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Dabigatran is a novel oral anticoagulant preferred due to its ease of use, favorable pharmacokinetics, decreased potential for drug-drug interactions, and the lack of monitoring requirements. With the growing use of dabigatran, it is important to highlight that dabigatran increases the risk of hemorrhage after some procedures. Therefore, when dabigatran is used before the elective or urgent procedures, it is necessary to compare the thromboembolic event risk with the relative risk of bleeding. Before the approval of a reversal agent, the lack of specific antidotes had been the major limitation against the widespread utilization of dabigatran. In October 2015, idarucizumab, a humanized monoclonal antigen-binding antibody fragment capable of reversing the anticoagulant activity of dabigatran, has been introduced into the market to be used in lifethreatening bleeding or urgent surgery. In this manuscript, the preoperative management of dabigatran and the initial experience of using idarucizumab in a patient with nonvalvular atrial fibrillation were described. We propose that the option of dabigatran reversal needs to be considered in patients with nonvalvular atrial fibrillation. However, additional research is needed to define optimal perioperative management of dabigatran and other novel oral anticoagulants, especially in high bleeding risk patients, and to determine whether pre-procedure coagulation testing should be performed.

Hemostasis represents an equilibrium between procoagulant and anticoagulant processes, but once this balance is shifted to one side, it leads to coagulopathy presented by pathological bleeding or thrombosis. Many conditions could cause coagulopathy. The most common are sepsis, severe traumas and malignancies. Widely used conventional coagulation tests (CCTs), focused only on clot initiation, are primary used to detect hypocoagulability. Viscoelastographic tests (VET), like rotational thromboelastometry (ROTEM), can detect problems in different stages of coagulation, from initiation thought clot elongation and propagation, to the clot lysis and might reveal both, hypercoagulability and hypocoagulability. Rotational thromboelastometry have gained popularity in the care of patients with TIC, as a tool to guide transfusion support. Nowadays it is widely used in other medical specialties, as well. Several studies in septic patients pointed out hypocoagulable ROTEM pattern as a predictor of poor prognosis. Additionally, there is great interest of ROTEM usage in malignancies, although limited research is currently available. It suggests ROTEM have the ability to identify a patient in high risk of thrombosis. Further investigation trough randomized studies is needed to confirm ROTEM utility and to help in making a consensus about its use in different medical occasions.

The efficacy of fresh frozen plasma (FFP) transfusion in enhancing thrombin generation in patients with cirrhosis and impaired conventional coagulation tests has not been sufficiently explored. Thus, we aimed to assess the effect of FFP transfusion on thrombin generation in these patients.Fifty-three consecutive patients receiving a standard dose of FFP to treat bleeding and/or before invasive procedures - if international normalized ratio (INR)/prothrombin time (PT) ratio were ≥1.5 - were prospectively enrolled. The primary endpoint was the amelioration of endogenous thrombin potential (ETP) with thrombomodulin (ETP-TM) after transfusion, which corresponds to the total amount of generated thrombin. INR/PT ratio and activated partial thromboplastin time (aPTT) were also assessed before and after transfusion.FFP enhanced ETP-TM by 5.7%, from 973 (731-1,258) to 1,028 (885-1,343 nM × min; p = 0.019). Before transfusion, evidence of normal or high ETP-TM was found in 94% of patients, even in those with bacterial infections. Only 1 (1.9%) patient had ETP-TM values reverting to the normal range after transfusion. Notably, no patients with low ETP-TM had bleeding. The median decrease in ETP-TM was 8.3% and the mean was 12.8% in 18 (34%) patients after transfusion (from 1,225 [1,071-1,537] to 1,124 [812-1,370] nM × min; p ≤0.0001). Similar responses to FFP transfusion were observed in patients with compensated and acute decompensated cirrhosis, acute-on-chronic liver failure, infection or shock. FFP significantly ameliorated INR and aPTT values (p0.0001), but in a minority of patients the values were reduced to less than the cut-off point of 1.5.FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, and slightly decreased thrombin generation in 34% of cases.Transfusion of fresh frozen plasma in patients with cirrhosis only slightly improves coagulation test values in a limited number of patients and even appears to worsen them in a third of cases. Transfusion for the purpose of preventing or treating bleeding events could cause inherent risks and costs without clear benefits.

In the coagulation laboratory, spurious hemolysis, icterus and lipemia (HIL) in test samples represent by far the leading diagnostic prenalytical challenges. The aim of this study was to assess the performance of the preanalytical module on the new hemostasis analyser Cobas Roche t511. We assessed the influence of HIL on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), antithrombin and D-dimer on plasma pools aliquots with different interference degrees. Moreover, we evaluated spontaneous hemolysis by comparing results on 50 paired samples (hemolysed versus nonhemolysed). Spurious hemolysis interference studies highlight the absence of a clinical significant impact on PT, APTT and antithrombin test results at all hemoglobin concentration investigated. For Fib and D-dimer assays a clinically significant difference was observed in the most hemolysed aliquot for Fib and in the two most hemolysed aliquots for D-dimer. Spontaneous hemolysis interference studies showed no clinical significant differences for PT and antithrombin assays, instead for APTT, Fib and D-dimer we found significant statistical and clinical differences between hemolysed and non hemolysed specimens. Bilirubin interference studies and lipemic samples interference studies enable us to confirm that the differences in the results obtained between the different aliquots and reference pool is not clinically significant for all assays. HIL check preanalytical module of Cobas Roche t511 analyzer displaied excellent performance for routine use in clinical laboratories. Regardless of analytical considerations, the type of interference encountered with spurious HIL is substantially different and requires different approaches.

INTRODUCTION The factor VIII mimetic emicizumab (Hemlibra, Hoffman-la Roche, Basel, Switzerland) has a novel mode of action that affects the laboratory monitoring of patients receiving this treatment. AIM This guideline from the United Kingdom Haemophilia Centre Doctors Organisation (UKHCDO) aims to provide advice for clinical and laboratory staff on appropriate use of laboratory assays in patients with Haemophilia A treated with emicizumab. METHODOLOGY The guideline was prepared by a review of the available literature and discussion and revision by the authors. RESULTS The guideline describes the effect of emicizumab on commonly used coagulations tests and provides recommendations on the use of assays for measurement of factor VIII and factor VIII inhibitor in the presence of emicizumab. The guideline also provides recommendations on measurement of emicizumab. CONCLUSION Knowledge of the effect of emicizumab on coagulation tests and factor assays is required to ensure appropriate testing and monitoring of therapy in patients receiving this drug.

Introduction Interference on biological assays due to hemolysis, icterus, or lipemia (HIL) could represent a significant source of analytical errors leading to inaccurate interpretation of results. The aim of this study was to assess the HIL interference on prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen, using mechanical and optical detection methods. Methods Control plasmas and plasmas from patients treated with vitamin K antagonists or unfractionated heparin, with or without HIL, were performed on two analytical detection systems in order to identify potential analytical biases. Whether HIL lead to significant biological interferences was also evaluated, and a cutoff point for HIL-induced analytical bias was determined. Results Hemolysis influenced PT and aPTT when hemoglobin was at 5 and 1.5 g/L in plasma, respectively. At 1.8 g/L, a positive relationship was found between the bias and the hemoglobin supernatant level only for fibrinogen measurement, using optical detection. For icteric interference, no significant bias was observed until a bilirubin concentration of 30 mg/dL. Lipamia (>500 mg/dL) led to analytical interference when using the optical analyzer. Conclusion The present study detected analytical interferences such as lipemia (>500 mg/dL) on coagulation tests on the optical analyzer. We also found a biological impact on the results in case of hemolyzed sample: Fibrinogen was decreased when the hemoglobin level was superior to 1.8 g/L, PT was prolonged beyond 5 g/L, and aPTT was shortened beyond 1.5 g/L hemoglobin concentration, especially in patients treated with heparin. Above these thresholds, it is important not to give results that could influence the clinical decision.

We report two cases of acquired factor XIII deficiency with bleeding events during veno-venous extracorporeal membrane oxygenation (ECMO). Case 1: A 76-year-old man diagnosed with aspiration pneumonia after near-drowning was started on ECMO. Later, the patient presented with hemoptysis and anemia. Blood tests showed a decreased factor XIII activity of 29%. Although the patient recovered after receiving 1200 International Units of factor XIII concentrate, the patient had another episode of decreased factor XIII activity and bloody stool and was treated again with factor XIII concentrate. Case 2: A 48-year-old female diagnosed with pneumonia was started on ECMO. Soon after, she presented with hemoptysis and anemia. Blood tests showed a decreased factor XIII activity of 39%. The patient was treated with 720 IU of factor XIII concentrate with good recovery. Acquired factor XIII deficiency cannot be detected by routine coagulation tests, therefore it may be under-diagnosed in the ICU. Detection of acquired factor XIII deficiency is essential when treating a bleeding ECMO patient.

