Miroslava Dobrotová

Comenius University in Bratislava, Presburg, Bratislavský, Slovakia

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Publications (16)24.01 Total impact

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    ABSTRACT: Sticky platelet syndrome (SPS) is a prothrombotic thrombocytopathy with familial occurence, characterized by hyperaggregability of platelets in response to adenosine diphosphate (ADP), epinephrine (EPI), or both. The syndrome has been identified in approximately 21 % of unexplained arterial thrombotic episodes, regarded to be the most common thrombophilia in arterial thrombosis and 13.2% of unexplained venous thromboembolism (VTE). The relatively young age at the first manifestation, relation to fertility and pregnancy, seriousness of the symptoms, easy and effective management of the disorder indicate to the necessity to take it into account in the differential diagnosis of the underlying cause of the thrombotic event. As the various localizations of the thrombosis in SPS have been reported, its management often requires a multidisciplinary approach. This review deals with the clinical aspects of thrombophilia, its etiopathogenesis, diagnosis, as well as novel advances in the treatment and outlines the challenges for the further research.
    No preview · Article · Nov 2015 · Expert Review of Hematology
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    Tomas Simurda · Lucia Stanciakova · Jan Stasko · Miroslava Dobrotova · Peter Kubisz

    Full-text · Article · Oct 2015 · Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis
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    ABSTRACT: Dabigatran, a new direct thrombin inhibitor, achieves strong anticoagulation that is more predictable than warfarin. Nevertheless, a patient on dabigatran therapy (DT) may suffer from thrombotic or bleeding events. The routine monitoring of DT is not recommended, and standard coagulation tests are not sensitive enough for the assessment of DT activity. The aim of this study was to examine the clinical usefulness of the Hemoclot(®) Thrombin Inhibitor (HTI) assay in the assessment of dabigatran plasma levels in patients with non-valvular AF. Nineteen patients (12 men, 7 women) on DT were included in this preliminary prospective observational study. Dabigatran was administrated twice daily in a two dose regimens: 150 mg (5 patients) and 110 mg (14 patients). Blood samples were taken for the assessment of trough and peak levels of dabigatran. Dabigatran concentrations were measured with the HTI assay. The average dabigatran trough level was 69.3 ± 55.5 ng/ml and the average dabigatran peak level was 112.7 ± 66.6 ng/ml. The dabigatran trough plasma concentration was in the established reference range in 15 patients and the dabigatran peak plasma concentration was in the established reference range in 9 patients, respectively. Despite the fact that the activated partial thromboplastin and thrombin times were generally changed (prolonged), these tests failed to identify the patients with too low or too high dabigatran concentrations. The study confirmed the high sensitivity of the HTI assay for the assessment of dabigatran plasma levels. When compared to standard coagulation tests, the HTI is a more suitable assay for the monitoring of patients treated with dabigatran. Monitoring of DT may be beneficial in selected patients; however, further studies will be needed for the final clarification of this issue.
    No preview · Article · Aug 2014 · Journal of Thrombosis and Thrombolysis
  • Pavol Hollý · Lenka Lisá · Ivana Plameňová · Miroslava Dobrotová · Peter Kubisz

    No preview · Article · Dec 2012 · Blood transfusion = Trasfusione del sangue
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    ABSTRACT: The GP6 gene encodes the GPVI, a crucial platelet membrane glycoprotein, for adequate platelet activation, adhesion and aggregation. The objectives of the present study were to assess the genetic variability of the GP6 gene in patients with platelet hyperaggregability phenotype, known as sticky platelet syndrome (SPS) manifesting as deep vein thrombosis (DVT), and/or pulmonary embolism, and in controls; and to evaluate its role in the pathogenesis of venous thromboembolism (VTE) in SPS. Seventy-seven patients with SPS and 77 healthy blood donors as controls were enrolled. Light transmission aggregometry was used to diagnose SPS according to the method of Mammen and Bick. Seven single-nucleotide polymorphisms (SNPs) of the GP6 gene (rs1654410, rs1671153, rs1654419, rs11669150, rs12610286, rs1654431, rs1613662) were assessed using restriction fragment length polymorphism analysis. A significant association between 1613662-G [P < 0.05, odds ratio (OR) 2.087, confidence interval (CI) 1.049-4.148], 1654419-A (P < 0.05, OR 2.161, CI 1.020-4.577) and VTE was found in patients with SPS. The analysis based on SPS type revealed a significantly higher occurrence of 1671153-G (P < 0.05, OR 2.317, CI 1.103-4.865) and 1654419-A (P < 0.05, OR 2.317, CI 1.103-4.865) in the SPS type II compared to the control group. No association between the studied GP6 genotypes and the severity of VTE (pulmonary embolism vs. DVT) was found. In the patients, significant positive relationship between the 1671153-G, 1654419-A, 1613662-G alleles and male sex was observed. GP6 SNPs 1613662-G, 1671153-G and 1654419-A alleles are associated with an increased risk of VTE in SPS. They could contribute to the SPS phenotype.
