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Background: The outcome of patients undergoing major surgery treated with HES for hemodynamic optimization is unclear. This post-hoc analysis of a randomized clinical pilot trial investigated the impact of low-molecular balanced HES solutions on the coagulation system, blood loss and transfusion requirements., Methods: The Trial was registered: EudraCT 2008-004175-22 and ethical approval was provided by the ethics committee of Berlin. Patients were randomized into three groups receiving either a 10% HES 130/0.42 solution, a 6% HES 130/0.42 solution or a crystalloid following a goal-directed hemodynamic algorithm. Endpoints were parameters of standard and viscoelastic coagulation laboratory, blood loss and transfusion requirements at baseline, at the end of surgery (EOS) and the first postoperative day (POD 1)., Results: Fifty-two patients were included in the analysis (HES 10% (n = 15), HES 6% (n = 17) and crystalloid (n = 20)). Fibrinogen decreased in all groups at EOS (HES 10% 338 [298;378] to 192 [163;234] mg dl-1, p<0.01, HES 6% 385 [302;442] to 174 [163;224] mg dl-1, p<0.01, crystalloids 408 [325;458] to 313 [248;370] mg dl-1, p = 0.01). MCF FIBTEM was decreased for both HES groups at EOS (HES 10%: 20.5 [16.0;24.8] to 6.5 [5.0;10.8] mm, p = <0.01; HES 6% 27.0 [18.8;35.2] to 7.0 [5.0;19.0] mm, p = <0.01). These changes did not persist on POD 1 for HES 10% (rise to 16.0 [13.0;24.0] mm, p = 0.88). Blood loss was not different in the groups nor transfusion requirements., Conclusion: Our data suggest a stronger but transient effect of balanced, low-molecular HES on the coagulation system. Despite the decline of the use of artificial colloids in clinical practice, these results may help to inform clinicians who use HES solutions., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Alexander Eckers, Oliver Hunsicker and Kerstin Rubarth have declared that no competing interests exist. Claudia Spies has received research funding from B.Braun during the study DOI: 10.1097/MD.0000000000010579. Outside the submitted manuscript she has received research funding and honoraria from German Research Society (DFG), German Aerospace Center (DLR), Einstein Foundation Berlin, German Federal Joint Commitee (G-BA), Inner University grants, Project Management Agency (DLR), Stifterverband, European Society of Anaesthesiology and Intensive Care, German Federal Ministry of Economic Affairs and Climate Action, Georg Thieme Verlag, Dr. F. Köhler Chemie GmbH, Sintetica GmbH, Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., Stifterverband für die deutsche Wissenschaft e.V./Metronic, Philips Electronics Nederland BV, BMBF/RKI, G-BA Innovationsfonds outside the submitted work. In addition, Dr. Spies has following patents licensed: 10 2014 215 211.9; 10 2018 114 364.8; 10 2018 110 275.5; 50 2015 010 534.8; 50 2015 010 347.7; 10 2014 215 212.7. Felix Balzer has received research grants from Einstein Foundation, German Federal Ministry of Education and Research, German Federal Ministry of Health, Berlin Institute of Health, Hans Böckler Stiftung, Berlin university Alliance, as well as honoraria from Medtronic, GE outside this work. Christian von Heymann has received honoraria from Artcline GmbH, CSL Behring, Daiichi Sankyo, HICC GbR, Mitsubishi Pharma, Novo Nordisk, Sobi Pharma and Shionogi Pharma that were not related to the topic of this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Eckers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding., Design: A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process., Results: So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%., Discussion: DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given., Conclusion: In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

(1) Background: The clinical management of anticoagulated patients treated with direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) needing emergency surgery is challenging. (2) Methods: The prospective German RADOA registry investigated treatment strategies in DOAC- or VKA-treated patients needing emergency surgery within 24 h after admission. Effectiveness was analysed by clinical endpoints including major bleeding. Primary observation endpoint was in hospital mortality until 30 days after admission. (3) Results: A total of 78 patients were included (DOAC: 44; VKA: 34). Median age was 76 years. Overall, 43% of the DOAC patients and 79% of the VKA patients were treated with prothrombin complex concentrates (PCC) ( p = 0.002). Out of the DOAC patients, 30% received no hemostatic treatment compared to 3% (1/34) of the VKA patients ( p = 0.002), and 7% of the DOAC patients and 21% of the VKA patients developed major or clinically relevant non-major bleeding at the surgical site ( p = 0.093). In-hospital mortality was 13% with no significant difference between the two treatment groups (DOAC: 11%, VKA: 15%; p > 0.20). (4) Conclusions: The 30-day in-hospital mortality rate was comparable between both patient groups. VKA patients required significantly more hemostatic agents than DOAC patients in the peri- and postoperative surgery period.

Clinical trial registration number: NCT02950168, NCT02951039., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AB, CC, JJ, and MU are employees of Daiichi Sankyo. PC reports grants and personal fees from Daiichi Sankyo; personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/BMS; and nonfinancial support from the European Society of Cardiology (ESC) and the Italian Cardiology Association (ANMCO). CvH reports grants and personal fees from Daiichi Sankyo; personal fees from Artcline GmbH, CSL Behring, HICC GbR, Mitsubishi Pharma, Novo Nordisk Pharma, Shionogi Pharma, and Sobi Pharma; receipt of a mandate from the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) to write the German Guidelines on Preoperative Anemia; receipt of a mandate from the Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI) to take part in the writing group of the guidelines on the Prevention of Venous Thromboembolism of the Gesellschaft für Thrombose- und Hämostaseforschung (GTH); participation in the writing group of the Patient Blood Management Guideline in cardiac surgery on behalf of the European Society of Cardiothoracic Anaesthesiologists (EACTA) in conjunction with the European Society of Cardiothoracic Surgery (EACTS); and receipt of a mandate to take part in the writing group of the guidelines on the Diagnostics and Treatment of Peripartum Haemorrhage of the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG). SK reports consulting fees from Daiichi Sankyo. AS reports nothing to disclose. MS reports grants and personal fees from Daiichi Sankyo and personal fees from Daiichi Sankyo; TV report grants and personal fees from Daiichi Sankyo; and personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and LEO Pharma.

Background: Optimising periprocedural management of direct oral anticoagulation in patients with atrial fibrillation on chronic treatment undergoing major surgeries is an important aspect of balancing the risk of surgery-related bleeding with the risk of thromboembolic events, which may vary by surgery type., Methods: This subanalysis of the prospective EMIT-AF/VTE programme assessed periprocedural-edoxaban management, according to physicians' decisions, and bleeding and thromboembolic event rates in patients who underwent major vs. nonmajor surgeries. Edoxaban interruption and clinical outcomes were compared between major vs. nonmajor surgeries and between renal function subgroups (creatinine clearance [CrCL] ≤ 50 mL/min vs. > 50 mL/min)., Results: We included 276 major and 512 nonmajor surgeries. The median pre- and postprocedural duration of edoxaban interruption in major vs. nonmajor surgeries was 4 vs. 1 days, whereas median duration of interruption for those with preprocedural-only and postprocedural-only interruption was 2 vs. 1 days and 2 vs. 0 days, respectively (P < 0.0001). Rates of all bleeding and clinically relevant nonmajor bleeding were numerically higher in major vs. nonmajor surgeries. Event rates (number of events per 100 surgeries) were low overall (< 6 events per 100 surgeries), independent of renal function subgroups., Conclusion: In this subanalysis of the EMIT-AF/VTE programme, periprocedural-edoxaban interruption was significantly longer in patients undergoing major vs. nonmajor surgery. This clinician-driven approach was associated with low rates of bleeding and thromboembolic events following both major and nonmajor surgeries., Trial Registration: NCT02950168, registered October 31, 2016; NCT02951039, registered November 1, 2016., (© 2023. The Author(s).)

The application of tranexamic acid (TXA) during endoprosthetic surgical procedures has significantly increased in recent years. Due its ability to reduce perioperative blood loss and avert the need for blood transfusions as well as wound drainage, TXA is becoming part of a 'standard practice'. However, TXA is currently not approved for the application during endoprosthetic procedures and therefore, a benefit-risk analysis should always be conducted. Prophylactic administration of TXA without prior patient consent is only justified if fibrinolytic bleeding is expected and there are no contraindications or relevant risk factors for thromboembolic complications. Respectively, no patient consent is required when a therapeutic dose of TXA is administered in the context of fibrinolytic bleeding. The following guidelines provide updated recommendations based on the current state of knowledge on TXA optimal timing, routes of administration and dosing regimen., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Literature reviews support continuing anticoagulation during dental procedures. However, studies often present grouped anticoagulation data, and information on individual anticoagulant management would be helpful to dentists. The Edoxaban Management in Diagnostic and Therapeutic Procedures (EMIT-AF/VTE) programme (NCT02950168; NCT02951039) demonstrated low periprocedural bleeding and thrombotic event rates in patients with atrial fibrillation receiving edoxaban., Aims: To report periprocedural edoxaban interruption and clinical events in patients from EMIT-AF/VTE who underwent dental procedures., Methods: Dental procedures were categorised by type (cleaning/noncleaning). Edoxaban interruption, bleeding events, and thrombotic events were observed 5 days preprocedure through 29 days postprocedure., Results: Overall, 196 patients underwent 350 cleaning and/or noncleaning procedures; most patients (171/196 [87.2%]) underwent noncleaning procedures (282/350 [80.6%]), whereas 48/196 (24.5%) underwent 68/350 (19.4%) cleaning procedures. Edoxaban was uninterrupted for most cleanings (53/68 [77.9%]). Preprocedural interruption was common for single and multiple tooth extractions (single, 67/100 [67.0%]; multiple, 16/30 [53.3%]). The only major bleeding occurred after an unrelated cleaning. Minor bleeding occurred in 1/68 (1.5%) cleaning and 4/282 (1.4%) noncleaning procedures. There were no thrombotic events., Conclusions: For most cleanings, edoxaban was not interrupted, whereas preprocedural interruption was more common for tooth extractions. Overall, bleeding rates were low, and no thrombotic events occurred., (© 2023. British Dental Association.)

Introduction: Patients undergoing revision total hip surgery (RTHS) have a high prevalence of mild and moderate preoperative anemia, associated with adverse outcomes. The aim of this study was to investigate the association of perioperative allogeneic blood transfusions (ABT) and postoperative complications in preoperatively mild compared to moderate anemic patients undergoing RTHS who did not receive a diagnostic anemia workup and treatment before surgery., Methods: We included 1,765 patients between 2007 and 2019 at a university hospital. Patients were categorized according to their severity of anemia using the WHO criteria of mild, moderate, and severe anemia in the first Hb level of the case. Patients were grouped as having received no ABT, 1-2 units of ABT, or more than 2 units of ABT. Need for intraoperative ABT was assessed in accordance with institutional standards. Primary endpoint was the compound incidence of postoperative complications. Secondary outcomes included major/minor complications and length of hospital and ICU stay., Results: Of the 1,765 patients, 31.0% were anemic of any cause before surgery. Transfusion rates were 81% in anemic patients and 41.2% in nonanemic patients. The adjusted risks for compound postoperative complication were significantly higher in patients with moderate anemia (OR 4.88, 95% CI: 1.54-13.15, p = 0.003) but not for patients with mild anemia (OR 1.93, 95% CI: 0.85-3.94, p < 0.090). Perioperative ABT was associated with significantly higher risks for complications in nonanemic patients and showed an increased risk for complications in all anemic patients. In RTHS, perioperative ABT as a treatment for moderate preoperative anemia of any cause was associated with a negative compound effect on postoperative complications, compared to anemia or ABT alone., Discussion: ABT is associated with adverse outcomes of patients with moderate preoperative anemia before RTHS. For this reason, medical treatment of moderate preoperative anemia may be considered., Competing Interests: Henning Uden, Franziska Büttner, Michael Krämer, Gerald Vorderwülbecke, Sebastian Hardt, and Jochen Kruppa: None. Christian von Heymann declares to have no financial conflict of interest related to the topic of this manuscript. He also declares that he was mandated from the German Society of Anesthesiology and lntensive Care Medicine (DGAI) to write the German Guideline on Preoperative Anemia (published in April 2018) and that he was part of the writing group of the Patient Blood Management Guideline in cardiac surgery on behalf of the European Society of Cardiothoracic Anaesthesiologists (EACTA) in conjunction with the European Society of Cardiothoracic Surgery (EACTS) (published in September 2017). Outside this work, Christian von Heymann discloses to have received research funding, speaker’s and consultancy honoraria, and travel reimbursements from CSL Behring, Daiichi Sankyo, HICC GbR, Mitsubishi Pharma GmbH, NovoNordisk Pharma GmbH, Shionogi Pharma, and Sobi Pharma. Lutz Kaufner declares to have no financial conflict of interest related to the topic of this manuscript. He also declares that he was mandated from the German Society of Anesthesiology and lntensive Care Medicine (DGAI) to write the German Guideline on Preoperative Anemia (published in April 2018). He discloses to received speaker’s and consultancy honoraria and travel reimbursements from HICC GbR., CSL Behring, and Novo Nordisk outside the submitted work. Claudia Spies reports grants from Deutsche Forschungs-gemeinschaft/German Research Society, grants from Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR)/German Aerospace Center, grants from Einstein Stiftung Berlin/Einstein Foundation Berlin, grants from Gemeinsamer Bundesausschuss/Federal Joint Committee (G-BA), grants from Inneruniversitäre Forschungsförderung/Inner University Grants, grants from Projektträger im DLR/Project Management Agency, grants from Stifterverband/Non-Profit Society Promoting Science and Education, grants from European Society of Anaesthesiology and Intensive Care, grants from Baxter Deutschland GmbH, grants from Cytosorbents Europe GmbH, grants from Edwards Lifesciences‚ Germany GmbH, grants from Fresenius Medical Care, grants from Grünenthal GmbH, grants from Masimo Europe Ltd‚ grants from Pfizer Pharma PFE GmbH, personal fees from Georg Thieme Verlag, grants from Dr. F. Köhler Chemie GmbH‚ grants from Sintetica GmbH, grants from Stifterverband für die deutsche Wissenschaft e.V./Philips, grants from Stiftung Charite, grants from AGUETTANT Deutschland GmbH, grants from AbbVie Deutschland GmbH & Co. KG, grants from Amomed Pharma GmbH, grants from InTouch Health, grants from Copra System GmbH, grants from Correvio GmbH, grants from Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., grants from Deutsche Gesellschaft für Anästhesiologie & Intensivmedizin (DGAI), grants from Stifterverband für die deutsche Wissenschaft e.V./Metronic, grants from Philips ElectronicsNederland BV, grants from BMG, grants from BMBF, grants from Deutsche Forschungsgemeinschaft/German Research Society, and grants from Drägerwerk AG & Co. KGaA, outside the submitted work. In addition, Dr. Spies has a patent 10 2014 215 211.9 licensed, a patent 10 2018 114 364.8 licensed, a patent 10 2018 110 275.5 licensed, a patent 50 2015 010 534.8 licensed, a patent 50 2015 010 347.7 licensed, and a patent 10 2014 215 212.7 licensed. Felix Balzer reports grants from German Federal Ministry of Education and Research, grants from German Federal Ministry of Health, grants from Berlin Institute of Health, personal fees from Elsevier Publishing, grants from Hans Böckler Foundation, other from Robert Koch Institute, grants from Einstein Foundation, and grants from Berlin University Alliance, outside the submitted work., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Peripartum haemorrhage (PPH) is a potentially life-threatening complication. Although still rare, the incidence of peripartal haemorrhage is rising in industrialised countries and refractory bleeding remains among the leading causes of death in the peripartal period., Summary: The interdisciplinary German, Austrian, and Swiss guideline on "Peripartum Haemorrhage: Diagnostics and Therapies" has reviewed the evidence for the diagnostics and medical, angiographic, haemostatic, and surgical treatment and published an update in September 2022 . This article reviews the updated recommendations regarding the early diagnosis and haemostatic treatment of PPH. Keystones of the guideline recommendations are the early diagnosis of the bleeding by measuring blood loss using calibrated collector bags, the development of a multidisciplinary treatment algorithm adapted to the severity of bleeding, and the given infrastructural conditions of each obstetric unit, the early and escalating use of uterotonics, the therapeutic, instead of preventative, use of tranexamic acid, the early diagnostics of progressive deficiencies of coagulation factors or platelets to facilitate a tailored and guided haemostatic treatment with coagulation factors, platelets as well as packed red blood cells and fresh frozen plasma when a massive transfusion is required., Key Messages: Essential for the effective and safe treatment of PPH is the timely diagnosis. The diagnosis of PPH requires the measurement rather than estimation of blood loss. Successful treatment of PPH consists of a multidisciplinary approach involving surgical and haemostatic treatments to stop the bleeding. Haemostatic treatment of PPH starts early after diagnosis and combines tranexamic acid, an initially ratio-driven transfusion with RBC:plasma:PC = 4:4:1 (when using pooled or apheresis PC) and finally a goal-directed substitution with coagulation factor concentrates for proven deficiencies. Early monitoring of coagulation either by standard parameters or viscoelastic methods facilitates goal-directed haemostatic treatment., Competing Interests: H.L. received travel expenses and lecture fees from Bayer Vital, DRK Blood Donation Service West, CSL Behring, Ferring, Mitsubishi Pharma, Novo Nordisk, and Werfen. T.A. received research support by the German Federal Ministry for Economics and Energy, Aerogen, Corpuls Germany, CytoSorbents, Anästhesiologie – Forschung und Fortbildung (AnFoFo) e.V., and travel expenses and lecture fees from FomF, Germany, AnFoFo e.V., and CSL Behring. T.G. received travel expenses and lecture fees from CSL Behring. G.P. received travel expenses and lecture fees from Arjo, Bayer, Böhringer, CSL Behring, Mitsubishi Pharma, Sanofi, and Vivor. W.K. received, within the last 3 years, travel support, advisory fees, lecture fees, and/or research support from CSL Behring, Novo Nordisk, HICC, Axonlab, Alexion, Siemens, Stago, Roche Diagnostics, Beckman Coulter, Vifor, Sobi, and Werfen. O.T. had no conflict of interest in relation to the published content. D.S. received travel expenses and lecture fees from CSL Behring, Cook Medical, Clinical Innovations, Jenapharm, and Hexal. Within the last 3 years, CvH has received travel expenses, research support, and advisory and lecture fees from Artcline GmbH, CSL Behring, Daiichi Sankyo GmbH, HICC GbR, Novo Nordisk, Shionogi Pharma, and Sobi Pharma., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Patients treated with edoxaban may require diagnostic and therapeutic procedures that involve edoxaban interruption. Although heparin bridging strategies are not recommended, heparin is frequently used in clinical practice. However, whether heparin use decreases thromboembolic risk remains unclear, and the potential for increased periprocedural bleeding remains a concern. Here, we report factors predicting edoxaban interruption and the use of heparin bridging strategies and associated clinical events from Global EMIT-AF/VTE, a multicenter, prospective, noninterventional study (Clinicaltrials.gov NCT02950168). Eligible patients are adults with atrial fibrillation or venous thromboembolism treated with edoxaban who underwent a diagnostic or therapeutic procedure. Edoxaban interruption, heparin bridging strategies, and clinical event data were collected from 5 days before procedure through 29 days afterwards. Edoxaban was interrupted in 1222/2089 procedures (58.5%); a heparin bridging strategy was used during 178 (14.6%) of these interruptions. Patients who received periprocedural heparin had higher baseline HAS-BLED (2.4±1.0 vs 1.9±1.1, P  <0.0001) scores and similar CHA 2 DS 2 -VASc (3.6±1.6 vs 3.4±1.6, P  = 0.09) scores versus patients who did not. HAS-BLED score >3 and high EHRA procedural risk predicted both edoxaban interruption and the use of a heparin bridging strategy, whereas CHA 2 DS 2 -VASc scores did not predict either. Bleeding and ischemic event rates were low; the all-bleeding rate was higher with the use of a heparin bridging strategy versus without (6.2% vs 3.1%, P  = 0.04). Periprocedural heparin use was associated with higher bleeding rates, but not with lower thromboembolic risk. Individual patient and procedural bleeding risks appear to contribute more than stroke risk to clinicians' consideration of a heparin bridging strategy.