Autoantibodies toward clotting factors may develop in people suffering from autoimmune or neoplastic diseases, after drug intake or even in subjects without apparent conditions. They are more commonly directed against factor VIII (FVIII) or von Willebrand factor leading to acquired hemophilia A or acquired von Willebrand syndrome, respectively. Rarely, autoantibodies develop against other clotting factors, such as fibrinogen, FII, FV, FVII, FX, FXI, and FXIII. The clinical picture of an acquired bleeding disorder includes a wide spectrum of clinical manifestations ranging from minimal or no bleeding to life-threatening events. Patients with no previous personal or family history of bleeding may have sudden-onset hemorrhagic manifestations, sometimes fatal, especially if an early diagnosis is not made. On the other hand, some patients may not have hemorrhagic symptoms at onset, and their diagnosis can therefore be delayed. The laboratory diagnostic assessment is performed by screening coagulation tests followed by specific factor-level measurement and inhibitor-titrating assays. An early diagnosis of acquired coagulopathies is mandatory for starting the appropriate treatment aimed at both controlling the acute bleeding episode mainly using the bypassing agents, and eradicating the anticlotting factor autoantibody, using immunosuppressive treatment. Therefore, prompt intervention by an expert and a specialized center is needed for immediate recognition and treatment of the disease.

Purpose of review Coagulopathy is the derangement of hemostasis that in surgical patients may result in excessive bleeding, clotting or no measurable effect. The purpose of this review is to provide an overview of the most current evidence and practical approach to trauma- and drug-induced coagulopathy in surgical patients. Recent findings Early identification and timely correction of coagulopathy in surgical patients with significant bleeding is paramount to prevent death and other consequences of hemorrhage. Trauma-induced coagulopathy is managed by protocols recommending fibrinogen replacement, FFP, platelets, TXA and frequent lab monitorization including viscoelastic tests. For warfarin- or DOAC-induced coagulopathy, the management follows similar principles plus drug reversal. Warfarin is diagnosed by prolonged international normalized ratio and reversed by PCC or FFP. DOACs are inconsistently diagnosed by routine coagulation tests, and reversed by a combination of TXA, PCC and specific antidotes (if available). Summary Despite different understandings of the pathophysiology, trauma- and drug-induced coagulopathies are managed following similar protocols. In most of cases of significant surgical bleeding, timely and protocolized approach to correct the coagulopathy is likely to improve patients' outcome.

Basic coagulation tests, activated partial thromboplastin time (APTT), prothrombin time (PT) and the related international normalised ratio (INR), are performed frequently in hospital settings. From a laboratory perspective, unexpected abnormal results require further action; either informing the ordering clinician, or second line testing to determine the underlying cause. To streamline laboratory workflow, a new system of expert laboratory rules was implemented. The medical implications of this new laboratory system are evaluated here. The electronic ordering system was updated to mandate clinical information regarding the presence of an anticoagulant, or 'no anticoagulant'. When the PT or APTT were abnormal, and no anticoagulant was reported, second line testing was automatically performed. The second line tests performed were: mixing studies, fibrinogen and thrombin time. Any sample with a mixing study that did not completely correct, or fibrinogen1.0 g/L, or INR7.0, was flagged for clinical review by the laboratory haematology registrar. In a 17-month period there were 362,692 APTT, PT/INR and fibrinogen tests performed. Of these, 14,160 (3.9%) were abnormal with either no reported anticoagulant, or an unknown anticoagulant status. A total of 934 (0.3%) were referred for review by the haematology registrar. Three (0.001%) cases received altered medical management as a result of the haematology registrar review. In hospital settings, most abnormal coagulation studies are anticipated by the ordering clinician. Unexpected abnormal coagulation results of clinical significance are rare. Automated second line coagulation testing and medical review improves laboratory workflow without compromising patient safety.

The purpose of this study was to determine if thromboelastography (TEG) is associated with reduced blood product utilization for trauma patients undergoing massive transfusion protocol (MTP) compared to traditional coagulation tests.A retrospective review was conducted on an intent-to-treat basis of trauma patients undergoing MTP (Pre-TEG = Period I vs. Post-TEG = Period II). Traditional coagulation tests guided transfusion during Period I (n = 20) and the intent was that TEG guided transfusions during Period II (n = 47). Blood product administration and outcomes were compared.Intent-to-treat analysis demonstrated a significant reduction in red blood cell transfusions (11 vs. 6 units, P = 0.001), number of patients receiving fresh frozen plasma (85.0 vs. 17.0%, P 0.001), and platelets (75.0 vs. 38.3%, P = 0.006) in Period II. No difference was seen between Periods I and II in ICU days (7.0 vs. 11.0 days, P = 0.073), hospital length of stay (10.5 vs. 14.0 days, P = 0.618), or mortality (55.0 vs. 31.9%, P = 0.076).Use of TEG-guided transfusion in the critically-ill trauma patient conserved blood product utilization and appears to offer similar outcomes when compared to traditional coagulation tests.

Introduction Plasma samples with gross lipaemia present a challenge for coagulation laboratories using optical analysers. High‐speed centrifugation may be used to remove excess lipids but it has not established whether this affects haemostasis tests. The aims were to determine whether the removal of lipid by centrifugation affects PT, APTT, fibrinogen, D‐dimer and von Willebrand factor activity measurements. Methods Twenty‐six lipaemic samples (median [range]): triglyceride 4.6 mmol/L [0.5‐17.0]; cholesterol: 4.06 mmol/L [2.20‐9.41] and 20 plasmas spiked with Intralipid 20 or lipid isolated from patient plasmas (median triglyceride of 11.95 mmol/L [5.0‐17.0] and cholesterol 4.33 [3.22‐7.06]), were tested before and after the removal of the lipid layer by centrifugation (10000 g for 10 minutes). Tests were performed using the CS‐5100 (Sysmex) coagulation analyser. Results Thirteen, 9, 3 and 1 of the lipaemic or spiked samples failed to give PT, APTT, fibrinogen and D‐dimer results, respectively. Centrifugation significantly reduced triglyceride (median 2.7, [0‐6.1 mmol/L]) and cholesterol (median 0.52 [0‐3.5]), allowing clot detection in all tests. There were no statistically significant differences in fibrinogen, D‐dimer or VWF levels in samples before and after lipid removal. A small but clinically insignificant change in PT and APTT was observed after lipid removal. Conclusion High‐speed centrifugation reduces lipaemia sufficiently to allow testing on an optical coagulation analyser without introducing clinically significant differences PT, APTT, fibrinogen, D‐dimer or VWF activity values.

Introduction: Fully-automated coagulation analyzers are key components of a high-throughput central laboratory. The novel Atellica COAG 360 (Siemens Healthineers) is a high-volume coagulation analyzer approved for hemostasis diagnostics. The aim of the study was to evaluate the analytical performance of this coagulation analyzer in a central laboratory. Methods: Intra (n=10)- and inter (n=20)-assay precision of the Atellica COAG 360 was determined using commercially available control samples. Patient samples (n=74-104) were used for comparison analyses with the Sysmex CS-5100 (Siemens Healthineers). Effects of visual interferences on coagulation testing were assessed and the sample throughput rate of the Atellica COAG 360 was determined. Results: Intra- and inter-assay precision of the Atellica COAG 360 showed coefficient of variations (CVs)&nbsp

Objectives To evaluate the association between bleeding from chest tubes and clinical outcomes in children supported by extracorporeal membrane oxygenation. Design Secondary analysis of a large observational cohort study. Setting Eight pediatric institutions within the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Collaborative Pediatric Critical Care Research Network. Patients Critically ill children supported by extracorporeal membrane oxygenation. Interventions None. Measurements and main results Daily chest tube bleeding, results from hemostatic assays, transfusion volumes, 90-day PICU-free days, and mortality were collected prospectively by trained bedside extracorporeal membrane oxygenation specialists and research coordinators. Extracorporeal membrane oxygenation was employed in the care of 514 consecutive patients. Sixty percent of patients had at least one episode of chest tube bleeding (median chest tube blood volume over the entire extracorporeal membrane oxygenation course was 123 mL/kg [interquartile range, 47-319 mL/kg]). Twenty-six percent had at least 1 day of bleeding from the chest tube greater than 100 mL/kg/d. The number of days with chest tube bleeding greater than 60 mL/kg/d was independently associated with increased in-hospital mortality (adjusted odds ratio, 1.43; 95% CI, 1.05-1.97; p = 0.02) and decreased PICU-free days (beta coefficient, -4.2; 95% CI, -7.7 to -0.6; p = 0.02). The total amount of bleeding from chest tube were independently associated with increased mortality (per mL/kg/extracorporeal membrane oxygenation run; adjusted odds ratio, 1.002; 95% CI, 1.000-1.003; p = 0.04). Fibrinogen, weight, indication for extracorporeal membrane oxygenation, and need for hemodialysis were independently associated with chest tube bleeding, whereas platelet count, coagulation tests, heparin dose, and thrombotic events were not. Conclusions In children supported by extracorporeal membrane oxygenation, chest tube bleeding above 60 mL/kg/d was independently associated with worse clinical outcome. Low fibrinogen was independently associated with chest tube bleeding, whereas platelet count and hemostatic tests were not. Further research is needed to evaluate if interventions to prevent or stop chest tube bleeding influence the clinical outcome.

