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Abstract Introduction Serious thrombembolic events occur in otherwise healthy marathon athletes during competition. We tested the hypothesis that during heavy endurance sports coagulation and platelets are activated depending on the type of endurance sport with respect to its running fraction. Materials and Methods 68 healthy athletes participating in marathon (MAR, running 42 km, n = 24), triathlon (TRI, swimming 2.5 km + cycling 90 km + running 21 km, n = 22), and long distance cycling (CYC, 151 km, n = 22) were included in the study. Blood samples were taken before and immediately after completion of competition to perform rotational thrombelastometry. We assessed coagulation time (CT), maximum clot firmness (MCF) after intrinsically activation and fibrin polymerization (FIBTEM). Furthermore, platelet aggregation was tested after activation with ADP and thrombin activating peptide 6 (TRAP) by using multiple platelet function analyzer. Results Complete data sets were obtained in 58 athletes (MAR: n = 20, TRI: n = 19, CYC: n = 19). CT significantly decreased in all groups (MAR -9.9%, TRI -8.3%, CYC -7.4%) without differences between groups. In parallel, MCF (MAR +7.4%, TRI +6.1%, CYC +8.3%) and fibrin polymerization (MAR +14.7%, TRI +6.1%, CYC +8.3%) were significantly increased in all groups. However, platelets were only activated during MAR and TRI as indicated by increased AUC during TRAP-activation (MAR +15.8%) and increased AUC during ADP-activation in MAR (+50.3%) and TRI (+57.5%). Discussion While coagulation is activated during physical activity irrespective of type we observed significant platelet activation only during marathon and to a lesser extent during triathlon. We speculate that prolonged running may increase platelet activity, possibly, due to mechanical alteration. Thus, particularly prolonged running may increase the risk of thrombembolic incidents in running athletes.

INTRODUCTION: Blood transfusion is associated with increased morbidity and mortality. We developed and implemented an algorithm for coagulation management in cardiovascular surgery based on first-line administration of coagulation factor concentrates combined with point-of-care thromboelastometry/impedance aggregometry. METHODS: In a retrospective cohort study including 3,865 patients, we analyzed the incidence of intraoperative allogeneic blood transfusions (primary endpoints) before and after algorithm implementation. RESULTS: Following algorithm implementation, the incidence of any allogeneic blood transfusion (52.5 vs. 42.2%; P < 0.0001), packed red blood cells (49.7 vs. 40.4%; P < 0.0001), and fresh frozen plasma (19.4 vs. 1.1%; P < 0.0001) decreased, whereas platelet transfusion increased (10.1 vs. 13.0%; P = 0.0041). Yearly transfusion of packed red blood cells (3,276 vs. 2,959 units; P < 0.0001) and fresh frozen plasma (1986 vs. 102 units; P < 0.0001) decreased, as did the median number of packed red blood cells and fresh frozen plasma per patient. The incidence of fibrinogen concentrate (3.73 vs. 10.01%; P < 0.0001) and prothrombin complex concentrate administration (4.42 vs. 8.9%; P < 0.0001) increased, as did their amount administered per year (179 vs. 702 g; P = 0.0008 and 162 x 10(3) U vs. 388 x 10(3) U; P = 0.0184, respectively). Despite a switch from aprotinin to tranexamic acid, an increase in use of dual antiplatelet therapy (2.7 vs. 13.7%; P < 0.0001), patients' age, proportion of females, emergency cases, and more complex surgery, the incidence of massive transfusion [(>=10 units packed red blood cells), (2.5 vs. 1.26%; P = 0.0057)] and unplanned reexploration (4.19 vs. 2.24%; P = 0.0007) decreased. Composite thrombotic/thromboembolic events (3.19 vs. 1.77%; P = 0.0115) decreased, but in-hospital mortality did not change (5.24 vs. 5.22%; P = 0.98). CONCLUSIONS: First-line administration of coagulation factor concentrates combined with point-of-care testing was associated with decreased incidence of blood transfusion and thrombotic/thromboembolic events. [ABSTRACT FROM AUTHOR]

(1) Diadenosine polyphosphates have been described to be present in the myocardium and exert purinergic- and nonreceptor-mediated effects. Since the electrophysiological properties of atrial myocardium are effectively regulated by A(1) receptors, we investigated the effect of diadenosine pentaphosphate (Ap(5)A) in rabbit myocardium. (2) Parameters of supraventricular electrophysiology and atrial vulnerability were measured in Langendorff-perfused rabbit hearts. Muscarinic potassium current (I(K(ACh/Ado))) and ATP-sensitive potassium current (I(K(ATP))) were measured by using the whole-cell voltage clamp method. (3) Ap(5)A prolonged the cycle length of spontaneously beating Langendorff perfused hearts from 225+/-14 (control) to 1823+/-400 ms (Ap(5)A 50 micro M; n=6; P<0.05). This effect was paralleled by higher degree of atrio-ventricular block. Atrial effective refractory period (AERP) in control hearts was 84+/-14 ms (n=6). Ap(5)A>/=1 micro M reduced AERP (100 micro M, 58+/-11 ms; n=6). (4) Extrastimuli delivered to hearts perfused with Ap(5)A- or adenosine (>/= micro M)-induced atrial fibrillation, the incidence of which correlated to the concentration added to the perfusate. The selective A(1)-receptor antagonist CPX (20 micro M) inhibited the Ap(5)A- and adenosine-induced decrease of AERP. Atrial fibrillation was no longer observed in the presence of CPX. (5) The described Ap(5)A-induced effects in the multicellular preparation were enhanced by dipyridamole (10 micro M), which is a cellular adenosine uptake inhibitor. Dipyridamole-induced enhancement was inhibited by CPX. (6) Ap(5)A (

A response from the authors of the article "Bleeding Risk Assessment in Patients Undergoing Elective Cardiac Surgery Using ROTEM Platelet and Multiplate Impedance Aggregometry" that was published in a previous issue is presented.

