Viscoelastic Hemostatic Testing as a Diagnostic Tool for Hypercoagulability in Liver Transplantation: A Narrative Review.

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.

Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.

OBJECTIVES: Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function. MATERIALS AND METHODS: We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/µL. RESULTS: Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units. CONCLUSIONS: End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.

Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia-a prospective, single-center, analytical, cross-sectional study.

Background: Patients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. Objectives: To evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. Methods: We performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. Results: Higher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. Conclusion: Patients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

Effect of ultrafiltration on whole blood coagulation profile during cardiopulmonary bypass in cardiac surgery: a retrospective analysis.

BACKGROUND: Ultrafiltration (UF) would enhance coagulation profiles by concentrating coagulation elements during cardiopulmonary bypass (CPB) for cardiac surgery. METHODS: We retrospectively reviewed electronic medical records of 75 patients who had undergone cardiac surgery with rotational thromboelastometry-based coagulation management in a university hospital and analyzed the UF-induced changes in the maximum clot firmness (MCF) of extrinsically activated test with tissue factor (EXTEM) during CPB in 30 patients. RESULTS: The median volume of filtered-free water was 1,350 ml, and median hematocrit was significantly increased from 22.5% to 25.5%. As the primary measure, UF significantly increased the median MCF-EXTEM from 48.0 mm to 50.5 mm (P = 0.015, effect size r = 0.44). The area under the receiver operating characteristic curve pre-UF MCF-EXTEM for discrimination of any increase of MCF-EXTEM after applying UF was 0.89 (95% CI [0.77, 1.00], P < 0.001), and its cut-off value was 50.5 mm (specificity of 81.8% and sensitivity of 84.2% in Youden's J statistic). In the secondary analyses using the cut-off value, UF significantly increased the median MCF-EXTEM from 40.5 mm to 42.5 mm in 18 patients with pre-UF MCF-EXTEM ≤ 50.5 mm. However, it did not increase MCF-EXTEM in 12 patients with pre-UF MCF-EXTEM > 50.5 mm. There was a significant interaction between pre-UF MCF-EXTEM values and applying UF (P < 0.001 for the subgroup, P = 0.046 for UF, P = 0.003 for interaction). CONCLUSIONS: Applying UF improved clot firmness, and the improvement was more pronounced when pre-UF MCF-EXTEM had been reduced during CPB.

Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review.

This is a narrative review of the published evidence for bleeding management in critically ill patients in different clinical settings in the intensive care unit (ICU). We aimed to describe "The Ten Steps" approach to early goal-directed hemostatic therapy (EGDHT) using point-of-care testing (POCT), coagulation factor concentrates, and hemostatic drugs, according to the individual needs of each patient. We searched National Library of Medicine, MEDLINE for publications relevant to management of critical ill bleeding patients in different settings in the ICU. Bibliographies of included articles were also searched to identify additional relevant studies. English-language systematic reviews, meta-analyses, randomized trials, observational studies, and case reports were reviewed. Data related to study methodology, patient population, bleeding management strategy, and clinical outcomes were qualitatively evaluated. According to systematic reviews and meta-analyses, EGDHT guided by viscoelastic testing (VET) has been associated with a reduction in transfusion utilization, improved morbidity and outcome in patients with active bleeding. Furthermore, literature data showed an increased risk of severe adverse events and poor clinical outcomes with inappropriate prophylactic uses of blood components to correct altered conventional coagulation tests (CCTs). Finally, prospective, randomized, controlled trials point to the role of goal-directed fibrinogen substitution to reduce bleeding and the amount of red blood cell (RBC) transfusion with the potential to decrease mortality. In conclusion, severe acute bleeding management in the ICU is still a major challenge for intensive care physicians. The organized and sequential approach to the bleeding patient, guided by POCT allows for rapid and effective bleeding control, through the rational use of blood components and hemostatic drugs, since VET can identify specific coagulation disorders in real time, guiding hemostatic therapy with coagulation factor concentrates and hemostatic drugs with individual goals.

Standardized in vitro bleeding tests in a non-coated novel hybrid prosthesis for frozen elephant trunk demonstrates minimal oozing during full heparinization, supported by clinical data.