BACKGROUND Orthotopic liver transplantation is associated with a risk of bleeding. Coagulation in cirrhotic patients is difficult to assess with standard coagulation tests because of rebalanced coagulation. This can be better assessed by thromboelastometry which can detect coagulation impairments more specifically in such patients. OBJECTIVES Our first objective was to compare the number of units of blood products transfused during liver transplantation when using an algorithm based on standard coagulation tests or a thromboelastometry-guided transfusion algorithm. DESIGN Randomised controlled trial. SETTING Single-centre tertiary care hospital in France, from December 2014 to August 2016. PARTICIPANTS A total of 81 adult patients undergoing orthotopic liver transplantation were studied. Patients were excluded if they had congenital coagulopathies. INTERVENTION Transfusion management during liver transplantation was guided either by a standard coagulation test algorithm or by a thromboelastometry-guided algorithm. Transfusion, treatments and postoperative outcomes were compared between groups. MAIN OUTCOME MEASURES Total number of transfused blood product units during the operative period (1 U is one pack of red blood cells (RBCs), fresh frozen plasma (FFP) or platelets). RESULTS Median [interquartile range] intra-operative transfusion requirement was reduced in the thromboelastometry group (3 [2 to 4] vs. 7 [4 to 10] U, P = 0.005). FFP and tranexamic acid were administered less frequently in the thromboelastometry group (respectively 15 vs. 46.3%, P = 0.002 and 27.5 vs. 58.5%, P = 0.005), whereas fibrinogen was more often infused in the thromboelastometry group (72.5 vs. 29.3%, P

Background Viscoelastic coagulation testing is increasingly used to diagnose trauma-induced coagulopathy. Two fully automated analysers, TEG 6s and ROTEM Sigma, were launched recently. No previous studies have compared these devices in trauma paients. Objective The aim of this study was to evaluate whether both fully automatic devices deliver comparable results. Design Prospective observational study. Setting Level one trauma centre from August 2017 to September 2018. Patients A total of 105 blood samples from 67 trauma patients were analysed simultaneously on TEG 6s and ROTEM Sigma. Main outcome measures TEG 6s assays kaolin (CK), RapidTEG (CRT), kaolin with heparinase (CKH) and functional fibrinogen were compared with ROTEM Sigma assays INTEM, EXTEM, HEPTEM and FIBTEM. TEG 6s functional fibrinogen level was compared with plasma fibrinogen concentration, measured using the Clauss method. Correlations were classified as weak (Spearman correlation coefficient 0.20 to 0.39), moderate (0.40 to 0.59), strong (0.60 to 0.79) or very strong (≥0.80). Results The TEG 6s parameters reaction time, kinetic time and α-angle (CK, CRT and CKH assays) mostly showed strong correlations with the corresponding ROTEM parameters clotting time, clot formation time and α-angle (INTEM, EXTEM and HEPTEM assays). The exceptions were CRT reaction time vs. EXTEM clotting time, and CK α-angle vs. INTEM α-angle, which correlated moderately. Absolute values for many of these parameters showed significant differences between the two devices. Very strong correlations and similar absolute values were observed between TEG 6s maximum amplitude (CRT, CK and CKH assays) and ROTEM maximum clot firmness (EXTEM, INTEM and HEPTEM assays). Correlations were also very strong for functional fibrinogen maximum amplitude vs. FIBTEM maximum clot firmness and functional fibrinogen level vs. Clauss fibrinogen concentration, but absolute values were significantly different. Conclusion Strong to very strong correlations were observed between corresponding TEG 6s and ROTEM Sigma parameters. However, absolute values showed significant differences for most of the measurements.

During pregnancy, the procoagulant activity increases (manifested by elevation in factor VII, factor VIII, factor X, and fibrinogen levels), while the anticoagulant activity decreases (characterized by reduction in fibrinolysis and protein S activity), resulting in hypercoagulation. Standard coagulation tests, such as prothrombin time or activated partial thromboplastin time, are still used despite the lack of evidence supporting its accuracy in evaluating the coagulation status of pregnant women. Thromboelastography and rotational thromboelastometry, which are used to assess the function of platelets, soluble coagulation factors, fibrinogen, and fibrinolysis, can replace standard coagulation tests. Platelet count and function and the effect of anticoagulant treatment should be assessed to determine the risk of hematoma associated with regional anesthesia. Moreover, anesthesiologists should monitor patients for postpartum hemorrhage (PPH), and attention should be paid when performing rapid coagulation tests, transfusions, and prohemostatic pharmacotherapy. Transfusion of a high ratio of plasma and platelets to red blood cells (RBCs) showed high hemostasis success and low bleeding-related mortality rates in patients with severe trauma. However, the effects of high ratios of plasma and platelets and the ratio of plasma to RBCs and platelets to RBCs in the treatment of massive PPH were not established. Intravenous tranexamic acid should be administered immediately after the onset of postpartum bleeding. Pre-emptive treatment with fibrinogen for PPH is not effective in reducing bleeding. If fibrinogen levels of less than 2 g/L are identified, 2–4 g of fibrinogen or 5–10 ml/kg cryoprecipitate should be administered.

Background Choosing Wisely Australia is an initiative aimed at reducing the incidence of unnecessary investigations. This study is an audit of Northern Health's adherence to two Choosing Wisely recommendations in the context of inguinal hernia repair. Recommendation 1: Avoid routinely performing pre-operative investigations in patients, but instead order in response to patient factors, signs and symptoms, disease or planned surgery. Recommendation 2: Do not order ultrasound for clinically apparent inguinal hernias. Methods Records of 264 patients who underwent elective inguinal hernia repair at Northern Health in 2016 were reviewed. Results Recommendation 1: Results demonstrated over-ordering of coagulation studies. Thirty-four percent of patients received coagulation studies, 86% of which were unindicated. There was better adherence to Choosing Wisely guidelines for other investigations: 38% of patients received a full blood examination (42% unindicated), 38% received a urea, electrolytes and creatinine (14% unindicated), 7% received a glycated haemaglobin (0% unindicated) and 38% received an electrocardiogram (11% unindicated). Recommendation 2: Seventy percent (n = 186) of patients received an ultrasound of which 25% (n = 46) had a documented indication. Correlation with surgical findings showed a positive predictive value of 95.6% and sensitivity of 97.8% for ultrasound. Conclusion Recommendation 1: Most pre-operative coagulation studies were unindicated, while adherence to Choosing Wisely guidelines was better for pre-operative full blood examination, urea, electrolytes and creatinine, glycated haemaglobin and electrocardiogram. Recommendation 2: The majority of patients received an inguinal hernia ultrasound, most of which had no documented indication.

Background It is widely accepted that Point-of Care Test (PoCT) devices are useful in the detection of coagulopathies in situations of massive bleeding such as major cardiac surgery. These devices contribute to the reduction of blood transfusion. However, their implementation remains limited in Japan because of their cost and lack of health insurance support. Study design and methods Conventional coagulation tests and thromboelastography (TEG)/Sonoclot values were measured in 50 consecutive cardiac surgery cases. Clinical background information such as operative procedures was obtained from electronic medical records, and the theoretical perioperative total blood loss was calculated by measuring the hemoglobin content and total red blood cell transfusion volume. The correlation between perioperative total blood loss and the measured laboratory values or clinical parameters was evaluated by a multivariate linear regression analysis. The risk factors of the total amount of platelet transfusion and postoperative drain bleeding volume were similarly evaluated. Results No significant association between the estimated perioperative total blood loss (eTBL) and the laboratory measurements including conventional coagulation tests, TEG and Sonoclot was observed. On the other hand, postoperative drain bleeding volume was significantly associated with postoperative Sonoclot CR (p = 0.039) as well as preoperative use of oral anticoagulants and cell saver treated blood volume. Platelet transfusion amount was significantly associated with post-CBP PF and time to peak value of Sonoclot (p = 0.014 and 0.001, respectively). Conclusion Sonoclot measurements may be useful to estimate the risks of postoperative bleeding and platelet transfusion in cardiac surgeries in Japan.

