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Activated partial thromboplastin time (aPTT) and unfractionated heparin (UFH) level via the anti-factor Xa activity assay (anti-Xa) are commonly used assays for UFH monitoring. While discordance between the two assays is common, its impact on critically ill patient outcomes is unclear. This study aimed to compare the incidence of major bleeding events among critically ill patients with discordant aPTT and anti-Xa activity while on UFH, to patients with no discordance. This was a single-center, retrospective cohort study of critically ill adult patients who had simultaneous anti-Xa and aPTT levels while receiving continuous UFH infusion. The primary outcome was the incidence of a major bleeding event up to 24 h after UFH discontinuation. Secondary outcomes included incidence of 30-day thrombosis and hospital length of stay (LOS). Among 264 included patients, 156 patients (59%) had at least one discordant paired level. Patients with discordance had an increased risk of major bleeding events (14% versus 5%; unadjusted risk ratio, 3.0; 95% CI 1.2-7.8; p = 0.01), and increased risk of thrombotic events (4% versus 0%; p = 0.04). Hospital LOS was similar between the two groups (13.8 days versus 11.4 days; p = 0.08). In this cohort of critically ill patients receiving continuous UFH, discordance in aPTT and anti-Xa activity was frequently observed and was associated with an increased risk of major bleeding events. While both assays remain viable monitoring options, evaluating simultaneous levels may aid in the management of critically ill patients. In patients with discordance, an individualized approach balancing bleeding and thrombotic risks should be considered., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The influence of weak radio-frequency electromagnetic field (RF-EMF) on living organisms raises new concern because of the Industrial, Scientific, and Medical (ISM) frequency band at 6.78 MHz being promoted by the AirFuel Alliance for mid-range wireless power transfer (WPT) applications and product development. Human exposure to the RF-EMF radiation is unavoidable. In this study, we employed in vitro cell culture and molecular biology approach coupled with integrated transcriptomic and proteomic analyses to uncover the effects of RF-EMF on cells at molecular and cellular levels. Our study has demonstrated that weak RF-EMF is sufficient to exert non-thermal effects on human umbilical vein endothelial cells (HUVEC). Exposure of weak RF-EMF promotes cell proliferation, inhibits apoptosis and deregulates ROS balance. Alteration of several signaling pathways and key enzymes involved in NADPH metabolism, cell proliferation and ferroptosis were identified. Our current study provide solid evidence for the first time that the present safety standards that solely considered the thermal effect of RF-EMF on cell tissue are inadequate, prompt response and modification of existing Guidelines, Standards and Regulation are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chow, Zhang, Ng, Hui, Solov’yov and Lui.)

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has also expanded. Among these are clinical conditions such as postcardiopulmonary bypass, sepsis, ECMO cardiopulmonary resuscitation, and even severe coronavirus disease 2019 (COVID-19). Not surprisingly, the number of ECMO cases has increased according to the Extracorporeal Life Support Organization Registry and prolonged ECMO support has become more prevalent. It is not uncommon for patients with COVID-19 to be on ECMO support for more than 1 year until recovery or lung transplant. With that being said, complications of bleeding, thrombosis, clot formation in the circuit, and intravascular hemolysis still remain and continue to be major challenges. Here, several clinical ECMO experts, including the "Father of ECMO"-Dr. Robert Bartlett, describe the history and advances of ECMO., Competing Interests: D.J.A. received research funding from Bayer plc and Leo Pharma. J.T. received honorarium from Entegrion and member of DSMB for Evaheart. T.R. has the patent of activators of factor XII. M.C. received grants from Genentech, Agios Pharmaceutical, and Novartis, and honoraria from Genentech, Agios Pharmaceuticals, Takeda, BPL, CSL Behring, Genzyme Corp, Emerging Therapies Solutions, and Novo Nordisk; all outside this article., (Thieme. All rights reserved.)

Background: This study aims to determine if coagulation abnormalities at presentation are associated with clinical severity of pediatric COVID-19 infection., Methods: We retrospectively reviewed admission coagulation studies (D-dimer, prothrombin time (PT), partial thromboplastin time with hepzyme, fibrinogen, and platelet count) with disease severity defined by need for ICU admission, ventilator support, and length of stay (LOS)., Results: There were 110 pediatric patients (0.5 months to 18 years) who had coagulation studies collected within 24 hours of admission. Patients who required ICU admission and ventilation support had significantly higher D-dimer and PT values at presentation compared to patients who required neither. In addition, D-dimer showed moderate correlation with LOS., Conclusions: Elevated D-dimer correlated significantly with severity of disease and LOS, while prolonged PT only correlated with disease severity. Our data suggest that D-dimer at presentation may predict a pediatric patient's need for ICU care or ventilator support.

Background: Platelet transfusions are routinely administered to neonates in intensive care units when there are concerns of bleeding, including high-risk situations like Extracorporeal Membrane Oxygenation (ECMO). Most platelets in ICUs are transfused prophylactically for thrombocytopenia based solely on the platelet count. Platelet Mass Index (PMI) has been proposed as an alternative to platelet count (PC) as a transfusion trigger. The objective of this study was to determine the relationship between PMI and platelet-specific maximal clot firmness (PMCF) in Rotational thromboelastometry (ROTEM), which gives an indication of platelet contribution to clot firmness and to investigate whether PMI may be a better choice as a trigger for platelet transfusions than PC., Methods: Retrospective review of medical records of neonates with congenital heart disease placed on ECMO support in the cardiovascular intensive care unit (CVICU) from 2015 to 2018 was conducted. Platelet count (PC), platelet mean volume (PMV), ROTEM parameters along with demographic data including gestation age, birth weight, gender and survival were collected. Mixed effects linear models with a first order autoregressive covariance structure were used to assess the associations of PMI, PC, and MPV against PMCF. In addition, generalized estimating equations with a first order auto-regressive covariance structure were used to compare odds of transfusion using PC versus PMI triggers., Results: A total of 92 tests on consecutive days were obtained for 12 ECMO patients (5 male, GA = 38.1 ± 1.6 weeks, BW = 3.1 ± 0.4 kgs, mean ± SD). A variation of 40.1% in PMCF was explained by platelet count (p < 0.001) while 38.5% of the variation in PMCF was explained by PMI (p < 0.001). If the platelet transfusion trigger was PC < 100 x 103 platelets/µL vs. PMI < 800. Using the PC trigger yielded significantly higher odds of transfusion compared to the PMI trigger (odds ratio = 1.31, 95% confidence interval: 1.18 - 1.45, p < 0.001)., Conclusions: While our study failed to demonstrate a superior correlation of PMI with PMCF than PC, our study did reveal that using PMI as transfusion trigger would result in significantly less platelet transfusions, when compared with the current practice of using PC as a trigger.

