IntroductionStudy aimed to determine the occurrence of 5 thrombosis-related single-nucleotide polymorphisms (SNPs) in patients with venous thromboembolism (VTE) (n = 2630) and a control group (n = 2637) in the Czech population.MethodsThe following gene SNPs were detected in both groups: F5 Leiden (rs6025), F2 (rs1799963), FGG, fibrinogen gamma' (rs2066865), F11 (rs2289252) and ABO (rs8176719). Statistical analysis was performed using SAS statistical software with population genetics tools.ResultsHeterozygotes for F5 Leiden were associated with a 5.58-fold and homozygotes F5 Leiden with a 33.46-fold increased risk of VTE. At SNP rs1799963 (F2, prothrombin), only heterozygotes had a significant 3.9-fold increased risk of VTE. The findings at SNP rs2066865 (fibrinogen gamma', FGG) showed a 1.37-fold increased risk of VTE for FGG heterozygotes and a 1.77-fold increased risk of VTE for FGG homozygotes. There is also a significant 1.42-fold increase risk of VTE in the heterozygotes and a 1.80-fold increase risk of VTE in the homozygotes of the SNP rs 2289252 (F11). Further higher increases in the risk of VTE in both variants were found in patients with VTE at rs8176719 (ABO, non-O). It corresponds to a 2.2-fold increase in the risk of VTE in heterozygotes and a 3.5-fold increase in the risk of VTE in homozygotes.ConclusionBesides F5 Leiden and prothrombin mutation, the study suggests that the gene polymorphisms of FGG (rs2066865), F11 (rs2289252) and ABO (rs8176719) play a role as an independent heritable risk factor for VTE in the Czech population.
- MeSH
- ABO systém krevních skupin genetika MeSH
- dospělí MeSH
- faktor V * genetika MeSH
- fibrinogen * genetika MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- prevalence MeSH
- protrombin genetika MeSH
- senioři MeSH
- žilní tromboembolie * genetika epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) and venous thromboembolism (VTE) are thought to share many common risk factors. Our study aimed to determine the frequencies of 5 thrombosis-related gene single nucleotide polymorphisms (SNPs) associated with VTE in patients with CTEPH (n 129) compared with a control group of healthy individuals without a history of VTE (n 2637). METHODS: The SNPs of the following genes were investigated: F5 (F V Leiden, rs6025), F2 prothrombin (rs1799963), fibrinogen gamma (FGG, rs2066865), F11 (rs2289252) and ABO (non-O, rs8176719) in both groups. RESULTS: The study found that the rs1799963 variant was more common in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to the control group (p < .0001). The GA heterozygous variant showed a significant increase with an odds ratio (OR) of 4.480 (95% CI: 2.344-8.562) or a finding by maximum likelihood analysis (MLA) with p < .0001. Additionally, there was a notable increase in the rs8176719 variant with p < .0001 in CTEPH patients. Both the homozygous G/G variant and the heterozygous -/G variant also showed an increase, with OR of 4.2317 (95% CI: 2.45571-7.2919) and 2.4324 (95% CI: 1.46435-4.0403) respectively, or MLA (p < .0001 and p .0006). The study also revealed a higher prevalence of the heterozygous C/T variant of rs2289252 in CTEPH patients, with an OR of 1.5543 (95% CI: 1.02503-2.3568) or MLA (p .0379). CONCLUSION: The study suggests that the observed gene polymorphisms F2 (rs1799963), ABO (rs8176719), and F11 (rs2289252) may play a role as independent heritable risk factors in the development of CTEPH.