Introduction: According to the several evidences, using thromboelastometry as a point of care test canbe effective in reduction in blood loss and transfusion requirements in cardiac surgeries. However,there are limited data regarding to the comparison of thromboelastometry and the standard coagulationtests. In this study, we compared thromboelastometry and standard coagulation tests (PT, PTT andfibrinogen level) in patients under combined coronary-valve surgery. Methods: Forty adult patients who were under on-pump combined coronary-valve surgery wereincluded in this study. Thromboelastometry tests Fibtem, Intem, Extem and Heptem), along withstandard coagulation tests (PT, PTT and fibrinogen assay) were simultaneously performed in two timepoints, before and after the pump (pre-CPB and post-CPB, respectively). Results: A total of 80 blood samples were analyzed. There were no significant correlation between PTtest and the CT-Extem parameter as well as PTT and CT-Intem parameter either in pre-CPB and post-CPB (P > 0.05). On the contrary, fibrinogen level had high correlation with A10-Fibtem and A10-Extemin pre-PCB (P < 0.05). 82% of PT and 84% of PTT measurements were outside the reference range,while abnormal CT in Extem and Intem was observed in 17.9%. Conclusion: For management of bleeding, adequate perioperative haemostatic monitoring isindispensable during cardiac surgery. Standard coagulation tests are time consuming and cannot beinterchangeably used with thromboelastomety and relying on their results to decide whether bloodtransfusion is necessary, leads to the inappropriate transfusion.

Background Depending on test assays and the time of last DOAC intake, direct thrombin inhibitors (DTI) and direct FXa inhibitors (DXI) may or may not affect prothrombin time (PT), international normalized ratio (INR) or activated thromboplastin time (aPTT) but the clinical impact is unknown. Methods Using data from the Dresden NOAC Registry, we evaluated the impact of DOAC on first PT, INR or aPTT tests during emergency hospitalizations of DTI/DXI patients and the assay performance across 50 coagulation laboratories. Results In 724 emergency admissions (77 DTI; 647 DXI), 490 cases (67.7%) had a reported last DOAC intake within 12 h before blood sampling. INR and PT were elevated above the upper limit of normal (ULN) in >65% of all cases and aPTT was elevated in 45%. On the other hand, >30% of all cases had normal values of INR, PR and aPTT despite a DOAC intake within the last 12 h. Assay performance for detecting or ruling out therapeutic DOAC levels was highly variable and, overall, insufficient to guide clinical decisions. DOAC specific testing was performed in Conclusion Many DOAC recipients present with elevated PT, INR or aPTT during emergency admissions but false negative values within 12 h of last intake as well as elevated values beyond 24 h after last DOAC intake are common. Both scenarios may result in clinical misinterpretation and, potentially, in patient harm, also because DOAC specific testing is rarely performed in emergency settings.

Background The monitoring of unfractionated heparin (UFH) reversal with protamine plays a crucial role for bleeding management after cardio-pulmonary bypass (CPB) in congenital cardiac surgery. The current standard for the monitoring of UFH and its reversal is the activated clotting time (ACT). While the ACT is affected by other CPB-associated pathologies a bedside technique with more specific heparin-related results would be very helpful. The new point-of-care viscoelastic test Haemonetics TEG® 6s, which is based on small blood samples may fulfill these requirements. This study aimed to compare the new TEG with laboratory assays. Methods A retrospective observational study was performed on 40 children with a median age of 130 days (interquartile range 13 to 310 days) undergoing congenital cardiac surgery. After separation of CPB, test results of the TEG® 6s, ACT, anti-Xa for UFH and PTT were compared and correlated with each other. Results No clinically relevant correlation was found for heparin specific TEG-derived parameters (CK/CKH R-time ratio) with ACT, PTT and anti-Xa measurements. After grouping in dependence to the CK/CKH R-time in patients with and without successful heparin reversal again no significant difference of anti-Xa-UFH-levels, post-/pre-CPB ratio of the PTT and ACT was observed. Conclusions In pediatric patients undergoing cardiac surgery using CPB there is no association of conventional coagulation tests and TEG-derived results. While bedside viscoelastic tests deliver rapid results, further studies are needed to compare whether the TEG based management of incomplete heparin reversal is sufficient to monitor heparin reversal and to reduce blood loss.

The aim of this study was to determine the rate of hemolyzed specimens sent to our laboratory for coagulation testing, assess the interference of hemolysis on coagulation for patients without anticoagulant therapy and to determine the reference intervals for PT, INR and aPTT for our laboratory in order to test our own limitations. Methods: To determine the hemolysis rate, 1,689 specimens were evaluated on a visual scale and with the hemolysis icterus lipemia (HYL) test on Architect c4000 instrument. 125 blood samples collected from subjects without anticoagulant therapy were hemolyzed in vitro and the PT, INR and aPTT results were compared before and after hemolysis.To determine reference intervals (RI) for PT, INR and aPTT in our population, 125 apparently healthy human subjects (according to CLSI C28-A2) were enrolled and tests were performed on Sysmex CS 2000i, using Siemens reagents. Results: Out of 1,689 samples, 9.46% were assessed as hemolyzed by the visual scale, while HYL test showed a 6.63% hemolysis rate. We found a shortening of 0.1s for PT, a diminution with 0.01 units for INR and a prolongation with 0.9s for aPTT from in vitro hemolyzed compared to non-lyzed samples. As to the reference intervals, we obtained in our laboratory versus reagents producer: for PT 9.8-13.9 s vs 9.8-12.1 s, and for aPTT 19.1-31.5s vs 23-31.9 s respectively; 28.38% more PT results and 13.44% more aPTT results were within range when we used local laboratory RI, compared to the manufacturer’s RI. Conclusions: The rate of hemolyzed coagulation samples in our laboratory is higher than the rate found in the literature. Nevertheless, for patients without anticoagulant therapy hemolyzed samples should be processed. Using our own reference interval leads to a significant reduced number of abnormal results.

Objectives Venomous fishes have different pharmacological effects and are useful. Among the venomous fish, stonefishes; especially Pseudosynanceia melanostigma has various pharmacological effects on the nervous, muscular and cardiovascular system of humans. In this study, toxicological characteristics, some blood effects, pharmacological and enzymatic properties of Pseudosynanceia melanostigma venom was investigated. Methods Crude venom purified by using gel filtration chromatography and the molecular weights of the venom and its fractions were estimated. The approximate LD values of this venom were determinedand the effects of LD50 dose on the blood of rabbits were studied. Hemolytic and Hemorrhagic activity of the venom sample was determined. In this case coagulation tests were performed. Results The LD50 of the Pseudosynanceia melanostigma crude venom was also determined to be 194.54 μg/mouse. The effect of two doses of LD50 showed a non-significant differences decrease in RBCs and MCV. In other cases, the results showed significant differences in WBC, Plt, Hb, MCH, MCHC and HCT; also it's showed a significant decrease. WBC count showed a significant increase with two doses of LD50 groups. The prothrombin time and partial prothrombin time were increased after venom treatment. As well as bleeding and clotting time were increased. According to the results, a minimum dose for Haemorrhagic effect 40 μg was obtained. Conclusion Venom of Pseudosynanceia melanostigma has inhibitory effect on platelet aggregation that can be used to design and develop of anticoagulant drugs.

