The abnormalities in blood coagulation in patients with diabetes can lead to a prothrombotic state and requirement for the administration of direct anticoagulants. However, no comparative studies have been conducted on the effects of different direct anticoagulants. A head-to-head investigation of the impact of anticoagulants in 50 patients of type 1 diabetes mellitus (DMT1) was performed, and the data were compared to 50 generally healthy individuals. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured in plasma treated with vehicle, heparin, or four direct anticoagulants at 1 μM. In addition to common biochemical parameters, novel inflammatory markers (neopterin, kynurenine/tryptophan ratio) and major vitamin K forms were measured. Heparin and dabigatran treatments resulted in prolonged coagulation in DMT1 patients compared to healthy individuals in both tests (both p < 0.001). The same phenomenon was observed for rivaroxaban and apixaban-treated samples in PT (p < 0.001). Interestingly, healthy volunteers had higher total vitamin K levels than DMT1. Further analysis suggested that observed coagulation differences were not caused by differences in glycemia but were rather associated with an unexpected, better lipid profile of our DMT1 group. There were also correlations between prolongation of coagulation brought about by the most active anticoagulants and inflammatory markers, and hence inflammatory state probably also contributed to the differences, as well as the mentioned differences in vitamin K levels. Conclusively, this paper suggests the suitability for controlling the effects of direct anticoagulants in DMT1 patients.

• MeSH
• antikoagulancia * farmakologie   terapeutické užití   MeSH
• dabigatran farmakologie   MeSH
• diabetes mellitus 1. typu * krev   farmakoterapie   MeSH
• dospělí MeSH
• hemokoagulace účinky léků   MeSH
• heparin farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• parciální tromboplastinový čas MeSH
• protrombinový čas MeSH
• rivaroxaban farmakologie   MeSH
• studie případů a kontrol MeSH
• vitamin K * krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Familial hypercholesterolemia (FH) is a relatively rare genetic disease associated with high serum cholesterol levels but also with abnormalities in blood coagulation. Novel pharmacotherapeutic approaches in FH including proprotein convertase subtilisin/kexin type 9 antibodies (PCSK9Ab) are very efficient in decreasing cholesterol levels but their impact on coagulation in FH is not yet established. Therefore, we hypothesized that these novel antidyslipidemic drugs can positively impact blood coagulation due to their more potent effect on cholesterol. A total of 15 healthy volunteers and all 15 available patients with severe FH treated at the University Hospital Hradec Králové were enrolled, coagulation was assessed by mechanic coagulometer, and the impact of four clinically used direct anticoagulants was analyzed ex vivo. FH patients were treated effectively as their total cholesterol was 4.11 ± 1.57 mM and LDL cholesterol was 2.44 ± 1.46 mM, which were even lower values than detected in our generally healthy controls. Twelve from the 15 FH patients were finally analyzed as 3 were treated with anticoagulants. Coagulation in FH patients was prolonged more extensively by dabigatran and rivaroxaban, when compared to healthy controls. Treatment with PCSK9Ab or lipid apheresis did not seem to have a significant effect on coagulation. The latter procedure however significantly decreased serum levels of one vitamin K form, MK4. Shorter coagulation time was associated with higher levels of LDL, non-HDL, and total cholesterol. Current treatment of FH seems to improve the effects of direct anticoagulants beyond known effects on LDL cholesterol levels.

• MeSH
• anticholesteremika terapeutické užití   MeSH
• antikoagulancia * terapeutické užití   farmakologie   MeSH
• cholesterol krev   MeSH
• dabigatran terapeutické užití   farmakologie   MeSH
• dospělí MeSH
• hemokoagulace * účinky léků   MeSH
• hyperlipoproteinemie typ II * krev   farmakoterapie   MeSH
• hypolipidemika * terapeutické užití   farmakologie   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• PCSK9 inhibitory MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• rivaroxaban terapeutické užití   farmakologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Ischemic stroke is a common and serious condition. Timely restoration of cerebral perfusion is crucial for improving patient outcomes and reducing economic impacts. For three decades, alteplase has been the only established pharmacological treatment, often combined with endovascular therapy. Tenecteplase, a newer generation of fibrinolytic therapy, is recommended by the ESO 2023 guidelines as a suitable alternative to alteplase, particularly if treatment is initiated within 4.5 hours of symptom onset. Tenecteplase offers higher fibrin specificity, lower binding to PAI-1, and a longer plasma half-life compared to alteplase, allowing for single bolus administration. Clinical studies have shown that tenecteplase 0.25 mg/kg achieves better recanalization and clinical improvement without increased risk of bleeding. It is equally effective and safe as alteplase, with meta-analyses indicating improved recanalization and clinical outcomes at a lower risk of bleeding. Tenecteplase is a suitable alternative for treating iNCMP, especially within 4.5 hours of symptom onset. Its single bolus administration simplifies hospital management and improves the logistics of transporting patients to specialized centers.

