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.

Coagulation profile of neonates with hyperbilirubinaemia in full-term newborns.

OBJECTIVE: To determine the relationship between coagulation system markers and hyperbilirubinaemia in full-term neonates. METHODS: This retrospective case-control study enrolled full-term neonates with hyperbilirubinaemia and healthy control full-term neonates. Prothrombin time (PT), thrombin time (TT), fibrinogen (Fbg), activated partial thromboplastin time (APTT) and international normalized ratio (INR) were recorded. The correlation between INR and total bilirubin and between INR and indirect bilirubin was analysed by linear regression analysis. Receiver operating characteristic curve analysis was used to assess the efficacy of INR to identify neonates with hyperbilirubinaemia. RESULTS: This study enrolled 40 full-term neonates with hyperbilirubinaemia and 30 healthy controls. PT, INR and APTT were significantly higher in the neonates with hyperbilirubinaemia compared with the healthy controls. There was a significant positive correlation between INR and the level of total bilirubin in neonates with hyperbilirubinaemia (R = 0.3327). There was also a significant positive correlation between INR and the level of indirect bilirubin in neonates with hyperbilirubinaemia (R = 0.3406). INR in neonates with hyperbilirubinaemia significantly achieved an area under the curve of 0.800 (95% confidence interval, 0.6288, 0.9712; cut-off value, 1.060; specificity, 71.43%; sensitivity, 80.00%). CONCLUSION: These findings suggest that INR is a novel biomarker for the diagnosis of neonatal hyperbilirubinaemia in full-term neonates.

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.

Coagulation profiles in patients with sepsis/septic shock identify mixed hypo-hypercoagulation patterns based on rotational thromboelastometry: A prospective observational study.

INTRODUCTION: Sepsis-induced hemostatic disturbances are common and are associated with poor outcomes. Additionally, conventional coagulation tests (CCTs) overdiagnose hypocoagulation and cannot detect hypercoagulation and hyperfibrinolysis. The aim of this study was to describe the coagulation profiles of patients with sepsis/septic shock using rotational thromboelastometry (ROTEM) and to compare coagulation states between sepsis and septic shock groups and between surviving and non-surviving groups. MATERIALS AND METHODS: This prospective, observational, single-center study was conducted in the intensive care unit (ICU) of the University Medical Center Ho Chi Minh City, from 6/2020-12/2021. Patients aged ≥18 years with sepsis or septic shock according to the Sepsis-3 criteria were included. ROTEM and CCTs were concurrently performed within the first 24 h of ICU admission. RESULTS: In total, 161 patients were enrolled. Based on ROTEM, 72.7 % of patients with sepsis/septic shock had coagulation disorders, including 25.5 % hypercoagulation, 54.7 % hypocoagulation, 13.6 % mixed hypo-hypercoagulation patterns, and 18.6 % hyperfibrinolysis. A common mixed disorder subtype was characterized by prolonged initial clotting time (CT) with subsequently increased clot firmness. Fibrinogen levels and maximum clot formation (MCF)-fibtem were strongly correlated (rho = 0.73, p < 0.05). Hypocoagulation was observed more in the septic shock group than in the sepsis group. Compared to survivors, non-survivors had more prolonged CT-extem. CONCLUSIONS: ROTEM could identify hypocoagulability, hypercoagulability, mixed hypo-hypercoagulability patterns, and hyperfibrinolysis in patients with sepsis/septic shock. Elevated MCF-fibtem and elevated fibrinogen levels were notably common and strongly correlated. The septic shock group had more hypocoagulation than the sepsis group. Lastly, non-survivors had more prolonged CT-extem than survivors.

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.

Plasma transfusion in critically Ill patients with abnormal coagulation tests before invasive procedures: A propensity-adjusted cohort study.

OBJECTIVE: To evaluate the association between plasma transfusion and bleeding complications in critically ill patients with an elevated international normalized ratios undergoing invasive procedures. METHODS: A retrospective study was conducted to evaluate a consecutive sample of critically ill adult patients undergoing invasive procedures (N = 487) with an international normalized ratio ≥ 1.5 between January 1, 2019 and December 31, 2019. Among the followed patients, 125 were excluded due to incomplete case records and 362 were finally included in this investigation. The exposure was whether plasma had been transfused within 24 h before the invasive procedure. The primary outcome was the occurrence of postprocedural bleeding complications. Secondary outcomes included transfusion of red blood cells within 24 h of the invasive procedure, and additional patient-important outcomes such as mortality and length of stay. Tests were performed with univariate and propensity-matched analyses. RESULTS: Of the 362 study participants, 99 (27.3 %) received a preprocedural plasma transfusion. In the propensity score-matched analysis, the rate of the occurrence of postprocedural bleeding complications between two groups was not statistically different (OR, 0.605[95 % CI, 0.341-1.071]; P = .085). The rate of postoperative red blood cell transfusion in the plasma transfusion group was higher than that in the non-plasma transfusion group (35.5 % vs 21.5 %; P < .05). No statistically significant difference in mortality was observed between the two groups (29.0 % vs 31.6 %; P = .101). CONCLUSIONS: Prophylactic plasma transfusion failed to reduce postprocedural bleeding complications in ill critically patients with a coagulopathy. Meanwhile, it was associated with increased red blood cell transfusion after invasive procedures. Findings suggest that abnormal preprocedural international normalized ratios should be managed more conservatively.

Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results.

PURPOSE: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. METHODS: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. RESULTS: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8-538.5, P=.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. CONCLUSIONS: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.

Pruebas de coagulación preoperatorias en pacientes pediátricos: relevancia clínica y consecuencias hemorrágicas de los resultados anómalos / Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results

Objetivo: Las pruebas de evaluación de la coagulación en niños siguen realizándose con frecuencia en muchos países, para evaluar el riesgo de hemorragia. El objetivo de este estudio fue valorar el manejo de la prolongación inesperada del tiempo de tromboplastina parcial activada (APTT) y el tiempo de protrombina (PT) en niños previa a la cirugía electiva, y el riesgo hemorrágico perioperatorio. Métodos: Se incluyó a los niños con APTT y/o PT prolongados que acudieron a consulta de anestesia preoperatoria desde enero del 2013 a diciembre del 2018. Se agrupó a los pacientes en función de si habían sido derivados a Hematología o habían sido programados para cirugía sin pruebas adicionales. El resultado primario fue comparar las complicaciones hemorrágicas perioperatorias. Resultados: Se evaluó para elegibilidad a 1.835 niños. Presentaron resultados anormales 102 de ellos (5,6%) y el 45% fue derivado a Hematología previo a la cirugía. Los trastornos hemorrágicos significativos estuvieron asociados a a una historia hemorrágica (personal y/o familiar) positiva, odds ratio de 51 (IC 95% de 4,8 a 538,5, p = 0,0011). No se encontró diferencia en términos de resultados de hemorragia perioperatoria entre los grupos. Se observó un coste adicional de 181 € por paciente y una mediana de demora preoperatoria de 43 días en los pacientes derivados a Hematología. Conclusiones: Nuestros resultados sugieren que la derivación a Hematología tiene un valor limitado en niños asintomáticos con APTT y/o PT prolongados. Las complicaciones hemorrágicas fueron similares entre los pacientes derivados y los no derivados a Hematología. Una historia familiar positiva de hemorragia puede ayudar a identificar a los pacientes con mayor riesgo de sangrado, por lo que debería guiar la petición de los análisis de coagulación y la derivación a Hematología. Esfuerzos adicionales son necesarios para estandarizar las herramientas preoperatorias de evaluación hemorrágica en niños.(AU)

Purpose: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. Methods: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. Results: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8 to 538.5, P = 0.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. Conclusions: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.(AU)

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 Abnormalities in Dogs with Parvoviral Enteritis.

Hemostatic alterations have been documented in dogs with canine parvoviral enteritis. This study's aims were to measure the standard coagulation parameters, and to assess the relationship between them and the clinical variables in dogs with canine parvoviral enteritis. Nine client-owned dogs with a canine parvoviral infection were included in a prospective, observational clinical study. Clinical score and coagulation status were assessed at admission. All nine dogs showed alterations of three or more standard coagulation variables. A correlation analysis evidenced a significantly high positive correlation between the activated partial thromboplastin time and clinical score. The present study concurs that dogs with canine parvoviral enteritis have coagulation disorders that are detectable by measuring the standard coagulation parameters.

Clinical Evaluation of the Pre-Analytical Capabilities of Hemostasis Instrument.