Background: Anemia is highly prevalent in patients before hip joint revision surgery (HJRS) and is associated with an increased complication rate. This paper is the first to investigate costs, real diagnosis-related group (DRG) revenues and case coverage of preoperative anemia in elective HJRS., Methods: Medical data, transfusions, costs, and revenues of all patients undergoing HJRS at two campuses of the Charité -Universitätsmedizin Berlin between 2010 and 2017 were used for subgroup analyses and linear regressions., Results: Of 1187 patients included 354 (29.8%) showed preoperative anemia. A total of 565 (47.6%) patients were transfused with a clear predominance of anemic patients (72.6% vs. 37.0%, p < 0.001). Costs (12,318€ [9027;20,044€] vs. 8948€ [7501;11,339€], p < 0.001) and revenues (11,788€ [8992;16,298€] vs. 9611€ [8332;10,719€], p < 0.001) were higher for preoperatively anemic patients and the coverage was deficient (-1170€ [-4467;1238€] vs. 591€ [-1441;2103€], p < 0.001). In anemic patients, case contribution margins decreased with increasing transfusion rates (p ≤ 0.001). Comorbidities had no significant economic impact., Conclusion: Preoperative anemia and perioperative transfusions in HJRS are associated with increased treatment costs and a financial undercoverage for healthcare providers and health insurance companies. Concepts for the treatment of preoperative anemia (e.g. patient blood management) could reduce treatment costs in the medium term., (© 2022. The Author(s).)

Background: Different preparations for therapeutic plasma are available on the market. The German hemotherapy guideline has been completely updated in 2020 and, for this purpose, has reviewed the evidence for the most frequent clinical indications for the use of therapeutic plasma in adult patients., Summary: The German hemotherapy guideline has reviewed the evidence for the following indications for the use of therapeutic plasma in the adult patient: massive transfusion and bleeding, severe chronic liver disease, disseminated intravascular coagulation, plasma exchange for TTP, and the rare hereditary FV and FXI deficiencies. The updated recommendations for each indication are discussed on the background of existing guidelines and new evidence. For most indications, the quality of evidence is low due to missing prospective randomized trials or rare diseases. However, due to the "balanced" content of coagulation factors and inhibitors therapeutic plasma remains an important pharmacological treatment option in clinical situations with an already activated coagulation system. Unfortunately, the "physiological" content of coagulation factors and inhibitors limits the efficacy in clinical scenarios with high blood losses., Key Messages: The evidence for the use of therapeutic plasma for the replacement of coagulation factors due to massive bleeding is poor. Coagulation factor concentrates seem to be more appropriate for this indication, although the quality of evidence is also low. However, for diseases with an activated coagulation or endothelial system (e.g., disseminated intravascular coagulation, TTP) the balanced replacement of coagulation factors, inhibitors, and proteases may be of advantage., Competing Interests: Christian von Heymann (CvH) declares to have no financial conflict of interest related to the topic of this manuscript. Christian von Heymann declares that he was mandated from the German Society of Anesthesiology and Intensive Care Medicine (DGAI) to write the German Guideline on Preoperative Anemia (published in April 2018, update will be published in 2023) and the guideline on Peripartum Hemorrhage: Diagnostics and Treatment (update published on September 12, 2022). Furthermore, CvH was part of the writing group of the Patient Blood Management Guideline in cardiac surgery on behalf of the European Society of Cardio-thoracic Anaesthesiologists (EACTA) in conjunction with the European Society of Cardiothoracic Surgery (EACTS) (published in September 2017). CvH also declares to have been part of the working group that wrote the revision of the German hemotherapy guidelines. CvH contributed as a co-author to the chapter “Therapeutic Plasma” of this guideline. Outside this work, Christian von Heymann discloses to have received research funding, speaker's and consultancy honoraria, and travel reimbursements from Artcline GmbH, Bayer AG, CSL Behring, Daiichi Sankyo, Grunenthal GmbH, HICC GbR, Mitsubishi Pharma GmbH, Novo Nordisk Pharma GmbH, and Sobi Pharma. Heiko Lier (HL) declares that he was mandated from the German Society of Anesthesiology and Intensive Care Medicine (DGAI) to write the coagulation therapy chapter of the German Guideline on Severe/Multiple Trauma (to be published in December 2022) and the guideline on Peripartum Hemorrhage: Diagnostics and Treatment (update published on September 12, 2022). HL has received travel expenses and lecture fees from Bayer Vital, blood donation service west (DRK = German Red Cross), CSL Behring, Ferring, Novo Nordisk, and Werfen. Christoph Rosenthal (CR) has received lecture fees from CSL Behring and Aspen Pharma. Lutz Kaufner (LK) declares to have no financial conflict of interest related to the topic of this manuscript. Lutz Kaufner declares that he was mandated from the German Society of Anesthesiology and Intensive Care Medicine (DGAI) to write the German Guideline on Preoperative Anemia (published in April 2018). Lutz Kaufner discloses to have received speaker's and consultancy honoraria and travel reimbursements from HICC GbR., CSL Behring, and Novo Nordisk outside the submitted work., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Background: Pleural effusions commonly occur in patients recovering from cardiac surgery; however, the impact on outcomes is not well characterized. The purpose of this study is to characterize the clinical outcomes of cardiac surgery patients with pleural effusion., Methods: All patients undergoing cardiac surgery between 2006 and 2019 at a tertiary care university hospital were included in this observational, cross-sectional analysis using propensity matching., Results: Of 11,037 patients that underwent cardiac surgery during the study period, 6461 (58.5%) had no pleural effusion (Group 0), 3322 (30.1%) had pleural effusion only (Group 1), and 1254 (11.4%) required at least one secondary drainage procedure after the index operation (Group 2). After propensity matching, the mortality of patients who underwent secondary drainage procedures was 6.1% higher than in Group 1 (p < 0.001). Intensive care unit (ICU) stay was longer for those with pleural effusions (18 [IQR 9-32] days in Group 2, 10 [IQR 6-17] days for Group 1, and 7 [IQR 4-11] days for Group 0, p < 0.001). Patients with pleural effusions had a higher incidence of hemodialysis (246 [20.0%] in Group 2, 137 [11.1%] in Group 1, 98 [7.98%] in Group 0), and a longer ventilation time in the ICU (57 [IQR 21.0-224.0] hours in Group 2, 25.0 [IQR 14.0-58.0] hours in Group 1, 16.0 [IQR 10.0-29.0] hours in Group 0)., Conclusion: Pleural effusions, especially those that require a secondary drainage procedure during recovery, are associated with significantly worse outcomes including increased mortality, longer length of stay, and higher complication rates. These insights may be of great interest to scientists, clinicians, and industry leaders alike to foster research into innovative methods for preventing and treating pleural effusions with the aim of improving outcomes for patients recovering from cardiac surgery., (© 2022. The Author(s).)

The current S2k guidelines on the diagnostics and treatment of peripartum hemorrhage are summarized in this article from the perspective of anesthesiology based on a fictitious case report. The update of the guidelines was written under the auspices of the German Society of Gynecology and Obstetrics with the participation of other professional societies and interest groups from Germany, Austria and Switzerland and published by the AWMF in 2022 under the register number 015/063., (© 2022. The Author(s).)

Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.

