture of the coagulation process during these periods. Several experiences with the use of these methods in cardiovascular surgery have been reported, but there is perspective for more frequent use of these assays in the assessment of platelet response to antiplatelet therapy and in the assessment of coagulation in patients on long-term dabigatran therapy. This article reviews the current role and future perspectives of thromboelastography and thromboelastometry in the management of cardiovascular diseases.

Proton Pump Inhibition in Patients Treated With Novel Antithrombotic Drugs: Should We Worry About Thrombosis?

Proton pump inhibition (PPI) administered together with antiplatelet and anticoagulant agents reduces the risk of gastrointestinal hemorrhage. Several novel antithrombotic agents have been recently introduced for patients with acute coronary syndrome (prasugrel and ticagrelor) or for patients requiring long-term anticoagulation (dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban). In fact, these agents might offer even stronger inhibition of platelets or coagulation compared with older agents; therefore, the need for gastroprotection might be even stronger when these new agents are used for long-term antithrombotic therapy. On the contrary, there are several reports regarding an adverse interaction between PPI and antithrombotic agents connected with a reduction in antithrombotic therapy on-treatment levels, implicating a higher risk of thrombosis. This interaction was demonstrated in clopidogrel-treated patients and more recently also in dabigatran-treated patients. This article discusses a possible novel antithrombotic therapy/PPI interaction leading to higher risk of thrombosis.

Outcomes of Patients with Newly Diagnosed Cardiac Myxoma: A Retrospective Multicentric Study.

The patient database at the First Department of Internal Medicine in Martin, the Central Slovak Institute for Cardiac and Vascular Diseases in Banska Bystrica, and the National Slovak Institute of Cardiovascular Diseases in Bratislava was searched to identify patients with benign tumors of the heart seen during the 5-year period between 2011 and 2016. Forty-one patients with primary cardiac myxomas were identified and their medical records were reviewed for details pertaining to presenting symptoms, staging modalities, treatment approaches, and outcomes. Most of the studied patients were diagnosed with echocardiography (n = 35, 85%). The occurrence of the tumor was higher in the female population (n = 25, 61%). The most common presenting symptoms were dyspnoea (n = 17, 42%), chest pain (n = 3, 7%), or pain and paraesthesia of the limbs (n = 2, 5%). Acute embolic event due to embolization of tumor fragments resulted in cerebral stroke (n = 5, 12%). All patients were treated by resection. Only one comorbid patient died due to multiple-organ dysfunction syndrome two weeks after the resection. The most common postoperative complication was bleeding (n = 2, 5%) and infection (n = 2, 5%). The early diagnosis and appropriate treatment are often curative, with very low risk of recurrence. Postoperative survival is high.

Anti-Xa activity in oral factor Xa inhibitor-treated patients with atrial fibrillation and a higher risk of bleeding: a pilot study.

: The number of patients with nonvalvular atrial fibrillation (NV-AF) who require long-term anticoagulation and also have a higher risk of bleeding is increasing. Recently, there is no information regarding real on-treatment anti-Xa activity in patients with NV-AF and a higher risk of bleeding who receive oral factor Xa inhibitors. The aim of this study was to determine trough and peak anti-Xa activity in these patients. This single-centre pilot study enrolled 41 patients with NV-AF and a higher risk of bleeding defined as Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score at least 3 points. Twenty-one patients were treated with rivaroxaban and 17 patients were treated with apixaban. The trough and peak samples of these patients were tested for anti-Xa activity with factor Xa-calibrated anti-Xa chromogenic analysis. The detected trough anti-Xa activity was 63.2 ±â€Š44.4 ng/ml. There was a significant increase in peak anti-Xa activity up to 170.3 ±â€Š99.6 ng/ml (P < 0.001) observed. There were no significant differences in trough (52.4 ±â€Š41.9 vs. 76.0 ±â€Š45.4 ng/ml; P = 0.12) and peak (187.2 ±â€Š122.5 vs. 151.5 ±â€Š64.0 ng/ml; P = 0.27) anti-Xa activity between rivaroxaban-treated and apixaban-treated patients. This study demonstrated the anti-Xa activity in oral factor Xa inhibitor-treated patients with NV-AF and a higher risk of bleeding. No significant differences in this activity between rivaroxaban-treated and apixaban-treated patients were found.