• MeSH
• fibrinolýza účinky léků   MeSH
• ischemická cévní mozková příhoda * diagnóza   farmakoterapie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• reperfuze klasifikace   metody   MeSH
• tenektepláza * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• tkáňový aktivátor plazminogenu farmakologie   terapeutické užití   MeSH
• trombolytická terapie klasifikace   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

An imbalance in coagulation is associated with cardiovascular events. For prevention and treatment, anticoagulants, currently mainly xabans and gatrans, are used. The purpose of the present study was to provide a head-to-head comparison since there are no studies directly evaluating these novel anticoagulants. An additional aim was to find whether selected anthropological and biochemical factors can affect their anticoagulant properties as they are used in fixed doses. In this cross-sectional study, blood from 50 generally healthy donors was collected, and coagulation responses to dabigatran, argatroban, rivaroxaban, and apixaban, at a concentration of 1 μM, were analyzed. Heparin was used as a positive control. Prothrombin time (PT) expressed as international normalized ratio (INR) and activated partial thromboplastin time (aPTT) were measured and compared. Rivaroxaban was the most active according to PT/INR while argatroban according to aPTT. The ex vivo anticoagulant effect measured by INR correlated inversely with body mass index (BMI) in all four anticoagulants tested. Shortening of aPTT was associated with higher cholesterol and triglyceride levels. No sex-related differences were observed in response to the anticoagulant treatments. As this was an ex vivo study and pharmacokinetic factors were not included, the influence of BMI is of high therapeutic importance.

• MeSH
• antikoagulancia * farmakologie   MeSH
• arginin * analogy a deriváty   MeSH
• dabigatran farmakologie   MeSH
• dospělí MeSH
• hemokoagulace * účinky léků   MeSH
• index tělesné hmotnosti MeSH
• INR MeSH
• kyseliny pipekolové * farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• parciální tromboplastinový čas MeSH
• protrombinový čas MeSH
• průřezové studie MeSH
• pyrazoly farmakologie   MeSH
• pyridony farmakologie   farmakokinetika   MeSH
• rivaroxaban * farmakologie   MeSH
• sulfonamidy farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using o-cresolphthalein complexone (o-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by o-CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure-activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.

• MeSH
• agregace trombocytů účinky léků   MeSH
• chelátory * chemie   MeSH
• hořčík * chemie   MeSH
• lidé MeSH
• preklinické hodnocení léčiv metody   MeSH
• trombocyty účinky léků   metabolismus   MeSH
• vápník * analýza   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Prevence a léčba krvácení nebo trombózy je u pacientů s jaterní cirhózou spojena s řadou úskalí, zažitých představ a zavedených stereotypů. V odborné veřejnosti přetrvává falešné paradigma, že změny hemostázy provázející jaterní cirhózu mají apriori krvácivý charakter. Ve skutečnosti se spolu s jaterním onemocněním vyvíjí nová hemostatická rovnováha. Problém je, že je křehká a snadno se vlivem vnitřních pohnutek nebo vnějších zásahů bortí. Výsledkem může být krvácení stejně jako trombóza. K těmto neblahým důsledkům mohou přispět i neadekvátní lékařské intervence vedené ve snaze upravit patologické výsledky koagulačních testů nebo trombocytopenii. Předložené doporučení pro klinickou praxi bylo vypracováno s cílem poskytnout praktické pokyny pro interpretaci výsledků laboratorních vyšetření hemostázy a počtu destiček, resp. shrnout současné názory na hemostázu u jaterní cirhózy, pravidla úpravy trombocytopenie a změn v koagulačním systému před invazivními výkony a pravidla tromboprofylaxe u hospitalizovaných pacientů. Hlavním východiskem je doporučení Evropské asociace pro studium jater „Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis“.

Prevention and treatment of bleeding or thrombosis in patients with liver cirrhosis is associated with a number of pitfalls, perceived ideas and established stereotypes. A false paradigm persists in the professional community that changes in haemostasis accompanying liver cirrhosis are a priori bleeding. In fact, a new haemostatic balance develops along with liver disease. The problem is that it is fragile and easily disrupted by internal drives or external interventions. The result can be bleeding as well as thrombosis. Inadequate medical interventions conducted in an attempt to correct pathological coagulation abnormalities or thrombocytopenia may contribute to these unfortunate consequences. The present guideline for clinical practice was developed to provide practical guidelines for the interpretation of the results of laboratory tests of haemostasis and platelet count, to summarize current views on haemostasis in liver cirrhosis, rules for the correction of thrombocytopenia and changes in the coagulation system before invasive procedures as well as rules for thromboprophylaxis in hospitalized patients. The main starting point is the recommendation of the European Association for the Study of the Live "Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis".

• MeSH
• hemostáza * účinky léků   MeSH
• hodnocení rizik metody   MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• jaterní cirhóza * komplikace   MeSH
• krvácení při operaci * ošetřování   prevence a kontrola   MeSH
• lidé MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• trombocytopenie etiologie   terapie   MeSH
• trombotická příhoda farmakoterapie   MeSH
• vyšetření krevní srážlivosti metody   MeSH
• Check Tag
• lidé MeSH

• MeSH
• agregace trombocytů účinky léků   MeSH
• antiflogistika nesteroidní MeSH
• Aspirin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lékové interakce * MeSH
• lékové postižení jater MeSH
• lidé MeSH
• metamizol * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: The pathology of primary hemostasis is a common complication of extracorporeal membrane oxygenation (ECMO) support. Scientific data describing its changes in patients on short-term ECMO support and the ability and speed of the restoration of its functions are limited. AIMS: The aim of this study was to describe the pathology of primary hemostasis induced by short-term ECMO support and its development over time using PFA-200, ROTEM platelet, and von Willebrand factor (vWF) analyses. METHODS: In patients undergoing lung transplantation surgery using intraoperative veno-arterial ECMO support, blood samples were analyzed using the following tests: PFA-200, ROTEM platelet tests, vWF antigen, ristocetin cofactor (RCo), and collagen-binding protein (CB) before, during, and after ECMO support. RESULTS: Blood samples from 32 patients were analyzed. All 3 PFA-200 tests (COL/EPI, COL/ADP, and COL/P2Y) showed significant deterioration during ECMO support with rapid restoration after ECMO cessation (p < 0.05), suggesting an ECMO-induced primary hemostasis disorder. A significant increase of vWF antigen after ECMO cessation (p < 0.05) was found with an increase of RCo and CB levels, although it was not significant (p > 0.05). CONCLUSIONS: Short-term ECMO support induces primary hemostasis pathology. It occurs immediately after initiation but is rapidly restored after ECMO cessation, which is detectable by PFA-200. Despite there being persistent platelet dysfunction after ECMO cessation, as seen with the ROTEM platelet results, the increased levels of vWF antigen might explain the normal results of primary hemostasis detected by PFA-200.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• hemostáza * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * metody   MeSH
• transplantace plic * MeSH
• von Willebrandův faktor metabolismus   analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile. TREATMENT GOALS: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care. These outcomes also do not address the complexity of health-related quality of life impacted by haemophilia and its treatment. CONCLUSION: Capitalizing on the major potential of therapeutic innovations, 'Normalization' of haemostasis, as a concept, should include the aspiration of enabling individuals to live as normal a life as possible, free from haemophilia-imposed limitations. To achieve this-being supported by the data reviewed in this manuscript-the concept of haemostatic and life Normalization needs to be explored and debated within the wider multidisciplinary teams and haemophilia community.

• MeSH
• cíle MeSH
• hemofilie A * farmakoterapie   terapie   MeSH
• hemostáza * účinky léků   MeSH
• kvalita života MeSH
• lidé MeSH
• rovnost ve zdraví * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Moderní medicína klade velký důraz nejen na účinnost, ale zejména na bezpečnost léčby. Společným nedostatkem antikoagulancií blokujících společnou cestu koagulační kaskády (inhibitorů trombinu, inhibitorů faktoru Xa či antivitaminů K) je zvýšené riziko klinicky významného krvácení. Přichází nová strategie zaměřená na inhibici vnitřní cesty koagulační kaskády, konkrétně na inhibici syntézy či blokádu funkce faktoru XI/XIa. Tato cesta je slibná, neboť k nejčastějším indikacím antikoagulancií patří aktivace hemostázy kontaktem (navozená např. polyfosfáty na povrchu aktivovaných trombocytů či kontaktem s negativním elektrostatickým povrchem) či reparačně-zánětlivými pochody (zejm. vlákny extracelulárně uvolněné DNA z neutrofilních leukocytů – NET či řadou cytokinů). Podmínkou aktivace této vnitřní cesty koagulace je stagnace krve umožňující dosažení účinné lokální koncentrace enzymů koagulační kaskády. Těmto podmínkám odpovídají dvě nejčastější indikace antikoagulační léčby – prevence tromboembolických příhod provázejících fibrilaci síní či profylaxe a léčba tromboembolické nemoci. Zachování aktivní vnější cesty koagulace pak umožní zachování hemostázy při poškození cévní stěny, tedy např. při poškození sliznic, při úrazech či operačních zákrocích. Typy léčiv prověřované při inhibici faktoru XI/XIa demonstrují současný posun možností farmakologické intervence. Vedle klasických léčiv s malou molekulou (např. asundexian, milvexian) jsou vyvíjeny monoklonální protilátky (např. abelacimab, osocimab) či inhibující oligonukleotidy (např. fesomersen). Řada těchto léčiv má ukončeny časné fáze klinického hodnocení a v řadě indikací (profylaxe tromboembolické nemoci po ortopedických zákrocích, v rámci prevence tromboembolických příhod při fibrilaci síní či v indikaci sekundární prevence po infarktu myokardu či iktu) probíhají poslední předregistrační fáze hodnocení.

Modern medicine places great emphasis not only on the efficacy but especially on the safety of the treatment. A common deficiency of anticoagulants inhibitingg the common pathway of the coagulation cascade (thrombin inhibitors, factor Xa inhibitors or antivitamins K) is an increased risk of clinically significant bleeding. A new strategy is being developed to inhibit the intrinsic pathway of the coagulation cascade, specifically to inhibit the synthesis or block the function of factor XI/XIa. This route is promising, as the most common indications of anticoagulants include activation of haemostasis by contact (induced e.g. by polyphosphates on the surface of activated platelets or by contact with a negative electrostatic surface) or by repair-inflammatory processes (especially by extracellularly released DNA fibres from neutrophilic leukocytes - NETs or by a number of cytokines). The condition for the activation of this intrinsic coagulation pathway is the stagnation of the blood, allowing the achievement of an effective local concentration of enzymes of the coagulation cascade. These conditions correspond to the two most common indications for anticoagulant therapy - prevention of thromboembolic events accompanying atrial fibrillation or prophylaxis and treatment of thromboembolic disease. Maintaining an active external coagulation pathway will then allow for the preservation of hemostasis in the event of damage to the vascular wall, e.g. damage to mucous membranes, injuries or surgeries. The types of drugs investigated in inhibition of factor XI/XIa demonstrate the current shift in pharmacological intervention options. In addition to classical small molecule drugs (e.g. asundexian, milvexian), monoclonal antibodies (e.g. abelacimab, osocimab) or oligonucleotide inhibitors (e.g. fesomersen) are being developed. A number of these drugs have completed the early phases of clinical trials, and in a number of indications (prophylaxis of thromboembolic disease after orthopaedic procedures, as part of the prevention of thromboembolic events in atrial fibrillation or in the indication of secondary prevention after myocardial infarction or stroke), the last preregistration phases of the trial are underway.

• MeSH
• antikoagulancia * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• faktor IX antagonisté a inhibitory   MeSH
• faktor IXa antagonisté a inhibitory   MeSH
• hemokoagulace účinky léků   MeSH
• hemostáza MeSH
• inhibitory koagulačních faktorů aplikace a dávkování   terapeutické užití   MeSH
• kardiovaskulární nemoci prevence a kontrola   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH