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1. Platelet miRNA Expression in Patients with Sticky Platelet Syndrome

Author

Belakova Kristina Maria, Zolkova Jana, Vadelova Lubica, Skerenova Maria, Ivankova Jela, Lisa Lenka, Sokol Juraj, and Stasko Jan

Subjects
sticky platelet syndrome, mirna, expression, Medicine
Abstract

Sticky platelet syndrome (SPS) is a disorder with familial occurrence and autosomal dominant trait characterized by platelet hyperaggregability in response to a low concentration of adenosine diphosphate (ADP) and/or epinephrine (EPI). The etiology of SPS may be associated with platelet microRNAs (miRNAs), which are considered as potential biomarkers of platelet function and antiplatelet therapy. We were monitoring the expression of platelet miRNAs in patients with laboratory diagnosed SPS and healthy controls. We have found a statistically significant increased expression of both miR-423-5p and miR-338-3p as well as a statistically significant decreased expression of miR-425-5p between the group of patients with diagnosed SPS type II and the group of healthy controls, which seems to be an interesting issue for a further research.

Published
2023
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3. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

Author

Kubisz Peter, Plamenova Ivana, Holly Pavol, and Stasko Jan

Subjects
Coagulation factor VIII inhibitor, Hemophilia A, Immune tolerance induction, Intravenous immunoglobulin, Recombinant activated factor VII, Medicine
Abstract

Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin) is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

Published
2012
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11. A Functional Assay for the Determination of Heparin-Induced Thrombocytopenia via Flow Cytometry

Author

Skornova, Ingrid, primary, Simurda, Tomas, additional, Stanciakova, Lucia, additional, Lauko, Viliam, additional, Holly, Pavol, additional, Samos, Matej, additional, Bolek, Tomas, additional, Schnierer, Martin, additional, Drotarova, Miroslava, additional, Belakova, Kristina Maria, additional, Sokol, Juraj, additional, Stasko, Jan, additional, Mokan, Marian, additional, Gumulec, Jaroslav, additional, and Chrastinova, Leona, additional

Published
2023
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12. Perioperative Monitoring with Rotational Thromboelastometry in a Severe Hemophilia A Patient Undergoing Elective Ankle Surgery.

Author

Simurda, Tomas, Drotarova, Miroslava, Skornova, Ingrid, Dobrotova, Miroslava, Brunclikova, Monika, Necas, Libor, Cibula, Zoltan, Kubisz, Peter, and Stasko, Jan

Subjects
HEMOPHILIACS, THROMBELASTOGRAPHY, ELECTIVE surgery, TOTAL ankle replacement, ENDOVASCULAR aneurysm repair, BLOOD coagulation factor VIII antibodies
Abstract

This article discusses the use of rotational thromboelastometry (ROTEM) in the perioperative management of a patient with severe hemophilia A undergoing ankle surgery. Hemophilia A is an inherited bleeding disorder caused by a deficiency of clotting factor VIII (FVIII). Standard laboratory tests are limited in predicting bleeding and guiding hemostasis management in patients with clotting factor disorders. ROTEM analysis allows for real-time evaluation of clotting function and monitoring of hemostatic treatment during the perioperative period. The article suggests that systematic monitoring using ROTEM could be a promising strategy for the use of FVIII concentrates in hemophilia A patients during surgery. However, further research is needed to validate this approach. [Extracted from the article]

Published
2024
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14. Association of Genetic Variability in Selected Genes with Platelet Hyperaggregability and Arterial Thrombosis

Author

Brunclikova Monika, Ivankova Jela, Skerenova Maria, Simurda Tomas, Stanciakova Lucia, Skornova Ingrid, Sterankova Miroslava, Zolkova Jana, Dobrotova Miroslava, Holly Pavol, Kubisz Peter, and Stasko Jan

Subjects
General Biochemistry, Genetics and Molecular Biology, General Nursing
Abstract

Introduction: Inherited platelet hyperaggregability, so called “Sticky platelet syndrome” (SPS), is a prothrombotic platelet disorder. The syndrome contributes more often to arterial than venous thrombosis. The most common localization of arterial occlusion involves cerebral or coronary arteries. However, SPS may also lead to thrombosis in the atypical sites of the circulation. This qualitative platelet alteration causes platelet hyperaggregability after a very low concentration of platelet inducers – adenosine diphosphate (ADP) and/or epinephrine (EPI). The precise genetic background of the syndrome has not been defined. In the present study we aimed to determine the association between selected single nucleotide polymorphisms (SNPs) within genes for platelet endothelial aggregation receptor 1 (PEAR1) and murine retrovirus integration site 1 (MRVI1) and the risk for arterial thrombosis in patients with SPS. The products of these selected genes play an important role in platelet aggregation. Patients and methods: We examined 69 patients with SPS and a history of arterial thrombosis and 69 healthy blood donors who served as controls. SPS was confirmed by a light transmission aggregometry (LTA) according to the method and criteria described by Mammen and Bick. We assessed two SNPs within PEAR1 gene (rs12041331, rs1256888) and two SNPs within MRVI1 gene (rs1874445, rs7940646). Results: Selected PEAR1 and MRVI1 polymorphisms seem not to be a risk factor for the development of SPS as the syndrome with an arterial thrombosis phenotype. However, in the subgroup of SPS1 patients there was found a decreased frequency of the minor A allele of SNP rs12041331 in PEAR1 gene (borderline p value, p=0.061) that can be hypothesized as protective against arterial thrombosis. In the same SPS1 subgroup the haplotype TA in PEAR1 gene also showed a decreased frequency with a borderline insignificance (p=0.056). We can theorize also about its protective role in SPS1 patients. We did not confirm the protective effect of polymorphism (T/T of rs 12566888) in PEAR1 against arterial thrombosis in SPS patients and SPS subgroups. Conclusion: Our results support the idea that examined genetic variability of the selected SNPs in PEAR1 and MRVI1 genes is not associated with platelet hyperaggregability manifested as arterial thrombosis. The possible protective role of the minor A allele of SNP rs12041331 as well as a role of haplotype TA in PEAR1 gene related to the arterial thrombosis found in the subgroup of SPS1 patients needs to be verified in further research.

