MicroRNA and hyperaggregability of platelets in women with sticky platelet syndrome and pregnancy complications.

AIMS: We aimed to characterize relationship between the expression profiles of platelet miR-96, miR-126 and miR-223 and platelet function examination in patients with sticky platelet syndrome (SPS) and in healthy controls. BACKGROUND: MicroRNAs (miRNA, miR) are a group of small and non-coding RNAs involved in many mechanisms as regulators of post-transcriptional protein expression in platelets. SPS is defined as platelet hyperaggregability after administration of low doses of adenosine diphosphate and/or epinephrine. Clear genetic abnormality of this syndrome is not known yet. METHODS: We examined 45 patients with SPS and 30 healthy volunteers. For functional platelet examination we used light transmission aggregometry, and qRT-PCR was used to determine the expression of the miRNAs. RESULTS: We observed no relationship of the platelet miRNA expression with functional platelet examination in the entire cohort of patients with SPS. However, in a group of patients with SPS and pregnancy complications, we found that the expression of platelet miR-96 (p = 0.009) was up-regulated. CONCLUSION: In spite of the multiple limitations of the study, it can be considered that the increased expression of platelet miR-96 found in a group of patients with SPS and pregnancy complications could be related to the hyperaggregability in these selected patients (Tab. 2, Ref. 31).

[Factor V Leiden and the Slovak population]. / Faktor V Leiden a slovenská populace.

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.

[Analysis of phenotype resistance to activated protein C (APC resistance)]. / Analýza fenotypu rezistence na aktivovaný protein C (APC-rezistence).

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.

[Heparin cofactor II and thrombophilic conditions]. / Heparinový kofaktor II a trombofilní stavy.

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.

[Hemostasis in patients with diabetes mellitus. II. Tissue factor and the extrinsic blood coagulation inhibitor]. / Hemostáza u chorých s diabetes mellitus. II. Tkanivový faktor a inhibítor vonkajsieho systému koagulácie.

In the submitted pilot study we examined 37 patients suffering from diabetes mellitus without vascular complications and 15 healthy blood donors. The diabetic patients had not, as compared with the blood donors, significantly elevated values of the tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The TFPI levels correlated with other markers of endothelial dysfunction, in particular thrombomodulin (r = 0.452, p < 0.01) and with triacylglycerol and cholesterol levels. They did not correlate with age, the C-peptide level and BMI.

[Hemostasis in patients with diabetes mellitus. I. Markers of endothelial dysfunction]. / Hemostáza u chorých s diabetes mellitus. I. Markery dysfunkcie endotelu.

In the submitted pilot study the authors examined 47 diabetic patients without vascular complications and 15 healthy blood donors. In an aged-matched sub-group the authors confirmed significantly elevated levels of Willebrand factor (vWF) in patients with non-insulin dependent diabetes mellitus (NIDDM), as compared with healthy blood donors, while the thrombomodulin (TM) levels did not differ significantly. The mutual correlation of parameters with calcium-dependent release (vWF, platelet factor PF4 and C-peptide) was confirmed in the group of patients with NIDDM with normal TM values and in the group of blood donors. These findings could be explained by the hypothesis that raised intracellular calcium levels, described already in early stages of diabetes could in diabetic patients participate also in the activation of haemostasis.

Thrombomodulin and von Willebrand factor in smokers and during smoking.

Circulating thrombomodulin (TM) and von Willebrand factor (vWF) were determined in smokers before and after smoking of two filter cigarettes and in control subjects. The basal levels of TM and vWF were significantly increased in smokers relative to controls (p < 0.001). However, levels of these two factors remained unchanged immediately after smoking of two filter cigarettes, while a statistically significant correlation was observed only between plasma TM and number of years of smoking (p < 0.05).

[Resistance to activated protein C, so-called APC resistance: the first two cases in Slovakia]. / Rezistence na aktivovaný protein C, tzv. APC-rezistence: první dva prípady na Slovensku.

For the anticoagulant action of activated protein C (APC) in addition to protein S another newly detected cofactor is essential. Its deficiency is described as APC-resistance. This defect which is closely associated with the molecule of the factor V seems to be the most frequent cause of thrombophilia. The authors describe two patients where APC-resistance was diagnosed for the first time in Slovakia.

[Elevated levels of plasma von Willebrand factor: a new risk factor for atherosclerosis?]. / Zvýsená hladina von Willebrandovho faktora v plazme: nový rizikový faktor aterosklerózy?

The authors assessed the plasma level of von Willebrand's factor in a total of 104 patients aged 32-60 years. Of these 10 patients are free from confirmed ischaemic heart disease with no history of acute myocardial infarction and 94 patients after acute myocardial infarction. Samplings for von Willebrand's factor in patients after acute myocardial infarction were made at least two months after the infarction. The patients were subjected to: A) ergometric examination, b) to ergometric and coronarographic examination. The patients after acute myocardial infarction with minimal atherosclerotic changes or without atherosclerotic changes on the coronaries had a normal or slightly elevated plasma level of von Willebrand's factor. With the number of coronary arteries affected with atherosclerosis the plasma level of von Willebrand's factor increased. In patients after infarction with evidence of atherosclerotic changes on the coronary arteries without other risk factors the plasma level of von Willebrand's factor was also high. The results stimulate the hypothesis that high plasma levels of von Willebrand's factor could be a risk factor of atherosclerosis.