Objective: Evaluate the technical performance of the pre-analytical hemolysis-icterus-lipemia (HIL) check module on the ACL-TOP-750. Methods: 8433 routine coagulation samples were evaluated for HIL, the presence of clotting and low sample volume by both visual inspection and the pre-analytical HIL check module on the ACL-TOP-750. Results: 7726 samples were in agreement with both methods and 707 were not consistent. 356 samples with low volume were identified by visual inspection and 920 by the instrument (2.7 mL threshold). Visual inspection identified 56 lipemic samples while 13 of those with moderate or high lipemia were identified by the instrument. Visual inspection identified 47 hemolyzed samples while 7 with moderate or high hemolysis were identified by the instrument. Both visual inspection and the instrument identified 36 icteric samples. For triglyceride concentration and bilirubin concentration, there was good correlation between the ACL-TOP-750 and the DXC800 biochemistry analyzer. Among 30 samples with varying amounts of clotting, 27 were discovered by visual inspection and 3 were discovered by the instrument. Conclusion: The pre-analytical check module on the ACL-TOP-750 improved the detection rate of samples below the target 2.7 mL volume, and the accuracy in detection of HIL. However, the automated method could not replace visual assessment of clotting in samples.

Consensus recommendations on appropriate coagulation tests during emicizumab administration in Saudi Arabia.

INTRODUCTION: Emicizumab is a bispecific monoclonal antibody with the ability to bridge FIXa and FX, mimic FVIII, and restore normal hemostasis in patients with hemophilia A. Moreover, substantial evidence has shown that emicizumab-treated patients do not require monitoring, except before surgery or invasive procedures. However, introducing this novel drug to the market poses some challenges to physicians and clinical laboratories due to its interaction with conventional coagulation tests. METHODS: Given the challenges and laboratory interactions posed by this novel drug, there is an unmet clinical need to develop clear recommendations for emicizumab laboratory monitoring to highlight which laboratory tests should be used, which tests should be avoided, and when these tests should be performed. These expert recommendations are essential to prevent inappropriate testing or misleading interpretations and reduce the extra costs of unnecessary monitoring. RESULTS: A consensus meeting was conducted in December 2019, including top experts on hemophilia from Saudi Arabia, to discuss this issue. CONCLUSION: The experts agreed that, aPTT (activated Partial Thromboplastin Time)-based tests are not suitable for laboratory monitoring patients treated with emicizumab. Only FVIII chromogenic assays based on bovine FIX and FX proteins can be used to measure FVIII levels. They reviewed and recommended the type and time of testing for anti-factor VIII antibodies. Drug levels should be measured using the recommended test only when the anti-drug antibody (ADA) is clinically suspected and after excluding other causes (such as patient non-compliance).

[Comparative Analysis of Thromboelastogram and Coagulation Items in Mongolian Patients with Thrombosis].

OBJECTIVE: To investigate the age distribution of Mongolian patients with cerebral infarction caused by thrombosis and the correlation and consistency between thromboelastography (TEG) and four parameters of coagulation. METHODS: The age distribution of 298 Mongolian patients with cerebral infarction treated in Affiliated Hospital of Inner Mongolia Minzu University from January 2020 to December 2021 and their TEG, four items of routin coagulation and platelet count were analyzed retrospectively. The correlation and consistency of above-mentioned two detection methods were statistically analyzed. RESULTS: The onset age of 298 Mongolian patients with cerebral infarction was mainly 61-70 years old, accounting for 38.3%, followed by 51-60 years old, accounting for 26.8%. The R time detected by TEG was linearly correlated with PT and APTT（r=0.186，r=0.152）. K value, MA value and α-Angle measured by TEG was linearly correlated with Fib (r=-0.364，r=0.616，r=0.359), K value, MA value and α-Angle measured by TEG was linearly correlated with Plt (r=0.318，r=0.519，r=0.301). The R time detected by TEG was consistent with PT and APTT, and the Kappa values were 0.252 (P<0.001), 0.336 (P<0.001). K, MA, and α-Angle measured by TEG was consistent with Fib, the Kappa values were 0.265 (P<0.001), 0.289 (P<0.001) and 0.290 (P<0.001), respectively; K、MA and α-Angle measured by TEG was consistent with Plt, the Kappa values were 0.276 (P<0.001), 0.285 (P<0.001) and 0.302 (P<0.001), respectively. CONCLUSION: The onset age of Mongolian patients with cerebral infarction caused by thrombosis is mainly 61-70 years old, followed by 51-60 years old. The onset age shows a younger trend. There is a significant correlation between TEG and coagulation, but the consistency is weak, therefore, the two methods can not be replaced each other.

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.