Background: Epidural blood patch is commonly used for management of post-dural puncture headache after accidental dural puncture. The primary aim was to determine factors associated with failed epidural blood patch., Methods: In this prospective, multicentre, international cohort study, parturients ≥18 yr receiving an epidural blood patch for treatment of post-dural puncture headache were included. Failed epidural blood patch was defined as headache intensity numeric rating scale (NRS) score ≥7 in the upright position at 4, 24, or 48 h, or the need for a second epidural blood patch, and complete success by NRS=0 at 0-48 h after epidural blood patch. All others were considered partial success. Multinominal logistic regression was used for statistical analyses with P<0.01 considered statistically significant., Results: In all, 643 women received an epidural blood patch. Complete data to classify failure were available in 591 (91.9%) women. Failed epidural blood patch occurred in 167 (28.3%) patients; 195 (33.0%) were completely successful and 229 (38.7%) partially successful. A total of 126 women (19.8%) received a second epidural blood patch. A statistically significant association with failure was observed in patients with a history of migraine, when the accidental dural puncture occurred between lumbar levels L1/L3 compared with L3/L5 and when epidural blood patch was performed <48 h compared with ≥48 h after accidental dural puncture. In patients having radiological investigations, three intracranial bleeds were diagnosed., Conclusions: Failed epidural blood patch occurred in 28.3% of women. Independent modifiable factors associated with failure were higher lumbar level of accidental dural puncture and short interval between accidental dural puncture and epidural blood patch. A history of migraine was associated with a higher risk of second epidural blood patch., Clinical Trial Registration: NCT02362828., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Necrotizing soft tissue infections (NSTI) require immediate radical debridement, broad-spectrum antibiotics and intensive care. Hyperbaric oxygen therapy (HBOT) may be performed adjunctively, but unequivocal evidence for its benefits is still lacking., Methods: We performed a retrospective single-center study including 192 patients with necrotizing fasciitis or Fournier's gangrene to assess in-hospital mortality and outcome dependent on patient, disease and treatment characteristics with or without HBOT., Results: The in-hospital mortality rate was 27.6%. Factors associated with increased mortality according to multivariate analysis were higher age, affection of multiple or problem localizations (odds ratio (OR) = 2.88, P = 0.003), ineligibility for HBOT despite clinical indication (OR = 8.59, P = 0.005), pathogens in blood cultures (OR = 3.36, P = 0.002), complications (OR = 10.35, P < 0.001) and sepsis/organ dysfunction (OR = 19.58, P < 0.001). Factors associated with better survival included vacuum-assisted wound closure (OR = 0.17, P < 0.001), larger number of debridements (OR = 0.83, P < 0.001) and defect closure with mesh graft (OR = 0.06, P < 0.001) or flap (OR = 0.09, P = 0.024). When participants were stratified into subgroups without requirement of HBOT (n = 98), treated with HBOT (n = 83) and ineligible for HBOT due to contraindications (n = 11), the first two groups had similar survival rates (75.5% vs. 73.5%) and comparable outcome, although patients with HBOT suffered from more severe NSTI, reflected by more frequent affection of multiple localizations (P < 0.001), sepsis at admission (P < 0.001) and intensive care treatment (P < 0.001), more debridements (P < 0.001) and a larger number of antibiotics (P = 0.001). In the subgroup ineligible for HBOT, survival was significantly worse (36.4%, P = 0.022)., Conclusion: These results point to a benefit from HBOT for treatment of NSTI in critically ill patients., (© 2022. The Author(s).)

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected., Objective: This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV‑2 positive pregnant women hospitalized for childbirth. We therefore launched a registry to gain timely information over the dynamic situation during the SARS-CoV‑2 pandemic in Germany., Material and Methods: As part of the COVID-19-related Obstetric Anesthesia Longitudinal Assessment (COALA) registry, centers reported weekly birth rates, numbers of suspected SARS-CoV‑2 cases, as well as the numbers of confirmed cases between 16 March and 3 May 2020. Data acquisition was continued from 18 October 2020 till 28 February 2021. The data were analyzed regarding distribution of SARS-CoV‑2 positive pregnant women hospitalized for childbirth between centers, calendar weeks and birth rates as well as maternal characteristics, course of disease and outcomes of SARS-CoV‑2 positive pregnant women., Results: A total of 9 German centers reported 2270 deliveries over 7 weeks during the first wave of infections including 3 SARS-CoV‑2 positive cases and 9 suspected cases. During the second survey period, 6 centers from Germany and Switzerland reported 41 positive cases out of 4897 deliveries. One woman presented with a severe and ultimately fatal course of the disease, while another one needed prolonged ECMO treatment. Of the women 28 presented with asymptomatic infections and 6 neonates were admitted to a neonatal intensive care unit for further treatment. There was one case of neonatal SARS-CoV‑2 infection., Conclusion: The number of pregnant women infected with SARS-CoV‑2 was at a very low level at the time of delivery, with only sporadic suspected or confirmed cases. Due to the lack of comprehensive testing in the first survey period, however, a certain number of asymptomatic cases are to be assumed. Of the cases 68% presented as asymptomatic or as mild courses of disease but the data showed that even in young healthy patients without the presence of typical risk factors, serious progression can occur. These outcomes should raise awareness for anesthesiologists, obstetricians, pediatricians and intensive care physicians to identify severe cases of COVID-19 in pregnant women during childbirth and to take the necessary precautions to ensure the best treatment of mother and neonate. The prospective acquisition of data allowed a timely assessment of the highly dynamic situation and gain knowledge regarding this vulnerable group of patients., (© 2021. The Author(s).)

Background and Purpose: The use of direct oral anticoagulants (DOAC) has increased sharply and DOAC are the oral anticoagulant therapy (OAT) of choice for the majority of patients with newly-diagnosed atrial fibrillation. Intracranial hemorrhage is the most severe adverse event of OAT. Systematic data on the course of intracranial hemorrhage under DOAC compared to vitamin K antagonists (VKA) are warranted to enable shared decision making in AF patients needing OAT., Methods: This is a secondary analysis of the patients with intracranial bleedings from the prospective multicenter emergency department-based RADOA registry, which collected data on patients admitted with major bleeding while taking VKA or DOAC. The primary endpoint was in-hospital mortality until day 30. We evaluated hematoma volume and short-term clinical outcomes in relation to the extent of active OAT according to coagulation parameters and OAT plasma levels measured by UPLC-MS/MS., Results: Of 193 patients with major bleeding, 109 (56.5%) had intracranial hemorrhage [52.3% intracerebral (ICH), 33.9% subdural (SDH), 11.0% subarachnoidal (SAH)]. 64 (58.7%) were on VKA and 45 (41.2%) were on DOAC. On admission, we could confirm active anticoagulation in 97.7% of VKA-treated patients based on either INR > 1.3 or phenprocoumon levels and in 75.8% of DOAC-treated patients based on DOAC levels. Patients suffering an intracranial hemorrhage under VKA showed significantly larger hematoma volumes and a higher in-hospital mortality. Especially in intracerebral hemorrhage, we observed a higher initial severity and numerically greater proportion of early changes towards palliative therapy under VKA, which coincided with a numerically higher case fatality., Conclusions: We show significantly smaller hematoma volumes for ICH and SDH under DOAC in comparison to VKA and a significantly lower 30-day in-hospital mortality rate of DOAC-ICH, even before the introduction of specific antidotes. These data strongly support the use of DOAC whenever possible in patients requiring OAT., Trial Registration: http://www., Clinicaltrials: gov ; Unique identifier: NCT01722786., (© 2022. The Author(s).)

Background: Direct oral anticoagulants (DOACs) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations., Methods: A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In samples collected as part of routine care DOAC drug concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Anticoagulant intensity at first presentation and drug half-life ( t 1/2 ), tested in repeat samples, were evaluated., Results: A total of 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. Note that 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban-treated patients t ½ was 17.3 hours (95% confidence interval [CI]: 15.4-19.7) without significant difference in both groups (major bleeding: t ½ 16.7 hours, 95% CI: 14.7-19.3; urgent surgery: t ½ 19.7 hours, 95% CI: 15.2-27.9; p  = 0.292). In apixaban-treated patients t ½ was 25.0 hours (95% CI: 22.9-27.6) with a longer t ½ after urgent surgery ( t 1/2 : 30.8 hours; 95% CI: 26.9-36.4) compared with severe bleeding ( t 1/2 : 20.8 hours; 95% CI: 18.8-23.2; p  < 0.001)., Conclusion: Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t ½ ., Competing Interests: E.L.-L. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Portola, CSL Behring, and Aspen and institutional research support from Bayer AG, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, and CSL-Behring. I.B. has received speaker's honoraria from Bristol-Myers Squibb/Pfizer, Siemens Healthcare, LFB biomedicaments, and CSL Behring and reimbursement for congress travelling and accommodation from Aspen and Bristol-Myers Squibb. She has performed contract research for Siemens Healthcare and is a member of the advisory board of LFB biomedicaments and of the expert groups of CSL Behring GmbH and Siemens Healthcare Diagnostics Products GmbH. S.K. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, MSD, Actelion, and Daiichi-Sankyo; and institutional research support from Bayer AG, Boehringer Ingelheim, MSD, Actelion, and Daiichi-Sankyo. O.G. has received research funding from Bayer Healthcare, Boehringer Ingelheim, Biotest, CSL Behring, Octapharma, Novo Nordisk, Nycomed, and Portola. He has also received honoraria for lectures and consultancy support from Bayer Healthcare, Boehringer Ingelheim, CSL Behring, Octapharma, Sanofi, Shire, Pfizer, and Portola. U.N.-G. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Octapharma, and LFB. C.v.H. has received honoraria for lectures and consultancy work potentially related to this topic, as well as travel reimbursements from Bayer GmbH, Biotest GmbH, Pfizer GmbH, Daiichi Sankyo, CSL Behring, NovoNordisk GmbH, and HICC GbR. J.B.-W. has received personal honoraria (lectures, advisory boards) and travel support from Bayer, Daiichi Sankyo, Janssen, and Portola and institutional research support from Bayer, Daiichi Sankyo, Janssen, LEO, Pfizer, and Portola. S.S. has received honoraria for lectures from Bayer, Boehringer, Daiichi Sankyo, and Pfizer, grants, and honoraria from BMS. P.M. has received grants from B. Braun Melsungen, CSL Behring, Fresenius Kabi, and Vifor Pharma for the implementation of Frankfurt's Patient Blood Management program and honoraria for scientific lectures from B. Braun Melsungen, Vifor Pharma, Fearing, CSL Behring, and Pharmacosmos. A.G. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer and Daiichi-Sankyo, ASPEN. The other authors report no conflict of interest. The funders had no role in the design of the registry, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Bleeding is a potential complication after neuraxial and peripheral nerve blocks. The risk is increased in patients on antiplatelet and anticoagulant drugs. This joint guideline from the European Society of Anaesthesiology and Intensive Care and the European Society of Regional Anaesthesia aims to provide an evidence-based set of recommendations and suggestions on how to reduce the risk of antithrombotic drug-induced haematoma formation related to the practice of regional anaesthesia and analgesia., Design: A systematic literature search was performed, examining seven drug comparators and 10 types of clinical intervention with the outcome being peripheral and neuraxial haematoma. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the methodological quality of the included studies and for formulating recommendations. A Delphi process was used to prepare a clinical practice guideline., Results: Clinical studies were limited in number and quality and the certainty of evidence was assessed to be GRADE C throughout. Forty clinical practice statements were formulated. Using the Delphi-process, strong consensus (>90% agreement) was achieved in 57.5% of recommendations and consensus (75 to 90% agreement) in 42.5%., Discussion: Specific time intervals should be observed concerning the adminstration of antithrombotic drugs both prior to, and after, neuraxial procedures or those peripheral nerve blocks with higher bleeding risk (deep, noncompressible). These time intervals vary according to the type and dose of anticoagulant drugs, renal function and whether a traumatic puncture has occured. Drug measurements may be used to guide certain time intervals, whilst specific reversal for vitamin K antagonists and dabigatran may also influence these. Ultrasound guidance, drug combinations and bleeding risk scores do not modify the time intervals. In peripheral nerve blocks with low bleeding risk (superficial, compressible), these time intervals do not apply., Conclusion: In patients taking antiplatelet or anticoagulant medications, practitioners must consider the bleeding risk both before and after nerve blockade and during insertion or removal of a catheter. Healthcare teams managing such patients must be aware of the risk and be competent in detecting and managing any possible haematomas., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Introduction: Limited data were published on the management of direct oral anticoagulants in the insertion of pacemaker and cardiac monitoring devices. This study describes the management and outcomes of edoxaban, a direct oral factor Xa inhibitor, in patients undergoing pacemaker or monitoring device implantation in routine clinical practice., Methods and Results: EMIT-AF/VTE collected data of patients from Europe, Korea, and Taiwan. Timing and duration of periprocedural interruption of edoxaban were at the treating physician's discretion. Pacemakers or monitoring devices were implanted into 136 patients who were evaluated from 5 days pre- until 30 days post-procedure. The primary outcomes were the incidences of acute thromboembolic events (ATE), ischemic events, and International Society on Thrombosis and Haemostasis-defined Major Bleeding; secondary outcomes included incidence of clinically relevant non-major bleeding (CRNMB) and perioperative edoxaban interruption times. Conformance with European Heart Rhythm Association (EHRA) Guidance on interruption of direct oral anticoagulant therapy was variable: of the cardiac monitoring device patients, where no interruption of therapy would be expected, nonetheless, 62.5% had interruption of treatment, whereas in pacemaker procedures, where interruption would be expected, 23.4% had no interruption. No ATE or ischemic events occurred. One case of CRNMB and two of minor bleeding occurred. All bleedings occurred more than 3 days after the procedure., Conclusion/relevance: The periprocedural complication risk for edoxaban treated patients undergoing pacemaker or invasive cardiac monitoring implantation was low. This population of patients was well managed in routine practice., (© 2021 Wiley Periodicals LLC.)

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg -1 . This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg -1 ) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy., (© 2020 Association of Anaesthetists.)

Background/objective: Postdural puncture headache (PDPH) is a severe complication after spinal anesthesia. The aim of this study was to investigate the incidence of PDPH in two different operative cohorts and to identify risk factors for its occurrence as well as to analyze its influence on the duration of hospital stay., Material and Methods: In a retrospective study over a period of 3 years (2010-2012), 341 orthopedic surgery (ORT) and 2113 obstetric (OBS) patients were evaluated after spinal anesthesia (SPA). Data were statistically analyzed using (SPSS-23) univariate analyses with the Mann-Whitney U‑test, χ 2 -test and Student's t-test as well as logistic regression analysis., Results: The incidence of PDPH was 5.9% in the ORT cohort and 1.8% in the OBS cohort. Patients with PDPH in the ORT cohort were significantly younger (median 38 years vs. 47 years, p = 0.011), had a lower body weight (median 70.5 kg vs. 77 kg, p = 0.006) and a lower body mass index (median 23.5 vs. 25.2, p = 0.037). Body weight (odds ratio (97.5 % Confidence Intervall [CI]), OR 0.956: 97.5% CI 0.920-0.989, p = 0.014) as well as age (OR 0.963: 97.5% CI 0.932-0.991, p = 0.015) were identified as independent risk factors for PDPH. In OBS patients, PDPH occurred more frequently after spinal epidural anesthesia than after combined spinal epidural anesthesia (8.6% vs. 1.2%, p < 0.001) and the type of neuraxial anesthesia was identified as an independent risk factor for PDPH (OR 0.049; 97.5% CI 0.023-0.106, p < 0.001). In both groups the incidence of PDPH was associated with a longer hospital stay (ORT patients 4 days vs. 2 days, p = 0.001; OBS patients 6 days vs. 4 days, p < 0.0005)., Conclusion: The incidence of PDPH was different in the two groups with a higher incidence in the ORT but considerably lower than in the literature. Age, constitution and type of neuraxial anesthesia were identified as risk factors of PDPH. Considering the functional imitations (mobilization, neonatal care) and a longer hospital stay, future studies should investigate the impact of an early treatment of PDPH.

Background: Accidental dural puncture is an uncommon complication of epidural analgesia and can cause postdural puncture headache (PDPH). We aimed to describe management practices and outcomes after PDPH treated by epidural blood patch (EBP) or no EBP., Methods: Following ethics committee approval, patients who developed PDPH after accidental dural puncture were recruited from participating countries and divided into two groups, those receiving EBP or no EBP. Data registered included patient and procedure characteristics, headache symptoms and intensity, management practices, and complications. Follow-up was at 3 months., Results: A total of 1001 patients from 24 countries were included, of which 647 (64.6%) received an EBP and 354 (35.4%) did not receive an EBP (no-EBP). Higher initial headache intensity was associated with greater use of EBP, odds ratio 1.29 (95% confidence interval 1.19-1.41) per pain intensity unit increase. Headache intensity declined sharply at 4 h after EBP and 127 (19.3%) patients received a second EBP. On average, no or mild headache (numeric rating score≤3) was observed 7 days after diagnosis. Intracranial bleeding was diagnosed in three patients (0.46%), and backache, headache, and analgesic use were more common at 3 months in the EBP group., Conclusions: Management practices vary between countries, but EBP was more often used in patients with greater initial headache intensity. EBP reduced headache intensity quickly, but about 20% of patients needed a second EBP. After 7 days, most patients had no or mild headache. Backache, headache, and analgesic use were more common at 3 months in patients receiving an EBP., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Annually > 10% of patients with atrial fibrillation on oral anticoagulation undergo invasive procedures. Optimal peri-procedural management of anticoagulation, as judged by major bleeding and thromboembolic events, especially in the elderly, is still debated., Methods: Procedures from 1442 patients were evaluated. Peri-procedural edoxaban management was guided only by the experience of the attending physician. The primary safety outcome was the rate of major bleeding. Secondary outcomes included the peri-procedural administration of edoxaban, other bleeding events, and the main efficacy outcome, a composite of acute coronary syndrome, non-hemorrhagic stroke, transient ischemic attack, systemic embolic events, deep vein thrombosis, pulmonary embolism, and mortality., Results: Of the 1442 patients, 280 (19%) were < 65, 550 (38%) were 65-74, 514 (36%) 75-84, and 98 (7%) were 85 years old or older. With increasing age, comorbidities and risk scores were higher. Any bleeding complications were uncommon across all ages, ranging from 3.9% in patients < 65 to 4.1% in those 85 years or older; major bleeding rates in any age group were ≤ 0.6%. Interruption rates and duration increased with advancing age. Thromboembolic events were more common in the elderly, with all nine events occurring in those > 65, and seven in patients aged > 75 years., Conclusion: Despite increased bleeding risk factors in the elderly, bleeding rates were small and similar across all age groups. However, there was a trend toward more thromboembolic complications with advancing age. Further efforts to identify the optimal management to reduce ischemic complications are needed., Trial Registration: NCT# 02950168, October 31, 2016.