First Evidence: TRAP-Induced Platelet Aggregation Is Reduced in Patients Receiving Xabans.

The availability of direct oral anticoagulants has caused a paradigm shift in the management of thrombosis. Rivaroxaban and apixaban are 2 direct oral anticoagulants whose target specificity is activated factor X (FXa). However, it is still not fully understood if and how xabans impact platelet function. This observational study aimed to assess the in vitro platelet function in patients with atrial fibrillation receiving xabans. This was a single-center study quantifying platelet aggregation in 41 patients treated with apixaban or rivaroxaban by light transmission aggregometry. The thrombin receptor activating peptide (TRAP)-induced platelet aggregation was significantly lower 2 hours after taking rivaroxaban or apixaban compared to baseline value (56.15% [8.53%] vs 29.51% [12.9%]; P = .000). Moreover, concomitant use of angiotensin-converting enzyme blockers, proton pump inhibitors, and statins reduces the efficiency of xabans. The TRAP-induced platelet aggregation was reduced in patients with cardiovascular disease 2 hours after receiving xabans.

Does type 2 diabetes affect the on-treatment levels of direct oral anticoagulants in patients with atrial fibrillation?

AIMS: Type 2 diabetes (T2D) is connected with several abnormalities in haemostasis; and with higher risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NV-AF). However, it is recently unknown whether T2D affects the activity of direct oral anticoagulants (DOACs). The aim of this study was to determine the impact of T2D on DOACs activity in patients with NV-AF. METHODS: This pilot prospective study enrolled totally 65 patients with NV-AF (20 dabigatran-treated, 110 mg/twice daily; 28 rivaroxaban-treated, 15 mg/daily; 17 apixaban-treated, 5 mg/twice daily). 25 patients had T2D (8 dabigatran-treated, 11 rivaroxaban-treated, and 6 apixaban-treated). DOAC activity was tested with Hemoclot® Thrombin Inhibitor assay in dabigatran-treated patients, and with factor Xa-calibrated anti-Xa chromogenic analysis in rivaroxaban- and apixaban-treated patients prior and two hours after drug administration. RESULTS: There were no significant differences in dabigatran baseline (62.1 ±â€¯8.0 vs. 51.8 ±â€¯38.9 ng/ml, p = .76) and 2-h-post-drug-administration (91.7 ±â€¯57.2 vs. 72.2 ±â€¯33.2 ng/ml, p = .48) activity comparing T2D and non-diabetic patients. Similarly, no significant differences were found in rivaroxaban baseline (35.9 ±â€¯22.5 vs. 55.3 ±â€¯45.1 ng/ml, p = .19) and 2-h-post-drug-administration (145.7 ±â€¯74.1 vs. 202.6 ±â€¯135.0 ng/ml, p = .22) anti-Xa activity. In addition, no significant differences were present in apixaban baseline (96.0 ±â€¯54.5 vs. 63.9 ±â€¯36.8 ng/ml, p = .24) and 2-h-post-drug-administration (151.0 ±â€¯78.3 vs. 151.7 ±â€¯59.1 ng/ml, p = .98) anti-Xa activity between T2D and non-diabetic patients. CONCLUSIONS: This pilot study did not detect differences in DOACs activity according to T2D status in patients with NV-AF.

Platelet Aggregation in Direct Oral Factor Xa Inhibitors-treated Patients With Atrial Fibrillation: A Pilot Study.

BACKGROUND: Activated factor X (factor Xa) plays an important role in regulation of platelets. The aim of this study was to test the effect of direct oral factor Xa inhibitors-rivaroxaban and apixaban-on platelet aggregation in patients with nonvalvular atrial fibrillation. PATIENTS AND METHODS: This single-center pilot study enrolled 21 factor Xa inhibitors-treated (9 rivaroxaban-treated and 12 apixaban-treated) patients with nonvalvular atrial fibrillation. The trough and peak samples of these patients were tested for adenosine diphosphate (ADP)-induced, epinephrine-induced, and collagen-induced platelet aggregation with light transmission aggregometry, and with factor Xa-calibrated anti-Xa chromogenic analysis. RESULTS: The detected trough anti-Xa activity was 57.5 ± 43.4 µg/L. There was a significant increase in peak anti-Xa activity to 175.9 ± 119.6 µg/L (P < 0.001) observed. The platelet aggregation was reduced with reduced inductor concentration. However, no significant changes in ADP-induced, or in epinephrine-induced, or in collagen-induced platelet aggregation were seen comparing trough and peak sample. There were no significant differences in anti-Xa activity or in platelet aggregation comparing rivaroxaban-treated and apixaban-treated patients. CONCLUSIONS: This study showed that factor Xa inhibition does not affect ADP-induced, epinephrine-induced, and collagen-induced platelet aggregation.

Prevalence of Conventional Cardiovascular Risk Factors in Patients with Acute Coronary Syndromes in Slovakia.

BACKGROUND: Acute coronary syndrome (ACS) is a major health problem and the leading cause of death and disability in Slovakia. This is the first study to describe the prevalence rate of conventional cardiovascular risk factors in patients hospitalized for ACS. METHODS: Hypertension, diabetes mellitus, hyperlipidemia and cigarette smoking were documented in 1,567 cases (mean age, SD: 66.1±12.0 years, 34.8% of females) enrolled in the SLOVAKS registry from August 2011 through September 2011. RESULTS: Overall, 83.5% (95% CI, 81.6-85.2%) of the patients with ACS had hypertension, 65.0% (62.5-67.2%) had a hyperlipidemic profile, 32.6% (30.3-34.9%) were diagnosed with diabetes, and 27.6% (25.1-29.8%) were smokers at the time of a heart-related event. Only 5% of patients with ACS lacked any of the 4 conventional risk factors. Higher prevalence rates of all major risk factors, except smoking, were detected in women than in men, in older (≥65 years of age) than younger patients, and in rural (<2,000 inhabitants) than in urban areas. Premature ACS (<45 years of age) was associated with smoking in men, and smoking and hypertension in women. Smoking, in all risk factor combinations, reduced the age at the time of a heart-related event, on average, by 10.0 years in men and by 12.4 years in women. CONCLUSION: The results of this study suggest an appreciable burden of major cardiovascular risk factors and also highlight differences that may aid the targeting of public health interventions.

Review of the Pharmacology of the Emerging Possibilities of the Direct Oral Anticoagulants' Reversal.

BACKGROUND: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with nonvalvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients. Despite their advantages, concerns persist about a lack of rapid reversal agents in urgent clinical situations. METHODS: This review is focused on the pharmacology of nonspecific and target-specific reversal agents for DOACs-induced anticoagulation. A systemic review of preclinical and clinical studies published in peer-reviewed scientific journals was performed. RESULTS AND CONCLUSIONS: Fresh frozen plasma and coagulation factors concentrates might be considered in bleeding emergencies; however, there is a lack of larger studies confirming the efficacy of coagulation factors concentrates for the reversal of DOACs-induced anticoagulation, and a particular risk of coagulation factors concentrates-induced thrombosis. Recently, idarucizumab has been approved commercially for acute reversal of dabigatran in emergencies as a first target-specific reversal agent. Moreover, andexanet alpha and aripazine are being extensively studied in several phase II and III clinical studies. It is likely that more target-specific agents for reversal of DOACs-induced anticoagulation will be introduced to clinical practice in near future.

Monitoring the hemostasis with rotation thromboelastometry in patients with acute STEMI on dual antiplatelet therapy: First experiences.

Rotation thromboelastometry (ROTEM) is a viscoelastometric point-of-care-test for the complex evaluation of changes in hemostasis, performed in whole blood. However, no prospective study evaluating the efficacy of the antiplatelet therapy using ROTEM was performed.Fifty-six patients (34 men, 22 women, mean age 67.75 years, and age range 34-88 years) with acute ST-elevation myocardial infarction (STEMI), treated with dual antiplatelet therapy, undergoing urgent coronary angiography and percutaneous coronary intervention (PCI) of culprit coronary lesion were included. Three blood samples were taken (sample 1 taken before the urgent coronary angiography, sample 2 in 24 hours after the admission, and sample 3 in 30 days after acute STEMI). Twenty-one healthy blood donors (17 men, 4 women, mean age 50.38 years, and age range 40-74 years) were recruited as the control group. Blood samples were tested with ROTEM Gamma (Pentapharm GmbH, Munich, Germany) and light transmission aggregometry (LTA).Clotting time (CT) was significantly prolonged and maximum clot firmness (MCF) was significantly higher in patients compared to controls. Mean platelet aggregation after the induction with arachidonic acid (33.2% vs 74.6% in sample 1 and 21.1% vs 74.6% in sample 2), as well as adenosine diphosphate (51.4% vs 72.7% in sample 1 and 37.1% vs 72.7% in sample 2), were significantly lower in patients with acute STEMI.Significantly prolonged CT and increased MCF was found in patients with acute STEMI. This study confirmed the ability of ROTEM to identify changes in hemostasis in ACS patients on antithrombotic therapy.

Does Pantoprazole Affect the On-Treatment Platelet Reactivity in Patients With Acute STEMI Treated With ADP Receptor Blockers?-A Pilot Prospective Study.

BACKGROUND: Proton pump inhibition (PPI) administrated together with adenosine diphosphate (ADP) receptor blockers (ADPRB) significantly reduces the risk of gastrointestinal bleeding. Nevertheless, there is a heated discussion about an interaction between PPI and ADPRB that leads to high on-treatment platelet reactivity (HTPR). STUDY QUESTION: Is there a relationship between pantoprazole PPI and HTPR on ADPRB therapy in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Single center pilot study in patients with acute STEMI was performed. This study enrolled totally 87 patients (34 clopidogrel-treated and 53 new ADPRB-treated patients). Pantoprazole was administrated in 33 patients. HTPR was detected with ADP-induced light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation analysis. Samples were taken before coronary angiography (sample 1) and on the next day after the procedure (sample 2). RESULTS: No significant differences were found in pantoprazole-treated patients and patients without PPI neither in sample 1 (59.2 ± 29.5% vs. 54.9 ± 22.7%, P = 0.49) nor in sample 2 (43.8 ± 27.2% vs. 37.0 ± 22.9%, P = 0.30). Similarly, there were no significant differences in the platelet reactivity index of vasodilator-stimulated phosphoprotein phosphorylation in both samples (sample 1: 53.3 ± 29.8% vs. 65.0 ± 20.5%, P = 0.11; sample 2: 30.8 ± 27.1% vs. 40.6 ± 27.5%, P = 0.19). A comparison of clopidogrel and new ADP receptor blockers in patients on pantoprazole PPI did not reveal significant differences in on-treatment platelet reactivity. CONCLUSIONS: This study did not reveal interaction between pantoprazole and ADPRB in patients with acute STEMI.

The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study.

Background. The aim of this study was to validate the impact of type 2 diabetes (T2D) on the platelet reactivity in patients with acute ST elevation myocardial infarction (STEMI) treated with adenosine diphosphate (ADP) receptor blockers. Methods. A pilot prospective study was performed. Totally 67 patients were enrolled. 21 patients had T2D. Among all study population, 33 patients received clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor blocker therapy had been tested in two time intervals using light transmission aggregometry with specific inducer and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Results. There were no significant differences in platelet aggregability among T2D and nondiabetic (ND) group. The platelet reactivity index of VASP-P did not differ significantly between T2D and ND group (59.4 ± 30.9% versus 60.0 ± 25.2% and 33.9 ± 25.3% versus 38.6 ± 29.3% in second testing). The number of ADP receptor blocker nonresponders did not differ significantly between T2D and ND patients. The time interval from ADP receptor blocker loading dosing to the blood sampling was similar in T2D and ND patients in both examinations. Conclusion. This prospective study did not confirm the higher platelet reactivity and higher prevalence of ADP receptor blocker nonresponders in T2D acute STEMI patients.

Heparin-induced Thrombocytopenia Presenting With Deep Venous Thrombosis and Pulmonary Embolism Successfully Treated With Rivaroxaban: Clinical Case Report and Review of Current Experiences.

Heparin-induced thrombocytopenia (HIT) is a life or limb-threatening thrombotic thrombocytopenia. HIT is traditionally treated with factor-IIa inhibitors such as bivalirudin, lepirudin, or argatroban. However, these agents usually require parenteral administration and are not generally available in all countries. Recently, several experiences with novel oral anticoagulants (NOACs) administration to treat HIT had been reported. NOACs generally offer advantages such as consistent and predictable anticoagulation, oral administration with good patient compliance, and a good safety profile. We report a case of HIT with severe thrombotic complications successfully treated with rivaroxaban and discuss the current knowledge about the use of NOACs for the treatment of this potentially fatal thrombocytopenia.

[The role of epicardial fat and obesity parameters in the prediction of coronary heart disease]. / Význam epikardiálneho tuku a obezitných parametrov pri predikcii koronárnej choroby srdca.

BACKGROUND: To assess the relationship of parameters of obesity in relationship to coronary angiography findings with correlation of epicardial fat (EF) thickness in uppermentioned context. METHODS: There were 80 patients examined (43 males, 37 postmenopausal females) undergoing elective coronary angiography. We examined the regular obesity parameters - BMI, waist circumference (WC), neck circumference (NC), total body fat (TBF), and visceral fat (VF) using bioimpedance. We assessed the echocardiographically measured EF thickness. We added examination of lipidogram, glycaemia, HOMA-IR (insulin resistance index) and AIP (aterogenic index of plasma). The set was divided into group with coronarographically proved stenosis or stenoses (withCS), and a group without finding of quantifiable stenosis or stenoses (withoutCS). RESULTS: The average thickness of EF in withCS group was 6.3 vs 5.6 mm in group withoutCS (p < 0.025). The differences in the thickness of EF in mentioned groups were 6.5 vs 5.2 mm in males (p < 0.025, = 20 %) and 6.1 vs 6.0 mm in females (p < 0.025, = 1.64 %). In males in withCS group, there was a dominant fat increase in epicardial region and TBF, and in females in withCS group, the fat deposits were increased in general. BMI was not a dominant parameter of adiposity in neither group (males in withCS group 31.11 vs withoutCS 30.41 kg/m(2); females in withCS group 31.40 vs withoutCS 31.20 kg/m(2)). EF was correlated the most by WC in males (r = 0.488; p < 0.005), and in females too (r = 0.564, p < 0.005). The patients in withCS group had increased HOMA-IR 4.75 vs 3.56 in withoutCS group, and AIP 0.22 vs 0.17. CONCLUSION: Thickness of EF in males and VT in females could be considered obesity parameters in assessment of pre-clinical stages of coronary atherosclerosis and prediction of risk of coronary heart disease. In adipose parameters, EF thickness was correlated the most by WC. Risk stratification of coronary artery disease is supplemented by increased HOMA-IR and AIP.

Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial.

