Factor XIII in major burns coagulation.

BACKGROUND: In the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. OBJECTIVE: To determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. METHODS: Prospective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. RESULTS: FXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. CONCLUSION: MBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation.

Evaluation of an aPTT guided versus a multimodal heparin monitoring approach in patients on extra corporeal membrane oxygenation: A retrospective cohort study.

INTRODUCTION: Bleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The optimal anticoagulation monitoring protocol in these patients is unknown. This study aims to compare the incidence of thrombotic and hemorrhagic complications before and after a protocol change. In addition, the association between hemostatic complications, coagulation tests and risk factors is evaluated. METHODS: This is a retrospective single center cohort study of adult ECMO patients. We collected demographics, ECMO parameters and coagulation test results. Outcomes of the aPTT guided and multimodal protocol, including aPTT, anti-Xa assay and rotational thromboelastometry were compared and the association between coagulation tests, risk factors and hemostatic complications was determined using a logistic regression analysis for repeated measurements. RESULTS: In total, 250 patients were included, 138 in the aPTT protocol and 112 in the multimodal protocol. The incidence of thrombosis (aPTT: 14%; multimodal: 12%) and bleeding (aPTT: 36%; multimodal: 40%), did not significantly differ between protocols. In the aPTT guided protocol, the aPTT was associated with thrombosis (Odds Ratio [OR] 1.015; 95% confidence interval [CI] 1.004-1.027). In both protocols, surgical interventions were risk factors for bleeding and thrombotic complications (aPTT: OR 93.2, CI 39.9-217.6; multimodal OR 17.5, CI 6.5-46.9). DISCUSSION: The incidence of hemostatic complications was similar between both protocols and surgical interventions were a risk factor for hemostatic complications. Results from this study help to elucidate the role of coagulation tests and risk factors in predicting hemostatic complications in patients undergoing ECMO support.

User Perceptions of Visual Clot in a High-Fidelity Simulation Study: Mixed Qualitative-Quantitative Study.

BACKGROUND: Viscoelastic hemostatic assays, such as rotational thromboelastometry (ROTEM) or thromboelastography, enable prompt diagnosis and accelerate targeted treatment. However, the complex interpretation of the results remains challenging. Visual Clot-a situation awareness-based visualization technology-was developed to assist clinicians in interpreting viscoelastic tests. OBJECTIVE: Following a previous high-fidelity simulation study, we analyzed users' perceptions of the technology, to identify its strengths and limitations from clinicians' perspectives. METHODS: This is a mixed qualitative-quantitative study consisting of interviews and a survey. After solving coagulation scenarios using Visual Clot in high-fidelity simulations, we interviewed anesthesia personnel about the perceived advantages and disadvantages of the new tool. We used a template approach to identify dominant themes in interview responses. From these themes, we defined 5 statements, which were then rated on Likert scales in a questionnaire. RESULTS: We interviewed 77 participants and 23 completed the survey. We identified 9 frequently mentioned topics by analyzing the interview responses. The most common themes were "positive design features," "intuitive and easy to learn," and "lack of a quantitative component." In the survey, 21 respondents agreed that Visual Clot is easy to learn and 16 respondents stated that a combination of Visual Clot and ROTEM would help them manage complex hemostatic situations. CONCLUSIONS: A group of anesthesia care providers found Visual Clot well-designed, intuitive, and easy to learn. Participants highlighted its usefulness in emergencies, especially for clinicians inexperienced in coagulation management. However, the lack of quantitative information is an area for improvement.

Clues of incomplete reversal of heparin in cardiac surgery.

OBJECTIVES: In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing. METHODS: In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1 month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added. RESULTS: Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 (p < .0001) and 0.95 (p = .0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58-97] and a specificity of 85% [58-97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30-94] and a specificity of 100% [18-100]. CONCLUSION: The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin.

Sources of bias and limitations of thrombinography: inner filter effect and substrate depletion at the edge of failure algorithm.

