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Tradiční antikoagulační terapie warfarinem nebo hepariny je v posledních letech často nahrazována cíleně působícími antikoagulačními léky označovanými jako nová orální antikoagulancia (NOAC). Pro rutinní klinické použití jsou v současnosti využívány přímý inhibitor trombinu dabigatran a přímé inhibitory aktivovaného faktoru Xa rivaroxaban a apixaban. Indikace NOAC patří nejčastěji do kompetence internistů, zvláště kardiologů, neurologů, angiologů a ortopedů. Hematolog je do problematiky často zapojen v případě potřeby interpretace hemostatických parametrů, v klinických situacích vyžadujících monitoraci terapie nebo vzniku krvácivých projevů spojených s léčbou a nutnosti stavění krvácení.

The standard anticoagulation therapy with warfarin or heparin is often replaced by new directly acting drugs known as the new oral anticoagulants (NOAC) in recent years. For routine clinical use direct thrombin inhibitor dabigatran and direct inhibitors of activated factor Xa rivaroxaban and apixaban are currently used. NOAC are administered mostly by the internists, particularly cardiologists, neurologists, orthopedists and angiologists. Hematologist is often involved in the issue, if interpretation of hemostatic parameters in anticoagulant therapy monitoring or therapy related hemorrhagic complications is necessary.

Klíčová slova
apixaban,
MeSH
antikoagulancia * aplikace a dávkování farmakologie škodlivé účinky terapeutické užití MeSH
antithrombiny aplikace a dávkování farmakologie škodlivé účinky terapeutické užití MeSH
dabigatran MeSH
hodnocení rizik MeSH
inhibitory faktoru Xa aplikace a dávkování farmakologie škodlivé účinky terapeutické užití MeSH
krvácení prevence a kontrola terapie MeSH
lidé MeSH
rivaroxaban MeSH
vyšetření krevní srážlivosti * trendy MeSH
Check Tag
lidé MeSH
Publikační typ
práce podpořená grantem MeSH
přehledy MeSH

Článek

Polymorphism of the Fcgamma Receptor II as a Possible Predisposing Factor for Heparin-Induced Thrombocytopenia

Clinical laboratory. 2015 ; 61 (8) : 1027-1032.

ISSN 1433-6510
Medvik
Zdroj

BACKGROUND: Heparin-induced thrombocytopenia (HIT) represents a serious complication of heparin treatment. IgG antibodies binding platelet factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. However, only a portion of the antibodies have the ability to activate platelets, and these can be identified by a platelet aggregation test (functional testing). However, this expression has been detected to have a molecular cause, which is a mutation of FcgammaRIIa. The FcgammaRIIa receptor is responsible for the activation of platelets by antibodies in HIT. METHODS: To determine HIT, impedance aggregometry using the Multiplate analyzer (MEA) as heparin-induced aggregation technique and the Technozym HIT IgG ELISA test were used. The MEA method uses sensitization of donor platelets with patient plasma in the presence of heparin at a concentration of 0.5 IU/mL. The results were compared with the ELISA test. Mutation of FcgammaRHa was assessed using the asymmetric real-time PCR method that is based on the reaction with two hybridization probes and melting curve analysis. RESULTS: Examined were 100 patients at a clinically intermediate and higher risk of HIT according to the 4T's score. All samples were examined by the ELISA test and MEA, with positive samples being further confirmed by high-concentration heparin. In the group of patients, 10.0% were positive by MEA as compared with 4% determined by ELISA. The results of genetic analysis of FcgammaRIIa did not provide statistically significant differences between positive patients found by the functional test as well as the ELISA test and seronegative patients. CONCLUSIONS: The genetic mutation FcgammaRIIa is a predisposing factor for manifestation of HIT in the form of thrombocytopenia, but the process of seroconversion apparently needs another inducing factor. Therefore, the examination of mutations can be classified as predisposing factors rather than to confirm the diagnosis of HIT.

Článek

Detection of clopidogrel resistance using ADP induced aggregometry with specific inhibitor PGE1

Clinical laboratory. 2014 ; 60 (9) : 1475-1480.

ISSN 1433-6510
Medvik
Zdroj

BACKROUND: Antiaggregation therapy is still the most frequently used approach to prevent thrombotic events in cardiovascular diseases. It has a good clinical effect but increasing evidence shows high residual platelet aggregation activity in a number of patients. Laboratory methods only allow us to detect clopidogrel "non-responders" or "low responders". Recent methods are based on monitoring residual platelet aggregation activity (aggregation methods) or detecting the number of free epitopes for binding a specific monoclonal antibody such as vasodilator-stimulated phosphoprotein phosphorylation (VASP). METHODS: The aims of our study were comparison light transmission aggregometry (LTA) and multiple electrode platelet aggregometry (MEA) with induction by ADP in concentrations of 20 micromol/L with or without prostaglandin E1 (PGE1) for monitoring clopidogrel resistance. RESULTS: In the group of 84 patients with cardiovascular disease (CAD) studied, an impaired individual response to clopidogrel therapy was found 11.9% and 10.7% of the patients using MEA and LTA, respectively, induced by ADP with PGE1. The LTA and MEA methods with induction by ADP with PGE1 and without PGE1 were statistically compared using Spearman's nonparametric correlation analysis. Both methods with using PGE, showed a positive significant correlation (p = 0.003) in contrast with the results without PGE1 with a no significant correlation (p = 0.732). CONCLUSIONS: The sensitivity for detecting clopidogrel resistance correlates well with other data in the literature suggesting that there are 5%-30% clopidogrel low-responders depending on the type of platelet function assay used and the criteria for defining a low-responder [16-18]. These results favor implementation of the ADP test with PGE1 by MEA specifically for identification of low-responders to clopidogrel.