A letter to the editor is presented in response to the article about thromboelastometry measurements in the previous issue.

Purpose: Fractures of the proximal femur in geriatric patients are life-changing and life-threatening events. Previous research has identified fluid volume as an independent factor contributing to trauma patients' complications. Therefore, we aimed to investigate the impact of intraoperative fluid volume on outcomes in geriatric patients undergoing hip fracture surgery., Methods: We conducted a retrospective single-center study with data from the hospital information systems. Our study included patients aged 70 years or older who had sustained a proximal femur fracture. We excluded patients with pathologic, periprosthetic, or peri-implant fractures and those with missing data. Based on the fluids given, we divided patients into high-volume and low-volume groups., Results: Patients with a higher American Society of Anesthesiologists (ASA) grade and more comorbidities were more likely to receive more than 1500 ml of fluids. We observed significant differences in anesthesiologic management between the two groups, with a higher rate of invasive blood pressure management (IBP) and central venous catheter usage in the high-volume group. High-volume therapy was associated with a higher rate of complications (69.7% vs. 43.6%, p < 0.01), a higher transfusion rate (odds ratio 1.91 [1.26-2.91]), and an increased likelihood of patients being transferred to an intensive care unit (17.1% vs. 6.4%, p = 0.009). These findings were confirmed after adjusting for ASA grade, age, sex, type of fracture, Identification-of-Seniors-At-Risk (ISAR) score, and intraoperative blood loss., Conclusions: Our study suggests that intraoperative fluid volume is a significant factor that impacts the outcome of hip fracture surgery in geriatric patients. High-volume therapy was associated with increased complications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Literature shows conflicting results regarding spinal (SA) or general anesthesia (GA) and their influence on the outcome of elderly patients with hip fractures. We, therefore, conducted an analysis from the Registry for Geriatric Trauma (ATR-DGU)., Methods: A retrospective, multicenter registry study including patients aged 70 years or above with hip fractures requiring surgery from 131 Centers for Geriatric Trauma (AltersTraumaZentrum DGU®) from 2016 to 2021. Patients with SA or GA were compared using matched-pair analysis and linear and logistic regression models., Results: A total of 43,714 patients were included, of whom 3,242 received SA. The median age was 85 (SA) and 84 years (GA). Adjustments for the American Society of Anesthesiologists (ASA) grade, sex, age, additional injuries, and anticoagulation resulted in a higher in-hospital (odds ratio (OR) 1.31; 95% confidence interval [CI], 1.07 - 1.61, p = 0.009) and 120 days mortality (OR 1.47; 95% CI, 1.1 - 1.95, p = 0.009) in the GA group. GA had a significant negative influence on walking ability seven days after surgery and on the quality of life (QoL). The length of hospital stay (LoS) was significantly shorter in the SA group., Conclusions: SA is associated with a higher survival rate, a better walking ability seven days after surgery, a higher QoL, and a shorter LoS., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Despite an increasing number of patients suffering from an acute coronary syndrome under novel oral anticoagulant therapy, specific treatment recommendations for anticoagulation are still lacking. For this reason, the German Society of Cardiology and the German Association of Interdisciplinary Intensive Care and Emergency Medicine developed a consensus statement for the treatment of these patients with the aim to summarize the current evidence and to increase the safety of this special patient group., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The mechanisms of trauma induced coagulopathy (TIC) are considered multifactorial. Amongst others, however, shedding of the endothelial glycocalyx resulting in increased concentrations of glycocalyx fragments in plasma might also play a role. Thus, we hypothesized that shedded glycocalyx components affect coagulation and may act as humoral mediators of TIC., Methods: To investigate effects of heparan sulfate, chondroitin sulfate, syndecan-1, versican, and thrombomodulin we added these fragments to in vitro assays of whole blood from healthy volunteers to yield concentrations observed in trauma patients. Platelet function, whole blood coagulation, and fibrinolysis were measured by standard coagulation tests, impedance aggregometry (IA), and viscoelastic tests (VET). To assess dose-response relationships, we performed IA with increasing concentrations of versican and VET with increasing concentrations of thrombomodulin., Results: Intrinsically activated clotting times (i.e., activated partial thromboplastin time and intrinsically activated VET with and without heparinase) were unaffected by any glycocalyx fragment. Thrombomodulin, however, significantly and dose-dependently diminished fibrinolysis as assessed by VET with exogenously added rt-PA, and increased rt-PA-induced lysis Indices after 30 (up to 108% of control, p <  0,0001), 45 (up to 368% of control, p <  0,0001), and 60 min (up to 950% of control, p <  0,0001) in VET. Versican impaired platelet aggregation in response to arachidonic acid (up to - 37,6%, p <  0,0001), ADP (up to - 14,5%, p <  0,0001), and collagen (up to - 31,8%, p <  0,0001) in a dose-dependent manner, but did not affect TRAP-6 induced platelet aggregation. Clotting time in extrinsically activated VET was shortened by heparan sulfate (- 7,2%, p = 0,024), chondroitin sulfate (- 11,6%, p = 0,016), versican (- 13%, p = 0,012%), and when combined (- 7,2%, p = 0,007)., Conclusions: Glycocalyx components exert distinct inhibitory effects on platelet function, coagulation, and fibrinolysis. These data do not support a 'heparin-like auto-anticoagulation' by shed glycosaminoglycans but suggest a possible role of versican in trauma-induced thrombocytopathy and of thrombomodulin in trauma-associated impairment of endogenous fibrinolysis.

Objective: To evaluate the effects of 6% hydroxyethyl starch 130/0.4 (HES) and a polyionic isotonic crystalloid (CRYS) on standard coagulation tests and rotational thromboelastometry (ROTEM) in dogs with spontaneous hemoperitoneum (SHP)., Design: Prospective randomized open-label clinical study., Setting: University teaching hospital., Animals: Forty-two client-owned dogs presented with SHP., Interventions: Dogs diagnosed with SHP and hypovolemic shock were randomly allocated to receive HES (10 mL/kg, n = 22) or CRYS (30 mL/kg, n = 20) intravenously over 20 minutes for hemodynamic stabilization., Measurements and Main Results: Parameters measured before (T 0 ) and after (T 1 ) treatment were HCT, platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and extrinsic activated (EXTEM), intrinsic activated (INTEM), and extrinsic activated with platelet inhibition ROTEM assays. Data were analyzed as absolute values and as the percentage change from T 0 to T 1 . No significant differences between groups were detected in any variable at T 0 , and for HCT, platelet counts, prothrombin time, activated thromboplastin time, and fibrinogen concentrations at T 1 . Clot formation time in EXTEM was significantly prolonged (P = 0.037), and maximum clot firmness was significantly decreased (P = 0.038) in the HES group compared to the CRYS group at T 1 . The percentage change in EXTEM clotting time (P = 0.012) and INTEM clot formation time (P = 0.031) was greater after HES than CRYS. Lysis indices remained at 100% for all ROTEM assays in both groups., Conclusion: Compared to a 3-fold volume of CRYS, administration of HES was associated with impairment in ROTEM parameters in dogs with SHP, but no evidence of hyperfibrinolysis was detected., (© Veterinary Emergency and Critical Care Society 2020.)

Patients with coronavirus disease 2019 (COVID-19) frequently experience a coagulopathy associated with a high incidence of thrombotic events leading to poor outcomes. Here, biomarkers of coagulation (such as D-dimer, fibrinogen, platelet count), inflammation (such as interleukin-6), and immunity (such as lymphocyte count) as well as clinical scoring systems (such as sequential organ failure assessment [SOFA], International Society on Thrombosis and Hemostasis disseminated intravascular coagulation [ISTH DIC], and sepsis-induced coagulopathy [SIC] score) can be helpful in predicting clinical course, need for hospital resources (such as intensive care unit [ICU] beds, intubation and ventilator therapy, and extracorporeal membrane oxygenation [ECMO]) and patient's outcome in patients with COVID-19. However, therapeutic options are actually limited to unspecific supportive therapy. Whether viscoelastic testing can provide additional value in predicting clinical course, need for hospital resources and patient's outcome or in guiding anticoagulation in COVID-19-associated coagulopathy is still incompletely understood and currently under investigation (eg, in the rotational thromboelastometry analysis and standard coagulation tests in hospitalized patients with COVID-19 [ROHOCO] study). This article summarizes what we know already about COVID-19-associated coagulopathy and-perhaps even more importantly-characterizes important knowledge gaps.

The outcome of transfemoral transcatheter aortic valve implantation (TF-TAVI) with a self-expanding (SEP) versus a balloon-expandable prosthesis (BEP) in patients with a reduced ejection fraction (rEF, ≤40%) has not been previously investigated. Patients with rEF have an increased risk of death after TF-TAVI compared to patients with a preserved ejection fraction (pEF), and prosthesis choice might influence the outcome of these patients. We, therefore, sought to compare all-cause mortality of patients with rEF using a SEP versus a BEP. We retrospectively analyzed data of 679 single-center TF-TAVI patients. Patients were censored at death or completion of 1-year follow-up, whichever occurred first. Patients with rEF (n = 141, 21%) had an increased 1-year mortality compared to patients with pEF (28% vs 19%, p = 0.007). SEP were implanted in 149 patients (49 with rEF, 33%), while BEP were implanted in 530 patients (92 with rEF, 17%). In patients with pEF, 1-year mortality was similar after SEP- and BEP-implantation (16% vs 19%, p = 0.516). In patients with rEF, however, 1-year mortality was higher after SEP- than after BEP-implantation (43% vs 21%, p = 0.004). These patients had a higher incidence of new permanent pacemaker implantation (26.5% vs 13%, p = 0.046) and paravalvular leak ≥II° (21% vs 10%, p = 0.07), but both factors could not explain the excess mortality after SEP-implantation in the multivariate analysis. In patients with rEF, the use of a SEP was an independent predictor of 1-year mortality (HR 2.44, 95% CI 1.27 to 4.27, p = 0.007). In conclusion, patients with rEF had a higher 1-year mortality after TF-TAVI when a SEP instead of a BEP was used., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Since inadequate heparin anticoagulation and insufficient reversal can result in complications during cardiopulmonary bypass (CPB) surgery, heparin anticoagulation monitoring by point-of-care (POC) activated clotting time (ACT) measurements is essential for CPB initiation, maintainance, and anticoagulant reversal. However, concerns exist regarding reproducibility of ACT assays and comparability of devices., Methods: We evaluated the agreement of ACT assays using four parallel measurements performed on two commonly used devices each (i.e., two Hemochron Signature Elite (Hemochron) and two Abbott i-STAT (i-STAT) devices, respectively). Blood samples from 30 patients undergoing cardiac surgery on CPB were assayed at specified steps (baseline, after heparin administration, after protamine administration) with four parallel measurements (two of each device type) using commercial Kaolin activated assays provided by the respective manufactures. Measurements were compared between identical and different device types using linear regression, Bland-Altman analyses, and calculation of Cohen's kappa coefficient., Results: Parallel i-STAT ACTs demonstrated a good linear correlation (r = 0.985). Bias, as determined by Bland-Altman analysis, was low (- 3.8 s; 95% limits of agreement (LOA): - 77.8 -70.2 s), and Cohen's Kappa demonstrated good agreement (kappa = 0.809). Hemochron derived ACTs demonstrated worse linear correlation (r = 0.782), larger bias with considerably broader LOA (- 13.14 s; 95%LOA:-316.3-290 s), and lesser concordance between parallel assays (kappa = 0.554). Although demonstrating a fair linear correlation (r = 0.815), parallel measurements on different ACT-devices showed large bias (-20s; 95% LOA: - 290-250 s) and little concordance (kappa = 0.368). Overall, disconcordant results according to clinically predefined target values were more frequent with the Hemochron than i-STAT. Furthermore, while discrepancies in ACT between two parallel iSTAT assays showed little or no clinical relevance, deviations from parallel Hemochron assays and iSTAT versus Hemochron measurements revealed marked and sometimes clinically critical deviations., Conclusion: Currently used ACT point-of-care devices cannot be used interchangeably. Furthermore, our data question the reliability of the Hemochron in assessing adequacy of heparin anticoagulation monitoring for CPB.