BACKGROUND: Fluorogenic thrombin generation (TG) is a global hemostasis assay that provides an overall representation of hemostasis potential. However, the accurate detection of thrombin activity in plasma may be affected by artifacts inherent to the assay-associated fluorogenic substrate. The significance of the fluorogenic artifacts or their corrections has not been studied in hemophilia treatment applications. METHODS: We sought to investigate TG in hemophilia plasma samples under typical and worst-case fluorogenic artifact conditions and assess the performance of artifact correction algorithms. Severe hemophilic plasma with or without added Factor VIII (FVIII) was evaluated using commercially available and in-house TG reagents, instruments, and software packages. The inner filter effect (IFE) was induced by spiking elevated amounts of fluorophore 7-amino-4-methylcoumarin (AMC) into plasma prior to the TG experiment. Substrate consumption was modeled by adding decreasing amounts of Z-Gly-Gly-Arg-AMC (ZGGR-AMC) to plasma or performing TG in antithrombin deficient plasma. RESULTS: All algorithms corrected the AMC-induced IFE and antithrombin-deficiency induced substrate consumption up to a certain level of either artifact (edge of failure) upon which TG results were not returned or overestimated. TG values in FVIII deficient (FVIII-DP) or supplemented plasma were affected similarly. Normalization of FVIII-DP resulted in a more accurate correction of substrate artifacts than algorithmic methods. CONCLUSIONS: Correction algorithms may be effective in situations of moderate fluorogenic substrate artifacts inherent to highly procoagulant samples, but correction may not be required under typical conditions for hemophilia treatment studies if TG parameters can be normalized to a reference plasma sample.

[Local necrosis and infection complicating envenomation with Echis ocellatus in a child in Mali]. / Nécrose et infection locales compliquant une envenimation par Echis ocellatus chez un enfant au Mali.

A 4-year-old child living with his parents in Kolokani, a town about 100 km from Bamako, was bitten on the left index finger by a snake of the species Echis ocellatus (fonfoni in local language). After 2 weeks of traditional treatment, local complications were observed. The child was admitted to the Néné clinic in Kati (Mali) on 19 July 2022. The signs observed were correlated with the degree of envenomation and the whole blood coagulation test showed coagulation disorders, which justified the administration of antivenom. Necrosis of the whole index finger required amputation of the finger, which was not followed by any complications. Snakebites require proper management to prevent complications such as necrosis and infection of the bite site. Administration of antivenom is necessary if coagulation disorders persist. Surgical treatment and broad-spectrum antibiotic therapy may improve the prognosis.

Blood coagulation test abnormalities in trauma patients detected by sonorheometry: a retrospective cohort study.

Background: Traumatic hemorrhage guidelines include point-of-care viscoelastic tests as a standard of care. Quantra (Hemosonics) is a device based on sonic estimation of elasticity via resonance (SEER) sonorheometry to assess whole blood clot formation. Objectives: Our study aimed to assess the ability of an early SEER evaluation to detect blood coagulation test abnormalities in trauma patients. Methods: We conducted an observational retrospective cohort study with data collected at hospital admission of consecutive multiple trauma patients from September 2020 to February 2022 at a regional level 1 trauma center. We performed a receiving operator characteristic curve analysis to determine the ability of the SEER device to detect blood coagulation test abnormalities. Four values on the SEER device were analyzed: clot formation time, clot stiffness (CS), platelet contribution to CS, and fibrinogen contribution to CS. Results: A total of 156 trauma patients were analyzed. The clot formation time value predicted an activated partial thromboplastin time ratio of >1.5 with an area under the curve (AUC) of 0.93 (95% CI, 0.86-0.99). The AUC of the CS value in detecting an international normalized ratio of prothrombin time of >1.5 was 0.87 (95% CI, 0.79-0.95). The AUC of fibrinogen contribution to CS to detect a fibrinogen concentration of <1.5 g/L was 0.87 (95% CI, 0.80-0.94). The AUC of platelet contribution to CS to detect a platelet concentration of <50 G/L was 0.99 (95% CI, 0.99-1.00). Conclusion: Our results suggest that the SEER device may be useful for the detection of blood coagulation test abnormalities at trauma admission.