Background: Approximately 30% of adults undergoing non-cardiac surgery suffer from preoperative anaemia. Preoperative anaemia is a risk factor for mortality and adverse outcomes in different surgical specialties and is frequently the reason for blood transfusion. The most common causes are renal, chronic diseases, and iron deficiency. International guidelines recommend that the cause of anaemia guide preoperative anaemia treatment. Recombinant human erythropoietin (rHuEPO) with iron supplementation has frequently been used to increase preoperative haemoglobin concentrations in patients in order to avoid the need for perioperative allogeneic red blood cell (RBC) transfusion., Objectives: To evaluate the efficacy of preoperative rHuEPO therapy (subcutaneous or parenteral) with iron (enteral or parenteral) in reducing the need for allogeneic RBC transfusions in preoperatively anaemic adults undergoing non-cardiac surgery., Search Methods: We searched CENTRAL, Ovid MEDLINE(R), Ovid Embase, ISI Web of Science: SCI-EXPANDED and CPCI-S, and clinical trial registries WHO ICTRP and ClinicalTrials.gov on 29 August 2019., Selection Criteria: We included all randomized controlled trials (RCTs) that compared preoperative rHuEPO + iron therapy to control treatment (placebo, no treatment, or standard of care with or without iron) for preoperatively anaemic adults undergoing non-cardiac surgery. We used the World Health Organization (WHO) definition of anaemia: haemoglobin concentration (g/dL) less than 13 g/dL for males, and 12 g/dL for non-pregnant females (decision of inclusion based on mean haemoglobin concentration). We defined two subgroups of rHuEPO dosage: 'low' for 150 to 300 international units (IU)/kg body weight, and 'high' for 500 to 600 IU/kg body weight., Data Collection and Analysis: Two review authors collected data from the included studies. Our primary outcome was the need for RBC transfusion (no autologous transfusion, fresh frozen plasma or platelets), measured in transfused participants during surgery (intraoperative) and up to five days after surgery. Secondary outcomes of interest were: haemoglobin concentration (directly before surgery), number of RBC units (where one unit contains 250 to 450 mL) transfused per participant (intraoperative and up to five days after surgery), mortality (within 30 days after surgery), length of hospital stay, and adverse events (e.g. renal dysfunction, thromboembolism, hypertension, allergic reaction, headache, fever, constipation)., Main Results: Most of the included trials were in orthopaedic, gastrointestinal, and gynaecological surgery and included participants with mild and moderate preoperative anaemia (haemoglobin from 10 to 12 g/dL). The duration of preoperative rHuEPO treatment varied across the trials, ranging from once a week to daily or a 5-to-10-day period, and in one trial preoperative rHuEPO was given on the morning of surgery and for five days postoperatively. We included 12 trials (participants = 1880) in the quantitative analysis of the need for RBC transfusion following preoperative treatment with rHuEPO + iron to correct preoperative anaemia in non-cardiac surgery; two studies were multiarmed trials with two different dose regimens. Preoperative rHuEPO + iron given to anaemic adults reduced the need RBC transfusion (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.38 to 0.80; participants = 1880; studies = 12; I 2 = 84%; moderate-quality evidence due to inconsistency). This analysis suggests that on average, the combined administration of rHuEPO + iron will mean 231 fewer individuals will need transfusion for every 1000 individuals compared to the control group. Preoperative high-dose rHuEPO + iron given to anaemic adults increased the haemoglobin concentration (mean difference (MD) 1.87 g/dL, 95% CI 1.26 to 2.49; participants = 852; studies = 3; I 2 = 89%; low-quality evidence due to inconsistency and risk of bias) but not low-dose rHuEPO + iron (MD 0.11 g/dL, 95% CI -0.46 to 0.69; participants = 334; studies = 4; I 2 = 69%; low-quality evidence due to inconsistency and risk of bias). There was probably little or no difference in the number of RBC units when rHuEPO + iron was given preoperatively (MD -0.09, 95% CI -0.23 to 0.05; participants = 1420; studies = 6; I 2 = 2%; moderate-quality evidence due to imprecision).  There was probably little or no difference in the risk of mortality within 30 days of surgery (RR 1.19, 95% CI 0.39 to 3.63; participants = 230; studies = 2; I 2 = 0%; moderate-quality evidence due to imprecision) or of adverse events including local rash, fever, constipation, or transient hypertension (RR 0.93, 95% CI 0.68 to 1.28; participants = 1722; studies = 10; I 2 = 0%; moderate-quality evidence due to imprecision). The administration of rHuEPO + iron before non-cardiac surgery did not clearly reduce the length of hospital stay of preoperative anaemic adults (MD -1.07, 95% CI -4.12 to 1.98; participants = 293; studies = 3; I 2 = 87%; low-quality evidence due to inconsistency and imprecision)., Authors' Conclusions: Moderate-quality evidence suggests that preoperative rHuEPO + iron therapy for anaemic adults prior to non-cardiac surgery reduces the need for RBC transfusion and, when given at higher doses, increases the haemoglobin concentration preoperatively. The administration of rHuEPO + iron treatment did not decrease the mean number of units of RBC transfused per patient. There were no important differences in the risk of adverse events or mortality within 30 days, nor in length of hospital stay. Further, well-designed, adequately powered RCTs are required to estimate the impact of this combined treatment more precisely., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Guidance for periprocedural anticoagulant management is mainly based on limited data from Phase III or observational studies and expert opinion., Hypothesis: EMIT-AF/VTE was designed to document the risks of bleeding and thromboembolic events in more than 1000 patients on edoxaban undergoing diagnostic and therapeutic procedures in clinical practice., Methods: Routine care in a multinational multicenter, prospective observational study. Participants were adult patients with atrial fibrillation and/or venous thromboembolism treated with edoxaban for stroke prevention or for secondary prevention in venous thromboembolic disease, undergoing a wide range of diagnostic and therapeutic procedures. Edoxaban therapy was interrupted periprocedurally at the treating physician's discretion. Patients were evaluated from 5 days pre- until 30 days postprocedure. Primary outcome was the incidence of International Society on Thrombosis and Haemostasis defined major bleeding; secondary outcomes included incidence of clinically relevant non-major bleeding, acute coronary syndrome, and acute thromboembolic events., Results: Outcomes and management are reported for the first procedures in 1155 unselected patients. Five cases of major bleeding (0.4%) and eight of clinically relevant non-major bleeding (0.7%) were documented, five (38%) of which occurred outside the period of likely edoxaban effect (last edoxaban dose ≥3 days prior to bleeding). Five (0.4%) deaths from any cause, seven acute thromboembolic events (0.6%) including two cardiac deaths (0.2%) in six patients, and one acute coronary event (0.1%) occurred., Conclusions: The periprocedural bleeding and acute thromboembolic event risks for patients treated with edoxaban were low. This can help inform both clinical routine and guidelines for the periprocedural management of edoxaban., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

An understanding of reversal strategies alone is important to safely and effectively care for patients in cases of bleeding or invasive procedures. The recent diversification in the number of licensed anticoagulants makes an understanding of drug-specific reversal strategies essential. Intravenous or oral vitamin K can reverse the effect of vitamin K antagonists (VKAs) within 12 to 48 hours and is indicated for any bleeding or an international normalized ratio >10 or 4.5 to 10 in patients with additional risk factors for bleeding. Furthermore, an additional administration of prothrombin complex concentrate (PCC) may be necessary in cases of major bleeding related to VKA. Protamine (chloride or sulfate) fully reverses the effect of unfractionated heparin and partially in low-molecular-weight heparin. Idarucizumab has been approved for dabigatran reversal, whereas andexanet alfa is approved for the reversal of some oral factor Xa inhibitors (apixaban, rivaroxaban). PCC seems to enhance the haemostatic potential for the reversal of the effect of FXa-inhibitors. So far, there are promising but only limited data on the efficacy of this approach available. Each reversal strategy needs an adequate management beyond the hemostatic treatment (volume replacement, stabilization of homeostasis, e.g., pH and temperature, resumption of anticoagulation after successful treatment of bleeding, etc.) that is crucial for the successful management of acute bleedings, urgent high-risk surgery, thrombolytic therapies or thrombectomies as well as overdosing of anticoagulants., Competing Interests: Adj. Prof. Dr. J. Koscielny declares the following conflicts of interest: speaker honoraria from Aspen, Bayer Health Care Pharmaceuticals, Biotest, Chugai, Daiichi Sankyo, Boehringer Ingelheim, CSL Behring, Pfizer, LFB, BMS, Mitsubishi, Roche, Sanofi, Novo Nordisk, and Shire (Takeda). Adj. Prof. Dr. Koscielny is also a medical advisor for CSL Behring International, Bayer HealthCare Pharmaceuticals (national and international), and Novo Nordisk (national).Dr. E. Rutkauskaite has no conflict of interest regarding the publication of this article.Adj. Prof. Dr. C. Sucker received honoraria for travel reimbursements, lectures, and consultancy work related to the topic of this article from Aspen, CSL Behring, DOASENSE, Chugai, Mitsubishi Pharma, Novo Nordisk, Novartis, Roche, Sanofi, and Werfen during the last 3 years.Prof. Dr. C. von Heymann received research grants, honoraria for travel reimbursements, lectures, and consultancy work related to the topic of this article from Bayer Pharma GmbH, Biotest GmbH, BMS, CSL Behring, Daiichi Sankyo Europe, HICC GbR, Novo Nordisk Pharma GmbH, Pfizer GmbH, and Takeda during the last 3 years., (Georg Thieme Verlag KG Stuttgart · New York.)

To date, data regarding the efficacy and safety of administering fibrinogen concentrate in cardiac surgery are limited. Studies are limited by their low sample size and large heterogeneity with regard to the patient population, by the timing of fibrinogen concentrate administration, and by the definition of transfusion trigger and target levels. Assessment of fibrinogen activity using viscoelastic point-of-care testing shortly before or after weaning from cardiopulmonary bypass in patients and procedures with a high risk of bleeding appears to be a rational strategy. In contrast, the use of Clauss fibrinogen test for determination of plasma fibrinogen level can no longer be recommended without restrictions due to its long turnaround time, high inter-assay variability and interference with high heparin levels and fibrin degradation products. Administration of fibrinogen concentrate for maintaining physiological fibrinogen activity in the case of microvascular post-cardiopulmonary bypass bleeding appears to be indicated. The available evidence does not suggest aiming for supranormal levels, however. Use of cryoprecipitate as an alternative to fibrinogen concentrate might be considered to increase plasma fibrinogen levels. Although conclusive evidence is lacking, fibrinogen concentrate does not seem to increase adverse outcomes (i.e., thromboembolic events). Large prospective multi-centre studies are needed to better define the optimal perioperative monitoring tool, transfusion trigger and target levels for fibrinogen replacement in cardiac surgery., (© 2019 Association of Anaesthetists.)