Background: Carcinoid heart disease (CHD) (Hedinger syndrome) is a rare manifestation, it has been described in up to 60% of patients with both neuroendocrine tumors (NETs) and carcinoid syndrome (CS) which, typically inducing right heart-sided abnormalities., Methods: Between 07/15 and 10/18, six patients (mean age 63±12 years; 3 females) presented with manifested (NYHA III-IV) Hedinger syndrome's related valvular(s) lesion and were operated at our center. Clinical data, adverse events and patient outcomes were recorded., Results: The tricuspid valve was involved in all patients. Tricuspid valve repair was possible in four patients and two needed replacement. In two patients, operation was performed on beating heart without cross-clamping. Concomitant pulmonary valve replacement in two patients and aortic valve replacement in another two patients. A mean cross-clamp time of 61±50 minutes was observed. One patient with severely impaired right ventricular function needed ECMO support, and died 3 days later due to neuroendocrine enzyme storm. At 13 months, one patient developed severe tricuspid stenosis and underwent re-operation with replacement. Another patient died 18 months after surgery related to the underlying tumour. At mean of 30 months follow-up, four patients were alive and asymptotic., Conclusions: Hedinger syndrome is a challenging entity in cardiac surgery characterized by aggressive valve lesions combined with metastatic neuroendocrine neoplasia affecting the systemic circulation. We advise a multidisciplinary collaboration to early diagnose cardiac involvement to offer an early and proper treatment regime., Competing Interests: Conflicts of Interest: The study has been presented at the 68th international congress of the European Society for Cardiovascular and Endovascular Surgery, on 22–24 May 2019 in Groningen, Netherlands.

Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic method and enables to assess viscoelastic profiles of whole blood in various clinical settings. ROTEM-guided bleeding management has become an essential part of patient blood management (PBM) which is an important concept in improving patient safety. Here, ROTEM testing and hemostatic interventions should be linked by evidence-based, setting-specific algorithms adapted to the specific patient population of the hospitals and the local availability of hemostatic interventions. Accordingly, ROTEM-guided algorithms implement the concept of personalized or precision medicine in perioperative bleeding management ('theranostic' approach). ROTEM-guided PBM has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs. Accordingly, several randomized-controlled trials, meta-analyses, and health technology assessments provided evidence that using ROTEM-guided algorithms in bleeding patients resulted in improved patient's safety and outcomes including perioperative morbidity and mortality. However, the implementation of ROTEM in the PBM concept requires adequate technical and interpretation training, education and logistics, as well as interdisciplinary communication and collaboration.

Background: Most centres use fresh frozen plasma (FFP) based protocols to prevent or treat haemostatic disturbances during liver transplantation. In the present study, we used a rotational thrombelastometry (ROTEM™, TEM, Munich, Germany) guided haemostasis management with fibrinogen concentrates, prothrombin complex concentrates (PCC), platelet concentrates and tranexamic acid without FFP usage and determined the effect on 30 day mortality., Methods: Retrospective data analysis with 372 consecutive adult liver transplant patients performed between 2007 and 2011., Results: Thrombelastometry guided coagulation management resulted in a transfusion rate for fibrinogen concentrates in 50.2%, PCC in 18.8%, platelet concentrates in 21.2%, tranexamic acid in 4.5%, and red blood cell concentrates in 59.4%. 30 day mortality for the whole cohort was 14.2%. The univariate analyses indicated that nonsurvivors received significantly more fibrinogen concentrates, PCC, red blood cell concentrates, platelet concentrates, and infusion volume, and had a higher MELD score. However, association with mortality was weak as evidenced by receiver operating characteristic curve analyses. Further univariate analyses demonstrated, that up to 8 g of fibrinogen did not increase mortality compared to patients not receiving the coagulation factor. Multivariate analysis demonstrated that platelet concentrates (p = 0.0002, OR 1.87 per unit), infused volume (p = 0.0004, OR = 1.13 per litre), and MELD score (p = 0.024; OR 1.039) are independent predictors for mortality. Fibrinogen concentrates, PCC, and red blood cell concentrates were ruled out as independent risk factors., Conclusions: ROTEM™ guided substitution with fibrinogen concentrates and PCC does not negatively affect mortality after liver transplantation, while the well-known deleterious effect associated with platelet concentrates was confirmed.

Objectives: To evaluate the impact of baseline left ventricular ejection fraction (LVEF) and its interaction with low-gradient aortic stenosis (LGAS) on all-cause mortality after transfemoral aortic valve implantation (TF-TAVI)., Methods: We reviewed mortality data of 624 consecutive single center TF-TAVI patients and categorized LVEF according to current ASE/EACVI recommendations (normal, mildly-, moderately-, and severely abnormal)., Results: Baseline LVEF was normal in 336 (53.8%), mildly abnormal in 160 (25.6%), moderately abnormal in 91 (14.6%), and severely abnormal in 37 (5.9%) patients, and 1-year mortality was 19%, 17%, 23%, and 43% (P = 0.002), respectively. Patients with LGAS had a similar 1-year mortality compared to those without LGAS in groups with normal (19% vs 19%, P = 0.899) and mildly abnormal LVEF (16% vs 17%, P = 0.898). One-year mortality of patients with LGAS was significantly greater than in those without LGAS in presence of moderately abnormal LVEF (31% vs 11%, P = 0.022), and it was numerically greater than in those without LGAS in presence of severely abnormal LVEF (48% vs 25%, P = 0.219). In multivariate analysis, only the combination of moderately/severely abnormal LVEF and LGAS predicted increased 1-year mortality (HR: 2.12, 95% CI: 1.4-3.2, P < 0.001). Other variables, including EuroSCORE I did not affect this result., Conclusions: Moderately/severely abnormal LVEF (≤40%) at baseline is associated with increased mortality after TF-TAVI, especially when the mean transvalvular aortic gradient is <40 mm Hg (LGAS), while outcomes in patients with normal and mildly abnormal LVEF are comparable regardless of the pressure gradient across the native aortic valve. (DRKS00013729)., (© 2018 Wiley Periodicals, Inc.)

In severely injured patients, trauma-induced coagulopathy (TIC) present at hospital admission is associated with increased transfusion requirements, morbidity and mortality. Early and effective treatment contributes to improved survival rates. Laboratory coagulation assays have long turn-around times and evidence for their usefulness, especially in the context of TIC, is weak. Due to the lack of appropriate guidance, transfusion of allogeneic blood products frequently follows a ratio-based concept (e.g., transfusion of erythrocytes and plasma in a 1 : 1 ratio). Point-of-care (PoC) tests enable the assessment of prothrombin time (PT) and activated partial thromboplastin time in few minutes. However, although normal PT in these tests allows to rule out relevant effects of several anticoagulants, they are not able to detect patients with TIC and/or requiring subsequent massive transfusion. Viscoelastic tests (VETs) make it possible to assess defects in thrombin generation, hypofibrinogenaemia, thrombocytopenia, and hyperfibrinolysis, and thus enable targeted therapy. Impairment of platelet function is the common blind spot not detectable using both standard laboratory-based tests and VETs. However, PoC platelet function tests enable to detect platelet defects and patients taking anti-platelet. Furthermore, impaired platelet function has been identified as a strong predictor for coagulopathy and massive transfusion in trauma patients. In other clinical settings, coagulation management based on VETs is associated with decreased transfusion requirements, incidence of acute kidney failure, and mortality, respectively. Data of the first small prospective randomised trial indicate superiority of VET guided coagulation management solely using coagulation factor concentrates, when compared to plasma transfusions in severe trauma., Competing Interests: Priv.-Doz. Dr. D. Dirkmann hat Vortrags-/Beraterhonorare und/oder Reisekostenunterstützung der Firmen CSL Behring, TEM International und Abbott Point of Care erhalten und war Mitglied im Advisory Board für Instrumentation Laboratory. Dr. Martin W. Britten hat Vortragshonorare und Reisekosten von der Firma CSL Behring erhalten. Prof. Ulrich H. Frey hat Vortrags-/Beraterhonorare und/oder Reisekostenunterstützung der Firmen CSL Behring, BBraun und Aerogen erhalten., (Georg Thieme Verlag KG Stuttgart · New York.)

We review contemporary coagulation management for patients undergoing liver transplantation. A better understanding of the complex physiologic changes that occur in patients with end-stage liver disease has resulted in significant advances in anesthetic and coagulation management. A group of internationally recognized experts have critically evaluated current approaches for coagulopathy detection and management. Strategies for blood component and factor replacement have been evaluated and recommended therapies proposed. Pharmacologic treatment and prevention of coagulopathy, management of patients receiving antiplatelet medications, and the role of transesophageal echocardiography for early detection and management of thromboses are presented.

Background: Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T 0 ), as well as 5 (T 5 ), 60 (T 60 ) and 120 (T 120 ) minutes after administration of HTS or mannitol. Data at T 5 , T 60 and T 120 were analyzed as a percentage of values at T 0 for comparison between groups, and as absolute values for comparison between time points, respectively., Results: No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T 5 (both groups) and T 60 (HTS group)., Conclusions: Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.

Objectives: The purpose of this study is to evaluate the effects of a tailor-made, non-technical skills seminar on medical student's behaviour, attitudes, and performance during simulated patient treatment., Methods: Seventy-seven students were randomized to either a non-technical skills seminar (NTS group, n=43) or a medical seminar (control group, n=34). The human patient simulation was used as an evaluation tool. Before the seminars, all students performed the same simulated emergency scenario to provide baseline measurements. After the seminars, all students were exposed to a second scenario, and behavioural markers for evaluating their non-technical skills were rated. Furthermore, teamwork-relevant attitudes were measured before and after the scenarios, and perceived stress was measured following each simulation. All simulations were also evaluated for various medical endpoints., Results: Non-technical skills concerning situation awareness (p<.01, r=0.5) and teamwork (p<.01, r=0.45) improved from simulation I to II in the NTS group. Decision making improved in both groups (NTS: p<.01, r=0.39; control: p<.01, r=0.46). The attitude 'handling errors' improved significantly in the NTS group (p<.05, r=0.34). Perceived stress decreased from simulation I to II in both groups. Medical endpoints and patients´ outcome did not differ significantly between the groups in simulation II., Conclusions: This study highlights the effectiveness of a single brief seminar on non-technical skills to improve student's non-technical skills. In a next step, to improve student's handling of emergencies and patient outcomes, non-technical skills seminars should be accompanied by exercises and more broadly embedded in the medical school curriculum.

