- Klíčová slova
- Haemate P,
- MeSH
- dospělí MeSH
- krvácení etiologie farmakoterapie MeSH
- kvalita života MeSH
- lidé MeSH
- rekombinantní proteiny * aplikace a dávkování terapeutické užití MeSH
- sekundární prevence MeSH
- von Willebrandova nemoc, typ 3 * diagnóza farmakoterapie genetika klasifikace MeSH
- von Willebrandův faktor analýza terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Background: To evaluate the association between hypertriglyceridemic waist (HTGW), a promising marker of visceral adiposity and cardiovascular (CV) risk, and different indicators of vascular damage in type 2 diabetes (T2D) patients. Methods: This case-control study included 161 patients with T2D (91 males, 70 females) and 40 healthy controls (24 males, 16 females). HTWG was defined as waist circumference >90 cm in men or >85 cm in women and triglyceride concentrations >2 mmol/L. In addition to anthropometric and metabolic parameters, markers of endothelial dysfunction, namely von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1), were assessed. Arterial stiffness parameters were examined using the SphygmoCor system. Results: Individuals with T2D and HTGW showed the highest elevation of PAI-1 levels and significantly increased vWF levels compared with healthy controls. No significant differences in arterial stiffness markers were observed between T2D individuals. Age and, for several markers, systolic and/or diastolic blood pressure were identified as the main predictors for arterial stiffness, whereas PAI-1 and vWF levels were predicted by metabolic parameters. Conclusions: HTGW represents increased CV risk in T2D patients, mainly due to endothelial damage. The presence of HTGW had no significant effect on arterial stiffness compared with other T2D individuals.
- MeSH
- biologické markery krev MeSH
- diabetes mellitus 2. typu * epidemiologie MeSH
- hypertriglyceridemický pas * epidemiologie MeSH
- inhibitor aktivátoru plazminogenu 1 krev MeSH
- kardiovaskulární nemoci * krev diagnóza epidemiologie MeSH
- lidé MeSH
- studie případů a kontrol MeSH
- von Willebrandův faktor analýza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Von Willebrandov faktor (vWF) je multimerický proteín, ktorý plní dve kľúčové funkcie v hemostáze. Podieľa sa na interakcii medzi doštičkami a subendotelom v mieste cievneho poškodenia a interakcii medzi doštičkami navzájom. vWF tvorí komplex s faktorom VIII v pomere (1: 1), čím ho chráni pred proteolýzou aktivovaným proteínom C. vWF je proteín, ktorý je zostavený z identických podjednotiek do lineárnych reťazcov rôznej veľkosti označovaných ako multiméry. Tieto multiméry môžu mať hmotnosť > 20 miliónov daltonov a dĺžku > 2 mikrometre. Klinicky významné a najúčinnejšie pri interakcii s kolagénom a trombocytovými receptormi sú multiméry s vysokou molekulovou hmotnosťou (HMW). V článku uvádzame porovnanie dvoch dostupných metód analýzy multimérov von Willebrandovho faktora - klasickú manuálnu metódu a novú semiautomatickú metódu prístroja Hydrasys. Nová metóda využíva vopred pripravený 2% agarózový gél, výsledky sú dostupné do 6 h, metóda je štandardizovaná a reprodukovateľná. Avšak abnormality multimérov sa musia ďalej podrobnejšie skúmať pomocou klasickej - manuálnej metódy s rôznymi koncentráciami agarózových gélov.
Von Willebrand factor (vWF) is a multimeric protein that plays a principal role in two key functions in hemostasis. It participates in the interaction between the platelets and the subendothelium at the site of the vascular damage and if is also important in the interaction between the platelets. vWF is complexed with factor VIII (1: 1) to protect it from proteolysis by activated Protein C. vWF is a protein that is assembled from identical subunits into linear strings of varying size referred to as multimers. These multimers can be > 20 million daltons in mass and > 2 micrometers in length. Clinically significant and most effective in interacting with collagen and thrombocyte receptors are high molecular weight multimers. In our article we present comparing of two available methods of von Willebrand factor multimer analysis - the classical manual method and the new semi-automatic method of the Hydrasys instrument. The new method uses a prepared 2% agarose gel, the results are available within 6 h, the method is standardized and reproducible. However, abnormalities of multimers must be further investigated in more detail using the classical-manual method with different concentrations of agarose gels.
Von Willebrand disease is a commonly inherited bleeding disorder caused by defects of von Willebrand factor (vWF). In the most common valve diseases, aortic valve stenosis (AVS) and mitral valve regurgitation (MVR), a bleeding tendency has been described in a number of patients. This has been associated to a high turbulence of blood flow through the compromised valve, promoting degradation of vWF with loss of high-molecular-weight multimers of vWF (HMWM), leading to an acquired von Willebrand syndrome (AvWS). We analysed three groups of patients, one affected by AVS, treated with transcatheter aortic valve implantation (TAVI), the second group of patients affected by MVR, treated with Mitraclip® mitral valve repair. The third group was represented by patients also affected by AVS, but not eligible for TAVI and treated with standard surgery. A fourth group of patients that underwent percutaneous coronary intervention (PCI) with stenting was used as a control. Our results demonstrated that the level of vWF measured as antigen concentration (vWF:Ag) increases in all cohorts of patients after treatment, while in control PCI patients, no modification of vWF:Ag has been registered. Western blot analysis showed only a quantitative loss of vWF in the pre-treatment time, but without significant HMWM modification. The monitoring of the vWF:Ag concentration, but not the quality of HMWM, can indicate the status of blood flow in the treated patients, thus introducing the possibility of using the vWF antigen detection in monitoring the status of replaced or repaired valves.
- MeSH
- aortální stenóza krev diagnóza MeSH
- koronární angioplastika MeSH
- krevní plazma MeSH
- lidé MeSH
- mitrální insuficience krev diagnóza MeSH
- transkatetrální implantace aortální chlopně MeSH
- von Willebrandova nemoc MeSH
- von Willebrandův faktor analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of von Willebrand factor (VWF). The heterogeneity of laboratory phenotyping makes diagnosing difficult. OBJECTIVE: A cross-sectional, family-based VWD study in a collaboration between University Hospital Brno (Czech Republic) and Antwerp University Hospital (Belgium) to improve the understanding of laboratory phenotype/genotype correlation. PATIENTS AND METHODS: A total of 205 patients with suspected VWD were identified from historical records. Complete laboratory analysis was established using all available VWD assays including VWF multimers and genetic analysis. RESULTS: Based on the current International Society of Thrombosis and Haemostasis (ISTH) - Scientific and Standardization Committee VWD classification and type 2A sub-division into 2A/IIA, IID, IIC and IIE, the majority was characterized as a type 1 VWD, followed by type 2. Proposed laboratory phenotypes were confirmed by their multimeric pattern within 98% of this cohort. All type 2, 3 and 75% of type 1 VWD patients were confirmed by underlying causative mutations. Forty-six different causal mutations (117 not previously described in the literature) could be identified. Fifty per cent of all cases was represented by eight individual mutations, mainly p.Pro812ArgfsX31. Thirteen patients had a large heterozygous gene alteration. CONCLUSION: Although an extensive panel of tests was used, VWD classification and (sub)typing remains difficult and fluid. This study provides a cross-sectional overview of the VWD population in the Czech Republic and provides important data to the ISTH/European Association for Haemophilia and Allied Disorders VWD mutation database in linking causal mutations with unique VWD (sub)types. It also identifies new, as not previously described in the literature, causal mutations.