Published
2022
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15. Basic Principles of Rotational Thromboelastometry (ROTEM ®) and the Role of ROTEM—Guided Fibrinogen Replacement Therapy in the Management of Coagulopathies.

Author

Drotarova, Miroslava, Zolkova, Jana, Belakova, Kristina Maria, Brunclikova, Monika, Skornova, Ingrid, Stasko, Jan, and Simurda, Tomas

Subjects
FIBRINOGEN, THROMBELASTOGRAPHY, BLOOD coagulation disorders, BLOOD transfusion, MEDICAL care costs
Abstract

Rotational thromboelastometry (ROTEM) is a viscoelastic method, which provides a graphical and numerical representation of induced hemostasis in whole blood samples. Its ability to quickly assess the state of hemostasis is used in the management of bleeding from a variety of causes. The separate activation of particular parts of hemocoagulation in INTEM, EXTEM, and FIBTEM tests allows for a more comprehensive and faster evaluation of the missing component of hemostasis followed by targeted therapy. One of the most common cause of coagulopathy is trauma-induced coagulopathy. Fibrinogen replacement therapy by ROTEM allows for the use of a standard dosage of fibrinogen, which has been shown to be successful in preventing dilutional coagulopathy following colloid and crystalloid replacement and excessive amount of allogeneic blood transfusions. The best reflection of fibrinogen activity is observed in the FIBTEM assay, where fibrinogen replacement therapy is recommended at an MCF (maximum clot firmness) of FIBTEM < 10 mm and FIBTEM A10 < 7 mm. ROTEM also plays an important role in the diagnostic and management of inherited fibrinogen disorders. These can be manifested by bleeding complications, where changes in the MCF parameter are the most useful tool for assessing the effectiveness of fibrinogen replacement therapy. ROTEM-guided bleeding management algorithms effectively reduce the number of transfusions, healthcare costs, and complications, leading to the improvement of patient safety and overall health. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Detection of Unknown and Rare Pathogenic Variants in Antithrombin, Protein C and Protein S Deficiency Using High-Throughput Targeted Sequencing

Author

Vrtel, Petr, primary, Slavik, Ludek, additional, Vodicka, Radek, additional, Stellmachova, Julia, additional, Prochazka, Martin, additional, Prochazkova, Jana, additional, Ulehlova, Jana, additional, Rohon, Peter, additional, Simurda, Tomas, additional, Stasko, Jan, additional, Martinkova, Ivana, additional, and Vrtel, Radek, additional

Published
2022
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22. Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis

Author

Brunclikova, Monika, primary, Simurda, Tomas, additional, Zolkova, Jana, additional, Sterankova, Miroslava, additional, Skornova, Ingrid, additional, Dobrotova, Miroslava, additional, Kolkova, Zuzana, additional, Loderer, Dusan, additional, Grendar, Marian, additional, Hudecek, Jan, additional, Stasko, Jan, additional, and Kubisz, Peter, additional

Published
2022
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24. How can Secondary Thromboprophylaxis in High-Risk Pregnant Patients be Improved?

Author

Stanciakova, Lucia, primary, Dobrotova, Miroslava, additional, Holly, Pavol, additional, Zolkova, Jana, additional, Vadelova, Lubica, additional, Skornova, Ingrid, additional, Ivankova, Jela, additional, Samos, Matej, additional, Bolek, Tomas, additional, Grendar, Marian, additional, Danko, Jan, additional, Kubisz, Peter, additional, and Stasko, Jan, additional

Published
2022
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27. Multimer Analysis of Von Willebrand Factor in Von Willebrand Disease with a Hydrasys Semi-Automatic Analyzer—Single-Center Experience

Author

Skornova, Ingrid, primary, Simurda, Tomas, additional, Stasko, Jan, additional, Zolkova, Jana, additional, Sokol, Juraj, additional, Holly, Pavol, additional, Dobrotova, Miroslava, additional, Plamenova, Ivana, additional, Hudecek, Jan, additional, Brunclikova, Monika, additional, Stryckova, Alena, additional, and Kubisz, Peter, additional