Background: Teaching emergency management should educate medical students not only for facts and treatment algorithms but also for time effective physical examination, technical skills, and team interaction. We tested the hypothesis, that using standardized emergency patients would be more effective in transmitting knowledge and skills compared with a more traditional teaching approach., Methods: Medical students (n = 242) in their fourth (second clinical) year were randomized to receive either training on standardized patients simulating 3 emergency settings ("acute chest pain," "stroke," and "acute dyspnea/asthma") or traditional small group seminars. Before and after the respective training pathways, the students' knowledge base (multiple-choice examination) and practical performance (objective structured clinical examination using 3 different emergency scenarios) were assessed., Results: Teaching using standardized patients resulted in a significant albeit small improvement in objective structured clinical examination scores (61.2 ± 3 for the standardized patient trained group vs 60.3 ± 3.5 for the traditional seminar group; P = 0.017, maximum achievable score: 66), but no difference in the written examination scores (27.4 ± 2.4 vs 27.0 ± 4.4; P = 0.341; maximum achievable score: 30)., Conclusion: Teaching management of emergencies using standardized patients can improve medical students' performance in clinical tests, and a change from traditional seminars in favor of practice sessions with standardized patients does not compromise the learning of medical facts., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays., Methods: Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay., Results: Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (-7%, P = 0.009; -7.8%, P < 0.0001; -6.9%, P < 0.0001; and -4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects., Conclusion: Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

Background: This multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients' postoperative analgesia without increasing surgical blood loss following radical open prostatectomy., Methods: 105 patients (64 ± 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed., Results: In each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 ± 24.1 mg versus 57 ± 28 mg, mean ± SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g⋅dL(-1) (3.6/4.9) versus (3.2 g⋅dL(-1) (2.4/4.95), p=0.02)., Conclusions: Following major abdominal surgery, parecoxib significantly improves patients' perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss., Trial Registration: ClinicalTrials.gov Identifier: NCT00346268.

Background: Allogeneic blood products transfusion during liver transplantation (LT) can be associated with increased morbidity and mortality. Data on thromboelastometry (ROTEM)-guided coagulation management with coagulation factor concentrates (CFCs)-fibrinogen concentrate and/or prothrombin complex concentrate (PCC)-are sparse. We aimed to retrospectively evaluate the safety events observed with this approach in our clinic., Study Design and Methods: LT patients from January 2009 to December 2010 (n = 266) were identified by chart review. A ROTEM-based algorithm with CFC guided the hemostatic therapy. Doppler ultrasound was used to evaluate thrombosis in the hepatic artery, portal vein, and hepatic veins. Stroke, myocardial ischemia, pulmonary embolism, and transfusion variables were recorded. Patients receiving CFC were included in the CFC group (n = 156); those not receiving CFC were included in the non-CFC group (n = 110). Safety events were compared between these two groups., Results: Allogeneic transfusion(s) in the 266 patients was low, with medians of 2 (interquartile range [IQR], 0-5), 0 (IQR 0-0), and 0 (IQR 0-1) units for red blood cells (RBCs), fresh-frozen plasma (FFP), and platelets (PLTs), respectively. Ninety-seven of 266 LTs (36.5%) were performed without RBCs transfusion, 227 (85.3%) without FFP, and 190 (71.4%) without PLTs. There were no significant differences in thrombotic, thromboembolic, and ischemic adverse events occurrence between the CFC group and the non-CFC group (11/156 patients vs. 5/110; p = 0.31)., Conclusion: In LT, ROTEM-guided treatment with fibrinogen concentrate and/or PCC did not appear to increase the occurrence of thrombosis and ischemic events compared to patients who did not receive these concentrates., (© 2014 AABB.)

Background: Although thromboelastometry (ROTEM®) and thrombelastography can be used for bedside diagnosis of fibrinolysis, the time needed for detection is often prolonged. Since untreated fibrinolysis can result in consumption of coagulation factors and bleeding, early diagnosis and decision making are desirable. Accordingly, we assessed ROTEM variables from extrinsically activated assays with (APTEM) and without (EXTEM) addition of aprotinin for their ability to rapidly identify fibrinolysis. Specifically, we tested the hypotheses that prolonged clotting time, clot formation time, low clot firmness (at 5, 10, 15, and 20 minutes, designated A5, A10, A15, and A20, respectively), low maximum clot firmness (MCF) in EXTEM assays, and differences in these variables from parallel APTEM and EXTEM assays (designated as Δvariables) predict fibrinolysis., Methods: Data from 411 thromboelastometric measurements (obtained from 352 patients) with fibrinolysis and from 2537 measurements without fibrinolysis (obtained from 1605 patients) were assessed and analyzed using receiver operating characteristics. Data were analyzed as a pooled fibrinolysis cohort, and subanalyses were performed from sets assigned to categories of fibrinolysis related to the timing of thrombus lysis (i.e., a decrease of clot firmness to <15% of MCF within 30, 45, and 60 minutes, respectively). A lower 95% confidence limit of the area under the receiver operating characteristic curve (AUC [SE] <0.6) was considered a failure to substantially improve detection of increased fibrinolysis. AUCs were compared to identify the variable providing the best predictive association with fibrinolysis. As a secondary end point, optimum cutoff values at the point estimate corresponding to the greatest Youden index were calculated along with the respective sensitivities and specificities., Results: In the pooled cohort, clot formation time (AUC: 0.652 [0.016]), α-angle (AUC: 0.675 [0.015]), A5 (AUC: 0.718 [0.013]), A10 (AUC: 0.734 [0.0.13]), A15 (AUC: 0.752 [0.013]), A20 (AUC: 0.771 [0.013]), and MCF (AUC: 0.799 [0.012]) predicted fibrinolysis. Fibrinolysis was also predicted by ΔA15 (AUC: 0.675 [0.016]), ΔA20 (AUC: 0.719 [0.015]), and ΔMCF (AUC: 0.812 [0.013]). AUCs increased in a time-related fashion. The ability to predict subsequent fibrinolysis based on thromboelastometry was higher when it occurred early rather than later during testing. However, for prediction of late fibrinolysis, only MCF (AUC: 0.655 [0.025]) appears to be potentially clinically useful., Conclusions: Low early values of clot firmness in extrinsically activated thromboelastometric assays are associated with fibrinolysis and improve its early detection. Additional assays with aprotinin fail to improve the early diagnosis of fibrinolysis compared with assays without aprotinin.

Bleeding is an important issue in cardiothoracic surgery, and about 20% of all blood products are transfused in this clinical setting worldwide. Transfusion practices, however, are highly variable among different hospitals and more than 25% of allogeneic blood transfusions have been considered inappropriate. Furthermore, both bleeding and allogeneic blood transfusion are associated with increased morbidity, mortality, and hospital costs. In the past decades, several attempts have been made to find a universal hemostatic agent to ensure hemostasis during and after cardiothoracic surgery. Most drugs studied in this context have either failed to reduce bleeding and transfusion requirements or were associated with severe adverse events, such as acute renal failure or thrombotic/thromboembolic events and, in some cases, increased mortality. Therefore, an individualized goal-directed hemostatic therapy ("theranostic" approach) seems to be more appropriate to stop bleeding in this complex clinical setting. The use of point-of-care (POC) transfusion and coagulation management algorithms guided by viscoelastic tests such as thromboelastometry/thromboelastography in combination with POC platelet function tests such as whole blood impedance aggregometry, and based on first-line therapy with fibrinogen and prothrombin complex concentrate have been associated with reduced allogeneic blood transfusion requirements, reduced incidence of thrombotic/thromboembolic and transfusion-related adverse events, and improved outcomes in cardiac surgery. This article reviews the current literature dealing with the management of hemorrhage in cardiothoracic surgery based on POC diagnostics and with specific coagulation factor concentrates and its impact on transfusion requirements and patients' outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose of Review: On the one hand, cardiac and aortic surgery is associated with a high rate of allogeneic blood transfusion. On the other hand, both bleeding and allogeneic blood transfusion is associated with increased morbidity, mortality, and hospital costs in cardiac and aortic surgery. This article reviews the current literature between 1995 and 2012 dealing with transfusion protocols in cardiovascular surgery. The 16 studies fitting these search criteria have evaluated the impact of the implementation of ROTEM/TEG based coagulation management algorithms on transfusion requirement and outcome in overall 8507 cardiovascular surgical patients., Recent Findings: The use of point-of-care (POC) transfusion and coagulation management algorithms based on viscoelastic tests such as thromboelastometry (ROTEM) and thrombelastography (TEG) in combination with POC platelet function tests such as whole blood impedance aggregometry (Multiplate) have been shown to be associated with reduced allogeneic blood transfusion requirements, reduced incidence of thrombotic/thromboembolic and transfusion-related adverse events, and improved outcomes in cardiac surgery., Summary: Implementation of POC algorithms including a comprehensive bundle of POC diagnostics (thromboelastometry and whole blood impedance aggregometry) in combination with first-line therapy using immediately available specific coagulation factor concentrates (fibrinogen and prothrombin complex concentrate) and defining strict indications, calculated dosages, and clear sequences for each haemostatic intervention seems to be complex but most effective in reducing perioperative transfusion requirements and has been shown to be associated with a decreased incidence of thrombotic/thromboembolic events, transfusion-related adverse events, as well as with improved patients' outcomes including 6-month mortality.

Background: Hypothermia and acidosis have been suggested as key initiators of trauma-induced coagulopathy, and severe bleeding caused by hyperfibrinolysis (HF) predicts mortality. We tested in vitro (1) whether clinically relevant grades of hypothermia, acidosis, and their combination impact on recombinant tissue-type plasminogen activator (r-tPA)-evoked HF and assessed (2) the efficacy of tranexamic acid (TA) in inhibiting fibrinolysis under such conditions., Methods: To assess the effects of r-tPA-evoked HF, venous blood (3,000 μL) from healthy volunteers was incubated with r-tPA (final concentration, 100 ng/mL) or saline (control) for 30 minutes at the final measurement temperature. Before thromboelastometric measurements, samples were acidified (addition of 40 μL of 0.5 or 1N hydrochloric acid, respectively) to achieve a pH (alpha-stat) of approximately 7.1 or 6.9, respectively. To assess effects of hypothermia, tests were performed at blood/thromboelastometer temperatures of 33°C and 37°C, respectively. Coagulation was analyzed using rotational thromboelastometry (ROTEM), particularly assessing the Clot Lysis Index (CLI) after 45 minutes (CLI45) in extrinsically activated assays (EXTEM)., Results: Addition of r-tPA evoked fibrinolysis (CLI45: median, 64; 25th/75th percentile, 48/80) compared with saline controls (CLI45: median, 93; 25th/75th percentile, 91/96). Moderate acidosis (pH [mean ± SD], 7.12 ± 0.03) did not affect r-tPA-induced fibrinolysis. However, severe acidosis (pH, 6.91 ± 0.02) significantly aggravated r-tPA-induced fibrinolysis (CLI45: median, 49; 25th/75th percentile, 26/71; p = 0.0039) compared with fibrinolysis with normal pH and normothermia (median, 77; 25th/75th percentile, 65.5/83). In contrast, hypothermia (33°C) at normal pH (median ± SD, 7.37 ± 0.02) markedly mitigated fibrinolysis (CLI45: median, 94; 25th/75th percentile, 88/96; p = 0.0156) compared with normothermia (CLI45: median, 64; 25th/75th percentile, 48/80). TA (final concentration, 0.33 mg/mL) abolished r-tPA-evoked fibrinolysis even during severe acidosis (CLI45: median, 92; 25th/75th percentile, 86.5/94; p = 0.0039)., Conclusion: Severe acidosis significantly increases r-tPA-evoked fibrinolysis, whereas hypothermia markedly mitigates HF. The latter finding may imply that rapid rewarming of trauma patients might aggravate fibrinolysis. TA reliably abolished fibrinolysis also under these conditions, supporting its role in trauma-induced coagulopathy.

The incidence of bleeding and thrombo-embolic complications in patients undergoing mechanical circulatory support therapy remains high and is associated with bad outcomes and increased costs. The need for anticoagulation and anti-platelet therapy varies widely between different pulsatile and non-pulsatile ventricular-assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) systems. Therefore, a unique anticoagulation protocol cannot be recommended. Notably, most thrombo-embolic complications occur despite values of conventional coagulation tests being within the targeted range. This is due to the fact that conventional coagulation tests such as international normalised ratio (INR), activated partial thromboplastin time (aPTT) and platelet count cannot detect hyper- or hypofibrinolysis, hypercoagulability due to tissue factor expression on circulating cells or increased clot firmness, and platelet aggregation as well as response to anti-platelet drugs. By contrast, point-of-care (POC) whole blood viscoelastic tests (thromboelastometry/-graphy) and platelet function tests (impedance or turbidimetric aggregometry) reflect in detail the haemostatic status of patients undergoing mechanical circulatory support therapy and the efficacy of their anticoagulation and antiaggregation therapy. Therefore, monitoring of haemostasis using POC thromboelastometry/-graphy and platelet function analysis is recommended during mechanical circulatory support therapy to reduce the risk of bleeding and thrombo-embolic complications. Notably, these haemostatic tests should be performed repeatedly during mechanical circulatory support therapy since thrombin generation, clot firmness and platelet response may change significantly over time with a high inter- and intra-individual variability. Furthermore, coagulation management can be hampered in non-pulsatile VADs by acquired von Willebrand syndrome, and in general by acquired factor XIII deficiency as well as by heparin-induced thrombocytopenia. In addition, POC testing can be used in bleeding patients to guide calculated goal-directed therapy with allogeneic blood products, haemostatic drugs and coagulation factor concentrates to optimise the haemostasis and to minimise transfusion requirements, transfusion-associated adverse events and to avoid thrombo-embolic complications, as well. However, coagulation management in patients undergoing mechanical circulatory support therapy is somehow like navigating between Scylla and Charybdis, and development of protocols based on POC testing seems to be beneficial., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Hyperfibrinolysis is a pathological state that often results in depletion of coagulation factors and platelets and can contribute to bleeding. Factor XIII (FXIII) and thrombin activatable fibrinolysis inhibitor have key roles in protecting clots against fibrinolysis. We tested the hypotheses that FXIII concentrate, prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), and tranexamic acid (TA) inhibit fibrinolysis to different degrees, and that platelets contribute to antifibrinolysis., Methods: Hyperfibrinolysis was induced by addition of recombinant tissue plasminogen activator (r-tPA) (final concentration: 100 ng · mL(-1)) to citrated whole blood obtained from 13 healthy volunteers. To assess inhibition of fibrinolysis, we added to the assays FXIII-A(2)B(2) (0.42 U · mL(-1)), PCC (0.42 U · mL(-1)), rFVIIa (final concentration: 1.6 μg · mL(-1)), TA (final concentration: 0.33 mg · mL(-1)), or saline. Coagulation was analyzed by rotational thromboelastometry (ROTEM®) using the clot lysis index (CLI) after 45 and 60 minutes in extrinsically activated assays, with (FIBTEM®) and without (EXTEM®) inhibition of platelet function by cytochalasin D., Results: After r-tPA-evoked fibrinolysis (CLI45: median 78%; 72/85.5, 25th/75th percentile), FXIII (90%; 82.5/96, P = 0.025), PCC (89%; 74/91, P = 0.0465), and TA (94%; 92/96, P = 0.001) but not rFVIIa (79%; 72/86.5, P = 1.0) significantly attenuated the decrease in CLI. Similarly, CLI60 increased only with FXIII (66%; 33/90.5, P = 0.017) and TA (90%; 89/92, P = 0.001) compared with r-tPA alone (21%; 7/59). After abolition of platelet function by cytochalasin D, only TA (95%; 89/97.5, P = 0.0025) and PCC (84%; 70.5/90, P = 0.0305) but not FXIII or rFVIIa significantly increased CLI45 and CLI60 (TA: 89%; 84.5/96, P = 0.01 and PCC: 55%; 29.5/60, P = 0.0405) compared with r-tPA alone (CLI45: 59%; 40.5/72.5 and CLI60: 10%; 0/30)., Conclusion: In thromboelastometric assays using whole blood, only TA, FXIII, and PCC significantly inhibited r-tPA-evoked hyperfibrinolysis whereas rFVIIa had no effect. We also found that the effects of exogenous FXIII were dependent on the presence of functional platelets.

BACKGROUND: Massive bleeding and transfusion of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets are associated with increased morbidity, mortality and costs. PATIENTS AND METHODS: We analysed the transfusion requirements after implementation of point-of-care (POC) coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in different perioperative settings (trauma surgery, visceral and transplant surgery (VTS), cardiovascular surgery (CVS) and general and surgical intensive care medicine) at 3 different hospitals (AUVA Trauma Centre Salzburg, University Hospital Innsbruck and University Hospital Essen) in 2 different countries (Austria and Germany). RESULTS: In all institutions, the implementation of POC coagulation management algorithms was associated with a reduction in the transfusion requirements for FFP by about 90% (Salzburg 94%, Innsbruck 88% and Essen 93%). Furthermore, PRBC transfusion was reduced by 8.4-62%. The incidence of intraoperative massive transfusion (≥10 U PRBC) could be more than halved in VTS and CVS (2.56 vs. 0.88%; p < 0.0001 and 2.50 vs. 1.06%; p = 0.0007, respectively). Platelet transfusion could be reduced by 21-72%, except in CVS where it increased by 115% due to a 5-fold increase in patients with dual antiplatelet therapy (2.7 vs. 13.7%; p < 0.0001). CONCLUSIONS: The implementation of perioperative POC coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and PCC is associated with a reduction in the transfusion requirements for FFP, PRBC and platelets as well as with a reduced incidence of massive transfusion. Thus, the limited blood resources can be used more efficiently.