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.

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.

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.

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.

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.

Validation and standardization of the ETP-based activated protein C resistance test for the clinical investigation of steroid contraceptives in women: an unmet clinical and regulatory need.

Background Regulatory bodies recommend the use of an assay based on the assessment of the endogenous thrombin potential (ETP) for the investigation of the activated protein C resistance (APCr) in the development of steroid contraceptives in women. However, the assays described in the literature are home-made and not standardized regarding the method, the reagents, the reference plasma and the quality controls. In the absence of any commercially available method, we aimed at validating the ETP-based APCr assay. Methods The validation was performed according to regulatory standards. The method targets a 90% inhibition of the ETP in healthy donors in the presence of APC compared to the same condition in the absence of APC. As a large-scale production of a pool of plasma from well-selected healthy donors is impossible, algorithms were applied to a commercial reference plasma to correlate with the selected pool. Results Repeatability and intermediate precision passed the acceptance criteria. The assay demonstrated a curvilinear dose response to protein S and APC concentrations (R2 > 0.99). Analysis of plasma samples from 47 healthy individuals (22 women not taking combined hormonal contraceptives [CHC], and 25 men not Factor V Leiden carriers) confirmed the validity of the test, with a mean inhibition percentage of 90%. Investigations in 15 women taking different contraceptives and in two subjects with Factor V Leiden confirmed the good sensitivity and performance of the assay. Conclusions This validation provides the pharmaceutical industry, the regulatory bodies and physicians with a reproducible, sensitive and validated gold-standard ETP-based APCr assay.

Analytical and between-subject variation of thrombin generation measured by calibrated automated thrombography on plasma samples.

BACKGROUND: The Calibrated Automated Thrombography (CAT) is an in vitro thrombin generation (TG) assay that holds promise as a valuable tool within clinical diagnostics. However, the technique has a considerable analytical variation, and we therefore, investigated the analytical and between-subject variation of CAT systematically. Moreover, we assess the application of an internal standard for normalization to diminish variation. METHODS: 20 healthy volunteers donated one blood sample which was subsequently centrifuged, aliquoted and stored at -80 °C prior to analysis. The analytical variation was determined on eight runs, where plasma from the same seven volunteers was processed in triplicates, and for the between-subject variation, TG analysis was performed on plasma from all 20 volunteers. The trigger reagents used for the TG assays included both PPP reagent containing 5 pM tissue factor (TF) and PPPlow with 1 pM TF. Plasma, drawn from a single donor, was applied to all plates as an internal standard for each TG analysis, which subsequently was used for normalization. RESULTS: The total analytical variation for TG analysis performed with PPPlow reagent is 3-14% and 9-13% for PPP reagent. This variation can be minimally reduced by using an internal standard but mainly for ETP (endogenous thrombin potential). The between-subject variation is higher when using PPPlow than PPP and this variation is considerable higher than the analytical variation. CONCLUSION: TG has a rather high inherent analytical variation but considerable lower than the between-subject variation when using PPPlow as reagent.

Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation.

BACKGROUND: Dabigatran is prescribed to increasing numbers of patients with atrial fibrillation (AF). Although routine monitoring is not considered to be useful, measuring drug concentrations can be clinically relevant in specific situations. The aim of this study was the comparison of different functional and non-functional assays for determination of dabigatran concentrations at different timepoints in a real-life patient population with AF. We focused on the differences between assays in identifying patients with low drug concentrations. Furthermore, we studied the effect of glucuronidation on the established concentration as determined with different assays. METHODS: This study established dabigatran concentration ranges in 40 real-life AF patients by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) reference method and compared these with results from coagulation assays (Hemoclot dTT, LD-dTT and ECA). Samples were taken just before and 2 and 4 h after taking the drug. RESULTS: A wide range of concentrations at different time points was found in this patient group. Coagulation assays correlate best with UPLC-MS/MS results that include the glucuronidated metabolites, showing that the pharmacologically active glucuronides are also measured in coagulation testing. The LD-dTT has the best agreement with UPLC-MS/MS and combines good sensitivity with high specificity. Several patients show consistently low or high drug concentrations, implying that drug exposure differs between patients. CONCLUSIONS: Based on the association of dabigatran concentrations with bleeding and thromboembolic risk, we believe that dabigatran monitoring could be beneficial for further optimizing anticoagulation therapy in AF.

Perioperative management of patients on direct oral anticoagulants.

Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10-15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published. The high inter-patient variability of DOAC plasma levels has challenged the traditional recommendation that perioperative DOAC interruption should be based only on the elimination half-life of DOACs, especially before invasive procedures carrying a high risk of bleeding. Furthermore, recent publications have highlighted the potential danger of heparin bridging use when DOACs are stopped before an invasive procedure. As antidotes are progressively becoming available to manage severe bleeding or urgent procedures in patients on DOACs, accurate laboratory tests have become the standard to guide their administration and their actions need to be well understood by clinicians. This review aims to provide a systematic approach to managing patients on DOACs, based on recent updates of various perioperative guidance, and highlighting the advantages and limits of recommendations based on pharmacokinetic properties and laboratory tests.

Video-assisted Thoracoscopic surgery (VATS) lobectomy for lung cancer does not induce a procoagulant state.

BACKGROUND: Changes in the coagulation system in patients undergoing surgery for lung cancer have been sparsely investigated and the impact of the surgical trauma on the coagulation system is largely unknown in these patients. An increased knowledge could potentially improve the thromboprophylaxis regimes. The aim of this study was to assess the coagulation profile evoked in patients undergoing curative surgery by Video-Assisted Thoracoscopic Surgery (VATS) lobectomy for primary lung cancer. METHODS: Thirty-one patients diagnosed with primary lung cancer undergoing VATS lobectomy were prospectively included. The coagulation profile was assessed preoperatively and in the first two days postoperatively using a wide range of standard coagulation tests, dynamic whole blood coagulation measured by rotational thromboelastometry (ROTEM®) and thrombin generation evaluated by calibrated automated thrombography. Patients did not receive thromboprophylactic treatment. Data was analyzed using repeated measures one-way ANOVA. RESULTS: The standard coagulation parameters displayed only subtle changes after surgery and the ROTEM® and thrombin generation results remained largely unchanged. CONCLUSIONS: Patients undergoing VATS lobectomy are normocoagulable in the preoperative state and a VATS lobectomy does not significantly influence the coagulation. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (Identifier: NCT01741506) and at EudraCTno. 2012-002409-23. Registered December 2012.

Severe Coagulopathy after Ingestion of "Snake Wine".

BACKGROUND: This report describes a patient who developed coagulopathy after ingesting snake wine, which is an alcoholic libation containing an entire venomous snake. CASE REPORT: A 68-year-old man was admitted to the hospital 19 h after ingesting snake wine. The laboratory features upon admission included unmeasurable activated partial thromboplastin (aPTT) values, prolonged prothrombin time (PT) values, increased fibrinogen levels, modestly elevated fibrin degradation product and D-dimer values, uncorrected aPTT and PT values after a mixing test, and normal levels of aspartate transaminase and alanine transaminase. No pesticides, warfarin, or superwarfarin in the patient's blood or urine were detected. His coagulation profile normalized on the 6(th) day after admission after antivenom treatment. He was discharged 10 days later without sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The physician should be aware that ingesting snake wine may lead to systemic envenomation. As for coagulopathy, which may develop by ingesting snake venom, related laboratory findings may differ from the features observed after direct envenomation by snakebite.

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.

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.

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.

[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.

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.

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.

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.