High levels of factor VIII activity in patients with acquired hemophilia A in remission are associated with unusually low coagulation potentials.

BACKGROUND: Elevated factor VIII activity (FVIII:C) is often observed in patients with acquired hemophilia A (PwAHA) in remission. However, comprehensive coagulation potentials in this patient group remain to be investigated. AIM: To evaluate comprehensive coagulation potentials in PwAHA. METHODS: We investigated coagulation function in eleven PwAHA with high FVIII:C (> 150 IU/dL) using thrombin generation assay (TGA) and/or rotational thromboelastometry (ROTEM), and compared findings with results obtained from contrived samples generated by spiking recombinant FVIII. RESULTS: The median FVIII:C and FVIII inhibitor titers during remission in enrolled PwAHA were 206 IU/dL and 0.44 BU/mL, respectively. In all patients, lag time and time to peak were either prolonged or normal compared to contrived samples corresponding to their FVIII:C. However, higher values of peak thrombin and endogenous thrombin potentials compared to contrived samples were observed in two patients. ROTEM parameters were within normal ranges in all cases. One patient (FVIII:C 171 IU/dL) developed venous thrombosis and pulmonary embolism, but TGA parameters showed low or normal coagulation potential compared to contrived samples corresponding to his FVIII:C. CONCLUSION: PwAHA with high FVIII:C could exhibit lower coagulation potentials than those corresponding to their FVIII:C.

Coagulation in pediatric extracorporeal membrane oxygenation: A systematic review of studies shows lack of standardized reporting.

Objectives: Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO-, coagulation-, and transfusion-related parameters were described in pediatric ECMO studies. Data sources: Embase, Medline, Web of Science, Cochrane Library and Google Scholar. Study selection: English original studies of pediatric ECMO patients describing hemostatic tests or outcome. Data extraction: Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO-, coagulation, and transfusion parameters were summarized. Data synthesis: A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively. Conclusions: This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research.

Inter- and intra-individual concentrations of direct oral anticoagulants: The KIDOAC study.

BACKGROUND: Direct oral anticoagulants (DOACs) do not require concentration monitoring. However, whether DOAC concentrations are stable and their variation between and within patients is not well studied. METHODS: Patients on vitamin K antagonists (VKA) who switched to rivaroxaban, apixaban, or dabigatran were included between 2018 and 2020. Blood was drawn at DOAC trough and peak concentrations at week 0, 2, and 8. Plasma drug concentrations were determined by anti-factor Xa concentrations (rivaroxaban, apixaban) or diluted thrombin time (dabigatran). Inter- and intra-individual variability was assessed by calculating the coefficient of variation (CV). Linear regression models were employed to evaluate associations between DOAC trough concentrations and previous VKA dosage, creatinine clearance, and body mass index (BMI). RESULTS: One hundred fifty-two patients were included, of whom 96 (63%) were male and with a mean age of 73.9 ± 8.4 years. For the inter-individual variability, the CV ranged between 48% and 81% for trough values and between 25% and 69% for peak values among patients using the recommended DOAC dose. Intra-individual variability was substantially lower, as here the CV ranged between 18% and 33% for trough values and between 15% and 29% for peak values among patients using the recommended DOAC dose. Previous VKA dosage and creatinine clearance were inversely associated with DOAC trough concentrations. No association was found between BMI and DOAC trough concentrations. CONCLUSION: Inter-individual variability of DOAC concentrations was higher than intra-individual variability. Lower previous VKA dosage and creatinine clearance were associated with higher DOAC trough concentrations. These findings support further study into an optimal target range, in which the risks of both bleeding and thrombosis are minimal.

Variability of three activated clotting time point-of-care systems in cardiac surgery: reinforcing available evidence.

BACKGROUND: Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400-600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement. METHODS: Simultaneous ACT measurements were performed with the Hemochron Response®, Hemostasis Management System Plus® (HMS Plus®) and Hemochron Signature® systems. RESULTS: A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature® 361.1 seconds (SD: 156.9), HMS Plus® 412.8 seconds (SD: 180.9) and Hemochron Response® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman's test p < 0.01). For comparisons the Bland-Altman method was used, resulting the Hemochron Response® has 61.7 seconds higher mean values than the Hemochron Signature®, the Hemochron Response® 10 seconds higher than the HMS Plus® and the HMS Plus® 51.7 seconds higher than the Hemochron Signature®. CONCLUSION: The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions.