- MeSH
- dítě MeSH
- doba krvácení MeSH
- dospělí MeSH
- fenotyp MeSH
- heterozygot MeSH
- klinické laboratorní techniky normy MeSH
- kojenec MeSH
- krvácení genetika MeSH
- lidé MeSH
- mezinárodní spolupráce MeSH
- mladiství MeSH
- mladý dospělý MeSH
- multimerizace proteinu MeSH
- mutace MeSH
- novorozenec MeSH
- odběr biologického vzorku MeSH
- předškolní dítě MeSH
- průřezové studie MeSH
- von Willebrandova nemoc krev diagnóza epidemiologie MeSH
- von Willebrandův faktor analýza genetika MeSH
- vyšetření krevní srážlivosti MeSH
- zdraví rodiny MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Belgie MeSH
- Česká republika MeSH
- Klíčová slova
- Haemate P,
- MeSH
- desmopresin aplikace a dávkování MeSH
- diferenciální diagnóza MeSH
- faktor VIII aplikace a dávkování MeSH
- fixní kombinace léků MeSH
- krvácení diagnóza etiologie farmakoterapie prevence a kontrola MeSH
- lidé MeSH
- von Willebrandova nemoc * diagnóza epidemiologie etiologie farmakoterapie MeSH
- von Willebrandův faktor analýza genetika terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- faktor VIIIa aplikace a dávkování MeSH
- imunosupresiva terapeutické užití MeSH
- intravenózní imunoglobuliny aplikace a dávkování MeSH
- krvácení při operaci patofyziologie prevence a kontrola MeSH
- krvácení diagnóza etiologie farmakoterapie imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální gamapatie nejasného významu diagnóza imunologie komplikace MeSH
- rekombinantní fúzní proteiny terapeutické užití MeSH
- von Willebrandova nemoc * diagnóza etiologie farmakoterapie imunologie MeSH
- von Willebrandův faktor analýza účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The European Clinical Laboratory and Molecular (ECLM) classification of von Willebrand disease (vWD) is based on the splitting approach which uses sensitive and specific von Willebrand factor (vWF) assays with regard to the updated molecular data on structure and function of vWF gene and protein defects. A complete set of FVIII:C and vWF ristocetine cofactor, collagen binding, and antigen, vWF multimeric analysis in low- and medium-resolution gels, and responses to desmopressin (DDAVP) of FVIII:C and vWF parameters are mandatory. The ECLM classification distinguishes recessive types 1 and 3 vWD from recessive vWD 2C due to mutations in the D1 and D2 domains and vWD 2N due to mutations in the D'-FVIII-binding domain of vWF. The ECLM classification differentiates between mild vWD type 1 with variable penetrance of bleedings from symptomatic dominant type 1 vWD secretion defect and/or clearance defect with normal vWF multimers versus vWD 1M and 2M with normal or smeary vWF multimers in low- and medium-resolution gels. High-quality multimeric analysis of vWF in medium-resolution gels based on a DDAVP challenge test clearly delineates and distinguishes each of the dominant type 2 vWDs 1/2E, 2M, 2B, 2A, and 2D caused by vWF gene mutations in the D3 multimerization domain, loss or gain-of-function mutations in the glycoprotein Ib receptor A1 domain, gene mutations in the A2 proteolytic domain, and the C-terminal dimerization domain, respectively.
- MeSH
- desmopresin farmakologie MeSH
- diferenciální diagnóza * MeSH
- lidé MeSH
- multimerizace proteinu MeSH
- mutace MeSH
- von Willebrandova nemoc, typ 1 diagnóza MeSH
- von Willebrandova nemoc, typ 2 diagnóza MeSH
- von Willebrandův faktor analýza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- imunoglobulin G farmakologie terapeutické užití MeSH
- klinické laboratorní techniky MeSH
- kongresy jako téma MeSH
- lidé MeSH
- von Willebrandova nemoc * diagnóza terapie MeSH
- von Willebrandův faktor analýza MeSH
- vyšetření krevní srážlivosti MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- novinové články MeSH
- zprávy MeSH