Bleeding and transfusion are common in cardiac surgery and associated with poorer outcome. Bleeding is frequently due to coagulopathy caused by the complex interaction between cardiopulmonary bypass, major surgical trauma, anticoagulation management, and perioperative factors. Patient blood management has emerged to improve outcome by the prediction, prevention, monitoring, and treatment of bleeding and transfusion. Each part of this chain has several individual modalities and when combined leads to result in a better outcome. This article reviews the hemostasis disturbances in cardiac surgery with cardiopulmonary bypass and gives an overview of the most important patient blood management strategies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: General (GA)- and epidural-anesthesia may cause a drop in body-core-temperature (BCT drop ), and hypothermia, which may alter tissue oxygenation (StO 2 ) and microperfusion after cytoreductive surgery for ovarian cancer. Cell metabolism of subcutaneous fat- or skeletal muscle cells, measured in microdialysis, may be affected. We hypothesized that forced-air prewarming during epidural catheter placement and induction of GA maintains normothermia and improves microperfusion., Methods: After ethics approval 47 women scheduled for cytoreductive surgery were prospectively enrolled. Women in the study group were treated with a prewarming of 43 °C during epidural catheter placement. BCT (Spot on®, 3 M) was measured before (T 1 ), after induction of GA (T 2 ) at 15 min (T 3 ) after start of surgery, and until 2 h after ICU admission (T ICU2h ). Primary endpoint was BCT drop between T 1 and T 2 . Microperfusion-, hemodynamic- and clinical outcomes were defined as secondary outcomes. Statistical analysis used the Mann-Whitney-U- and non-parametric-longitudinal tests., Results: BCT drop was 0.35 °C with prewarming and 0.9 °C without prewarming (p < 0.005) and BCT remained higher over the observation period (ΔT 4  = 0.9 °C up to ΔT 7  = 0.95 °C, p < 0.001). No significant differences in hemodynamic parameters, transfusion, arterial lactate and dCO 2 were measured. In microdialysis the ethanol ratio was temporarily, but not significantly, reduced after prewarming. Lactate, glucose and glycerol after PW tended to be more constant over the entire period. Postoperatively, six women without prewarming, but none after prewarming were mechanical ventilated (p < 0.001)., Conclusion: Prewarming at 43 °C reduces the BCT drop and maintains normothermia without impeding the perioperative routine patient flow. Microdialysis indicate better preserved parameters of microperfusion., Trial Registration: ClinicalTrials.gov ; ID: NCT02364219 ; Date of registration: 18-febr-2015.

Approximately 14-40% of patients in industrialized countries present with preoperative anemia. Depending on the severity, anemia is associates with increased perioperative morbidity and mortality. One of the most important causes of preoperative anemia is iron deficiency which is usually easy to treat. Implemented in the multimodal concept of patient blood management, the diagnostics and treatment of preoperative anemia are important aspects for improvement of perioperative outcome. Adequate and early diagnostics of the cause of anemia before treatment is important because treatment options, e.g. with iron, erythropoetin, folic acid and vitamin B 12 , may be expensive, may have severe side effects, and in the case of a wrong indication, will not improve anemia. In addition, an adequate regeneration of the erythrocyte volume requires time. This review article presents important aspects of the epidemiology and prognostic implications of preoperative anemia, the physiology and pathophysiology of anemia as well as diagnostic features and the evidence base for preoperative treatment options.

Introduction : Current guidelines recommend the administration of prothrombin complex concentrate in combination with vitamin K for normalization of coagulation in patients presenting with vitamin K antagonist-associated major bleeding, but until recently no adequately powered comparative trials had been conducted to support these recommendations. In this article, the authors review the evidence from studies assessing prothrombin complex concentrate treatment in these patients. Areas covered : A PubMed search (spanning January 1900 to September 2018) was conducted using the following search terms: prothrombin complex concentrate* AND (warfarin or (vitamin K antagonist*)), and papers relevant to major hemorrhagic events were identified; results from studies that used a randomized controlled trial (RCT) or a prospective design are presented here. Overall, the identified studies support the current guideline recommendations and indicate that prothrombin complex concentrates have at least similar safety profiles to other treatment options, such as fresh frozen plasma and recombinant activated factor VII. Expert opinion : It is hoped that the results from studies discussed here will inform future guideline updates; however, local clinical practice may also occasionally act as a barrier to adoption of guideline recommendations. There is an urgent need for further RCTs/prospective trials directly comparing PCC and plasma administration in acute bleeding settings.

Background: Apixaban is a direct oral anticoagulant (DOAC) with a specific inhibition of activated factor X (FXa). In case of bleeding or need of urgent surgery a direct antidote is not yet available. Off-label application of non-specific haemostatic agents, such as prothrombin complex concentrate (PCC) and recombinant FVIIa (rFVIIa), has been reported to reverse the effects of apixaban in in vitro and animal studies. The aim of this study is to measure the reversal potential of PCC and rFVIIa in patients with prophylactic apixaban concentrations., Material and Methods: Whole blood from patients under prophylactic therapy with apixaban was spiked with two doses of PCC or rFVIIa. Thromboelastometry (ROTEM ® ), prothrombin time (PT), and activated partial prothrombin time (aPTT) were performed., Results: Prolongations in PT and aPTT were corrected by the different concentrates with variable efficacies (PCC

Background: Adult cardiac surgery is often complicated by elevated blood losses that account for elevated transfusion requirements. Perioperative bleeding and transfusion of blood products are major risk factors for morbidity and mortality. Timely diagnostic and goal-directed therapies aim at the reduction of bleeding and need for allogeneic transfusions., Methods: Single-centre, prospective, randomized trial assessing blood loss and transfusion requirements of 26 adult patients undergoing elective cardiac surgery at high risk for perioperative bleeding. Primary endpoint was blood loss at 24 h postoperatively. Random assignment to intra- and postoperative haemostatic management following either an algorithm based on conventional coagulation assays (conventional group: platelet count, aPTT, PT, fibrinogen) or based on point-of-care (PoC-group) monitoring, i.e. activated rotational thromboelastometry (ROTEM®) combined with multiple aggregometry (Multiplate®). Differences between groups were analysed using nonparametric tests for independent samples., Results: The study was terminated after interim analysis (n = 26). Chest tube drainage volume was 360 ml (IQR 229-599 ml) in the conventional group, and 380 ml (IQR 310-590 ml) in the PoC-group (p = 0.767) after 24 h. Basic patient characteristics, results of PoC coagulation assays, and transfusion requirements of red blood cells and fresh frozen plasma did not differ between groups. Coagulation results were comparable. Platelets were transfused in the PoC group only., Conclusion: Blood loss via chest tube drainage and transfusion amounts were not different comparing PoC- and central lab-driven transfusion algorithms in subjects that underwent high-risk cardiac surgery. Routine PoC coagulation diagnostics do not seem to be beneficial when actual blood loss is low. High risk procedures might not suffice as a sole risk factor for increased blood loss., Trial Registration: NCT01402739 , Date of registration July 26, 2011.

Background: Maternal hypotension is a common side effect of spinal anaesthesia for Caesarean section. The combination of colloid coloading and vasopressors was considered our standard for its prevention and treatment. As the safety of hydroxyethyl starch is under debate, we replaced colloid with crystalloid coloading., Objective: We hypothesize that the mean blood pressure drop is greater when coloading with crystalloids., Design: Prospective, observational clinical trial., Setting: Two-centre study conducted in Berlin, Germany., Patients: Parturients scheduled for a Caesarean section were screened for eligibility., Intervention: The study protocol and patient monitoring were based on the standard operating procedure for Caesarean section in both centres. The data from the crystalloid group were prospectively collected between November 2014 and July 2015., Main Outcome Measures: The primary endpoint was the median drop in mean blood pressure after induction of spinal anaesthesia. Secondary endpoints were incidence of hypotension (drop > 20% of baseline systolic pressure /drop < 100 mmHg), vasopressor and additional fluid requirements (mL), incidence of bradycardia (heart rate < 60 beats per minute), blood loss, Apgar score, and umbilical artery pH. In case of hypotension, patients received phenylephrine or cafedrine/theodrenaline according to their heart rate. A p < 0.05 was considered significant., Results: 345 prospectively enrolled patients (n = 193 crystalloid group vs. n = 152 colloid group) were analysed. The median drop in mean blood pressure was greater in the crystalloid group [34 mmHg (25; 42 mmHg) vs. 21 mmHg (13; 29 mmHg), p < 0.001]. Incidences of hypotension [93.3% vs. 83.6%, p: 0.004] and bradycardia [19.7% vs. 9.9%, p: 0.012] were also significantly greater in the crystalloid group. Vasopressor requirements, blood loss and neonatal outcome were not different between the groups., Conclusions: Crystalloid coloading was associated with a greater drop in mean blood pressure and a higher incidence of hypotension when compared with colloid coloading. Neonatal outcome was, however, unaffected by the type of fluid., Trial Registration: DRKS00006783 ( http://www.drks.de ).