Comprehensive blood coagulation potential in patients with acquired hemophilia A: retrospective analyses of plasma samples obtained from nationwide centers across Japan.

Global coagulation potential was assessed in 59 patients with acquired hemophilia A (PwAHA) by clot waveform analysis (CWA) and/or thrombin and plasmin generation assay. Relationships between factor VIII activity (FVIII:C) and the parameters from CWA and T/P-GA in patients with congenital HA were compared by grading coagulation potential related to FVIII:C: T1 (FVIII:C < 1 IU/dL), T2 (1 ≤ , ≤ 5 IU/dL), T3 (5 < , 12 ≤ IU/dL), and T4 (12 < , ≤ 50 IU/dL). The median FVIII:C and inhibitor titers in PwAHA on admission were 3.3 IU/dL and 63.0 BU/mL, respectively, but global coagulation parameters corresponded to T1 or less. Median FVIII:C levels during follow-up in PwAHA were 1.7-9.6-6.7-40.0-21.7 IU/dL on days 0-14-28-56-93, respectively. CWA-based data corresponded to less than T2 until day 28, but more closely reflected FVIII:C after day 56. Peak thrombin was severely low (near T1) until day 28 and improved modestly after day 56 but remained less than T2. Peak plasmin was lower than T1 until day 56, and returned to T4 on day 93. In conclusion, global coagulation function in PwAHA was impaired to a greater extent than could be anticipated from assays of FVIII:C, until approximately 1 month after immunosuppression and treatment with FVIII-bypassing agents.

Management of bone marrow biopsy related bleeding risks: a retrospective observational study.

Bone marrow biopsies are largely used for the diagnosis and prognostic of various hematological diseases. Complications are rare but can be as serious as hemorrhage. However, little is known about management of patients deemed at high hemorrhagic risk like thrombocytopenic patients or patients receiving antithrombotic drugs. The aim of the study was to describe the management of patients regarding their laboratory profile and antithrombotic treatment prior to bone marrow biopsy and the short-term outcomes, notably hemorrhage. We conducted a retrospective observational study between February 2007 and March 2018. A standardized form was used to collect data from patients' records, blood tests results, management of antiplatelet and anticoagulant treatment before biopsy and complications including bleeding and thromboembolic events until 3 months after the biopsy. A total of 524 bone marrow biopsies were performed. No major bleeding events were reported. The incidence of clinically relevant non-major bleeding was 0.19% (CI 95% 0.00-1.20) and was linked to low platelets counts (p = 0.002) and not to abnormal coagulation profile or antithrombotic therapy, whether or not a bridging therapy has been used. Anticoagulants were temporarily stopped before biopsy in most cases without subsequent thrombotic complications. Our data suggest that thrombocytopenic patients have a non-negligible bleeding risk. Coagulation profiling seems irrelevant. We propose an algorithm to assist the management of those patients, notably when receiving antithrombotic drugs.

Interlaboratory variability of activated protein C resistance using the ETP-based APC resistance assay.

BACKGROUND AND OBJECTIVE: Although the endogenous thrombin potential (ETP)-based activated protein C (APC) resistance is recommended for the development of steroid contraceptive agents, one of the main limitations of this technique was its lack of standardization, which hampered study-to-study comparison. A validated methodology that meets all the regulatory requirements in terms of analytical performances has been developed recently. To ensure a wide implementation of this test, the assessment of the interlaboratory variability was needed. METHOD: The assay was implemented in three testing laboratories. First, dose-response curves were performed to locally define APC concentration leading to 90% of ETP inhibition on healthy donors. Intra- and inter-run repeatability were assessed on a reference plasma and three quality controls. To investigate the variability in results among the different testing units, 60 donor samples were analyzed at each site. RESULTS: The APC concentration leading to 90% of ETP inhibition was defined at 1.21 µg/ml and 1.14 µg/ml in the two receiving units. Intra- and inter-run repeatability showed standard deviation below 3%. Analyses of the 60 donor samples showed no statistically significant difference. The sensitivity of the test in the different laboratories was maintained and subgroup analyses still reported significant differences depending on hormonal status of donors. CONCLUSION: This study is the first reporting the interlaboratory variability of the ETP-based APC resistance assay. Data revealed excellent intra- and interlaboratory reproducibility. These results support the concept that this blood coagulation test provides an appropriate sensitivity irrespective of the laboratory in which analyses are performed.