Background: In order to control the treatment of haemophilia patients, classical coagulation methods (APTT, FVIII (IX)) and global tests are used. One of the tests for a comprehensive coagulation assessment is thromboelastography (TEG), which can provide immediate results and reflect the hemostatic status of the patient during therapy. Some of the parameters obtained from the TEG can be compared with the coagulation tests since they describe similar processes of coagulation. Purpose: To carry out a correlation analysis of TEG parameters with coagulation test parameters to determine the role of TEG in the control of prophylactic treatment and the development of inhibitors in patients with severe haemophilia A. Materials and methods: 9 haemophilia A patients were treated with 45 ± 5 IU/kg of FVIII of body weight twice a week prophylactically an incremental recovery test (IR) at a dose of 60 ± 5 IU/kg body weight was performed. Prior to and after administration, TEG was performed and the PT, APTT, fibrinogen, FVIII, FVIII:Ag, vWF:Ag and the platelet count were measured. The possible dependencies of 10 TEG parameters (R, K, α-Angle, MA, TMA, SI, SP, G, LY30, TPI/c) and coagulation tests results were analyzed. Results: Significant direct correlation of the R and SP on the PT and APTT was found (r > 0.71) prior to the administration of the FVIII concentrate. The negative average correlation between R and FVIII:Ag (r = ‑0.56) was established. The elongation of the PT and APTT and the decrease in the activity of FVIII:Ag causes a decrease in the total hemostatic potential of the SI in the direction of hypocoagulation (r = 0.75). Prior to administration of the calculated dose, the concentration of MA, TMA and α-Angel inclination strongly and directly depends on the level of vWF:Ag and platelet count (in all cases r > 0.7). After administration of the FVIII concentrate in haemophilia A patients, a significant positive correlation between the response time R and the APTT (r = 0.64) was found. The growth of the CІ coagulation index is associated with an increase in the level of FVIII: Ag (r = 0.75) and a shortening of the APTT (r = -0.76). Other dependencies between TEG parameters and hemostatic tests have not been established. Conclusion: Correlation of TEG parameters and results of traditional coagulation tests characterized similar processes of coagulation and was revealed in haemophilia A patients on prophylactic treatment. For R, SI, SP depending on the values of the PT, APTT, FVIII: Ag, the end point is coagulation. MA, TMA, α-Angel depend on the level of vWF: Ag and platelet count which reflects the initiation of haemostasis and the strength of clot. TEG fully reflects the changes in hemostasis, so thromboelastography can be successfully applied to control the treatment and the development of FVIII (IX) inhibitors in hemophilia patients.

Introduction Lipemia in samples can cause analytical errors in coagulation tests using photometric assays. To define the level of this interference, some studies assessed lipemic interferences by in vitro 'spiking' of different types of lipids obtaining interesting information, but spiked samples do not represent a real-world situation as natively lipemic samples do. Methods A total of 101 samples flagged as 'lipemic' by a Sysmex CS-5100 coagulometer were analyzed for PT, aPTT, fibrinogen Clauss assay, antithrombin activity, D-dimer concentration, before and after a double high-speed centrifugation procedure to reduce lipemic interference. We evaluated using Bland-Altman test if high-speed centrifugation and retesting are justified, considering that's a resource-consuming procedure; when a statistically significant difference was found, quality specification for imprecision was considered and compared to the observed delta. Results Statistically significant differences were found for PT, antithrombin activity and fibrinogen. Considering the Bland-Altman plot, fibrinogen results were split into two groups, and statistically significant difference was confirmed only for samples >2 g/L. Conclusions For PT and antithrombin activity a mean percentual difference between the two determinations lower than within-subject biologic variation and one of the Fraser's quality specifications can be considered as a confounding 'noise' factor that is neither analytically nor clinically relevant. If the instrument determines a result on the first run, for PT, aPTT, D-dimer concentration and antithrombin activity tests, the double plasma high-speed centrifugation is unnecessary. It is instead necessary if fibrinogen >2 g/L or if the instrument cannot determine a result on the first run.

BACKGROUND: The American Society of Anesthesiologists’ (ASA) Choosing Wisely Top-5 list of activities to avoid includes: “Don’t obtain baseline laboratory studies in patients without significant systemic disease (ASA I or II) undergoing low-risk surgery - specifically complete blood count, basic or comprehensive metabolic panel, coagulation studies when blood loss (or fluid shifts) is/are expected to be minimal.” Accordingly, we define low value preoperative tests (LVTs) as those performed prior to minor surgery in patients without significant systemic disease. The objective of the current study was to examine the extent, variability, drivers, and costs of LVTs prior to carpal tunnel release (CTR) surgeries in the US Veterans Health Administration (VHA). METHODS: Using Fiscal Year (FY) 2015–17 data derived from the VHA Corporate Data Warehouse, we determined the overall national and facility-level rates and associated costs of receiving any of eight common LVTs in the 30 days prior to CTR in ASA Physical Status (ASA-PS) I-II patients. We also examined the patient, procedure, and facility factors associated with receiving at least one LVT with mixed-effects logistic regression, and the number of tests received with mixed-effects negative binomial regression. RESULTS: From FY15–17, 10,000 ASA Class I-II patients received a CTR by 699 surgeons in 125 VHA facilities. Overall, 47.0% of patients had a CTR that was preceded by at least one LVT, with substantial variability between facilities (range = 0–100%; Interquartile Range = 36.3%), representing $339,717 in costs. Older age and female gender were associated with higher odds of receiving at least one LVT. Local vs. other modes of anesthesia was associated with lower odds of receiving at least one LVT. Several facilities experienced large (>25%) increases or decreases from FY15 to FY17 in the proportion of patients receiving at least one LVT. CONCLUSIONS: Counter to guidance from the ASA, we found that almost half of CTRs performed on ASA Class I-II VHA patients were preceded by at least one LVT. Although the total cost of these tests is relatively modest, CTR is just one of many low-risk procedures (e.g., trigger finger release, cataract surgery) that may involve similar preoperative testing practices. These results will inform site selection for qualitative investigation of the drivers of low value testing, and the development of interventions to improve preoperative testing practice, especially in locations where rates of LVT are high.

Background Syzygium cumini (L.) Skeels. is one of the very popular traditionally used medicinal plants with numerous pharmacological activities including antioxidant, hypoglycemic and anti-inflammatory. However, actions of S. cumini on blood coagulation and other parameters of blood were poorly pharmacologically studied. Therefore, aim of this present investigation is to examine the effects of methanolic extract of S. cumini on blood coagulation and anticoagulation factors in healthy white albino rabbits at different doses. Methods Blood samples were drawn twice during this study and biochemical assays were performed to determine the effect on different parameters such as coagulation, anticoagulation, hematological, Protein C (PC) and thrombin antithrombin (TAT) complex and platelet aggregation. Results The results showed significant increase in RBCs, hemoglobin, hematocrit and platelets counts up to 1.4 × 103/cm, 2.2 g/dl, 6%, 248.2 × 103/cm respectively. While, thrombin and bleeding time were also prolonged in dose dependent manner which is highly significant (p ≤ 0.005) as compared to control. Similarly, highly significantly increased (p ≤ 0.005) in levels of protein C, thrombin antithrombin complex at dose of 500 mg/kg were observed. Whereas, levels of platelets aggregation and fibrinogen were decreased at high doses. Conclusion The obtained findings of hematological and coagulation tests concludes possibly S. cumini possess anticoagulant and antiplatelet effects.

Perioperative allogeneic blood product transfusion is common in lung transplantation and has various implications on the short- and long-term outcomes of lung recipients. This review summarizes the effect of transfusion on outcomes including primary graft dysfunction, chronic lung allograft dysfunction, and all-cause mortality. We outline known risk factors for increased transfusion requirement in lung transplantation and present current evidence regarding the effect of hemostatic agents including antifibrinolytics, recombinant factor VII, and prothrombin complex concentrates. Finally, we highlight the roles of point-of-care coagulation testing and goal-directed transfusion strategies in reducing transfusion requirements in lung transplantation.

Background Published evidence on the risk of additive carryover during phlebotomy remains elusive. We aimed to assess potential carryover of citrated and heparinized blood and the relative volume needed to bias clinical chemistry and coagulation tests. Methods We simulated standardized phlebotomies to quantify the risk of carryover of citrate and heparin additives in distilled water, using sodium and lithium as surrogates. We also investigated the effects of contamination of heparinized blood samples with increasing volumes of citrated blood and pure citrate on measurements of sodium, potassium, chloride, magnesium, total and ionized calcium and phosphate. Likewise, we studied the effects of contamination of citrated blood samples with increasing volumes of heparinized blood on heparin (anti-Xa) activity, lithium, activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). We interpreted these results based on measurement deviations beyond analytical, biological and clinical significance. Results Standardized phlebotomy simulations revealed no significant differences in concentration of surrogate markers. Clinically significant alterations were observed after contamination of heparinized blood samples with volumes of citrated blood beyond 5–50 μL for ionized calcium and beyond 100–1000 μL for sodium, chloride and total calcium. Investigations of pure citrate carryover revealed similar results at somewhat lower volumes. Heparinized blood carryover showed clinically significant interference of coagulation testing at volumes beyond 5–100 μL. Conclusions Our results suggest that during a standardized phlebotomy, heparin or citrate contamination is highly unlikely. However, smaller volumes are sufficient to severely alter test results when deviating from phlebotomy guidelines.

