Lukas Duraj

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.

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.

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.

Role of VASP Phosphorylation Assay in Monitoring the Antiplatelet Therapy

Abstract Dual antiplatelet treatment with clopidogrel and aspirin represents standard regimen in prevention of thromboembolic events in patients with ischemic heart disease undergoing percutaneous coronary intervention (PCI). One of the greatest pitfalls of clopidogrel treatment is large inter-individual variability in response. Large amount of patients does not respond adequately and therefore are not „protected“ even in spite of receiving the therapy. Poor responders are exposed to three-fold increased risk of myocardial infarction, stent thrombosis and cardiac death. Clopidogrel is an antiplatelet prodrug, whose active metabolite inhibits platelet function by irreversible binding to the (adenosine diphosphate) platelet receptor P2Y12. Receptor P2Y12 plays primal role in ADP-mediated platelet activation, and also in mechanism of action of ADP inhibitors such as clopidogrel, prasugrel etc. Reasons stated above, raised the necessity for implementing reliable laboratory test in order to identify the unprotected patients. In an ideal scenario, such test would serve to adjust the dose and guide the individual tailored treatment. Vasodilator Stimulated Phosphoprotein (VASP) is an intracellular platelet protein which is non phosphorylated at basal state. Since its relation in cascade with P2Y12 receptor, VASP phosphorylation corerlates with inhibition of P2Y12 which is the receptor of prime importance in ADP mediated activation of platelets and as is primary target of ADP inhibitors action. Outcome of the assay is represented as the value of platelet reactivity index (PRI), where PRI values above 50% are considered inadequate response to treatment and signal exposure to increased risk of myocardial infarction, post-PCI stent thrombosis and cardiac death. VASP-P flow cytometric assay is emerging into the spotlight as the promising method, mostly for its specificity for ADP inhibitors, better outlook for standardising results and lesser sample manipulation compared to multiple electrode aggregometry.

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.

Monitoring of Hemostasis and Management of Anticoagulant Thromboprophylaxis in Pregnant Women with Increased Risk of Fetal Loss.

Physiological prothrombotic changes during pregnancy and the postpartum period, along with other preexisting maternal risk factors, increase the risk of both venous thromboembolism (VTE) and adverse pregnancy outcomes. Pregnancy complications that develop due to placental insufficiency as a result of inappropriate activation of coagulation are present in more than 5% of pregnancies and can contribute to significant maternal morbidity and mortality. Therefore, anticoagulant prophylaxis in women with congenital and acquired thrombophilic conditions should be actively considered. According to the Guidelines of American College of Chest Physicians, the use of low-molecular-weight heparin is suggested for prophylaxis of VTE and pregnancy complications in high-risk pregnant women. However, personalized refinements of such thromboprophylaxis remains unspecified, despite the necessity of better targeted recommendations for life-threatening conditions. We, therefore, review the possibilities of longitudinal monitoring and comprehensive assessment of changes in hemostasis in the group of high-risk pregnant women, which can then be used for early prediction and individualization of the optimal anticoagulant thromboprophylaxis of pregnancy complications. Simultaneously, we present our single-center experience with such monitoring and our first series of results.

Thrombelastography and Thrombelastometry

Abstract The term thrombelastography / thrombelastometry was used to describe the trace produced from measurement of the viscoelastic changes associated with fibrin polymerization. The result of measurement is a compact mapping of the various stages of haemostasis. One of the first real clinical applications of this method was the haemostatic monitoring of liver transplantation and cardiac surgery using extracorporeal circulation. In trauma patients the thrombelastography /thrombelastometry was proved to predict early transfusion requirements. Another authors suggest thrombelastography /thrombelastometry as a possible tool for early identification of pregnant women at increased risk of fetal loss. This article provides overview on the development of thrombelastography / trombelastometry and its possible use in laboratory of haemostasis.