Objective: Massive transfusion protocols are widely implemented in obstetrical practice in case of severe hemorrhage; however, different recommendations exist regarding the appropriate ratios of blood product components to be transfused. We report our extensive experience with massive component transfusion in a referral center in which the standard massive transfusion protocol is modified by ongoing clinical and laboratory evaluation., Study Design: A retrospective chart review of all patients who had massive transfusion protocol activation in a level 4 referral center for obstetrical practice was performed from January 2014 to January 2020. Data collected included the etiology of obstetrical hemorrhage, number of blood products of each type transfused, crystalloid infusion, and several indices of maternal morbidity and mortality. Data are presented with descriptive statistics., Results: A total of 62 patients had massive transfusion protocol activation, of which 97% received blood products. Uterine atony was found to be the most common etiology for massive hemorrhage (34%), followed by placenta accreta spectrum (32%). The mean estimated blood loss was 1,945 mL. A mean of 6.5 units of packed red blood cells, 14.8 units of fresh frozen plasma and cryoprecipitate, and 8.3 units of platelets were transfused per patient. No maternal deaths were seen., Conclusion: The ratios of transfused packed red blood cell to fresh frozen plasma/cryoprecipitate and of packed red blood cell to platelet units varied significantly from the fixed initial infusion ratio called for by our massive transfusion protocol resulting in universally favorable maternal outcomes. When rapid laboratory evaluation of hematologic and clotting parameters is available, careful use of this information may facilitate safe modification of an initial fixed transfusion ratio based on etiology of the hemorrhage and individual patient response., Key Points: · Massive transfusion protocols in obstetrics follow fixed ratios of blood products.. · Actual usage of blood components is different than the standardized protocols.. · We recommend to modify the initial fixed transfusion ratio according to clinical response.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Objectives: Blood transfusion is frequently needed to maintain adequate haemostasis and improve oxygenation for patients treated with extracorporeal membrane oxygenation (ECMO). It is more so for neonates with immature coagulation systems who require surgical intervention such as congenital diaphragmatic hernia (CDH) repair. There is growing evidence suggesting an association between blood transfusions and increased mortality. The aim of this study is to evaluate the association of blood transfusions during the peri-operative period of CDH repair, among other clinical parameters, with mortality in neonates undergoing on-ECMO CDH repair., Materials and Methods: We performed a single centre retrospective chart review of all neonates with CDH undergoing on-ECMO surgical repair from January 2010 to December 2020. Logistic regression was used to investigate associations with survival status., Results: Sixty-two patients met the inclusion criteria. Platelet transfusions (odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.06-1.90) in the post-operative period and ECMO duration (OR 1.17, 95% CI: 1.05-1.30) were associated with increased mortality. Major bleeding complications had the strongest association with mortality (OR 10.98, 95% CI: 3.27-36.91). Gestational age, birth weight, Apgar scores, sex, blood type, right versus left CDH, venovenous versus venoarterial ECMO and duration of ECMO before CDH repair and circuit change after adjusting for ECMO duration were not significantly associated with survival., Conclusion: Platelet transfusion in the post-operative period and major bleeding are associated with increased mortality in CDH neonates with surgical repair. The data suggest a need to develop robust plans for monitoring and preventing coagulation aberrancies during neonatal ECMO support., (© 2022 International Society of Blood Transfusion.)

Bivalirudin, an IV direct thrombin inhibitor, and unfractionated heparin (UFH) are frequently used anticoagulants in the pediatric critical care setting. An accurate, specific, point-of-care test to quantify and detect anticoagulation resistance is not currently available. This study evaluates the ability of a rapid (< 10 min), micro-volume ( < 50 uL) coagulation test to detect and quantify the anticoagulation effect of bivalirudin and UFH using a functional, clot time endpoint in pediatric critical care patients., Design: Single-site retrospective laboratory sample analysis and chart review., Setting: A 105-bed pediatric and cardiac ICUs delivering extracorporeal membrane oxygenation., Subjects: Forty-one citrated, frozen, biobanked plasma specimens comprising 21 with bivalirudin and 20 with UFH from 15 anticoagulated pediatric patients were analyzed. Thirteen patients were on extracorporeal membrane oxygenation, one had a submassive pulmonary embolism, and one was on a left ventricular assist device., Interventions: None., Measurement and Main Results: A Clotting Time Score (CTS) was derived on each sample. The CTS detected patients that had developed a pathologic clotting event with 100% sensitivity and 82% specificity compared with prothrombin time with 25% sensitivity/76% specificity and activated partial thromboplastin time with 0% sensitivity/0% specificity. Additionally, the CTS detected subtherapeutic anticoagulation in response to UFH in patients that were clinically determined to be UFH resistant requiring alternative anticoagulation with bivalirudin., Conclusions: The CTS appears to be a clinically valuable indicator of coagulation status in patients treated with either UFH or bivalirudin. Results outside of the therapeutic range due to inadequate dosing or anticoagulation resistance appeared to be associated with clot formation. CTS testing may reduce the risk of anticoagulation-related complications via the rapid identification of patients at high risk for pathologic thrombotic events., Competing Interests: Dr. Frydman is the Chief Scientific Officer of Coagulo Medical Technologies. Dr. Berger is the Chief Medical Officer of Coagulo Medical Technologies. Dr. Papageorgiou is a scientist at Coagulo Medical Technologies. Dr. Teruya is a consultant of Agios and Apelo and a board member of Data Safety Monitoring of Evaheart. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Although blood transfusions are considered a potentially life-saving therapy, noninfectious and infectious adverse events can lead to significant morbidities and even mortality. Vital signs and visual observation of patients during blood transfusions are thoroughly taught in nursing school. Updated terms of hemovigilance and transfusion-associated adverse events ( TAAEs ) are presented through this case study. A patient with factor V deficiency, which requires chronic plasma transfusions, experienced 2 types of TAAEs, anaphylaxis and transfusion-associated circulatory overload. The patient's history and TAAEs are presented and discussed to provide evidence for the importance of vigilant bedside surveillance. Early identification of TAAEs may prevent unnecessary morbidity and/or mortality. The primary nursing functions and responsibilities are presented with algorithmic supplementation to facilitate better understanding of best practice. Ongoing assessment of hemovigilance practices is indicated to ascertain which monitoring tools can lead to optimal patient care., (Copyright © 2022 Infusion Nurses Society.)