Introduction: Recent reports have questioned the blood impermeability of the novel frozen elephant trunk (FET) device E-vita Open NEO© (EO-NEO). Therefore, standardized in vitro bleeding tests using porcine heparinized blood were performed, as well as stress testing on the blood tightness of the collar suture line, to investigate this observation. Material and methods: EO-NEO prostheses were examined in vitro for blood permeability in three test series. Initially, antegrade perfusion with heparinized porcine blood [activated clotting time (ACT) of 500 s, with a 60 min duration] was performed, followed by ante/retrograde testing via the EO-NEO side port. Testing of the collar suture line under a tension of 10 Newton (N) within a suspension device (blood pressure 120 mmHg, ACT of 560 s, 1 min duration) was carried out with the suture material force fiber white (FFWs) yarn, using standard fixation (5 stitches/cm), FFWh yarn in hemostatic fixation (15 stitches/cm), and flow weave yarn (FWYh). Results: Blood permeability testing of EO-NEO through the prosthetic lumen or via the side port demonstrated minor leakage without statistical difference between the standard and hemostatic suture lines or suture materials used, or positioning on the crimped or tapered portion (p > 0.05). The specific collar anastomosis testing demonstrated leakage volumes of 140 ml/min for FFWs vs. 16 ml/min for FFWh (p = 0.02), vs. 9 ml/min with the FWYh (p = 0.01). Conclusion: Different blood leakage tests showed minimal oozing and no difference in blood loss through the fabric and different collar suture lines, but unphysiological pressurized retrograde perfusion of the collar region showed significantly less leakage using FWYh and FFWh, prompting production modification of EO-NEO. Clinical results confirmed low blood loss using this novel FET device.

Detection and quantification of perioperative heparin-like effects by rotational thromboelastometry in living-donor liver transplant recipients: A prospective observational study.

Background and Aims: Heparin-like effects (HLEs) can affect hemostasis during liver transplantation. The aim of this study was to assess the perioperative incidence and severity of HLE with rotational thromboelastometry (ROTEM) and activated partial thromboplastin time (aPTT). Material and Methods: ROTEM and aPTT were measured intraoperatively and on postoperative days (POD) 1, 3, and 7. HLE was identified if ROTEM INTEM/HEPTEM CT-ratio was >1.25 and severe forms of HLE when ratio was ≥2. Based on aPTT, HLE was defined when aPTT ratio was >1.25 (patient aPTT/control aPTT). Results: Thirty-eight recipients were included. Variable degrees of HLE were detected by aPTT-ratio and INTEM/HEPTEM CT ratio. No significant correlation existed between both ratios. Based on INTEM/HEPTEM CT ratio, HLE was detected in 7/38 during anhepatic phase, 19/38 post-reperfusion, 10/38 on POD1, 4/38 on POD3, and 0/38 on POD7. Four cases of severe HLE were identified by INTEM/HEPTEM CT ratio only in the anhepatic phase. Postoperative infusion of unfractionated heparin led to mild-moderate HLE on POD1 and 3 as evident by both tests. Red blood cell and plasma transfusion were higher with severe HLE (1350 ± 191 ml and 3558 ± 1407 ml). Composite adverse outcome of any complication or death within 3 months for patients without HLE, mild-moderate HLE, and severe HLE as detected by ROTEM was 27.8%, 42.9%, and 66.7%, respectively. Conclusion: INTEM/HEPTEM CT ratio was able to detect and quantify HLE as aPTT ratio. The ability of the INTEM/HEPTEM CT ratio to identify severe HLE earlier in the anhepatic phase needs to be studied in a larger population. HLE is self-limiting, but when identified in a severe form, it is associated with worse outcome.

Prospective assessment of platelet function in patients undergoing elective resection of glioblastoma multiforme.

This prospective study was aimed to test changes in hemostasis in patients with GBM, occurring at baseline (before surgery, time 0, T0) and 2 (T2), 24 (T24), and 48-hour (T48) after surgery. We enrolled consecutive patients subjected to GBM resection (GBR group; N = 60), laparoscopic colon cancer resection (comparative CCR group; N = 40), and healthy blood donors (HBD group; N = 40). We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01-1.06)). This study suggests that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.

What is the context? Glioblastoma has an impact on the platelet number and the functional state of platelets. Platelets can be activated by tumor cells, and platelets count and function may impact patient survival. It has been showed an association between thrombocytosis and a decreased overall survival, with a small reduction in glioma risk associated with the long-term use of low-dose aspirin.Platelet function before and during the perioperative period in patients with glioblastoma has not been systematically investigated. Limited data suggest that platelet function may be impaired before and throughout the perioperative period, and that impaired platelet function affects clinical outcome.What is new? In this prospective study, we systematically investigated how glioblastoma provokes systemic alterations of hemostasis. We enrolled 60 consecutive patients (sample size calculated) subjected to resection of glioblastoma multiforme, and other 40 consecutive patients undergoing laparoscopic resection of colon cancer, as a comparative group, in order to differentiate hemostasis and coagulation profiles of two tumors (glioblastoma and colon adenocarcinoma) with high prothrombotic power. Forty healthy volunteers were also included to establish local reference values.We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. All these analyses were carried out at baseline (T0, time 0, before surgery) and 2 (T2), 24(T24) and 48-hour (T48) after surgery.We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01­1.06)).What is the impact? This study provides further evidence that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.The cut-offs obtained can potentially to provide risk stratification for clinical outcome and to be hypothesis generating research to be confirmed by RCTs.

Patient Blood Management in Liver Transplant-A Concise Review.

Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance. This review emphasizes the importance of the three-pillar nine-field matrix of patient blood management to improve patient outcomes in liver transplant recipients.

Haemostasis patterns in patients with acute-on-chronic liver failure and acute decompensation of cirrhosis including thromboelastometric tests with and without the addition of Protac: a pilot study.

BACKGROUND: Thromboelastometry is considered the best method to assesses hemostasis in liver disease. Diagnostic performance could be improved by adding protein C activators such as thrombomodulin or Protac®. We assessed changes in ROTEM parameters after the addition of Protac® in patients with acute-on-chronic liver failure (ACLF), acute decompensation (AD), and healthy individuals (HI) to define different hemostasis patterns, considering standard and velocity ROTEM parameters, and assess whether Protac® can improve the definition of the pattern. METHODS: Pre-test, we investigated whether diluted EXTEM reagent improved the effect of Protac® on the clotting time (CT)-ratio with and without Protac®. Ten ACLF and 20 AD patients and 21 HI were included in the main study. RESULTS: Standard EXTEM was used in the main study. INTEM CFT, INTEM A5 (inverse), and INTEM TPI (inverse) were the parameters that best differentiated liver disease from HI (ROC AUC, 0.921, 0.906, and 0.928, respectively; all P-values < 0.001). Combining INTEM CFT with EXTEM LI60-ratio only slightly improved the diagnostic performance (ROC AUC, 0.948; P < 0.001). EXTEM LI60 and INTEM maxV-t were the parameters that best differentiated between ACLF and AD patients (ROC AUC, 0.743, P = 0.033; and 0.723, P = 0.050; respectively). Combining EXTEM LI60 + INTEM maxV-t moderately improved the diagnostic performance (ROC AUC, 0.81, P < 0.001). CONCLUSIONS: ROTEM velocity, fibrinolysis parameters and the indices calculated improve the diagnosis in combination with standard parameters (e.g., CFT and A5). Ratios calculated with and without Protac® (e.g., EXTEM LI60-ratio) only slightly increased the diagnostic performance in discriminating hemostasis patterns.

Thromboelastometry Predicts Thromboembolic Events, Hospital Length of Stay, and Mortality in Patients with COVID-19 Infection and Mild Hypoxemia: A Prospective Observational Study.

Background: The aim of this study was to assess changes in hemostasis and associated outcome of hospitalized patients with COVID-19 infection and mild hypoxemia. Methods: Adult patients with COVID-19 infection and hypoxemia admitted to ICU were included in this prospective observational study. The primary outcome was defined as an unfavorable course of the disease if a patient: (1) developed a thromboembolic event while receiving anticoagulation prophylaxis, (2) had prolonged ICU stay, or (3) died. Demographic data, laboratory parameters and thromboelastometry (ROTEM) test results were collected. Results: Twenty-five patients were recruited into the study. There were 16 patients with an unfavorable course of the disease. Compared to the 9 patients in the favorable course group, patients with an unfavorable course had a lower platelet count, median difference of 154 (95% CI, 26 to 223 x109/L), P = 0.012, and lower clot firmness parameters in EXTEM assay: amplitude at 20 minutes (A20), median difference of 7 (95% CI, 2 to 11) P = 0.006, maximum clot firmness (MCF), median difference of 6 (95% CI, 3 to 10) P = 0.006 and area under the curve (AUC) with a median difference of 671 (95% CI, 244 to 1029) P = 0.005. They also demonstrated suppression of fibrinolysis: higher lysis index 60, median difference of -3 (95% CI, -6 to 0), P = 0.023. Results of functional fibrinogen (FIBTEM) assay were similar between the groups. Conclusion: The platelet count and the results of EXTEM assay, but not FIBTEM assay, were associated with the difference in clinical outcome among patients with COVID-19 infection and hypoxemia. The role of platelets in the outcome of COVID-19 infection calls for further investigation. Future studies on adjusting anticoagulant therapy based on the results of viscoelastic testing may be beneficial.

Modified thromboelastometric tests provide improved sensitivity and specificity to direct oral anticoagulants compared to standard thromboelastometric tests in-vitro.

BACKGROUND: The detection of direct oral anticoagulants (DOACs) is still challenging but important in emergency patients. We recently demonstrated that modified thromboelastometry can detect rivaroxaban and dabigatran. Data on the detection rates of modified compared to standard thromboelastometric tests of apixaban and edoxaban, are missing. The aim of this in-vitro dose-effect-study was to add data on these DOACs and to evaluate thromboelastometric tests in-vitro using data of both studies. METHODS: The study was approved by the Ludwig-Maximilians-University ethics committee (No 17-525-2). Written informed consent was obtained from all individuals. Blood samples of healthy volunteers and samples of 10 volunteers for each DOAC were used. Blood samples were spiked with six different concentrations of edoxaban and apixaban (0ng/ml; 31.25ng/ml; 62.5ng/ml; 125ng/ml; 250 ng/ml; 500ng/ml). Modified tests (low-tissue-factor test TFTEM and ecarin-based test ECATEM) as well as standard tests (e.g. FIBTEM) analyzing extrinsic pathway of coagulation were used. Receiver operating characteristics analyzes were performed as well as regression analyzes. RESULTS: TFTEM CT correlated well with anti-Xa levels of apixaban and edoxaban (apixaban: r2 = 0.8064 p < 0.0001; edoxaban: r2 = 0.8603; p < 0.0001). The detection of direct FXa inhibitors (> 30 ng/mL) was successful with FIBTEM CT with a sensitivity and specificity of 81% and 90%, respectively. As expected, ECATEM CT was not prolonged by direct FXa-inhibitors due to its specificity for direct thrombin inhibitors. Again, TFTEM CT provided the highest sensitivity and specificity for the detection of direct FXa inhibitors with 96% and 95%, respectively. ECATEM test showed 100% sensitivity and 100% specificity for the detection of dabigatran. CONCLUSIONS: Our study presents modified thromboelastometric tests with improved detection of even low DOAC concentrations > 30 ng/mL, including apixaban in-vitro. The study thus complements the previously published data on dabigatran and rivaroxaban. Validation studies must confirm the results due to the explanatory design of this study.

"In Less than No Time": Feasibility of Rotational Thromboelastometry to Detect Anticoagulant Drugs Activity and to Guide Reversal Therapy.

Anticoagulant drugs (i.e., unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants) are widely employed in preventing and treating venous thromboembolism (VTE), in preventing arterial thromboembolism in nonvalvular atrial fibrillation (NVAF), and in treating acute coronary diseases early. In certain situations, such as bleeding, urgent invasive procedures, and surgical settings, the evaluation of anticoagulant levels and the monitoring of reversal therapy appear essential. Standard coagulation tests (i.e., activated partial thromboplastin time (aPTT) and prothrombin time (PT)) can be normal, and the turnaround time can be long. While the role of viscoelastic hemostatic assays (VHAs), such as rotational thromboelastometry (ROTEM), has successfully increased over the years in the management of bleeding and thrombotic complications, its usefulness in detecting anticoagulants and their reversal still appears unclear.

Point-of-care detection and differentiation of anticoagulant therapy - development of thromboelastometry-guided decision-making support algorithms.

BACKGROUND: DOAC detection is challenging in emergency situations. Here, we demonstrated recently, that modified thromboelastometric tests can reliably detect and differentiate dabigatran and rivaroxaban. However, whether all DOACs can be detected and differentiated to other coagulopathies is unclear. Therefore, we now tested the hypothesis that a decision tree-based thromboelastometry algorithm enables detection and differentiation of all direct Xa-inhibitors (DXaIs), the direct thrombin inhibitor (DTI) dabigatran, as well as vitamin K antagonists (VKA) and dilutional coagulopathy (DIL) with high accuracy. METHODS: Following ethics committee approval (No 17-525-4), and registration by the German clinical trials database we conducted a prospective observational trial including 50 anticoagulated patients (n = 10 of either DOAC/VKA) and 20 healthy volunteers. Blood was drawn independent of last intake of coagulation inhibitor. Healthy volunteers served as controls and their blood was diluted to simulate a 50% dilution in vitro. Standard (extrinsic coagulation assay, fibrinogen assay, etc.) and modified thromboelastometric tests (ecarin assay and extrinsic coagulation assay with low tissue factor) were performed. Statistical analyzes included a decision tree analyzes, with depiction of accuracy, sensitivity and specificity, as well as receiver-operating-characteristics (ROC) curve analysis including optimal cut-off values (Youden-Index). RESULTS: First, standard thromboelastometric tests allow a good differentiation between DOACs and VKA, DIL and controls, however they fail to differentiate DXaIs, DTIs and VKAs reliably resulting in an overall accuracy of 78%. Second, adding modified thromboelastometric tests, 9/10 DTI and 28/30 DXaI patients were detected, resulting in an overall accuracy of 94%. Complex decision trees even increased overall accuracy to 98%. ROC curve analyses confirm the decision-tree-based results showing high sensitivity and specificity for detection and differentiation of DTI, DXaIs, VKA, DIL, and controls. CONCLUSIONS: Decision tree-based machine-learning algorithms using standard and modified thromboelastometric tests allow reliable detection of DTI and DXaIs, and differentiation to VKA, DIL and controls. TRIAL REGISTRATION: Clinical trial number: German clinical trials database ID: DRKS00015704 .

Paving the way for E-vita open NEO hybrid prosthesis implantation for complex aortic arch disease in Asia-Pacific.

We report first in man implantations of the newly designed Evita-open-NEO hybrid prosthesis for complex aortic arch disease from three different countries in Asia-Pacific including instructions on how to proceed with perioperative coagulation management.

Patient blood management in India - Review of current practices and feasibility of applying appropriate standard of care guidelines. A position paper by an interdisciplinary expert group.

In a developing country like India, with limited resources and access to healthcare facilities, dealing with massive hemorrhage is a major challenge. This challenge gets compounded by pre-existing anemia, hemostatic disorders, and logistic issues of timely transfer of such patients from peripheral hospitals to centers with adequate resources and management expertise. Despite the awareness amongst healthcare providers regarding management modalities of bleeding patients, no uniform Patient Blood Management (PBM) or perioperative bleeding management protocols have been implemented in India, yet. In light of this, an interdisciplinary expert group came together, comprising of experts working in transfusion medicine, hematology, obstetrics, anesthesiology and intensive care, to review current practices in management of bleeding in Indian healthcare institutions and evaluating the feasibility of implementing uniform PBM guidelines. The specific intent was to perform a gap analysis between the ideal and the current status in terms of practices and resources. The expert group identified interdisciplinary education in PBM and bleeding management, bleeding history, viscoelastic and platelet function testing, and the implementation of validated, setting-specific bleeding management protocols (algorithms) as important tools in PBM and perioperative bleeding management. Here, trauma, major surgery, postpartum hemorrhage, cardiac and liver surgery are the most common clinical settings associated with massive blood loss. Accordingly, PBM should be implemented as a multidisciplinary and practically applicable concept in India in a timely manner in order to optimize the use the precious resource blood and to increase patients' safety.