Článek

The advantages and limitations of impedance aggregometry in detection of heparin-induced thrombocytopenia

Clinical laboratory. 2014 ; 60 (8) : 1319-1324.

ISSN 1433-6510
Medvik
Zdroj

BACKGROUND: Heparin-induced thrombocytopenia (HIT) represents a serious complication of heparin treatment. IgG antibodies binding platelet factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. However, only a portion of the antibodies have the ability to activate platelets, and these can be identified by a platelet aggregation test (functional testing). Current methods HIPA and SRA are time-consuming and difficult if HIT is clinically suspected; therefore, numerous new methods have recently been developed. METHODS: To determine HIT, impedance aggregometry using the Multiplate analyzer (MEA) as heparin-induced aggregation techniques and the Technozym HIT Ig ELISA test were used. The MEA method uses sensitization of donor platelets with patient plasma in the presence of heparin at a concentration of 0.5 IU/mL. The results were compared with the ELISA test. RESULTS: We examined 190 patients at clinically intermediate and higher risk of HIT according to the 4T score. All samples were examined by the ELISA test and MEA, with positive samples being further confirmed by high-concentration heparin. The methodology was modified with respect to the dilution for high positive samples and assessment has been extended to an index of inhibition. CONCLUSIONS: In the studied group, we demonstrated that MEA has sufficient sensitivity and higher specificity. In the group of patients, 10.0% showed positive results by MEA as compared with 7.3% determined by ELISA. Unlike the ELISA methods of the same quality, MEA is more suitable for detecting platelet-activating HIT antibodies in practice.

MeSH
agregace trombocytů * účinky léků MeSH
elektrická impedance MeSH
ELISA MeSH
heparin * chemie škodlivé účinky MeSH
imunoglobulin G chemie MeSH
lidé MeSH
pravděpodobnost MeSH
reprodukovatelnost výsledků MeSH
senioři MeSH
senzitivita a specificita MeSH
statická elektřina MeSH
trombocytopenie * chemicky indukované MeSH
trombocyty MeSH
vyšetření funkce trombocytů MeSH
Check Tag
lidé MeSH
mužské pohlaví MeSH
senioři MeSH
ženské pohlaví MeSH

Abstrakt

Bifázické koagulační křivky u aPTT v diagnostice různých typů inhibitorů

OHD. 2014 ; () : 80-81.

ISBN 978-80-244-4099-6
Medvik
Zdroj

Publikační typ
abstrakt z konference MeSH

Článek

Genetic polymorphisms of platelet receptors in patients with acute myocardial infarction and resistance to antiplatelet therapy

Genetic testing and molecular biomarkers. 2014 ; 18 (9) : 599-604.

Genet Test Mol Biomarkers
ISSN 1945-0257
Medvik
Zdroj

METHODS: The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E1 for detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T>C; rs2046934), P2Y12 (34C>T; rs6785930), COX-1 (-842A>G; rs10306114), GPVI (13254T>C; rs1613662), and GPIbA (5T>C; rs2243093) polymorphisms, DNA of patients with AIM was tested by real-time-polymerase chain reaction and melting curve analysis using the LightCycler 480 analyzer (Roche Diagnostics). RESULTS: The cut-off points used for patients with effective ASA therapy are 25% of aggregated platelets and 220 area under the curve (AUC)/min if LTA or MEA, respectively. The cut-off points used for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively. Both LTA and MEA found that aspirin and thienopyridine therapies failed in 14.51% and 25.8%, respectively. The data were statistically processed using the SPSS version 15 software (SPSS, Inc.). Associations between receptor mutation status and response to therapy were assessed with Fisher's exact test. The significance level was set at 0.05. CONCLUSION: The aim of our work was to use the two functional laboratory methods described earlier to assess both aspirin and thienopyridine resistance and to determine the contribution of genetic polymorphisms of platelet receptors to resistance to antiplatelet therapy in AIM. Fisher's exact test showed a significant statistical correlation between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of COX1_A1 (-A842G). Fisher's exact test showed no statistically significant correlations between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of GP1bA (-5T>C) and GP6 (T13254C). Fisher's exact test showed no statistically significant correlation between mutational statuses of the receptors P2RY12 (i-T744C), P2RY12 (C34T), GP1bA (-5T>C), or GP6 (T13254C) and response to antiplatelet therapy with 75 mg of clopidogrel.