Use of rotational thromboelastometry to predict hemostatic complications in pediatric patients undergoing extracorporeal membrane oxygenation: A retrospective cohort study.

BACKGROUND: The incidence of hemostatic complications in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) is high. The optimal anticoagulation strategy in children undergoing ECMO is unknown. OBJECTIVES: To study the association between hemostatic complications, coagulation tests, and clinical parameters in pediatric patients undergoing ECMO and their effect on survival. METHODS: We performed a retrospective cohort study of pediatric patients undergoing centrifugal pump ECMO. Collected data included patient characteristics, risk factors, and coagulation test results. Statistical analysis was done using logistic regression analysis for repeated measurements. Dependent variables were thrombosis and bleeding, independent variables were rotational thromboelastometry (ROTEM), activated partial thromboplastin time (aPTT) and antifactor-Xa assay (aXa) results, ECMO duration, age <29 days, sepsis and surgery. RESULTS: Seventy-three patients with 623 ECMO days were included. Cumulative incidences of thrombosis and bleeding were 43.5% (95% confidence interval [CI], 26.0%-59.8%) and 25.4% (95% CI, 13.4%-39.3%), respectively. A lower maximum clot firmness of intrinsic ROTEM (INTEM; odds ratio [OR], 0.946; 95% CI, 0.920-0.969), extrinsic ROTEM (OR, 0.945; 95% CI, 0.912-0.973), and INTEM with heparinase (OR, 0.936; 95% CI, 0.896-0.968); higher activated partial thromboplastin time aPTT; OR, 1.020; 95% CI, 1.006-1.024) and age <29 days (OR, 2.900; 95% CI, 1.282-6.694); surgery (OR, 4.426; 95% CI, 1.543-12.694); and longer ECMO duration (OR, 1.149; 95% CI, 1.022-1.292) significantly increased thrombotic risk. Surgery (OR, 2.698; 95% CI, 1.543-12.694) and age <29 days (OR 2.242, 95% CI 1.282-6.694) were significantly associated with major bleeding. Patients with hemostatic complications had significantly decreased survival to hospital discharge (P = .009). CONCLUSION: The results of this study help elucidate the role of ROTEM, aPTT, anti-factor Xa, and clinical risk factors in predicting hemostatic complications in pediatric patients undergoing ECMO.

Comparison of Acquired Activated Protein C Resistance, Using the CAT and ST-Genesia® Analysers and Three Thrombin Generation Methods, in APS and SLE Patients.

BACKGROUND: Acquired activated protein C resistance (APCr) has been identified in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). OBJECTIVE: To assess agreement between the ST-Genesia® and CAT analysers in identifying APCr prevalence in APS/SLE patients, using three thrombin generation (TG) methods. METHODS: APCr was assessed with the ST-Genesia using STG-ThromboScreen and with the CAT using recombinant human activated protein C and Protac® in 105 APS, 53 SLE patients and 36 thrombotic controls. Agreement was expressed in % and by Cohen's kappa coefficient. RESULTS: APCr values were consistently lower with the ST-Genesia® compared to the CAT, using either method, in both APS and SLE patients. Agreement between the two analysers in identifying APS and SLE patients with APCr was poor (≤65.9%, ≤0.20) or fair (≤68.5%, ≥0.29), regardless of TG method, respectively; no agreement was observed in thrombotic controls. APCr with both the ST Genesia and the CAT using Protac®, but not the CAT using rhAPC, was significantly greater in triple antiphospholipid antibody (aPL) APS patients compared to double/single aPL patients (p < 0.04) and in thrombotic SLE patients compared to non-thrombotic SLE patients (p < 0.05). Notably, the ST-Genesia®, unlike the CAT, with either method, identified significantly greater APCr in pregnancy morbidity (median, confidence intervals; 36.9%, 21.9-49.0%) compared to thrombotic (45.7%, 39.6-55.5%) APS patients (p = 0.03). CONCLUSION: Despite the broadly similar methodology used by CAT and ST-Genesia®, agreement in APCr was poor/fair, with results not being interchangeable. This may reflect differences in the TG method, use of different reagents, and analyser data handling.

Physicians' Perceptions of a Situation Awareness-Oriented Visualization Technology for Viscoelastic Blood Coagulation Management (Visual Clot): Mixed Methods Study.

BACKGROUND: Viscoelastic tests enable a time-efficient analysis of coagulation properties. An important limitation of viscoelastic tests is the complicated presentation of their results in the form of abstract graphs with a multitude of numbers. We developed Visual Clot to simplify the interpretation of presented clotting information. This visualization technology applies user-centered design principles to create an animated model of a blood clot during the hemostatic cascade. In a previous simulation study, we found Visual Clot to double diagnostic accuracy, reduce time to decision making and perceived workload, and improve care providers' confidence. OBJECTIVE: This study aimed to investigate the opinions of physicians on Visual Clot technology. It further aimed to assess its strengths, limitations, and clinical applicability as a support tool for coagulation management. METHODS: This was a researcher-initiated, international, double-center, mixed qualitative-quantitative study that included the anesthesiologists and intensive care physicians who participated in the previous Visual Clot study. After the participants solved six coagulation scenarios using Visual Clot, we questioned them about the perceived pros and cons of this new tool. Employing qualitative research methods, we identified recurring answer patterns, and derived major topics and subthemes through inductive coding. Based on them, we defined six statements. The study participants later rated their agreement to these statements on five-point Likert scales in an online survey, which represented the quantitative part of this study. RESULTS: A total of 60 physicians participated in the primary Visual Clot study. Among these, 36 gave an interview and 42 completed the online survey. In total, eight different major topics were derived from the interview field note responses. The three most common topics were "positive design features" (29/36, 81%), "facilitates decision making" (17/36, 47%), and "quantification not made" (17/36, 47%). In the online survey, 93% (39/42) agreed to the statement that Visual Clot is intuitive and easy to learn. Moreover, 90% (38/42) of the participants agreed that they would like the standard result and Visual Clot displayed on the screen side by side. Furthermore, 86% (36/42) indicated that Visual Clot allows them to deal with complex coagulation situations more quickly. CONCLUSIONS: A group of anesthesia and intensive care physicians from two university hospitals in central Europe considered Visual Clot technology to be intuitive, easy to learn, and useful for decision making in situations of active bleeding. From the responses of these possible future users, Visual Clot appears to constitute an efficient and well-accepted way to streamline the decision-making process in viscoelastic test-based coagulation management.

Magnesium Therapy Improves Rotational Thromboelastometry Findings Prior to Liver Transplantation: A Randomized Clinical Trial.

An important challenge during orthotopic liver transplantation (OLT) is optimal coagulation management. There are diverse studies regarding effect of Mg sulfate on coagulation system. This study evaluates the impact of Mg sulfate on the coagulation parameters of the rotational thromboelastometry (ROTEM) in patients about to undergo OLT. In this randomized clinical trial, 60 patients who were going to undergo OLT were randomly allocated into two groups. In the Mg group, the patients received a 1.5 g infusion of Mg 5 min before the surgical incision. In the control group, patients received a physiological saline instead of Mg. Plasma Mg levels before and after the infusions were measured in both groups. Also, three ROTEM tests: EXTEM, INTEM and FIBTEM were performed before and after the infusions. Baseline mean plasma magnesium levels were within normal range in the control and Mg groups: 2.06 and 2.18 mg/dl, respectively. After magnesium therapy, the mean plasma Mg level in the Mg group increased to 2.78 mg/dl in compared to the control group that was 2.01 mg/dl (P < 0.000). Mean value of the clotting time (CT) in the magnesium group were significantly decreased from 129.50 ± 7.76, 381.86 ± 8.51 and 114.26 ± 6.80 to 86.13 ± 3.4, 209.33 ± 6.68 and 81.56 ± 5.01 in the EXTEM, INTEM, and FIBTEM respectively after intervention in the Mg group (P = 0.001). Among patients with end-stage liver diseases who have ROTEM evidence of hypocoagulability, magnesium could correct CT parameter of the ROTEM tests.