The high level of morbidity of dogs from mammary gland tumours and deficiencies in the pathogenesis give relevance to study of the disorders of the hemostatic system for predicting the neoplasia process. Our research concerned the determination of markers of the hemostatic system and endothelial function at different sizes (≤ 2, 5–7 and >10 cm) of benign (n = 28) and malignant (n = 27) breast tumours in dogs, taking into account their histological structure. The progression of the tumour process was accompanied by a 1.24–1.81 times increase in the fibrinogen content in the benign forms and 1.39–2.38 times in malignant against the background of progressive excess accumulation of soluble fibrin. The results of coagulation tests indicate that the increase in blood coagulation, which correlates with the magnitude of tumours, occurred mainly externally. In malignant neoplasms reliable, compared to clinically healthy dogs, reduction of total fibrinolytic activity occurred due to deficient inhibition of tissue plasminogen activator by 1.62–2.03 times. Increase in the size of benign neoplasms was accompanied by increased activity of the α1-inhibitor of proteinases, and in malignant – only in tumours of the size of 5–7 cm, against the background of its decrease in dogs with small and giant neoplasia. The progression of the disease was characterized by an increase in the content of α2-macroglobulin in benign lesions from 1.19–1.24 times, malignant – from 1.25–2.03 times. At the same time, there was a deepening of oxidative stress, as evidenced by the excess accumulation in the blood of malondialdehyde by 1.29–1.70 times in benign tumours, and 1.58–2.73 times in malignant. Regardless of the pathomorphologic form, the magnitude of the neoplasia foci is directly correlated with excess accumulation of nitric oxide and the level of hypoproteinemia, and vice versa – the content of ceruloplasmin. Further research should be undertaken to study the hemostatic status in certain nosological forms of breast tumours in dogs, which will improve the diagnosis and development of effective treatment protocols.

Background Both thrombelastography (TEG) and rotational thromboelastometry (ROTEM) have been investigated for diagnosis of coagulopathy and guidance of resuscitation in trauma and surgery. Given similarities between the two systems, it is important to determine whether one is superior to the other and how comparable they are to conventional coagulation tests (CCTs). Therefore, we conducted a comparative study of functional fibrinogen and coagulation assays using TEG and ROTEM and CCTs to determine their capability to monitor coagulation profiles, diagnose coagulopathy and predict blood transfusion requirements in trauma patients. Methods Blood samples were collected from 45 patients at admission and during 48-h hospitalization as part of a randomized control trial on early fibrinogen replacement in trauma. Functional fibrinogen (FF) TEG, ROTEM FIBTEM and EXTEM, and CCTs were performed and compared. Results We found significant differences between the placebo and fibrinogen groups over hospitalization time in FF TEG MA, ROTEM CT, MCF and LI30. FF TEG MA and ROTEM FIBTEM MCF mirrored plasma fibrinogen profiles, reached a maximum difference between the two groups 1–3 h after fibrinogen administration. In comparison, CCTs detected minimal hemostatic changes by fibrinogen treatment. TEG and ROTEM showed various degrees of correlations with CCTs. TEG MA and ROTEM MCF provided better predictions for plasma and RBC transfusions than CCTs, but poor accuracy for cryoprecipitate transfusion. Both TEG and ROTEM well predicted hypofibrinogenemia (fibrinogen concentration Conclusions TEG and ROTEM detected increases in clot strength following early use of fibrinogen. ROTEM also detected changes in coagulation time and clot lysis. Both were better than CCTs for monitoring coagulation profiles and predicting transfusion requirements.

This study describes the use of a simple charcoal product (DOAC-RemoveTM ) to allow haemostasis assays on patients taking direct oral anticoagulants (DOAC). In the proposed algorithm, patients taking DOAC are screened using the dilute thrombin time (dTT) and anti-Xa assay. If either are positive then DOAC-Remove is utilised. In a validation, DOAC-Remove did not interfere with coagulation testing in normal plasma or in patients on DOAC with a known lupus anticoagulant (LA). Of 1566 routine patient samples tested, 125 (8%) had evidence of anti-Xa activity (>0·1 iu/ml) or prolonged dTT suggestive of either a direct/indirect Xa inhibitor or direct thrombin inhibitor. All of these 125 patients had a prolonged dilute Russell viper venom time (dRVVT) screening test and 106 had a LA detected by dRVVT after phospholipid correction. After DOAC-Remove, 91 patients (73%) had a negative dRVVT screen. After further investigation only 9 (7%) had a positive LA. DOAC-Remove prevented 5% of patients having a LA inappropriately detected. DOAC did not significantly affect the LA activated partial thromboplastin time (aPTT) ratio, protein S antigen or protein C activity. DOAC cause low intrinsic factor assays, high prothrombin time/aPTT and high activated protein C sensitivity ratio, which DOAC-Remove reversed (P < 0·05). Despite recommendations, haemostasis testing for patients on DOAC continues; this algorithm aids diagnostic accuracy. Further validation and research are warranted.

Background: Thromboelastography (TEG) allows a dynamic assessment of clot formation and dissolution that might be useful for assessing the relative contribution of the coagulation components to overall clot formation and dissolution, but it has not been fully defined in patients with portal cavernoma (PC). Methods: We retrospectively recruited consecutive patients with PC between July 2006 and June 2016 who had no abdominal malignancy or liver cirrhosis. Blood samples were drawn on admission and were subjected to coagulation parameter assessment, including conventional coagulation tests, measurement of the circulating levels of procoagulant and anticoagulant factors, and TEG assessment. Results: Compared with controls, patients with PC showed significant reductions in the serum levels of procoagulant factors and anticoagulants factors, whereas factor VIII was slightly elevated. TEG showed clot formation (α-angle), and the maximal clot strength (MA) was higher in patients with PC than in controls, indicating a hypercoagulable state. Thrombocytopenia decreased both clot formation (α-angle) and the maximal clot strength (MA) but was still significantly higher than the control. Furthermore, patients with PC had a higher level of D-dimer and LY30 than did controls, indicating the in vivo activation of coagulation and fibrinolysis. Conclusion: TEG analysis showed that patients with PC were in a hypercoagulable state that could be partially masked by thrombocytopenia secondary to splenomegaly and hypersplenism in these patients, which indicates that our current prophylaxis and therapy regimen could be improved.

Objective: Open repair of thoraco-abdominal aortic aneurysm (TAAA) is a challenging procedure, associated with high rates of peri-operative bleeding and blood product transfusions. A large intra-operative volume transfusion has been associated with higher in hospital mortality and prolonged mechanical ventilation. A propensity score matched study was carried out to assess whether the introduction of a rotational thromboelastometry (ROTEM) based transfusion strategy reduces allogenic blood transfusion and affects morbidity in patients undergoing open TAAA repair. Methods: All patients undergoing open TAAA repair at the San Raffaele Scientific Institute between 2009 and 2017 were included. Until 2016, a protocol based on estimated blood loss and conventional coagulation tests was used. After March 2016 a ROTEM guided transfusion protocol was developed and adopted. To account for selection bias, propensity score matching was performed. Results: Five hundred and forty-seven consecutive patients were included. After propensity score matching, 77 patients in the ROTEM algorithm group were successfully matched with 77 patients in the standard algorithm group. Patients managed with ROTEM received fewer red blood cells units (3.5 [range 0–11] vs. 4 [range 0–17]; p = .026) and a lower volume of fresh frozen plasma (286 ± 496 vs. 2,050 ± 1,120; p < .001). In addition, fewer patients received fresh frozen plasma (35% vs. 97%; p < .001). Patients in the ROTEM group showed a significant decrease in the occurrence of pulmonary complications (44% vs. 83%; p = .01). Cost analysis showed a relevant reduction of per-patient expense after the introduction of ROTEM (€834 ± €577 vs. €1,285 ± €851; p < .001) Conclusion: A ROTEM guided transfusion strategy significantly limited the quantity of transfused blood products during open TAAA repair, improving clinical outcomes while reducing costs, allowing for better resource distribution in a setting where blood loss is relevant.

Normal haemostasis requires maintenance of a careful equilibrium between the necessity to clot when bleeding and the retention of fluid phase at all other times. Disruption of this equilibrium can result in catastrophic outcomes, e.g. acute myocardial infarction and pulmonary embolism. However, despite the significant therapeutic advances in cardiovascular medicine over recent years, our ability to provide an accurate cardiovascular risk assessment remains an unmet need. Routine coagulation testing is not a useful reflection of haemostasis and cannot be reliably used to predict bleeding and thrombosis risks. Global coagulation assays such as viscoelastic testing, thrombin and fibrin generation have been proposed as better measures of the haemostatic function. These assays, particularly viscoelastic testing, have been increasingly used to assess bleeding risks and guide blood product replacement in trauma and massive transfusion settings. However, the role of these assays in thrombosis is less well-defined but given the complexities of the coagulation system, these global coagulation assays when used in combination may provide a better assessment of cardiovascular and thrombosis risk at an individual level. Hence, we explore the role of some of the currently available global coagulation assays - the viscoelastic, thrombin generation and fibrin generation tests - and provide a review of the literature of the current evidence for these assays specifically in the field of venous thromboembolism and cardiovascular diseases.

Antiphospholipid syndrome (APS) is an immune-mediated violation of coagulation, the diagnosis of which requires mandatory laboratory confirmation. Since the clinical manifestations of APS are extremely diverse, various specialists are involved in the diagnostic process – neurology, cardiologists, surgeons, hematologists, endocrinologists, laboratory medicine specialists, etc. So far, it remains an open question what specialist exactly should make the final diagnosis and supervise patient with APS. The experience of a separate diagnostic center shows the distribution of prescriptions and their compliance with the international recommendations. This study also provides data on the frequency of prescribing laboratory tests to confirm APS, which is 1.2% of all coagulation tests. Among the patients with suspected APS on the basis of clinical signs, only 12.2% of the diagnosis was confirmed. Presents the dangers of obtaining false-positive results that should be taken into account when prescribing laboratory tests.

The aim of this study is to evaluate the anomalies of coagulation (by assaying the factor VIII, fibrinogen, D-dimer and resistance to activated protein C) in patients with lung cancer. Methods 101 patients newly diagnosed with lung cancer before treatment and 72 control blood donors were included in the study after informed consent. All coagulation tests were performed on Stago STA-Compact. Statistical analyses were performed using the SPSS software version 22. Results The study of the coagulation showed that plasma levels of all coagulation parameters were significantly higher in patients compared to controls. Coagulation was not influenced by the age of patients. No significant difference was found between the histological types in terms of coagulation. Factor VIII level was significantly elevated in stage IV patients compared to stage I + II + III patients. At the cut-off value of 6.22 g/L, the elevation of fibrinogen had a significant statistical relationship with thromboembolic disease (p=0.014) giving an hazard ratio of 3.868, confidence interval [1.358-11.012]. In multivariate analysis the hazard ratio doubled to 6.398, confidence interval [1,970-20,778]. Discussion Lung cancer patients showed an increase in coagulation factors that resulted in a state of hypercoagulability that was independent of the histology of lung cancer. The elevation of fibrinogen was predictive of thromboembolic disease at the early diagnosis of lung cancer before any therapy.

Objectives Coagulation point-of-care tests for the diagnosis and management of bleeding commonly are used in cardiac surgery. Recently, a new viscoelastic point-of-care device, Quantra (HemoSonics, Charlottesville, VA), which is based on sonic estimation of elasticity via resonance sonorheometry, entered the market. Prior studies have compared the Quantra parameters with conventional coagulation tests and thromboelastography or rotational thromboelastography, but no study has assessed the correlation of the platelet-derived Quantra parameter platelet contribution to stiffness (PCS) with platelet function assays. The present study compared the Quantra-derived coagulation parameters with conventional coagulation tests, rotational thromboelastography–derived parameters, and platelet function measured using multiplate aggregometry. Design Prospective cohort study. Setting University research hospital. Participants The study comprised 30 cardiac surgery patients before and after cardiopulmonary bypass. Interventions None. Measurements and Main Results Quantra clot stiffness showed a very strong correlation with the EXTEM maximum clot firmness before and after cardiopulmonary bypass and in the overall samples (r values 0.94-0.96). Quantra fibrinogen contribution to stiffness was compared with the corresponding FIBTEM and Clauss fibrinogen levels, which also showed a strong level of correlation (r values between 0.74 and 0.87). Quantra PCS strongly correlated with platelet count (r = 0.71) in the overall samples and moderately with adenosine diphosphate–dependent platelet function (r = 0.67). In a multivariable model, both the adenosine diphosphate test value and the platelet count remained independently associated with Quantra PCS. Conclusions Fibrinogen-dependent clot stiffness properties are well-reflected by the Quantra fibrinogen contribution to stiffness parameter, and PCS incorporates platelet count and function.

Objectives: Critically ill patients with deranged conventional coagulation tests are often perceived to have an increased bleeding risk. Whether anticoagulant prophylaxis for these patients should be withheld is contentious. This study assessed the ability of using in vitro clot strength, as measured by thromboelastography, to predict thromboembolism in patients with abnormal coagulation profiles. Design: Prospective cohort study. Setting: A tertiary ICU. Patients: Two-hundred and fifteen critically ill coagulopathic patients with thrombocytopenia and/or a derangement in at least one conventional coagulation test (international normalized ratio or activated partial thromboplastin time) within 48 hours of ICU admission. Interventions: None. Measurements and Main Results: Thromboelastography was performed for all study patients, and plasma thrombotic biomarkers were measured in a nested cohort (n = 40). Of the 215 patients included, 34 patients (16%) developed subsequent thromboembolism—predominantly among those with a normal (maximum amplitude, 54–72 mm) or increased (maximum amplitude, > 72 mm) in vitro clot strength on thromboelastography (91%; area under the receiver-operating characteristic curve, 0.74; 95% CI, 0.64–0.83). The ability of the maximum amplitude to predict thromboembolism was comparable to plasma P-selectin concentrations (thromboembolism, 78.3 ng/mL vs no thromboembolism, 59.5 ng/mL; p = 0.031; area under the receiver-operating characteristic curve, 0.73; 95% CI, 0.52–0.95). In addition, patients with an increased maximum amplitude were also less likely to receive blood product transfusions within 24 hours of testing compared with those with a subnormal maximum amplitude (12.8% vs 69.2%, respectively; area under the receiver-operating characteristic curve, 0.74; 95% CI, 0.67–0.80). Conclusions: In patients with abnormal coagulation profiles, an increased in vitro clot strength on thromboelastography was associated with an increased risk of thromboembolism, and a reduced risk of requiring transfusion compared with those with a normal or reduced in vitro clot strength.

Coagulation factor (F) V is a glycoprotein that plays an essential role in the formation of the prothrombinase complex, which is critical for progressing clot formation. FV deficiency is a rare bleeding disorder with an estimated incidence of one per 1 million in the general population. The disorder is manifested with a wide array of clinical bleeding events. The most common bleeding features of FV deficiency are mucosal bleedings. Life-threatening manifestations are rarely seen in this disorder. FV deficiency is diagnosed using routine coagulation tests and FV activity assay. A wide spectrum of mutations including missense, nonsense, and frameshift is observed throughout the F5 gene. Although fresh frozen plasma is the dominant therapeutic choice, a newly introduced plasma-derived FV concentrate was found effective in in vitro correction of prothrombin time, activated partial thromboplastin time, and thrombin generation parameters in severe FV deficiency and should provide more targeted treatment for patients with FV deficiency in the future.

The relationship between malignancy and coagulopathy is one that is well documented yet incompletely understood. Clinicians have attempted to quantify the hypercoagulable state produced in various malignancies using common coagulation tests such as prothrombin time, activated partial thromboplastin time, and platelet count; however, due to these tests' focus on individual aspects of coagulation during one specific time point, they have failed to provide clinicians the complete picture of malignancy-associated coagulopathy (MAC). Viscoelastic tests (VETs), such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are whole blood analyses that have the advantage of providing information related to the cumulative effects of plasma clotting factors, platelets, leukocytes, and red cells during all stages of the coagulation and fibrinolytic processes. VETs have gained popularity in the care of trauma patients to objectively measure trauma-induced coagulopathy (TIC), but the utility of VETs remains yet unrealized in many other medical specialties. The authors discuss the similarities and differences between TIC and MAC, and propose a mechanism for the hypercoagulable state of MAC that revolves around the thrombomodulin–thrombin complex as it switches between activating the protein C anticoagulation pathway or the thrombin activatable fibrinolysis inhibitor coagulation pathway. Additionally, they review the current literature on the use of TEG and ROTEM in patients with various malignancies. Although limited research is currently available, early results demonstrate the utility of both TEG and ROTEM in the prediction of hypercoagulable states and thromboembolic complications in oncologic patients.

