Marián Fedor

Staphylococcus intermedius—rare pathogen of acute meningitis

We report the first case of acute meningitis caused by a rare, atypical pathogen. An 11-month-old infant was admitted to hospital with clinical symptoms typical of acute meningitis. Cerebrospinal fluid analysis revealed an elevated neutrophil cell count and high proteins. Microbiological examination of the fluid confirmed an atypical cause of meningitis--Staphylococcus intermedius. Antibiotic therapy with cefotaxime was successful and the child made a full recovery.

A case of complicated cerebral toxocariasis in a 4-year old child

SummaryWe report the case of a 4-year-old boy suffering from a cerebral form of toxocariasis. High serum titres of anti-Toxocara antibodies indicated that the primary infection was induced by a high number of Toxocara eggs and that the larvae did not penetrate to cerebrospinal fluid due to the hematoencephalic barrier. MRI of the patient’s brain showed multiple focal lesions spread diffusely in almost all parts of the brain, predominantly paraventricularly. These might be eosinophil-rich granulomatous infiltrates enclosing larvae. Extensive morphological changes were the cause of serious neurological symptoms, most of them being reversible after follow-up therapy. Radiology proved to be useful diagnostic method, but the specific serological assessment had a key role for the final diagnosis. In conclusion, diagnosis of this patient was intracranial primary Toxocara infection with central quadruparesis and parainfective myocarditis.

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.

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 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.

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.