- MeSH
- ABO systém krevních skupin genetika MeSH
- chronická nemoc MeSH
- dospělí MeSH
- faktor V genetika MeSH
- fibrinogen genetika MeSH
- incidence MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní embolie genetika MeSH
- plicní hypertenze * genetika MeSH
- protrombin genetika MeSH
- senioři MeSH
- trombofilie genetika MeSH
- žilní tromboembolie genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and MK-7 concentrations (LC-MS/MS) in 63 pancreatic insufficient and modulator naïve CF patients, and compared to 61 healthy subjects (HS). Vitamin K1 levels did not differ between studied groups. MK-4 concentrations were higher (median <1st-3rd quartile>: 0.778 <0.589-1.086> vs. 0.349 <0.256-0.469>, p < 0.0001) and MK-7 levels lower (0.150 <0.094-0.259> vs. 0.231 <0.191-0.315>, p = 0.0007) in CF patients than in HS. MK-7 concentrations were higher in CF patients receiving K1 and MK-7 supplementation than in those receiving vitamin K1 alone or no supplementation. Moreover, vitamin K1 concentrations depended on the supplementation regime. Based on multivariate logistic regression analysis, we have found that MK-7 supplementation dose has been the only predictive factor for MK-7 levels. In conclusion, vitamin K1 levels in CF are low if not currently supplemented. MK-4 concentrations in CF patients supplemented with large doses of vitamin K1 are higher than in HS. MK-7 levels in CF subjects not receiving MK-7 supplementation, with no regard to vitamin K1 supplementation, are low. There do not seem to be any good clinical predictive factors for vitamin K status.
- MeSH
- cystická fibróza * krev MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nedostatek vitaminu K krev MeSH
- nutriční stav MeSH
- potravní doplňky MeSH
- protrombin * analýza MeSH
- průřezové studie MeSH
- vitamin K 1 * aplikace a dávkování krev MeSH
- vitamin K 2 * krev analogy a deriváty MeSH
- vitamin K krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Život ohrožující krvácení je jedním z nejzávažnějších akutních stavů v medicíně. Tato situace vyžaduje multimodální terapii, jejíž nedílnou součástí je i podávání transfuzních přípravků a krevních derivátů, které bývá standardizováno pomocí doporučených postupů. Pro Českou republiku a Slovensko je v současnosti platný dokument „Diagnostika a léčba život ohrožujícího krvácení u dospělých pacientů v intenzivní a perioperační péči. Česko-slovenský mezioborový doporučený postup“ z roku 2017. V roce 2023 byl publikován update obou evropských doporučení, ze kterých zmíněný mezioborový postup majoritně vychází. Cílem této práce je identifikovat a představit změny v evropských doporučených postupech pro život ohrožující krvácení, které se objevily od roku 2017. Celkem jsou zahrnuty 4 texty, jejichž analýza je rozčleněna dle jednotlivých transfuzních přípravků a krevních derivátů. Samotný text práce nabízí kromě představení nových evropských doporučených postupů pro léčbu život ohrožujícího krvácení také jejich srovnání s česko-slovenským postupem z roku 2017.
Major bleeding is one of the most serious emergencies in medicine. This situation requires a complex therapeutic approach, including standardised administering transfusion products and blood derivatives. In the Czech Republic and Slovakia, the document “Diagnosis and Treatment of Life-Threatening Bleeding in Adult Patients in Intensive and Perioperative Care. Czech-Slovak Interdisciplinary Guideline” from 2017 remains valid. In 2023, an update of both European guidelines, from which the mentioned interdisciplinary procedure predominantly derives, was published. This work aims to identify and present changes in the European guidelines for severe bleeding since 2017. A total of 4 texts are included. Their analysis was divided according to individual transfusion products and blood derivatives. This work not only presents the new European guidelines for treating severe bleeding, but also compares these with the Czech-Slovak guideline from 2017.
- MeSH
- antifibrinolytika farmakologie terapeutické užití MeSH
- faktor VIII farmakologie terapeutické užití MeSH
- fibrinogen farmakologie terapeutické užití MeSH
- krevní plazma MeSH
- krevní transfuze metody MeSH
- krvácení * terapie MeSH
- lidé MeSH
- protrombin farmakologie terapeutické užití MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- transfuze erytrocytů metody MeSH
- transfuze trombocytů metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.