Introduction: Unfractionated heparin is widely used as an anticoagulant for extracorporeal life support (ECLS) and usually monitored with activated partial thromboplastin time (aPTT). Due to its limitations in pediatric populations and interferences with monitoring, bivalirudin is being utilized more frequently in these settings. For bivalirudin, other tests have emerged such as dilute thrombin time (dTT) and ecarin chromogenic assay (ECA); however, their utilities in pediatrics are unexplored. Development of suitable, accurate testing for bivalirudin monitoring is paramount to prevent complications. We sought to compare aPTT, aPTT with heparinase (HPTT), dTT1:4, modified dTT1:10, and ECA for monitoring of pediatric ECLS patients anticoagulated with bivalirudin., Methods: aPTT, HPTT, dTT1:4, dTT1:10, and ECA were measured in 51 specimens from 17 children on bivalirudin-anticoagulated ECLS. Normal pooled plasma was spiked with various bivalirudin concentrations, and aPTT, dTT1:4, dTT1:10, and ECA were measured. In addition, dTT assays were performed using plasma from normal donors spiked with bivalirudin, heparin, and cryoprecipitate., Results: dTT1:4 showed excellent correlation with ECA, while dTT1:4 correlated moderately with aPTT or HPTT. Fifty to 75% of specimens showed discordant results between dTT1:4 and HPTT. We found that dTT1:4 and ECA prolongations are associated with bivalirudin infusion rate; however, there are age-based differences that should be accounted for. The performance of dTT1:10 was similar to dTT1:4, though it was less sensitive to interfering factors (heparin or hyperfibrinogenemia)., Conclusion: dTT1:10 appears to be more suitable for routine practice due to fewer variations and lower cost for monitoring bivalirudin in pediatric ECLS., (© 2021 John Wiley & Sons Ltd.)

Background: Published data on coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) use in children and obstetric patients are limited. We describe a single-center experience of hospitalized patients who received CCP for acute COVID-19., Methods: A retrospective review of children 0-18-years-old and pregnant patients hospitalized with laboratory-confirmed acute COVID-19 who received CCP from March 1, 2020 to March 1, 2021 was performed. Clinical and laboratory data were collected to assess the safety of CCP administration. Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured in the CCP products and in patients before transfusion and at various time points post-transfusion. Correlation between the administered SARS-CoV-2 administered versus the SARS-CoV-2 anti-spike immunoglobulin response in patient serum was assessed., Results: Twenty-two children and ten obstetric patients were eligible. Twelve pediatric and eight obstetric patients had moderate disease and ten pediatric and two obstetric patients had severe disease. Five pediatric patients died. Eighteen of 37 (48.6%) CCP titers that were measured met US Food and Drug Administration (FDA) criteria for high immunoglobulin G (IgG) antibody titer. There were no complications with transfusion. High-titer CCP showed a positive correlation with rise in patient total immunoglobulin levels only in obstetric patients but not in pediatric patients. Among pediatric patients, the median serum antibody level increased over time after transfusion., Conclusions: Coronavirus 2019 convalescent plasma was administered safely to our patients. Our study suggested that CCP did not interfere with endogenous antibody production. The antibody titer of CCP correlated with post-transfusion response only in obstetric patients. Randomized trials in pediatric and obstetric patients are needed to further understand how to dose CCP and evaluate efficacy., (© 2022 Japan Pediatric Society.)

Introduction: Rotational thromboelastometry (ROTEM) rapidly identifies deficits underlying coagulopathy during massive hemorrhage. Prompt coagulopathy correction is balanced with the risk of blood product overutilization, making the ability to quickly target therapy highly desirable. However, data about ROTEM reference ranges in pregnancy are limited. We hypothesized that ROTEM parameters change across trimesters of pregnancy and differ from the nonpregnant state. Also, we sought to identify which hemostatic test best predicts coagulation activation during pregnancy., Methods: A prospective cohort study in healthy pregnant patients in the first (n = 34), second (n = 34), and third trimesters (n = 41) against healthy, nonpregnant controls (n = 33) was performed. Citrated blood was collected, and ROTEM, complete blood count, and plasma-based assays of coagulation were performed. Mean ± SD or median [IQR] were compared across trimesters and between each trimester against the nonpregnant state. ROTEM parameters vs. plasma-based assays were also compared., Results: Maximum clot firmness and A10 in FIBTEM correlated strongly with fibrinogen level. INTEM and EXTEM values demonstrated only weak to modest correlation with corresponding tests using plasma assays. Thrombin antithrombin complex (TAT) increased from the first trimester onward, whereas other coagulation activation markers did not show difference compared with control group., Conclusion: Rotational thromboelastometry parameters differ variably across trimesters of pregnancy and compared with the nonpregnant state. The development and use of pregnancy-specific values are critical to the proper clinical interpretation of ROTEM in women with serious hemorrhage during different stages in pregnancy. TAT was the earliest laboratory marker for coagulation activation among others., (© 2021 John Wiley & Sons Ltd.)

The diagnosis of coagulopathy or thrombophilia in pediatric patients can be challenging. Congenital coagulopathies often present in the pediatric period and require appropriate work-up for diagnosis and ongoing management. Acquired coagulopathies of childhood are frequently encountered in hospitalized children and warrant appropriate coagulation testing for goal-directed therapy. The incidence of thrombosis is increasing in pediatric patients. After identifying the presence of thrombus, acute management includes initiating therapeutic anticoagulation. Choice of anticoagulant depends on patient's clinical status, along with availability of the anticoagulant. Thrombophilia evaluation is performed when children present with spontaneous thrombosis. Thrombophilia tests are inaccurate during acute illness., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Neonates have lower levels of antithrombin (AT) due to immature liver synthetic function. AT deficiency may lead to inadequate anticoagulation with heparin during cardiac surgery resulting in consumption of coagulation factors and increased blood transfusion. The goal of this study is to examine the effect of AT level on the transfusion requirements of neonates and infants undergoing open heart surgery., Study Design and Methods: This is a prospective, observational study at a tertiary pediatric referral center. Neonates and infants up to 6 months of age undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were enrolled. Demographic, intraoperative, transfusion, and complications data were collected. Preoperative AT level was measured after induction of anesthesia. Prior to separation from CPB, a second blood sample was drawn and AT, thrombin antithrombin complex (TAT), D-dimer, and anti-Xa levels were measured. Linear and logistic regression were performed for data analysis., Results: Preoperative low AT level was significantly associated with increased transfusion of red blood cells (RBCs) and fresh frozen plasma (FFP) during CPB, but not after separation from CPB. The incidence of thrombosis and re-operation were not associated with preoperative AT levels. There was no association between TAT, D-dimer, and anti-Xa levels at the end of CPB and preoperative AT levels., Conclusion: Low preoperative AT level is associated with increased transfusion of RBC and FFP on CPB in neonates and infants undergoing congenital heart surgery. Low preoperative AT level did not result in coagulation activation after CPB and after surgery., (© 2020 AABB.)

