Proximal femur fractures (PFF) pose a major challenge in elderly patients with severe comorbidities and receiving antithrombotic therapy since according to the latest guidelines the surgery should be performed as soon as possible, preferably within 24 hours, to reduce mortality and morbidity. This review outlines the practical approach to surgical management of PFF that relies on increasing evidence of safety of early surgery in patients with PFF receiving antiplatelet and anticoagulant therapy. We have also used information from the existing evidence-based guidelines for elective/planned surgery in patients with antithrombotic therapy. The practical approach can be summarised as follows: • Antiplatelet therapy - discontinuation of acetylsalicylic acid (ASA) and clopidogrel in monotherapy or in combination is not necessary prior to surgery. In case of bleeding, antifibrinolytic therapy is recommended as well as administration of platelet concentrate which is rarely needed. • In patients taking warfarin, reversal of its effects is recommended by early administration of vitamin K to allow surgery to be performed within 24 hours. Prothrombin complex concentrate (PCC) as a second-line drug is reserved for extreme cases only. Warfarin therapy is resumed 24 hours after surgery. • Direct oral anticoagulants must be discontinued 24-48 hours prior to surgery, possibly longer depending on the type of drug, time of administration of the last dose, and renal function. In extreme cases, an antidote (idarucizumab, off-label andexanet) can be administered prior to surgery, or PCC in case they are unavailable. Anticoagulation therapy is resumed in 24-48 hours. • Neuraxial anaesthesia is possible when ASA is taken by the patient and in case of effective warfarin reversal. • In early surgery and rapid restart of anticoagulant therapy, bridging therapy with LMWH is not indicated except for in cases with extreme risk of thrombosis. Key words: proximal femur fracture, antiplatelet therapy, anticoagulant therapy, perioperative management.

• MeSH
• antikoagulancia * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• Aspirin škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• fraktury femuru chirurgie   MeSH
• fraktury proximálního femuru MeSH
• inhibitory agregace trombocytů * škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• warfarin škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).

• MeSH
• akutní nemoc MeSH
• cerebrální krvácení * farmakoterapie   chemicky indukované   MeSH
• faktor Xa * terapeutické užití   škodlivé účinky   MeSH
• fibrilace síní farmakoterapie   komplikace   MeSH
• hematom * chemicky indukované   farmakoterapie   MeSH
• inhibitory faktoru Xa * škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rekombinantní proteiny * terapeutické užití   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Prevention of bleeding and its consequences is the main goal of hemophilia treatment and determines treatment choices for patients who develop inhibitors. To assess bleeding before and during immune tolerance induction (ITI) and its association with ITI regimen and inhibitor titer, we selected and analyzed data on patients receiving high-titer inhibitors from the international prospective PedNet cohort study. In total, 222 patients with severe hemophilia A and inhibitor titers of >5 Bethesda units (BU) were followed from the first positive to the first negative inhibitor result (median overall follow-up, 1.7 years). Mean annual (joint) bleeding rates (AJBR) and 95% confidence intervals (CIs) were compared according to treatment and inhibitor titer using multivariable negative binomial regression. Before ITI, 115 patients showed an ABR of 6.1 (5.0-7.4) and an AJBR 2.6 (2.1-3.2). Bleeding was independent of inhibitor titer. During ITI, 202 patients had an ABR of 4.4 (3.9-5.1) and an AJBR of 1.7 (1.5-2.0). AJBR during ITI increased with inhibitor titer (hazard ratio [HR] for ≥200 BU vs 5 to 39 BU [4.9; CI, 3.2-7.4]) and decreased with daily ITI infusions (HR, 0.4; CI, 0.3-0.6) or activated prothrombin complex concentrate prophylaxis (HR, 0.4; CI, 0.2-0.8), whereas ITI dose and recombinant activated factor VII prophylaxis did not independently affect bleeding. These data provide evidence for a protective effect of repeated FVIII infusions (ITI) on bleeding in patients who have developed inhibitors; these data should be used to plan ITI and/or serve as a comparator for prophylaxis with nonreplacement therapy.

• MeSH
• faktor VIII MeSH
• hemofilie A * komplikace   MeSH
• imunologická tolerance MeSH
• kohortové studie MeSH
• krvácení etiologie   MeSH
• lidé MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Trauma is a leading cause of mortality, with major bleeding and trauma-induced coagulopathy (TIC) contributing to negative patient outcomes. Treatments for TIC include tranexamic acid (TXA), fresh frozen plasma (FFP), and coagulation factor concentrates (CFCs, e.g. prothrombin complex concentrates [PCCs] and fibrinogen concentrate [FCH]). Guidelines for TIC management vary across Europe and a clear definition of TIC is still lacking. METHODS: An advisory board involving European trauma experts was held on 02 February 2019, to discuss clinical experience in the management of trauma-related bleeding and recommendations from European guidelines, focusing on CFC use (mainly FCH). This review summarises the discussions, including TIC definitions, gaps in the guidelines that affect their implementation, and barriers to use of CFCs, with suggested solutions. RESULTS: A definition of TIC, which incorporates clinical (e.g. severe bleeding) and laboratory parameters (e.g. low fibrinogen) is suggested. TIC should be treated immediately with TXA and FCH/red blood cells; subsequently, if fibrinogen ≤ 1.5 g/L (or equivalent by viscoelastic testing), treatment with FCH, then PCC (if bleeding continues) is suggested. Fibrinogen concentrate, and not FFP, should be administered as first-line therapy for TIC. Several initiatives may improve TIC management, with improved medical education of major importance; generation of new and stronger data, simplified clinical practice guidance, and improved access to viscoelastic testing are also critical factors. CONCLUSIONS: Management of TIC is challenging. A standard definition of TIC, together with initiatives to facilitate effective CFC administration, may contribute to improved patient care and outcomes.

• MeSH
• fibrinogen terapeutické užití   MeSH
• hemostatika * terapeutické užití   MeSH
• koagulační faktory farmakologie   terapeutické užití   MeSH
• koagulopatie * terapie   MeSH
• krvácení farmakoterapie   etiologie   MeSH
• kyselina tranexamová * terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors' clinical experience in treating patients with AHA.

• MeSH
• autoprotilátky MeSH
• faktor VIII MeSH
• hemofilie A * diagnóza   farmakoterapie   MeSH
• krvácení MeSH
• lidé MeSH
• prasata MeSH
• rituximab terapeutické užití   MeSH
• vyšetření krevní srážlivosti MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Každá antikoagulační terapie je spojena s větším rizikem krvácení. Riziko krvácení stoupá s věkem a závisí na typu a intenzitě antikoagulační léčby. Léčba krvácení závisí na tíži krvácení, indikaci antikoagulační léčby a ostatních chorobách. Při těžkých až život ohrožujících krváceních máme k dispozici antidota, a to protamin u nefrakcionovaného heparinu a idarucizumab u dabigatranu. U nízkomolekulárního heparinu je účinek protaminu limitován, v případě xabanů je t. č. lékem volby koncentrát protrombinového komplexu. Ten je také spolu s vitaminem K přístupem volby u krvácení spojeného s warfarinem.

Every anticoagulation therapy is associated with an increased risk of bleeding. The risk of bleeding raises with the age and depends on the type and intensity of anticoagulation. Therapy of bleeding depends on a severity of bleeding, indication of anticoagulation therapy and the comorbidities. In major and life-threatening bleeding we have at the disposal the antidotes protamine for unfractionated heparin and idarucizumab for dabigatran. The effect of protamine is limited in low molecular weights heparin, in the case of xabans the concentrate of prothrombin complexes is therapy of choice. This concentrate and vitamin K are indicated in the bleeding associated with warfarin.

• MeSH
• antidota MeSH
• antikoagulancia * škodlivé účinky   terapeutické užití   MeSH
• dabigatran antagonisté a inhibitory   MeSH
• heparin nízkomolekulární antagonisté a inhibitory   MeSH
• heparin aplikace a dávkování   MeSH
• krvácení * farmakoterapie   komplikace   terapie   MeSH
• lidé MeSH
• protaminy MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• výsledek terapie MeSH
• warfarin antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy 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

Podáváme přehled o farmakologii a klinickém použití 4F‑PCC (four‑factor prothrombin complex concentrate) přípravku Beriplex® při obnově koagulace u nemocných léčených antagonisty vitaminu K, při substituci koagulačních faktorů II, VII, IX, X a také v případě život ohrožujícího krvácení, včetně krvácení vyvolaného užíváním nových perorálních antikoagulancií apixabanu, edoxabanu a rivaroxabanu, pro něž zatím není k dispozici specifické antidotum.

We present an overview of pharmacology and clinical use of 4F‑PCC (four‑factor prothrombin complex concentrate) manufactured as Beriplex® with respect to restitution of coagulation in patients treated with vitamin K antagonists, to substitution of coagulation factors (II, VII, IX, X), and also to life‑threatening hemorrhages including those affecting patients using new oral anticoagulants such as apixaban, edoxaban, and rivaroxaban with no specific antidotes available.

