František Kovář

Monitoring the Efficacy of ADP Inhibitor Treatment in Patients With Acute STEMI Post-PCI by VASP-P Flow Cytometry Assay

Introduction: Dual antiplatelet treatment (DAPT) with clopidogrel and aspirin represents common approach in prevention of thromboembolic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). The drawback of clopidogrel treatment is large interindividual variability in response. Aim: Our article aims to suggesting the most convenient method in monitoring the DAPT of post-PCI patients. Methods: We analyzed the on-treatment platelet reactivity by light transmission aggregometry and vasodilator-stimulated phosphoprotein (VASP) flow cytometric assay. Samples were obtained in 3 intervals: first prior to PCI, then 1, and 30 days after PCI. Results: Based on VASP-platelet reactivity index (PRI), we observed 100% response rate in prasugrel-treated patients and 62% to 73 % in the clopidogrel group. Overall, only 2 (7%) patients with the VASP-PRI value in therapeutic range had major adverse cardiovascular events. Conclusion: Our results hint VASP-phosphorylation assay as a relevant method for guiding and tailoring DAPT.

Sticky platelets syndrome in a young patient with massive pulmonary embolism.

Patient: Female, 51 Final Diagnosis: Sticky platelets syndrome Symptoms: Pulmonary embolism Medication: — Clinical Procedure: Thrombolysis Specialty: Hematology Objective: Disease of unknown ethiology Background: Sticky platelets syndrome (SPS) is an inherited thrombophilia characterized by platelet hyperaggregability, which can lead to the higher risk of thrombosis. The etiology of SPS remains unclear, but several gene polymorphisms have been recently studied and autosomal dominant heredity is suspected. Although SPS is traditionally connected with arterial thrombosis, several cases of SPS as a cause of venous thromboembolism have been described. Case Report: We report the case of a 51-year-old apparently healthy woman with massive pulmonary embolism, who required thrombolytic therapy. In this patient SPS was identified as the only condition leading to higher risk of developing thromboembolic disease. Conclusions: Although at present few physicians have practical experience with SPS, this syndrome may lead to serious health problems or even death. The presented case points to the benefit of SPS diagnostics in standard screening of inherited thrombophilia for effective prophylaxis and treatment in patients with venous thromboembolism.

Clopidogrel resistance in diabetic patient with acute myocardial infarction due to stent thrombosis.

Stent thrombosis is a morbid complication after percutaneous coronary intervention. Dual antiplatelet therapy significantly reduces stent thrombosis risk and forms currently the basis in acute ST elevation myocardial infarction pharmacologic treatment. The introduction of clopidogrel has made a major advance in the acute coronary syndrome treatment. However, there is growing evidence about failure in antiplatelet response after clopidogrel, which may lead to subsequent risk of future thrombotic events. The antiplatelet inhibitory effect of clopidogrel varies widely among individuals. High on-treatment platelet reactivity has been repeatedly associated with a hazard for cardiovascular events, including stent thrombosis. Laboratory monitoring of antiplatelet therapy efficacy may help identify patients with insufficient antiplatelet response. Prasugrel therapy was repeatedly described as an effective method to overcome clopidogrel resistance. We report a case of diabetic patient in whom myocardial reinfarction due to stent thrombosis developed. Clopidogrel resistance was detected in this patient using light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation assessment. After prasugrel administration, no other ischemic event occurred, and patient was released to outpatient care in good general condition.

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

Abstract: 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.

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.

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 ± 8.0 vs. 51.8 ± 38.9 ng/ml, p = .76) and 2-h-post-drug-administration (91.7 ± 57.2 vs. 72.2 ± 33.2 ng/ml, p = .48) activity comparing T2D and non-diabetic patients. Similarly, no significant differences were found in rivaroxaban baseline (35.9 ± 22.5 vs. 55.3 ± 45.1 ng/ml, p = .19) and 2-h-post-drug-administration (145.7 ± 74.1 vs. 202.6 ± 135.0 ng/ml, p = .22) anti-Xa activity. In addition, no significant differences were present in apixaban baseline (96.0 ± 54.5 vs. 63.9 ± 36.8 ng/ml, p = .24) and 2-h-post-drug-administration (151.0 ± 78.3 vs. 151.7 ± 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.

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.

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.

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

Abstract 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.

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 &mgr;g/L. There was a significant increase in peak anti-Xa activity to 175.9 ± 119.6 &mgr;g/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.