Hypercoagulability (thrombin generation) in patients with cirrhosis is detected with ST-Genesia.

BACKGROUND: Thrombin generation assays (TGAs) performed with calibrated automated thrombography (CAT) in the presence of thrombomodulin (TM) indicate plasma hypercoagulability in cirrhosis. OBJECTIVE: To evaluate, in the presence of TM, the new ST-Genesia automated device developed for improving TGA vs the previously used CAT method, with plasma samples of patients with cirrhosis. PATIENTS/METHODS: Platelet-poor plasma samples were prepared from citrated blood samples of 52 healthy controls and 85 patients with cirrhosis (severity evaluated using the Child-Pugh score [CP]). TGAs were performed using CAT with PPP-Reagent and ST-Genesia with the STG-ThromboScreen reagent, in the presence of TM. Endogenous thrombin potential (ETP) was chosen as the main parameter. RESULTS: Whatever the method, ETP values were higher in patients than in healthy controls. All patients identified as hypercoagulable with ST-Genesia and STG-ThromboScreen were found hypercoagulable with CAT and PPP-Reagent. Conversely, eight and ten patients in the CP-A and CP-B classes respectively were identified as hypercoagulable only with CAT. The use of ST-Genesia with the STG-ThromboScreen reagent with TM led to a bias, with higher ETP values for healthy controls and lower for patients compared with CAT. Crossover analysis (CAT with the STG-ThromboScreen reagent) evidenced a substantial effect of the STG-ThromboScreen reagent; the analyzer (including calibration and data analysis) plays a lesser role. CONCLUSION: ST-Genesia evidences hypercoagulability in patients with cirrhosis when TG is studied in the presence of TM, but the results are not interchangeable with those obtained with CAT.

Influence of alcohol consumption on blood coagulation in rotational thromboelastometry (ROTEM): an in-vivo study.

BACKGROUND: Twenty-five to 85% of trauma patients are under the influence of alcohol in addition to experiencing injury-related coagulation impairment. Viscoelastic point-of-care tests (thrombelastography [TEG], rotational thromboelastometry [ROTEM]) are popular tools for rapid hemostasis assessment and therapeutic decision-making in this and other settings. While alcohol affects these tests in-vitro, their specific effects in-vivo are unclear. Therefore, we evaluated the effects of alcohol ingestion on ROTEM parameters. METHODS: Twenty volunteers provided informed consent to drinking red wine, whisk(e)y, or vodka to a target blood alcohol concentration of 1 ‰ within one hour, calculated with the Widmark formula. Blood samples were collected before drinking, at a breath alcohol concentration of 0.5 ‰, and at 1.0 ‰, but no later than one hour. After each blood collection, ExTEM and FibTEM tests were performed directly "at the bedside." RESULTS: All participants had a blood alcohol concentration (BAC) of 0.00 ‰ at the beginning. The mean BACs at the second and third collection were 0.48 and 0.76 ‰, respectively. There were no significant differences in the ExTEM parameters. FibTEM measurements showed a significant difference at the A10 value (13.0 vs. 14.0 mm, P = 0.014) and a trend at the maximum amplitude (maximum clot firmness [MCF] 13.7 vs. 16.2 mm, P = 0.075). We saw no significant differences in fibrinolysis parameters and no hyperfibrinolysis in our ROTEM measurements. CONCLUSIONS: Ethanol ingestion can impair early fibrin polymerization. These results might be of special relevance in trauma and support routine application of ROTEM/TEG in such cases.