Background Correct handling and storage of blood samples for coagulation tests are important to assure correct diagnosis and monitoring. The aim of this study was to assess the pre-analytical practices for routine coagulation testing in European laboratories. Methods In 2013–2014, European laboratories were invited to fill in a questionnaire addressing pre-analytical requirements regarding tube fill volume, citrate concentration, sample stability, centrifugation and storage conditions for routine coagulation testing (activated partial thromboplastin time [APTT], prothrombin time in seconds [PT-sec] and as international normalised ratio [PT-INR] and fibrinogen). Results A total of 662 laboratories from 28 different countries responded. The recommended 3.2% (105–109 mmol/L) citrate tubes are used by 74% of the laboratories. Tube fill volumes ≥90% were required by 73%–76% of the laboratories, depending upon the coagulation test and tube size. The variation in centrifugation force and duration was large (median 2500 g [10- and 90-percentiles 1500 and 4000] and 10 min [5 and 15], respectively). Large variations were also seen in the accepted storage time for different tests and sample materials, for example, for citrated blood at room temperature the accepted storage time ranged from 0.5–72 h and 0.5–189 h for PT-INR and fibrinogen, respectively. If the storage time or the tube fill requirements are not fulfilled, 72% and 84% of the respondents, respectively, would reject the samples. Conclusions There was a large variation in pre-analytical practices for routine coagulation testing in European laboratories, especially for centrifugation conditions and storage time requirements.

Multiple myeloma (MM) is a rare malignancy, characterized by clonal proliferation of plasma cells, secreting monoclonal immunoglobulin. It is usually diagnosed based on histopathologic and immunophenotypic bone marrow examination. Abnormal results of screening coagulation tests, including prothrombin time, activated partial thromboplastin time and thrombin time, are commonly encountered in patients with plasma cell neoplasms. They do not, however, reflect bleeding tendency. We describe a 71-year-old patient who was accidentally diagnosed with multiple myeloma during coagulation diagnostics.

Current recommendations advocate that blood tubes for coagulation testing should be filled not less than 90% of their nominal filling volume, since under- or over-filling >10% may generate unreliable results of some hemostasis assays. This study was hence aimed to explore filling accuracy and precision of commercial blood tubes. Between-lot variations of 3 different lots (20 tubes per lot) of 3.2% citrate blood tubes manufactured by Becton Dickinson, Greiner and Kima were studied. One additional lot from each manufacturer was assessed in triplicate (three series of 20 tubes), to assess within-lot variation. All tubes were first weighed empty and then filled with distilled water by a syringe, under ideal filling conditions. Filled tubes were weighed again, in duplicate. For each 20 tubes series, mean bias (deviation from the ideal tube filling volume) and imprecision (coefficient of variation; CV%) were calculated. All biases were within ±10%. Within-lot and between-lot variation in filling volume was acceptable, and comprised between 0.4 and 2.4%. Greiner tubes were the most accurate (bias, -1.0 to 2.4%), followed by Kima (bias, -7.8 to -5.9%) and Becton Dickinson (bias, -9.6 to 3.3%) tubes. The highest between-lot difference was noted for Becton Dickinson tubes (up to 12.9%), followed by Greiner and Kima tubes (up to 3.4 and 1.8%, respectively). Although coagulation tubes filling accuracy was within ±10% for all three tested manufacturers, the overall bias was found to be variable among manufacturers and lots. Major effort shall be made by blood tube manufacturers for improving standardization of their products.

Coagulopathy in patients with traumatic brain injury is associated with an increase in morbidity and mortality. Although timely and aggressive treatment of coagulopathy is of paramount importance, excessive transfusion of blood products has been linked with poor long-term outcomes in patients with traumatic brain injury. A point-of-care thromboelastometric-guided algorithm could assist in creating a more individually tailored approach to each patient. The aim of this study was to evaluate the feasibility of implementing a thromboelastometric-guided algorithm in centres that were formerly naïve to thromboelastometry. Hence, we developed such an algorithm and provided training to four centres across Europe to direct the haemostatic management of patients with severe traumatic brain injury. The primary outcome was adherence to the algorithm and timing of the availability of relevant results. Thirty-two patients were included in the study. Complete adherence to the algorithm was observed in 20 out of 32 cases. The availability of thromboelastometric results after hospital admission was reported significantly earlier than conventional coagulation tests (median (IQR [range]) 33 (20-40 [14-250]) min vs. 71 (51-101 [32-290]) min; p = 0.037). Although only 5 out of 32 patients had abnormalities of conventional coagulation tests, 21 out of 32 patients had a coagulopathic baseline thromboelastometric trace. Implementing a thromboelastometric-guided algorithm for the haemostatic therapy of traumatic brain injury is feasible in centres formerly naïve to this technology and may lead to more rapid and precise coagulation management. Further large-scale studies are warranted to confirm the results of this pilot trial and evaluate clinical outcomes.

Background Cirrhotic patients have impaired hemostasis with variable incidence of hypersplenism necessitating splenectomy. Rotation thromboelastometery (ROTEM) facilitates diagnosis and guides management. This study evaluates perioperative effects of desflurane versus propofol on hemostasis in cirrhotic patients undergoing splenectomy guided by ROTEM and laboratory hemostatic tests. Methods Thirty hepatic Child A patients, ASA II- III, of either sex, aged 25–55 years, undergoing splenectomy were randomly allocated into two equal groups: Group D; anesthetized with desflurane 1 MAC (6%) and Group P; with propofol Target Controlled Infusion 2–5 µg/ml. Six blood samples were collected; preoperatively, after splenic artery ligation, immediately, first, third postoperative day then one month later. The samples were handled to measure complete blood picture, liver and kidney functions, screening coagulation tests (INR, PT and PTT), specific hemostatic factors (P-Selectin/CD62P, fibrinogen and D-dimer) as well as ROTEM criteria; clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) via EX-TEM, IN-TEM and FIB-TEM commercial kits. Results This study displayed postoperative hemoglobin reduction; however, platelet and WBCs as well as CT, CFT and MCF increased versus baseline. Screening and specific hemostatic factors as all other changes were within reference range and comparable between both groups. Conclusions The current study concluded comparable effects of desflurane and propofol anesthesia on coagulation parameters within acceptable range as monitored by ROTEM and laboratory coagulation tests in cirrhotic patients with hypersplenism. Thus both anesthetics are considered safe in such patients who have high incidence of coagulopathy.

Introduction: The liver is the main site of organ for coagulation system. Liver plays a predominant role in regulation of hemostasis. Hepatic disorders are widely prevalent in tropical countries are responsible for morbidity and mortality. Aims and Objective: The diagnosis of liver diseases by assisting in differential diagnosis with various coagulation tests. In assessment of prognosis of patients of various liver disease. Materials and Methods: The study was conducted in the laboratory of Guru Gobind Singh Hospital, Jamnagar. This study included 100 patients clinically diagnosed with liver disease who were divided into three categories – cirrhosis, viral hepatitis, and obstructive jaundice. The coagulation tests PT, APTT, BT, CT, and platelet count were performed and the results were evaluated in groups. Result: Out of the 100 patients, 40 were diagnosed with cirrhosis, 40 were of viral hepatitis, and 20 were of obstructive jaundice. About 75% (75/100) had prolonged PT. About 39% (39/100) had prolonged APTT. Thrombocytopenia was seen in 58% (138/300) patients.17 cases out of 100 patients (17%) show result of Hypofibrinogenemia. Conclusion: The conclusion of this study reveals various coagulation abnormalities vary with different liver diseases, duration and severity of disorders. In advancing liver cirrhosis, raised level of PT and APTT indicates damage to liver parenchyma resulting in reduced production of coagulation proteins with increased risk of bleeding tendencies which can be detected before these ensue. Keywords: Coagulation, Cirrhosis, Viral hepatitis, Obstructive jaundice.

Background Little is known about repeat testing for patients admitted to children's hospitals from the emergency department (ED). Objective The objective of this study was to describe the trend of repeat laboratory testing from a children's hospital ED. Methods Laboratory studies were analyzed for July 2002 to June 2010 for complete blood counts (CBCs; 7 years), basic metabolic panels (BMPs; 2.5 years), and coagulation studies (7 years) ordered and reordered in the ED within 8 hours for patients admitted to the hospital. Results for tests were generated and classified into high, low, and normal based on reference ranges. To reflect actual practice, we expanded the normal range from 95% of lower bound to 105% of upper bound. Results A total of 37,035 CBCs, 11,414 BMPs, and 3903 coagulation studies were ordered. Proportions of these tests repeated were 0.9%, 1.9%, and 1.9%, respectively. Mean time to repeat was 2 hours. For CBCs, 25% of repeats were for a missing component; 35% were for low platelet counts. Sixty-eight percent of initial BMPs were repeated for high potassium. Half of coagulation studies were repeated for high prothrombin time; 36% were repeated for a missing component. On repeat, 75% of BMPs with high potassium levels and 65% of CBCs with low platelet count returned normal values, but 16% of coagulation studies repeated for high prothrombin time returned normal values. Conclusions Repeat ED laboratory testing occurs infrequently at a children's hospital, and a large proportion of repeats is attributed to missing results. When repeated, abnormal results on initial studies are often returned as normal.