Published
2021
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28. Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management

Author

Simurda, Tomas, primary, Asselta, Rosanna, additional, Zolkova, Jana, additional, Brunclikova, Monika, additional, Dobrotova, Miroslava, additional, Kolkova, Zuzana, additional, Loderer, Dusan, additional, Skornova, Ingrid, additional, Hudecek, Jan, additional, Lasabova, Zora, additional, Stasko, Jan, additional, and Kubisz, Peter, additional

Published
2021
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34. A

Author

Simurda, Tomas, Vilar, Rui, Zolkova, Jana, Ceznerova, Eliska, Kolkova, Zuzana, Loderer, Dusan, Neerman-Arbez, Marguerite, Casini, Alessandro, Brunclikova, Monika, Skornova, Ingrid, Dobrotova, Miroslava, Grendar, Marian, Stasko, Jan, and Kubisz, Peter

Subjects
protein modelling, Bβ-chain gene, bleeding phenotype, hypofibrinogenemia, novel nonsense mutation, functional analysis
Abstract

Congenital hypofibrinogenemia is a rare bleeding disorder characterized by a proportional decrease of functional and antigenic fibrinogen levels. Hypofibrinogenemia can be considered the phenotypic expression of heterozygous loss of function mutations occurring within one of the three fibrinogen genes (FGA, FGB, and FGG). Clinical manifestations are highly variable, most patients are usually asymptomatic, but may appear with mild to severe bleeding or thrombotic complications. We have sequenced all exons of the FGA, FGB, and FGG genes using the DNA isolated from the peripheral blood in two unrelated probands with mild hypofibrinogenemia. Coagulation screening, global hemostasis, and functional analysis tests were performed. Molecular modeling was used to predict the defect of synthesis and structural changes of the identified mutation. DNA sequencing revealed a novel heterozygous variant c.1421G&gt, A in exon 8 of the FGB gene encoding a B&beta, chain (p.Trp474Ter) in both patients. Clinical data from patients showed bleeding episodes. Protein modelling confirmed changes in the secondary structure of the molecule, with the loss of three &beta, sheet arrangements. As expected by the low fibrinogen levels, turbidity analyses showed a reduced fibrin polymerisation and imaging difference in thickness fibrin fibers. We have to emphasize that our patients have a quantitative fibrinogen disorder, therefore, the reduced function is due to the reduced concentration of fibrinogen, since the B&beta, chains carrying the mutation predicted to be retained inside the cell. The study of fibrinogen molecules using protein modelling may help us to understand causality and effect of novel genetic mutations.

Published
2020
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36. How Can Rotational Thromboelastometry as a Point-of-Care Method Be Useful for the Management of Secondary Thromboprophylaxis in High-Risk Pregnant Patients?

Author

Stanciakova, Lucia, primary, Dobrotova, Miroslava, additional, Holly, Pavol, additional, Zolkova, Jana, additional, Vadelova, Lubica, additional, Skornova, Ingrid, additional, Ivankova, Jela, additional, Bolek, Tomas, additional, Samos, Matej, additional, Grendar, Marian, additional, Danko, Jan, additional, Kubisz, Peter, additional, and Stasko, Jan, additional

Published
2021
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38. Type 2 Diabetes and Fibrinolysis

Author

Stasko, Jan, primary, Chudy, Peter, additional, Kotulicova, Daniela, additional, Galajda, Peter, additional, Mokan, Marian, additional, and Kubisz, Peter, additional

Published
2011
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41. A Novel Nonsense Mutation in FGB (c.1421G>A; p.Trp474Ter) in the Beta Chain of Fibrinogen Causing Hypofibrinogenemia with Bleeding Phenotype

Author

Simurda, Tomas, primary, Vilar, Rui, additional, Zolkova, Jana, additional, Ceznerova, Eliska, additional, Kolkova, Zuzana, additional, Loderer, Dusan, additional, Neerman-Arbez, Marguerite, additional, Casini, Alessandro, additional, Brunclikova, Monika, additional, Skornova, Ingrid, additional, Dobrotova, Miroslava, additional, Grendar, Marian, additional, Stasko, Jan, additional, and Kubisz, Peter, additional

Published
2020
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42. Genetic Variants in the FGB and FGG Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype

Author

Simurda, Tomas, primary, Brunclikova, Monika, additional, Asselta, Rosanna, additional, Caccia, Sonia, additional, Zolkova, Jana, additional, Kolkova, Zuzana, additional, Loderer, Dusan, additional, Skornova, Ingrid, additional, Hudecek, Jan, additional, Lasabova, Zora, additional, Stasko, Jan, additional, and Kubisz, Peter, additional

Published
2020
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48. Anticoagulation therapy in Slovakia

Author

Stanciakova, Lucia, primary, Dobrotova, Miroslava, additional, Plamenova, Ivana, additional, Holly, Pavol, additional, Bolek, Tomas, additional, Samos, Matej, additional, Kubisz, Peter, additional, and Stasko, Jan, additional

Published
2019
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