Despite current recommendations on the management of severe peri-operative bleeding, there is no pragmatic guidance for the peri-operative monitoring and management of cardiac surgical patients taking direct oral anticoagulants. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology, of their own volition, performed an independent systematic review of peer-reviewed original research, review articles and case reports and developed the following consensus statement. This has been endorsed by the European Association of Cardiothoracic Anaesthesiology. In our opinion, most patients on direct oral anticoagulant therapy presenting for elective cardiac surgery can be safely managed in the peri-operative period if the following conditions are fulfilled: direct oral anticoagulants have been discontinued two days before cardiac surgery, corresponding to five elimination half-live periods; in patients with renal or hepatic impairment or a high risk of bleeding, a pre-operative plasma level of direct oral anticoagulants has been determined and found to be below 30 ng.ml -1 (currently only valid for dabigatran, rivaroxaban and apixaban). In cases where plasma level monitoring is not possible (e.g. assay was not available), discontinuation for 10 elimination half-live periods (four days) is required. For FXa inhibitors, a standard heparin-calibrated anti-Xa level of < 0.1 IU.ml -1 should be measured, indicating sufficient reduction in the anticoagulant effect. Finally, short-term bridging with heparin is not required in the pre-operative period., (© 2018 Association of Anaesthetists.)

Despite the widespread use of DOAC and recommendations of regulatory agencies and first consensus meetings on handling of bleeding situation under DOAC uncertainty still exists. In case of mild bleeding, the medical care of these patients and the delay of the next dose is advised. A laboratory analysis is indicated i. e. in case of known higher grade liver and kidney failure. The administration of factor concentrates or antidots is not indicated in this situation. In case of moderate to severe bleeding, the primary focus lies on stabilization of cardiopulmonary and circulatory function and parallel on the treatment depending on the localization of the bleeding source. In life-threatening bleeding in addition to the measures of hemodynamic stabilization a special haemostasis management may be required. In severe life-threatening bleeding treatment algorithms should be applied. In factor Xa-inhibitor-associated bleeding the use of factor concentrates (procoagulants), i. e. PCC in addition to unspecific measures, is indicated, as the direct antagonist andexanet alpha has not been approved in the EU. In contrast, the specific antagonist idarucizumab for acute dabigatran reversal is available in Germany., Competing Interests: JK hat Vortragshonorare von Aspen, Bayer Health Care Pharmaceuticals, Daiichi Sankyo, Boehringer Ingelheim, CSL Behring, Sanofi-Aventis, Pfizer, BMS, Mitsubishi Pharma, Ferring GmbH und Novo Nordisk erhalten. JK war in den vergangenen 3 Jahren zudem als medizinischer Berater für CSL Behring International, Bayer HealthCare Pharmaceuticals (national und international) und Novo Nordisk (national) tätig.CR hat Vortragshonorare von Daiichi Sankyo erhalten.CH hat in den vergangenen 3 Jahren Honorare für Vorträge und Beratungstätigkeiten sowie Reisekostenerstattungen von Bayer AG, Boehringer Ingelheim, Pfizer GmbH, Bristol Myers Squibb, Daiichi Sankyo, CSL Behring, Novo Nordisk, Ferring GmbH, TEM International, Mylan Healthcare GmbH, Sanofi-Aventis und HICCGbR erhalten. Im selben Zeitraum hat er Forschungsgelder von Bayer AG, Boehringer Ingelheim und Bristol Myers Squibb erhalten., (© Georg Thieme Verlag KG Stuttgart · New York.)

Non-vitamin K dependent oral anticoagulants (NOAC) are now widely used in patients with nonvalvular atrial fibrillation (NVAF) for stroke prevention and in patients with venous thromboembolism (VTE) for the treatment and secondary prevention of the disease. Among NOAC, edoxaban demonstrated noninferiority to warfarin for stroke prevention in NVAF and for VTE treatment, with superior safety. EMIT-AF/VTE (Edoxaban Management in Diagnostic and Therapeutic Procedures) (NCT02950168) is a multicenter, prospective, and noninterventional registry study designed to collect detailed information on the periprocedural management of patients with NVAF and VTE receiving edoxaban. The primary objective of EMIT-AF/VTE is to document the periprocedural management of patients receiving edoxaban and to collect data on safety and other outcomes in these patients. The primary safety outcome is the rate of major bleeding. Other assessments include the evaluation of efficacy outcomes, periprocedural dosing, and timing of edoxaban. The observation period will start 5 days prior to the procedure and end 30 days post-procedure. EMIT-AF/VTE will aim to prospectively enroll up to approximately 1400 procedures from Europe. Enrollment commenced in December 2016 and will be completed in July 2018. As of July 2018, before database lock and with several procedure forms still temporarily inserted, a preliminary number of 1204 patients have been enrolled, who underwent a total of 1453 procedures. The prospective EMIT-AF/VTE registry program will expand the knowledge of periprocedural management of patients with NVAF and VTE receiving edoxaban in clinical practice., (© 2018 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

The study focuses the dose administration of dabigatran to avoid the deaths due to hemorrhagic complications and thromboembolic stroke in clinics worldwide. To target the issue, a novel emerging acoustic technology, namely ''Quartz Crystal Microbalance with Dissipation'' (QCM-D) has been applied, while the acoustic assays namely ''activated Partial Thromboplastin Time'' (aPTT) and ''Prothrombinase complex-induced Clotting Test'' (PiCT) have been compared with the standard methods in parallel. Both techniques have been applied to 300 samples, including 220 plasma samples of patients suffering coagulation disorders and 80 plasma samples of non-patients. In comparison, the coagulation times of the acoustic aPTT and PiCT yielded an excellent correlation with the standard methods with in analytical standard deviation limits. Finally, the acoustic aPTT assay is the ''gold standard'' for a dose administration of the new oral anticoagulant, where the Δf/ΔΓ ratio of the acoustic assay demonstrates that dabigatran with FEIBA 50 combination could be a safe remedy to avoid the deaths in clinics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Summary Peripartum haemorrhage remains one of the main causes of maternal mortality world-wide. The German, Austrian and Swiss Societies of Gynaecology and Obstetrics have updated the current guidelines for the treatment of peripartum haemorrhage together with the German Society of Anaesthesiology and Intensive Care Medicine and the Society of Thrombosis and Haemostasis Research. The recommendations have been the result of a thorough review of the available scientific literature and a consensus process involving all members of the guideline group. A key element of the anaesthesiological and haemostatic management is the development of a multidisciplinary standard operating procedure combining surgical as well as medical and haemostatic treatments depending on the severity of bleeding. The guideline underscores the value of clinical and laboratory diagnostics of peripartum haemorrhage as early as possible, even pre-emptively. This allows for an early identification of causes of bleeding and a specific treatment. The guideline comprises evidence-based recommendations for the use of uterotonics, tranexamic acid and blood products such as factor concentrates, fresh frozen plasma, platelet concentrates, packed red blood cells, recombinant activated factor VII and desmopressin. In addition, recommendations for blood conservation strategies involving the use of cell salvage, permissive hypotension and transfusion triggers are given.

Background: While hydroxyethyl starch (HES) solutions are not recommended any longer in critically ill patients, data on efficacy and safety during surgery are still limited., Methods: In a randomized controlled trial 63 patients were assigned to receive 10% HES (130/0.42), 6% HES (130/0.42), or crystalloid within a goal-directed hemodynamic algorithm during pancreatic surgery. The primary endpoints were intraoperative volume of HES and time until fully on oral diet., Results: The trial was terminated early upon recommendation of an independent data monitoring committee due to futility for efficacy at a planned interim analysis. The intraoperative volume of HES was not different between 10% and 6% HES group (2000 [1500; 2250] vs 2250 [1750; 3000] mL, P=.059). However, considering an inhomogeneity of patient's body weight between HES groups, there was a significant difference in intraoperative volume of HES between 10% and 6% group after adjusting for patient's body weight (24.0 [21.6; 28.3] vs 33.3 [28.2; 46.2] mL kg BW, P = .002). Patients in the HES groups required less additional fluid after dose limit than those in the crystalloid group, resulting in lower intraoperative net balances. The time until fully on oral diet was not different between all study groups. Applying KDIGO oliguria criterion, patients receiving 10% HES had more AKI compared to patients receiving crystalloids (86.7 vs 45.0%, P = .010), whereas those receiving 6% HES and crystalloids did not differ (58.8 vs 45.0%, P = .253). Further explorative analyses using a gray-zone approach indicated that patients receiving 6% HES below 18.8 mL kg will not experience AKI with near certainty., Conclusions: After adjusting for patient's body weight, patients receiving 6% HES required more volume of HES than patients receiving 10% HES. The relation of 140% represents very well the volume effect of a hyperoncotic 10% HES solution. Nonetheless, both HES solutions were similarly effective in reducing intraoperative fluid administration compared with crystalloid, but this did not result into differences in gastrointestinal outcomes. Patients receiving 10% HES showed an increased rate of AKI, whereas those receiving 6% HES and crystalloid did not differ. However, 6% HES should not be applied beyond 18 mL kg during surgery.

Purpose: This is an official interdisciplinary guideline, published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG), the Austrian Society of Gynaecology and Obstetrics (OEGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking countries and is backed by the German Society of Anaesthesiology and Intensive Medicine (DGAI), the Society of Thrombosis and Haemostasis Research (GTH) and the German Association of Midwives. The aim is to provide a consensus-based overview of the diagnosis and management of peripartum bleeding obtained from an evaluation of the relevant literature., Methods: This S2k guideline was developed from the structured consensus of representative members of the various professional associations and professions commissioned by the Guideline Commission of the DGGG., Recommendations: The guideline encompasses recommendations on definitions, risk stratification, prevention and management.