- MeSH
- antifosfolipidové protilátky MeSH
- antifosfolipidový syndrom * komplikace MeSH
- antikardiolipinové protilátky MeSH
- beta-2-glykoprotein I MeSH
- fosfatidylseriny MeSH
- lidé MeSH
- protein C MeSH
- protrombin MeSH
- těhotenství MeSH
- trombin MeSH
- trombóza * etiologie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
High incidence of thrombosis and venous thromboembolism was reported in patients with COVID-19. In this study, we focused on analysis of thrombophilic mutations performed without a standard DNA extraction step. In one hundred of COVID-19 positive outpatients, real-time PCR for Leiden mutation in the FV gene and G20210A mutation in the FII gene was carried out from DNA extracts and modified whole blood samples, and their cycle threshold (Ct) values were evaluated. In the extracts, healthy homozygotes (wt/wt), heterozygotes (M/wt), and homozygous carriers of Leiden mutation (M/M) provided median Ct values of 18.5, 19.4/22.0, and 20.9. In the whole blood, Ct values were 25.3 (wt/wt), 24.8/27.2 (M/wt), and 26.9 (M/M). Median Ct values for G20210A in the extracts were 19.6 for homozygotes (wt/wt), and 19.7/20.4 for heterozygous carriers. The whole blood samples provided Ct values of 23.9 in healthy homozygotes and 26.3/27.2 in heterozygotes for G20210A mutation. No homozygous subjects for G20210A and no double heterozygotes (for Leiden and G20210A mutations) were found. Despite significant differences in the Ct values, genotyping showed complete result concordance of the DNA extracts and the whole blood samples. The integrity and amplificability of DNA molecules in the whole blood samples during 28 days of deep freezing, interrupted by four cycles of thawing, did not significantly change. In conclusion, we demonstrated a new protocol for the detection of the thrombophilic mutations via real time PCR on the modified whole blood of COVID-19 positive patients. The blood modification was reliable, easy, cheap, and saving costs and turnaround time of the whole laboratory process.
- MeSH
- COVID-19 * diagnóza genetika MeSH
- DNA MeSH
- faktor V genetika MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- mutace MeSH
- protrombin genetika MeSH
- rizikové faktory MeSH
- SARS-CoV-2 genetika MeSH
- testování na COVID-19 MeSH
- trombofilie * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Inherited thrombophilias represent a concerning risk factor due to a proclivity to an aberrant clot formation. However, in patients with left ventricular assist device (LVAD), their impact on bleeding and thrombotic complications remains still poorly understood. The aim of the present study was to evaluate the effect of thrombophilic mutation directed anticoagulation therapy on adverse clinical outcomes in LVAD patients. MATERIALS AND METHODS: About 138 consecutive patients indicated for LVAD implant (HeartMate II, Abbott, Plymouth, USA) were prospectively screened for three major thrombophilic mutations: factor II (prothrombin), factor V Leiden, and homozygous methylenetetrahydrofolate reductase (MTHFR). Subsequently, discordant individualized anticoagulation targets of INR 2.5-3.0 in thrombophilia positive and INR 1.8-2.2 in negative patients were established; notably without anti-platelet agents given the center standard of care. RESULTS: Mean age was 50 ± 12.7 years, 83% male. Mean duration of support was 464.5 days (SD 482.9; SEM 41.1) and median of 310 days (IQR 162; 546). Full thrombophilia positive cohort analysis has not revealed any significant impact on event free survival. In contrast, detailed analysis of specific thrombophilias subsets has revealed Factor II prothrombin mutation as a significant predisposition for the pump thrombosis risk (SHR 10.48; p = 0.001) despite more aggressive prespecified anticoagulation target. Moreover, the incidence of bleeding events in prothrombin group was also significantly increased (SHR 6.0; p = 0.03). CONCLUSIONS: Our observations suggest that specific thrombophilias in LVAD patients may pose different intensity predisposition for thrombotic complications. Factor II (prothrombin) positive mutation was identified as significant risk factor associated with the pump thrombosis.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- podpůrné srdeční systémy * škodlivé účinky MeSH
- prospektivní studie MeSH
- protrombin MeSH
- trombofilie * diagnóza genetika MeSH
- trombóza * genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- Protromboplex, NovoSeven,
- MeSH
- antikoagulancia terapeutické užití MeSH
- diseminovaná intravaskulární koagulace * etiologie farmakoterapie krev patofyziologie MeSH
- faktor VIIa terapeutické užití MeSH
- komplikace porodu MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- plazma bohatá na destičky MeSH
- protrombin terapeutické užití MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
Idarucizumab, monoklonální protilátka fungující jako antidotum dabigatranu, vykazuje jednu značnou výhodu. Podání idarucizumabu není totiž časově omezené. Jeho účinku v zastavení krvácení může být tedy využito i později v terapeutickém procesu. A to i po několika dnech od příjmu pacienta, po získání validních anamnestických informací, kterých nebylo možné na akutním interním příjmu dosáhnout.
Idarucizumab, a monoclonal antibody designed for the reversal of anticoagulant effects of dabigatran, has one considerable advantage. Idarucizumab can be administered to patients without time limits. therefore this therapy can be used for successful cessation of bleeding even later when we realize taking medical history, especially medication history, was inaccurate.
- Klíčová slova
- idarucizumab,
- MeSH
- akutní poškození ledvin komplikace MeSH
- anemie chemicky indukované MeSH
- angiodysplazie diagnostické zobrazování patologie MeSH
- antidota terapeutické užití MeSH
- antikoagulancia aplikace a dávkování škodlivé účinky MeSH
- aplikace orální MeSH
- dabigatran aplikace a dávkování krev škodlivé účinky MeSH
- endoskopie MeSH
- hemoglobiny analýza MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- INR MeSH
- komorbidita MeSH
- krvácení diagnostické zobrazování farmakoterapie MeSH
- lidé MeSH
- protrombin terapeutické užití MeSH
- senioři MeSH
- warfarin aplikace a dávkování škodlivé účinky MeSH
- žaludek diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
NOAC (Non-vitamin K Oral Anticoagulants) jsou v současné době stále častěji užívané preparáty k prevenci a léčbě tromboembolie. Jejich obliba spočívá v praktickém perorálním podání, bez nutnosti monitorovat jejich efekt. V naší kazuistice popisujeme případ 81letého muže s paroxysmální fibrilací síní léčeného dabigatranem, u kterého došlo ke kumulaci léčiva a rozvoje život ohrožujícího krvácení do trávicího traktu. Uvedený pacient byl námi léčen nejprve pomocí koncentrátu protrombinového komplexu a poté selektivním antagonistou dabigatranu idarucizumabem. Hlavní poučení z kazuistiky je existence fenoménu návratu antikoagulační aktivity kumulovaného NOAC po odeznění účinku antagonisty.
NOAC (Non-Vitamin K Oral Anticoagulants) are currently increasingly used for treatment of thromboembolism. The main reason for their popularity is the possibility of oral application without the need to monitor their effect. In our report we describe the case of an 81-year-old man with paroxysmal atrial fibrillation treated with dabigatran, which accumulated in the patient, resulting in a life-threatening gastrointestinal bleeding. The patient was first treated with a prothrombin complex concentrate and then the selective dabigatran antagonist idarucizumab. An important finding from the case report was the existence of rebound phenomenon of returning anticoagulant activity of NOAC after application of idarucizumab due to accumulation of the dabigatran.
- Klíčová slova
- idarucizumab,
- MeSH
- antidota aplikace a dávkování terapeutické užití MeSH
- antifibrinolytika MeSH
- antikoagulancia MeSH
- antitrombiny MeSH
- dabigatran * aplikace a dávkování terapeutické užití MeSH
- fatální výsledek MeSH
- fibrilace síní farmakoterapie MeSH
- gastrointestinální krvácení MeSH
- humanizované monoklonální protilátky MeSH
- koagulancia MeSH
- krvácení * diagnóza etiologie farmakoterapie MeSH
- lidé MeSH
- meléna MeSH
- multiorgánové selhání MeSH
- protrombin aplikace a dávkování terapeutické užití MeSH
- renální insuficience MeSH
- senioři nad 80 let MeSH
- ventilátorová pneumonie MeSH
- vitamin K aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