Rising anthropogenic CO 2 emissions and their climate warming effects have triggered a global response in research and development to reduce the emissions of this harmful greenhouse gas. The use of CO 2 as a feedstock for the production of value-added fuels and chemicals is a promising pathway for development of renewable energy storage and reduction of carbon emissions. Electrochemical CO 2 conversion offers a promising route for value-added products. Considerable challenges still remain, limiting this technology for industrial deployment. This work reviews the latest developments in experimental and modeling studies of three-dimensional cathodes towards high-performance electrochemical reduction of CO 2 . The fabrication-microstructure-performance relationships of electrodes are examined from the macro- to nanoscale. Furthermore, future challenges, perspectives and recommendations for high-performance cathodes are also presented.

Accurate assessment of blood thrombosis and antithrombotic therapy is essential for the management of patients in a variety of clinical conditions, including surgery and on extracorporeal life support. However, current monitoring devices do not measure the effects of hemodynamic forces that contribute significantly to coagulation, platelet function and fibrin formation. This limits the extent to which current assays can predict clotting status in patients. Here, we demonstrate that a biomimetic microfluidic device consisting stenosed and tortuous arteriolar vessels would analyze blood clotting under flow, while requiring a small blood volume. When the device is connected to an inline pressure sensor a clotting time analysis is applied, allowing for the accurate measurement of coagulation, platelets and fibrin content. Furthermore, this device detects a prolonged clotting time in clinical blood samples drawn from pediatric patients on extracorporeal membrane oxygenation receiving anticoagulant therapy. Thus, this tortuosity activated microfluidic device could lead to a more quantitative and rapid assessment of clotting disorders and their treatment.

Cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) cause hemostatic derangements that can predispose patients to both bleeding and thrombotic complications. Often, patients present for urgent surgery while taking medications including antiplatelet agents, vitamin K antagonists, and direct oral anticoagulants, which must be recognized, monitored, and managed. During extracorporeal circulation, appropriate anticoagulation, most commonly with heparin, is required to maintain blood flow and avoid thrombotic complications. However, anticoagulation and other effects of extracorporeal circuits can also have an undesired consequence of bleeding. Extracorporeal circulation leads to coagulopathy that may require therapy with blood products such as platelets, cryoprecipitate, and plasma in case a patient bleeds. Platelet dysfunction related to exposure to a foreign circuit is a primary concern, as is the development of acquired von Willebrand syndrome, which frequently remains undetected on routine testing. Hemorrhagic complications in ECMO, such as intracranial hemorrhage, pulmonary hemorrhage, and hemithorax, can occur. Hemostatic agents including antifibrinolytics, desmopressin, fibrinogen concentrates, and other factor concentrates may be needed to achieve hemostasis in these often-challenging patients. Managing bleeding on extracorporeal support requires careful monitoring and a thoughtful approach., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: Bivalirudin is an alternative to heparin anticoagulation in infants and children in the setting of extracorporeal life support (ECLS). While activated partial thromboplastin time (aPTT) is widely accepted as the standard test to monitor bivalirudin therapy, the usefulness of thromboelastometry (ROTEM) to monitor bivalirudin infusion in the setting of ECLS is unknown., Objective: We aimed to assess the utility of ROTEM in monitoring hemostasis and bivalirudin effect in children on either extracorporeal membrane oxygenation (ECMO) or ventricular assist devices (VAD) compared to standard plasma based coagulation assays., Methods: A retrospective study of children undergoing bivalirudin infusion for ECMO/VAD support from a tertiary care pediatric hospital (January 2017-June 2018) was performed. ROTEM assays for extrinsic (EXTEM) and intrinsic (INTEM) coagulation pathways, INTEM with heparinase (HEPTEM), fibrin formation (FIBTEM) with measurement of the clotting time (CT) and maximum clot firmness (MCF) were compared to routine hemostasis testing including: aPTT, aPTT Hepzyme (HPTT), prothrombin time (PT), fibrinogen and platelet count., Results: One hundred and six blood samples from 18 children were tested. There was a strong positive correlation between HPTT and HEPTEM CT, and moderate correlation between aPTT and INTEM CT. The bivalirudin dose did not correlate with any test, but displayed strong age-dependence, with infants requiring higher doses of bivalirudin to maintain therapeutic targets. Excellent correlation was found between FIBTEM MCF values and fibrinogen, but FIBTEM overestimated fibrinogen level when platelet count was >300 × 10 9 /L. Heparin-like effect was identified in 39% of specimens, and an improved correlation between aPTT and INTEM CT was observed in specimens without heparinoids., Conclusions: In the setting of bivalirudin therapy, prolongation of CT on INTEM and HEPTEM showed moderate to strong correlation with aPTT and HPTT, and therefore, may provide a good alternative to these assays. In addition, HPTT and HEPTEM CT might be preferable for monitoring bivalirudin in the setting of ECLS due to frequent detection of heparin-like effect., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to determine predictive factors for severe hypocalcemia in women with placenta accreta spectrum., Material and Methods: Study of 123 women with histology-proven placenta accreta spectrum with cesarean hysterectomy between 2011 and 2017. Two groups were selected: Cases: critically low ("panic value") serum total calcium (≤7 mg/dL) and Controls: normal serum total calcium (≥8.5 mg/dL). Regression and receiver operating characteristic (ROC) analyses were performed to evaluate the potential associations., Results: There were 13 women with critically low (cases) and 18 with normal calcium (controls). Baseline characteristics were not statistically different. The median estimated blood loss, units of red blood cells (RBCs) transfused and volume of crystalloid transfused, were higher in the low calcium group. Six out of 13 (46.2%) cases had received ≥4 units of RBCs during surgery vs 2 of 18 (11.1%) controls (P = 0.04). ROC analysis showed that estimated blood loss, units of RBCs transfused, and crystalloid transfused were associated with severe hypocalcemia and univariate regression analysis confirmed that estimated blood loss ≥1500 mL, RBC transfusion ≥4 units, and crystalloid transfused ≥4L were associated with severe hypocalcemia., Conclusions: Intraoperative transfusion of ≥4 units RBCs is predictive of the development of severe hypocalcemia in placenta accreta spectrum patients experiencing active bleeding. Empiric replacement of 1 g CaCL 2 is recommended for every 4 U RBC transfused., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure that requires careful coagulation management. Indications for ECMO continue to expand, leading to more complicated patients treated by ECMO teams. At our pediatric institution, we utilize a Coagulation Team to guide anticoagulation, transfusion and hemostasis management in an effort to avoid the all-to-common complications of bleeding and thrombosis. This team formulates a coagulation plan in conjunction with a multidisciplinary ECMO team after careful review of all available laboratory data as well as the patient's clinical status. Here, we present our general strategies for ECMO management in various clinical scenarios and a review of the literature pertaining to coagulation management in the pediatric ECMO setting.

ABO-ILT have re-emerged as an alternate option for select patients awaiting transplant. However, treatment protocols for children undergoing deceased donor ABO-ILT are not standardized. We implemented a novel IS protocol for children undergoing deceased donor ABO-ILT based on pretransplant IH titers. Children with high pretransplant IH titers (≥1:32) underwent an enhanced IS protocol including plasmapheresis, rituximab, IVIG, and mycophenolate, while children with IH titers ≤1:16 received steroids and tacrolimus. We retrospectively assessed our outcomes of ABO-ILT with ABO-compatible recipients of similar age and diagnosis over a 2-year period. Ten children with median age of 8.9 months underwent ABO-ILT, 4 of 10 patients underwent enhanced IS due to high IH titers. Rates of complications (rejection, infections, biliary, and vascular) at both 1 year and up to 3 years post-transplant were comparable between the groups. Patients with ABO-ILT had good graft function with 100% survival at a median follow-up of 3.3 years. In conclusion, IS tailored to pretransplant IH titers in pediatric deceased donor ABO-ILT is feasible and can achieve outcomes similar to ABO-CLT at 1 and 3 years post-transplantation., (© 2018 Wiley Periodicals, Inc.)