IMPORTANCE: p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes. OBJECTIVE: To evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: LATITUDE-TIMI 60, a randomized, placebo-controlled, double-blind, parallel-group trial conducted at 322 sites in 34 countries from June 3, 2014, until December 8, 2015. Part A consisted of a leading cohort (n = 3503) to provide an initial assessment of safety and exploratory efficacy before considering progression to part B (approximately 22,000 patients). Patients were considered potentially eligible for enrollment if they had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk. INTERVENTIONS: Patients were randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765) on a background of guideline-recommended therapy. Patients were treated for 12 weeks and followed up for an additional 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization with the principal analysis specified at week 12. RESULTS: In part A, among the 3503 patients randomized (median age, 66 years; 1036 [29.6%] were women), 99.1% had complete ascertainment for the primary outcome. The primary end point occurred by 12 weeks in 123 patients treated with placebo (7.0%) and 139 patients treated with losmapimod (8.1%; hazard ratio, 1.16; 95% CI, 0.91-1.47; P = .24). The on-treatment rates of serious adverse events were 16.0% with losmapimod and 14.2% with placebo. CONCLUSIONS AND RELEVANCE: Among patients with acute MI, use of losmapimod compared with placebo did not reduce the risk of major ischemic cardiovascular events. The results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02145468.

Type 2 Diabetes and ADP Receptor Blocker Therapy.

Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy.

Ticagrelor: a safe and effective approach for overcoming clopidogrel resistance in patients with stent thrombosis?

Stent thrombosis is a morbid complication following percutaneous coronary intervention (PCI). Dual antiplatelet therapy significantly reduces stent thrombosis risk. However, the antiplatelet response to clopidogrel - the most frequently used ADP receptor antagonist in post-PCI patients - varies among individuals. High on-treatment platelet reactivity was repeatedly associated with the risk of stent thrombosis. Ticagrelor is a novel ADP receptor blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. This agent offers a unique mechanism of action, no relevant pharmacological interactions, consistent platelet inhibition, and a good safety profile. This article reviews the prospective use of ticagrelor in the treatment of stent thrombosis in acute coronary syndrome patients undergoing PCI of culprit coronary lesion.

Monitoring of dabigatran therapy using Hemoclot(®) Thrombin Inhibitor assay in patients with atrial fibrillation.

Dabigatran, a new direct thrombin inhibitor, achieves strong anticoagulation that is more predictable than warfarin. Nevertheless, a patient on dabigatran therapy (DT) may suffer from thrombotic or bleeding events. The routine monitoring of DT is not recommended, and standard coagulation tests are not sensitive enough for the assessment of DT activity. The aim of this study was to examine the clinical usefulness of the Hemoclot(®) Thrombin Inhibitor (HTI) assay in the assessment of dabigatran plasma levels in patients with non-valvular AF. Nineteen patients (12 men, 7 women) on DT were included in this preliminary prospective observational study. Dabigatran was administrated twice daily in a two dose regimens: 150 mg (5 patients) and 110 mg (14 patients). Blood samples were taken for the assessment of trough and peak levels of dabigatran. Dabigatran concentrations were measured with the HTI assay. The average dabigatran trough level was 69.3 ± 55.5 ng/ml and the average dabigatran peak level was 112.7 ± 66.6 ng/ml. The dabigatran trough plasma concentration was in the established reference range in 15 patients and the dabigatran peak plasma concentration was in the established reference range in 9 patients, respectively. Despite the fact that the activated partial thromboplastin and thrombin times were generally changed (prolonged), these tests failed to identify the patients with too low or too high dabigatran concentrations. The study confirmed the high sensitivity of the HTI assay for the assessment of dabigatran plasma levels. When compared to standard coagulation tests, the HTI is a more suitable assay for the monitoring of patients treated with dabigatran. Monitoring of DT may be beneficial in selected patients; however, further studies will be needed for the final clarification of this issue.