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.

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 (T0 ) and after (T1 ) 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 T0 to T1 . No significant differences between groups were detected in any variable at T0 , and for HCT, platelet counts, prothrombin time, activated thromboplastin time, and fibrinogen concentrations at T1 . 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 T1 . 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.

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.

Objectives: Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion can reduce myocardial injury and improve patients’ prognosis following cardiac surgery in proof-of-concept and smaller randomized controlled trials (RCT), while two recent large Phase III RCTs were neutral for troponin release and outcome after 90 days and 1 year.

The outcome of transfemoral transcatheter aortic valve implantation (TF-TAVI) with a selfexpanding (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 pace-maker implantation (26.5% vs 13%, p = 0.046) and paravalvular leak >= II degrees (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. (C) 2020 Elsevier Inc. All rights reserved.

Patients with 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 SOFA, ISTH DIC and SIC score) can be helpful in predicting clinical course, need for hospital resources (such as ICU beds, intubation and ventilator therapy, and 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 (e.g., in the ROHOCO study). This paper summarizes what we know already about COVID-19 associated coagulopathy and - perhaps even more importantly - characterizes important knowledge gaps.

Background: Carcinoid heart disease (CUD) (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.

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. Retrospective data analysis with 372 consecutive adult liver transplant patients performed between 2007 and 2011. 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. 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.

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.

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.

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.

ZusammenfassungJeder 4. Schwerverletzte weist bereits bei Krankenhausaufnahme eine traumainduzierte Koagulopathie (TIK) auf, die mit einer 4-fach erhöhten Mortalität einhergeht. Rasche und zielgenaue Behandlung kann die TIK-assoziierte Sterblichkeit senken. Point-of-Care-Tests ermöglichen im Vergleich mit herkömmlichen Labormethoden eine zeitnahe und umfassende Bestimmung des Gerinnungsstatus sowie eine zielgerichtete Therapie.

ObjectivesTo 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).MethodsWe 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).ResultsBaseline 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.ConclusionsModerately/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).