BACKGROUND: Enoxaparin is often diluted to accurately deliver doses to neonatal and infant patients. Current recommendations for dilutions may not be adequate for the smallest patients. METHODS: Review of dosing at our institution occurred, and an 8 mg/mL concentration of enoxaparin was chosen. A concentration of 8 mg/mL was compounded by diluting 0.4 mL of enoxaparin (100 mg/mL) into 4.6 mL of sterile water for injection into an empty sterile vial. Four syringes of the 8 mg/mL concentration were prepared by 5 technicians (20 total syringes). Stability and sterility testing occurred a 0, 7, 14, and 30 days. One-way repeated-measures analysis of variance was used to detect significant differences in Anti-Factor Xa concentrations at the testing time points. RESULTS: The dilution of enoxaparin was sterile at 30 days but exhibited significant degradation at the 30-day point (p < 0.05). CONCLUSION: A dilution of enoxaparin 8 mg/mL is stable and sterile for 14 days refrigerated but is not stable at 30 days.

Background: Protein induced by vitamin K absence (PIVKA)-II, inactive precursor of prothrombin, is elevated in vitamin K (VK) deficiency. Our aims were to find the prevalence of VK deficiency in neonates, assess the utility of international normalized ratio (INR) as a screening tool, and explore the relationship between PIVKA-II, activated partial thromboplastin time (aPTT) and VK dependent anticoagulants., Methods: INR, aPTT, PIVKA-II, and proteins C and S activities were measured in neonatal cord blood prior to VK administration., Results: We found 45% of neonates had subclinical VK deficiency based on PIVKA-II levels and 7% based on INR. Receiver operating characteristic (ROC) analysis assessed the utility of INR in detecting >4 ng/mL of PIVKA-II and ROC of the area under the curve was 0.70 (95% CI 0.46-0.92, p = 0.07). Proteins C and S activities were normal for age and did not correlate with PIVKA-II [(r = 0.40, p = 0.14) and (r = 0.29, p = 0.29), respectively]. There was no association between aPTT and PIVKA-II (p = 0.83)., Conclusion: PIVKA-II seems to be a sensitive indicator of mild VK deficiency. Further studies are needed to investigate the lack of relationship between PIVKA-II and functional protein C or S levels.

Background and Objectives: Kell antigens are encoded by the KEL gene on the long arm of chromosome 7. Kx antigen is encoded by the XK gene on the short arm of the X chromosome. Kell and Kx proteins in the red cell membrane are covalently linked by a disulphide bond. The McLeod phenotype is characterized by weakened expression of antigens in the Kell blood group system, absence of Km and Kx antigens, and acanthocytosis. It has an X-linked mode of inheritance with transmission through carrier females. Some males with the McLeod syndrome also have chronic granulomatous disease (CGD). It is generally believed that patients with non-CGD McLeod may develop anti-Km but not anti-Kx, but that those with CGD McLeod can develop both anti-Km and anti-Kx., Materials and Methods: We present serological data, DNA genotyping and gene sequencing, monocyte monolayer assay and neutrophil oxidative burst test from a patient with the McLeod phenotype without clinical evidence of CGD., Results: We report here the second example of a patient with non-CGD McLeod who developed anti-Kx in addition to anti-Km. Sequencing of our patient's XK gene confirmed the presence of a mutation resulting in a premature stop codon and lack of Kx protein in the red cell membrane, which is consistent with the diagnosis of McLeod syndrome. Neutrophil oxidative burst test was normal, indicating that our patient did not have CGD. The challenge of providing 10 compatible blood units for multiple surgeries was met., Conclusion: The second case of a rare entity, a patient with non-CGD McLeod who developed anti-Kx and anti-Km, was managed successfully with a combination of autologous donations and procurement of compatible units from national and international sources.