• Klíčová slova
• Beriplex, NOAC, 4F-PCC,
• MeSH
• akutní nemoc MeSH
• antidota MeSH
• antikoagulancia škodlivé účinky   MeSH
• faktor IX terapeutické užití   MeSH
• faktor VII terapeutické užití   MeSH
• faktor X terapeutické užití   MeSH
• fixní kombinace léků MeSH
• hemokoagulace účinky léků   MeSH
• inhibitory faktoru Xa škodlivé účinky   MeSH
• krvácení při operaci prevence a kontrola   MeSH
• krvácení * farmakoterapie   chemicky indukované   prevence a kontrola   MeSH
• lidé MeSH
• protrombin terapeutické užití   MeSH
• vitamin K antagonisté a inhibitory   MeSH
• výpočet dávky léku MeSH
• warfarin škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Antikoagulační léčba je neoddělitelně spjata se zvýšeným rizikem krvácivých komplikací. V článku jsou popsány nejvýznamnější příčiny krvácivých komplikací u pacientů léčených nefrakcionovaným heparinem, nízkomolekulárním heparinem, antagonisty vitaminu K, dabigatranem a přímými perorálními inhibitory faktoru Xa včetně mnohočetných lékových interakcí warfarinu. Jsou uvedeny laboratorní testy hemostázy, které mohou být užitečné při určení role antikoagulancií v genezi krvácení. Článek se také zaměřuje na léčbu krvácivých komplikací antikoagulační léčby, shrnuje účinnost i nedostatky antidot dostupných v současné době. Je zdůrazněna role koncentrátů protrombinového komplexu v léčbě krvácivých komplikací u pacientů užívajících warfarin a význam idarucizumabu – specifického antidota dabigatranu –, který se stal v poslední době dostupným v České republice.

The anticoagulant therapy is inseparably accompanied by an increased risk of bleeding complications. The most prominent causes of bleeding complications in patients treated with unfractionated heparin, low molecular weight heparin, vitamin K antagonists, dabigatran and direct oral inhibitors of factor Xa are described in the article, including multiple drug interactions of warfarin. Laboratory tests of haemostasis, which can be useful for determination of the role of anticoagulant drugs in pathogenesis of bleeding, are mentioned. The article also focuses on the management of bleeding complications of anticoagulant therapy, reviewing the effectiveness and limits of antidotes, which are currently available. The role of prothrombin complex concentrates in treatment of bleeding complications in patients taking warfarin is pointed out as well as the importance of idarucizumab – a specific antidote of dabigatran, which became available in Czech Republic recently.

• Klíčová slova
• idarucizumab, apixaban, andexanet,
• MeSH
• antidota * aplikace a dávkování   terapeutické užití   MeSH
• antikoagulancia * škodlivé účinky   MeSH
• dabigatran škodlivé účinky   MeSH
• faktor Xa terapeutické užití   MeSH
• heparin nízkomolekulární škodlivé účinky   MeSH
• heparin škodlivé účinky   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• inhibitory faktoru Xa škodlivé účinky   MeSH
• koagulační faktory terapeutické užití   MeSH
• krvácení * farmakoterapie   chemicky indukované   MeSH
• lékové interakce MeSH
• lidé MeSH
• protrombin terapeutické užití   MeSH
• rekombinantní proteiny terapeutické užití   MeSH
• rivaroxaban škodlivé účinky   MeSH
• rizikové faktory MeSH
• vitamin K antagonisté a inhibitory   škodlivé účinky   MeSH
• warfarin škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Hypothermic coagulopathy is very challenging in bleeding trauma patients. Therefore, we decided to evaluate the efficacy of fibrinogen and prothrombin complex in 30°C hypothermia in vitro to investigate if higher levels of fibrinogen and prothrombin complex concentrate can compensate for the hypothermic effect on coagulation as measured by thromboelastometry/thromboelastography. METHODS: Blood samples were obtained from 12 healthy volunteers (six men and six women) in our study. Measurements were performed at 37°C and 30°C simultaneously, then at 30°C with adding fibrinogen and prothrombin complex and in the last step samples with added coagulation factors were warmed back to 37°C. RESULTS: We found that 30°C hypothermic coagulopathy can be detected both by thromboelastometry and thromboelastography. Hypothermic coagulopathy can be restored by fibrinogen to the point where the results do not significantly differ from 37°C values (p > 0.05). After warming the sample with fibrinogen to 37°C, the thrombodynamic potential index was not significantly different from baseline (p > 0.05), although there was a trend to prothrombotic status. The addition of prothrombin complex concentrate to 30°C hypothermic sample was not able to correct hypothermic coagulopathy in vitro. CONCLUSIONS: Coagulopathy caused by the 30°C hypothermia in vitro model can be corrected by fibrinogen concentrate compared to prothrombin complex concentrate. In spite of a tendency to prothrombotic status, this was not significant with the use of the recommended dose of fibrinogen even after warming the blood to 37°C. However, measurement performed at 37°C seems to be safer than at 30°C.

• MeSH
• biologické modely * MeSH
• dospělí MeSH
• fibrinogen farmakologie   MeSH
• hemokoagulace účinky léků   MeSH
• koagulační faktory farmakologie   MeSH
• lidé MeSH
• rotace MeSH
• terapeutická hypotermie * MeSH
• tromboelastografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH