More on: thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population-based case-control study.
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Adolescent↗
Biomedical subjects
P Kubisz
Publications and source records attributed to P Kubisz.
[Thrombin activatable fibrinolysis inhibitor (TAFI) and its importance in the regulation of fibrinolysis].
Thrombin activatable fibrinolysis inhibitor (TAFI) also named procarboxypeptidase U (CPU), procarboxypeptidase R (CPR) and plasma procarboxypeptidase B (CPB) provides an important link between fibrinolysis and coagulation cascade. Activated TAFI (TAFIa) reduces a generation of plasmin because it cleaves off the carboxy-terminal lysine residues from partially degraded fibrin and thereby abrogates the fibrin cofactor function in the tPA-mediated catalysis of plasminogen to plasmin. TAFI is activated by thrombin-thrombomodulin complex. TAFI transformation to the activated TAFI (TAFIa) induced by thrombin supports the important role of coagulation cascade in regulation of fibrinolysis. This can be proved by a fact that the patients with a factor XI (FXI) deficiency are prone to bleeding from tissues with a high local fibrinolytic activity (urinary tract, nose, oral cavity, tonsils) that can be explained by a decreased thrombin-mediated TAFI activation. On the other hand the prothrombotic mutation of factor V (FV Leiden) associated with a resistance to activated protein C (APC-resistance) possess both mechanisms-an increased thrombin generation in coagulation cascade and a down regulation of fibrinolysis by a way of the thrombin-induced TAFI activation. For the future an inhibition of TAFI (e.g. by FXI inhibitors) offers the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders. In bleeding disorders (hemophilia A, B) the drugs with a higher efficiency of TAFI for down regulation of an increased fibrinolysis could be used.
Blood Coagulation↗
[Infection and hemostasis].
Localised and following systemic inflammatory reaction accompanying progression of infection causes generation of anti-inflammatory cytokines. They activate leucocytes, endothelium, coagulation and fibrinolysis. Sepsis is usually accompanied by already decompensated disseminated intravascular coagulation which significantly affects mortality of patients with this disease. The main cause of hypercoagulation state during sepsis seems to be inhibition of fibrinolysis as a result of overproduction of plasminogen activator inhibitor-1 in later stages of the disease. Some microorganisms have specific properties which affect individual components of hemostasis and thus increase their virulence. Because natural inhibitors of coagulation have not only anticoagulation but also strong anti-inflammatory effect, they seem to be an optimum remedy for fluorid coagulopathy during sepsis. Moreover, their use usually does not increase risk of bleeding.
Blood Coagulation↗
Leukemic cells and aberrant phenotypes in acute leukemia patients: a flow cytometry analysis.
The aim of this study was to evaluate the heterogeneity of immunophenotype features in acute leukemia patients and to detect the presence of leukemia-associated immunophenotypes. We prospectively investigated the phenotype of blast cells from 44 adult acute leukemia patients using a large panel of monoclonal antibodies by multiparametric flow cytometry. Thirty-three patients were classified as AML according to the FAB classification. Eleven patients were diagnosed as ALL (10 cases B-ALL, 1 case T-ALL) according to both FAB and immunnophenotyping. We found leukemia-associated phenotypes in 28 of 33 AML patients (84.8%) and in 8 of 11 ALL patients (72.7%). In 61.1% of patients more than one aberrant phenotype was observed. Linear infidelity was the most frequent aberrancy in both AML (64.3%) and ALL (37.5%) subgroups. The present study shows that MFC is a helpful method for sufficient identification of leukemic cells and for determination of blast cells immunophenotype heterogeneity. The double stain flow cytometry in our study revealed aberrant phenotypes in up to 81.8% patients.
Adolescent↗
[Factor V Leiden and the Slovak population].
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.
Activated Protein C Resistance↗
Metabolic syndrome X and fibrinolytic disturbances.
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Diabetes Mellitus, Type 2↗
[A multicompartmental and multifactorial model of production of plasminogen activator inhibitor (PAI-1). II. Clinical study in patients with insulin resistance].
PAI-1 levels are closely associated with insulin resistance (IR) syndrome, including patients with obesity, hypertension, hypertriglyceridaemia and type 2 diabetes mellitus (DM). Clinical studies demonstrated PAI-1 correlations with insulin (IRI), triglycerides (TG) and body mass index (BMI) values, but these relations have not been confirmed in all studies. In obesity PAI-1 levels correlate with IRI and BMI in the relation to increased adipocyte PAI-1 production, which is dependent on stimulative insulin action. In the case of endothelial hyperproduction in patients with IR elevated PAI-1 levels correlate with TG values. Insulin inhibits induced endothelial PAI-1 production. PAI-1 levels in patients with IR represent cumulative production in described tissues.
Adipocytes↗
Plasma levels of TPA, PAI-1 and thrombospondin in patients with systemic vasculitis.
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Adult↗
[Analysis of phenotype resistance to activated protein C (APC resistance)].
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.
Activated Protein C Resistance↗
[Successful treatment of hemothorax with recombinant factor VIIa in a hemophilic child with inhibitor].
rFVIIa is at present the most progressive treatment in different haemorrhages and operations in patients with haemophilia A and a high titre of inhibitor. As apparent from the presented case of a 4-year-old boy with haemorrhage into the pleural cavity, rFVIIa is sufficiently effective to induce haemostasis, while it is safe and has no side-effects. It does not induce systemic activation of haemostasis. Its application requires, due to the high price, that all criteria should be met which were elaborated for the Slovak Republic in the National centre of haemostasis and thrombosis.
Child, Preschool↗
[Tissue plasminogen activator and diabetes mellitus].
tPA has been the independent risk factor of the thrombosis associated with atherosclerosis. There are increased tPA levels in type 1 diabetic patients with vascular complications and tPA is endothelial injury marker in this case. In type 2 diabetes mellitus elevated tPA antigen levels in early disease stage are caused by increased production of complexes with inhibitor (PAI-1) and tPA or fibrinolytic activity has been decreased.
Diabetes Mellitus↗
[A new model of hemostasis].
Haemostasis is a complexly controlled process which takes place in two stages. The first initial stage leads to the formation of a small amount of thrombin. The crucial step of initiation is the bond between the activated factor VIIa and the tissue factor. It is regulated by interaction between factors promoting and inhibiting the process of thrombogenesis. The initiation of haemostasis must be associated with the formation of the thrombus and for effective fibrinogenesis the second stage, amplification of haemostasis, is necessary. A new two-stage model of coagulation imitates the process of haemostasis in vivo as the classical MacFarlan cascade model and makes it possible to explain the pathogenesis of prothrombotic conditions.
Hemostasis↗
[A multicomparmental and multifactorial model of production of plasminogen activator inhibitor (PAI-1). I. Experimental studies].
Hypofibrinolysis caused by increased PAI-1 levels in patients with insulin resistance (IR) is one of the most common acquired prothrombotic states with higher risk of arterial thrombosis associated with atherosclerosis. Increased PAI-1 levels are caused by PAI-1 hyperproduction in various compartments owing to various factors (multicompartmental and multifactorial model). Metabolic compartment, including visceral adipocytes and hepatocytes, is sensitive on stimulative action of insulin, proinsulin and some cytokines. This pool is responsible for elevated PAI-1 levels in obesity. Vascular compartment, including mainly endothelium, is sensitive on thrombin, angiotensin IV, cytokines, biological active lipids and oxidative stress effect, while insulin inhibits cytokine induced PAI-1 production on contrary. This compartment is responsible for elevated PAI-1 levels in patients with type 2 diabetes mellitus and hypertension with endothelial dysfunction. PAI-1 levels in patients with IR represent cumulative production in described compartments.
Adipocytes↗
[Plasminogen activator inhibitor (PAI-1) and diabetes mellitus. II. PAI-1 in insulin resistant conditions].
Insulin resistance (IR) is associated with an elevated PAI-1 level and by correlation with insulin and triacylglycerol (TG) levels. While in IR non-diabetics this relationship is close, in patients with NIDDM the mutual relationship is less marked and there are other factors which raise the PAI-1 levels such as proinsulin, oxidation stress or cytokines. Therefore achievement of satisfactory metabolic control, reduction of insulin and TG levels need not be associated with normalization of PAI-1. As it is an independent risk factor of atherosclerosis, further examinations are necessary in order to differentiate in more detail the possible causes of its rising level in order to obtain a rational basis for effective therapy.
Diabetes Mellitus↗
Endothelial markers in diabetes mellitus.
In this study we examined 22 NIDDM patients without vascular complications and 17 age-matched healthy blood donors. Von Willebrand factor (vWF) levels were significantly increased in NIDDM patients compared to healthy blood donors (1.33 +/- 0.39 vs 1.01 +/- 0.27 IU/ml p = 0.006), while thrombomodulin (TM) levels were similar in the both groups. vWF levels correlated with calcium dependent secretion parameters such as C-peptide (r = 0.680, p < 0.001) and PF4 (r = 0.613, p < 0.01) and did not correlate with calcium-independent markers of endothelial injury such as TM (r = 0.287, p = 0.196) and TFPI (r = 0.296, p = 0.181). Therefore it seems that increased levels of Cai-dependent endothelial and platelet activation markers may precede the signs of endothelial damage. This hypothesis requires further research.
Adult↗
[Treatment of MALT lymphoma of the digestive tract].
Mucosa-associated lymphoid tissue (MALT) is an autonomous part of the immune system with a specific function, histological structure and circulation of cells. As a result of malignant transformation of this tissue maltomas develop, peripheral extranodal non-Hodgkin lymphomas of B-origin more than two-thirds of which are found in the digestive system. The authors investigated in a retrospective study the effectiveness of different types of treatment of maltomas of the digestive tract with a low and high grade of malignity in 16 patients. It appears that splenectomy is not necessary in these patients and that the effectiveness of primary chemotherapy with a view of inducing complete remission of the disease is comparable with surgical treatment and subsequent adjuvant treatment without deterioration of the patient s life by mutilating surgery. An integral part of treatment of gastric maltomas is eradication of infection caused by Helicobacter pylori.
Adult↗
[Heparin cofactor II and thrombophilic conditions].
Heparin co-factor II is in addition to antithrombin III another heparin dependent thrombin inhibitor. This glycoprotein blocks thrombin action not only in haemostasis but also in its other effects. Congenital deficiency of heparin co-factor II was found equally frequently among asymptomatic subjects and patients with thrombotic complications. Although its deficiency probably is not a serious risk factor of thromboembolic disease, it can promote its development in a significant way. The authors describe the case of a child with thrombotic complications and a congenital deficiency of heparin co-factor II.
Child, Preschool↗
[New findings in the diagnosis of minimal residual disease in acute leukemia with emphasis on flow cytometry].
The authors present a review of contemporary findings of investigations of minimal residual disease in patients with acute leukaemia. They present brief information on different monitoring techniques and on their practical application. Attention is paid above all to multiparameter flow cytometry as this method is used in their laboratory work.
Acute Disease↗