    No preview · Article · Jul 2012 · Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis
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    Peter Kubisz · Ivana Plamenová · Ján Stasko · Miroslava Dobrotová · Pavol Hollý

    Full-text · Article · Feb 2010 · Thrombosis and Haemostasis
  • Peter Kubisz · Lenka Lisá · Miroslava Dobrotová · Ján Staško
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    ABSTRACT: During a pregnancy is present a physiologic thrombophilic state characterized by predominance of procoagulant factors to fibrinolytic factors to minimize blood loss during pregnancy a delivery. On the other hand this significantly increases the risk of VTE (venous thromboembolism) during pregnancy and apparently in puerperium. Although the incidence of VTE in pregnancy is quite low (1/1000), it may very seriously endanger life of pregnant woman. In many studies the significant increase of VTE risk in pregnant women with hereditary or acquired thrombophilic states was shown. In addition to venous thrombosis the fetal loss syndrome occurs very often in women with thrombophilia. By appropriate secondary prophylaxis it is possible to prevent recurrence of VTE in these women, to ensure optimal course of pregnancy and delivery of healthy newborn. Key words: pregnancy, thrombophilic states, prophylaxis and treatment of VTE in pregnancy.
    No preview · Article · Jan 2010
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    ABSTRACT: The fact that leukaemic cells are primarily or secondarily resistant to cytostatics is a serious phenomenon, which leads to the failure of chemotherapy of malignant diseases in clinical practise. Some detoxification and transporting systems are responsible for the generation of chemoresistance on the cellular level and the decrease of effectiveness in treatment. In vitro testing of chemoresistance of leukaemic cells is presently an inseparable component of “tailoring” therapy in the developing field of predictive oncology. The aim of this work was to estimate profiles of drug resistance, based on the predictive in vitro test, and to help in choosing the most effective cytostatic. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoline (MTT) assay was used, based on the direct effect of cytostatics on the viability of leukaemic cells in vitro. The number of living leukaemic cells was evaluated by a computer program, where LC50 (concentration of cytostatics lethal to 50% of leukaemic cells) was established from the achieved dose-relation curves. Seventy-one samples of leukaemic cells isolated from the patients’ peripheral blood or bone marrow were examined. All samples were tested to 3 cytostatics minimally. It was found by the in vitro assay, that resistance to dexamethasone, prednisolone, etoposide and vincristine is increased in patients with acute myeloid leukaemia disease, compared to the acute lymphoblastic leukaemia patients. In patients with a relapsed disease population, leukaemic cells are highly heterogeneous in the MTT assay. It was concluded that the MTT assay can be used to study drug interactions in vitro in leukaemia samples. The type of interaction was highly different between patients, and depended on drug concentrations.
    Full-text · Article · Feb 2009 · Biologia
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    ABSTRACT: Thrombophilia is inherited or acquired disorder of hemostasis that leads to the increased tendency to thrombosis and predisposes patients to thrombosis and to its recurrence. Clinically hereditary and acquired thrombophilias participate in onset of venous thromboembolism and arterial thrombosis, especially in coronary artery thrombosis manifested as acute coronary syndrome or in cerebral thrombosis, as recurrent deep vein thrombosis or recurrent spontaneous abortions. According to the Conception of health care in Hematology and transfusiology (No. 13100/2006-OZS, 26.6.2006, Bulletin of MH SR 2006, issue of 31.8.2006, vol. 54, p. 13-18) "National Centre of hemostasis and thrombosis (NCHT) seated at Department of Hematology and transfusiology, Jessenius medical faculty of Comenius University and Faculty hospital in Martin preserve of health care predominantly in patients with inherited and acquired thrombophilias in whole Slovak territory and manage the National registry of thrombophilic states.".
    No preview · Article · Jan 2009 · Lekársky obzor
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    ABSTRACT: Sticky platelet syndrome (SPS) was described for the first time by Holliday in 1983 at the 9 th Conference on stroke and cerebral circulation in Arizona (5). It is hereditary, autosomal dominant thrombophilia associated with an increased incidence of arterial and venous thrombosis as well. Platelet hyperaggregability after stimulation by low concentrations of platelet inducers - after adenosindiphosphate (ADP) and epinephrine (EPI) is typical for this syndrome, whilst platelet response to other inducers is normal (7). According Mammen and Bick SPS is the second most common hereditary thrombophilia, after resistance to activated protein C (APC-R) and the most common thrombophilia associated with arterial thrombosis with the incidence of 21% (5, 8, 11). The cause of sticky platelet syndrome remains still unknown. It is suggested that there is an abnormality of platelet membrane surface glycoprotein receptors leading to their hyperfunction. However the treatment by low dose aspirin normalizes platelet hyperaggregability and prevents patients against recurrent thrombo-embolic episodes and consequent morbidity and mortality. Therefore in the clinical practice there is really important to think of this disorder, to diagnose it properly and to treat it appropriately.
    No preview · Article · Jan 2008 · Lekársky obzor
  • Miroslava Dobrotová · Peter Kubisz
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    ABSTRACT: 1. vyd. Na obálce uvedeno též logo Avicenum Na obálce uveden autor: Peter Kubisz a kolektiv
    No preview · Article · Jan 2006
  • Peter Kubisz · Ján Stasko · Miroslava Dobrotová · Jela Ivanková · Dusan Mesko
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    ABSTRACT: Patients with hemophilia demonstrate quite variable clinical phenotype even in cases with the same level of deficient factor or the same molecular abnormality. Different interacting factors including congenital and acquired alterations of coagulation inhibitors can modulate both clinical expression and severity of hemophilia. In this study, plasma levels of factor VIII (FVIII), factor IX (FIX) as well as protein C (PC), protein S (PS), and antithrombin (AT) plasma levels were measured in 80 patients with severe hemophilia A and B. Patients were divided into two groups according to the risk of bleeding: the first group (n = 32) with mild bleeding (< 2 bleeds/year), and the second group (n = 48) with severe bleeding (> or = 2 bleeds/year). Both hemophilia groups showed significantly decreased PC plasma levels compared to levels in healthy control subjects (the first group: p < 0.0001 and second group: p < 0.01). The difference in PC plasma levels between the first and second hemophilia group was significant (p < 0.05). Moreover, there was positive correlation between age and the functional PC in both hemophilia groups. Our results suggest that decreased PC plasma levels can testify to a slightly protective effect of the PC pathway on the severity and frequency of bleeding in patients with severe hemophilia A and B.
    No preview · Article · Aug 2005 · Clinical and Applied Thrombosis/Hemostasis
  • J Hudecek · M Dobrotová · J Hybenová · J Ivanková · V Melus · R Pullmann · P Kubisz
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    ABSTRACT: The resistance to activated protein C (APC-resistance) based on the presence of factor V Leiden (F V Leiden) is the most frequent thrombophilic condition in the white race population. It contributes to the origin of thrombosis especially in the venous part of blood vessels. Significant geographic differences have been detected within Europe. The aim of this retrospective study was to determine the frequency in the occurrence of F V Leiden: 1. in healthy (asymptomatic) Slovak population, 2. in their consanguineously unrelated members with thrombosis and 3. in patients with myocardial infarction (IM) without or with other known risk factors of this disease (nicotinism, obesity, hypertension, dyslipoproteinemia, diabetes mellitus), respectively. The detection of FV Leiden was made by molecular biology methods. The occurrence in a group of 152 healthy individuals was four % (6 persons) and this frequency corresponds to the geographic localization of the Slovak Republic in Europe. In a group of 349 patients with thrombosis in anamnesis, FV Leiden was detected in 103 persons (29.5%). The occurrence was higher than the usually reported incidence in these patients (20%). Likewise, in a group of 35 patients with IM without risk factors in anamnesis, the occurrence of FV Leiden (8.6%) was significantly higher in comparison with healthy population and the incidence further increased significantly in a group of 41 patients with IM and the presence of at least one risk factor (14.6%). The authors therefore suppose an active role of the Leiden mutation of FV gene in the pathogenesis of this disease.
    No preview · Article · Dec 2003 · Vnitr̆ní lékar̆ství
  • J Hudecek · J Ivanková · M Dobrotová · J Hybenová · R Pullmann · P Kubisz
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    ABSTRACT: The laboratory diagnosis of resistance to activated C protein (APC-resistance) involves examination of the phenotype and genotype of this thrombophilia. For examination of the phenotype coagulation and chromogenic tests are used. Their essence is examination in the presence and absence of exogenous APC. While the result of the original coagulation examination of APC-resistance which uses the APTT principle is influenced by a number of factors, the sensitivity and specificity of the modification of this examination (dilution of the examined plasma sample by FV deficient plasma before making the test) in relation to detection of FV Leiden is almost 100% and eliminates the majority of limitations of the original examination. The chromogenic assessment of APC-resistance has similar advantages, however, it cannot differentiate between the heterozygous and homozygous form of FV Leiden. During examination of the genotype of subjects with APC-resistance the mutation of FV Leiden is detected in as many as 90%. The group of subjects with the phenotype of APC-resistance comprises in particular subjects with acquired APC-resistance caused by conditions which lead to a disbalance between procoagulation and anticoagulation proteins of haemostasis which influence the reactions of the applied laboratory examinations. The acquired phenotype of APC-resistance can be also associated with an increased risk of thrombosis and the clinical manifestations of this thrombophilia resemble the classical, FV Leiden conditioned APC resistance. Rarely also congenital causes of the phenotype of APC-resistance are encountered caused by another mutation than the Leiden mutation of gene FV. The concurrent examination of the patient's plasma with the original and modified coagulation test makes it possible to assess the inborn cause of APC-resistance (positive finding also in modified examination). The presence of FV Leiden is then confirmed by examination of the genotype by the polymerase chain reaction.
    No preview · Article · Jan 2000 · Vnitr̆ní lékar̆ství
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    ABSTRACT: Cell surface adhesion molecule expression is likely to be important in inflammation, atherosclerosis and cancer, and soluble forms of many of these molecules are present in plasma. We measured levels of the soluble form of platelet endothelial cell adhesion molecule-1 (sPECAM) by ELISA in the serum of 77 patients with frank atherosclerosis, 69 patients with inflammatory connective tissue disease, and 39 patients with cancer. Each group of patients was controlled by an equal number of age- and sex-matched healthy subjects. There was no difference between sPECAM in patients with atherosclerosis and their matched controls or between patients with connective tissue disease and their controls. However, sPECAM levels were lower (16.6 +/- 5.0 ng/ml, mean +/- SD) in patients with cancer than in their controls (21.1 +/- 4.4 ng/ml, P < 0.001). No differences were found in sPECAM levels between the major subgroups of each type of disease, or as a result of factors such as age, sex or smoking in the controls. In contrast to levels of many other soluble adhesion molecules, levels of sPECAM are not altered in inflammatory or atherosclerotic vascular disease and therefore appear to have little relevance in these conditions. However, there may be significant differences in sPECAM levels in patients with low levels in cancer. Additional investigations are therefore justified.
    No preview · Article · Feb 1998 · Blood Coagulation and Fibrinolysis
  • A D Blann · M Dobrotova · P Kubisz · C N McCollum
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    ABSTRACT: Tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor antigen (PAI-1), soluble P-selectin and von Willebrand factor antigen (vWf) were measured by ELISA in 41 patients with peripheral vascular disease (PVD), 41 with ischaemic heart disease (HD) and in 46 age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0002) and in patients with PVD (p = 0.0011) relative to the controls but levels did not differ between the two patients groups. Raised tPA found in both PVD (p = 0.0006) and IHD (p = 0.0061) compared to the controls also failed to differentiate the two groups of patients. Soluble P-selectin was also raised in both groups (p = 0.003 in IHD and p = 0.0102 in PVD) with no difference between the groups. There were no differences in levels of PAI-1 between the groups. In the subjects taken as a whole, there were significant Spearman's correlations between tPA and vWf (r = 0.37, p < 0.001), tPA and triglycerides (r = 0.38, p < 0.001), tPA and P-selectin (r = 0.19, p = 0.032), vWf and age (r = 0.25, p = 0.005) and inversely between vWf and HDL (r = -0.25, p = 0.006). These data support the concept that increased levels of tPA may be important in atherosclerosis, and indicate that soluble P-selectin may be useful in further analysis of the role of platelets and the endothelial cell in this disease.
    No preview · Article · Sep 1995 · Thrombosis and Haemostasis