The History of Extracorporeal Membrane Oxygenation and the Development of Extracorporeal Membrane Oxygenation Anticoagulation.

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.

Bleeding outcomes in critically ill patients on heparin with discordant aPTT and anti-Xa activity.

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.

Convalescent plasma in hospitalized pediatric and obstetric coronavirus disease 2019 (COVID-19) patients.

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.

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation.

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.

Low antithrombin levels in neonates and infants undergoing congenital heart surgery result in more red blood cell and plasma transfusion on cardiopulmonary bypass.

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.

Severe hypocalcemia during surgery for placenta accreta spectrum: The case for empiric replacement.

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 CaCL2 is recommended for every 4 U RBC transfused.

ABO-incompatible deceased donor pediatric liver transplantation: Novel titer-based management protocol and outcomes.

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.

Maternal morbidity in patients with morbidly adherent placenta treated with and without a standardized multidisciplinary approach.

OBJECTIVE: The purpose of this study was to test the hypothesis that a standardized multidisciplinary treatment approach in patients with morbidly adherent placenta, which includes accreta, increta, and percreta, is associated with less maternal morbidity than when such an approach is not used (nonmultidisciplinary approach). STUDY DESIGN: A retrospective cohort study was conducted with patients from 3 tertiary care hospitals from July 2000 to September 2013. Patients with histologically confirmed placenta accreta, increta, and percreta were included in this study. A formal program that used a standardized multidisciplinary management approach was introduced in 2011. Before 2011, patients were treated on a case-by-case basis by individual physicians without a specific protocol (nonmultidisciplinary group). Estimated blood loss, transfusion of packed red blood cells, intraoperative complications (eg, vascular, bladder, ureteral, and bowel injury), neonatal outcome, and maternal postoperative length of hospital stay were compared between the 2 groups. RESULTS: Of 90 patients with placenta accreta, 57 women (63%) were in the multidisciplinary group, and 33 women (37%) were in the nonmultidisciplinary group. The multidisciplinary group had more cases with percreta (P = .008) but experienced less estimated blood loss (P = .025), with a trend to fewer blood transfusions (P = .06), and were less likely to be delivered emergently (P = .001) compared with the nonmultidisciplinary group. Despite an approach of indicated preterm delivery at 34-35 weeks of gestation, neonatal outcomes were similar between the 2 groups. CONCLUSION: The institution of a standardized approach for patients with morbidly adherent placentation by a specific multidisciplinary team was associated with improved maternal outcomes, particularly in cases with more aggressive placental invasion (increta or percreta), compared with a historic nonmultidisciplinary approach. Our standardized approach was associated with fewer emergency deliveries.

Granulocyte transfusions for children with infection and neutropenia or granulocyte dysfunction.

Transfusions of granulocytes can be used as an adjunct therapy to antimicrobials in patients with infection and neutropenia or granulocyte dysfunction. However, there is a lack of strong clinical evidence to support the use of this treatment strategy, particularly in children. We retrospectively reviewed the medical records of children who received granulocytes at our institution from April 2009 to October 2012, with emphasis on primary indication for the transfusion and clinical outcome in terms of infection. The patients had granulocyte dysfunction or severe neutropenia, defined as absolute neutrophil count (ANC) < 500 cells/mm(3) due to chemotherapy or hematopoietic stem cell transplant (HSCT), and reasonable hope for bone marrow recovery or engraftment. Eighteen children received granulocytes during 20 distinct episodes: 62% (n = 13) for acute infection, 29% (n = 5) for unresolved chronic infection during the time of HSCT, and 9% (n = 2) for other clinical conditions such as typhilitis and appendectomy. Overall, 92% (n = 12) of the episodes of acute infection had complete or partial resolution, as determined by review of vital signs, physical exam findings and discontinuation of antimicrobials. A substantial number (46%) of children who received granulocytes for acute infection developed respiratory adverse events, but all of these recovered. We conclude that granulocyte transfusions continue to be primarily used in neutropenic patients with acute infections, and that its use in this group of patients is reasonable. However, a prospective randomized clinical trial is needed to evaluate safety and whether the use of granulocytes is superior to antimicrobial-only therapy.

Transfusion-Associated Adverse Events: A Case Report of Nurse Hemovigilance and Recognition of Respiratory Distress.

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.

How to best monitor bivalirudin anticoagulant effect for ECMO and VAD-Comparison of four assay methods.

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.

Novel Coagulation Test Detects Anticoagulation Resistance and Is Associated With Thrombotic Events in Pediatric Patients Requiring Extracorporeal Membrane Oxygenation.

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.

Evaluation and Management of Coagulopathies and Thrombophilias in Pediatric Patients.

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.

Trimester-specific thromboelastic values and coagulation activation markers in pregnancy compared across trimesters and compared to the nonpregnant state.

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.

Monitoring bivalirudin therapy in children on extracorporeal circulatory support devices: Thromboelastometry versus routine coagulation testing.

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 × 109/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.

Tortuosity-powered microfluidic device for assessment of thrombosis and antithrombotic therapy in whole blood.

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.

Coagulation and Bleeding Management in Pediatric Extracorporeal Membrane Oxygenation: Clinical Scenarios and Review.

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.

Stability and Sterility of Enoxaparin 8 mg/mL Subcutaneous Injectable Solution.

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.