Unfractionated Heparin Infusion Research Articles

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 24h 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.

Clinical case of successful thrombolysis in a newborn with thrombosis of the left renal vein

Thrombosis occurring in the neonatal period is a nosology with a large number of complications, often leading to disability and death. This article highlights the successful treatment of a newborn child with renal vein thrombosis using systemic thrombolysis. A clinical case of successful systemic thrombolysis in a full-term boy in the early neonatal period with thrombosis of the left renal vein and transition of the floating part of the thrombus to the inferior vena cava is presented. A child aged 3 days was admitted to the neonatal intensive care unit from a maternity hospital, where thrombosis was suspected. Gross hematuria was observed. Laboratory data revealed thrombocytopenia and increased levels of fibrinogen and D-dimer. Ultrasound showed a sharp increase in the volume of the left kidney, a diffuse change in its parenchyma, a sharp depletion of blood flow, and accumulation of fluid in the perinephric tissue on the left, and a thrombus was observed in the lumen of the left renal vein with the presence of a floating part extending into the inferior vena cava. Thrombolytic therapy with the drug alteplase was started in combination with an infusion of unfractionated heparin. Doses were selected based on coagulogram parameters. On day 2 of therapy, hematuria resolved. On day 4 of therapy, the alteplase infusion was completed, and heparin therapy was continued. On day 13, the child was switched to a low-molecular-weight-heparin therapy. Dynamic ultrasound revealed size reduction, recanalization and further thrombus lysis, and normalization of intrarenal blood flow and kidney size. No renal dysfunction was recorded during observation. The child was transferred to the further care unit at aged 14 days and was discharged home at the age of 25 days in satisfactory condition on ongoing anticoagulant therapy under outpatient supervision of a hematologist. During follow-up observation at aged 1.5 months of life, no clinical, laboratory, and ultrasound indicators of renal function disorders were noted. Currently, there are no approved recommendations and protocols for individual thrombosis in newborns, although this particular age group is due to the vulnerability of hemostasis to the development of a thrombotic process.

Time in Therapeutic Range of Unfractionated Heparin-Based Therapy in Critically Ill Patients with COVID-19 Pneumonia.

Anticoagulation therapy aims to improve the outcome of critically ill patients with severe COVID-19-associated pneumonia. Activated partial thromboplastin time (aPTT) is commonly used to maintain the target therapeutic range of continuous infusion of unfractionated heparin (UFH). The UFH infusion efficacy can be evaluated by determining the time in therapeutic range (TTR) using a modified Rosendaal method. The present study's primary aim was to evaluate TTR based on the aPTT in critically ill patients with severe forms of COVID-19 pneumonia and its influence on survival. The secondary aim was to evaluate the time spent above (TATR) and below the therapeutic range (TBTR). We performed a retrospective analysis of critically ill patients with COVID-19-associated pneumonia. All patients received a continuous infusion of UFH from the 2nd to 8th day since admission to the ICU. TTR, TATR, and TBTR were calculated using the modified Rosendaal method, and survival days were analyzed by regression (censored after 60 days). Of 103 patients, the median TTR was 49% (IQR 38-63%), TATR 11% (IQR 5-20%), and TBTR 33% (IQR 22-51%). The regression analysis indicated a positive impact of higher TTR and TATR on the number of survival days [β=0.598 (p=0.0367) and β=1.032 (p=0.0208), respectively] and a negative impact of higher TBTR [β=-0.681 (p=0.0033)] on the number of survival days. Higher TTR and TATR were associated with better survival of critically ill patients with a severe course of COVID-19-associated pneumonia. Higher TBTR was associated with worse survival in these patients.

Anticoagulation Monitoring Using Activated Clotting Time in Patients Receiving Extracorporeal Membrane Oxygenation: A Meta-Analysis of Correlation Coefficients

ObjectiveExtracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to maintain the circuit patency. However, the use of anticoagulation carries a risk of severe haemorrhage, necessitating rigorous monitoring. Activated clotting time (ACT) is a widely used monitoring tool, however the evidence on its correlation with unfractionated heparin (UFH) infusion dose is limited. Therefore, we aimed to analyse the correlation between ACT and UFH infusion during ECMO. DesignSystematic literature review and meta-analysis of correlation coefficients (Scopus and PubMed, up to July 13, 2024). PROSPERO: CRD42023448888 SettingAll retrospective and prospective studies ParticipantsPatients receiving ECMO support InterventionAnticoagulation monitoring during ECMO support Measurements and maim resultsNineteen studies were included in the analysis, and the meta-analysis encompassed 16. The vast majority of authors (n = 16) found a weak correlation, and none reported a strong correlation between ACT and UFH infusion dose. The meta-analysis (n = 12625 samples) identified a weak correlation, with the pooled estimate of correlation coefficients being 0.132 (95% CI 0.03; 0.23). Lastly, the most common adverse events were haemorrhage (pooled 45%) and thrombosis (30%), and 47% of patients died during the hospital stay. ConclusionsDespite ACT being a widely used UFH monitoring tool in ECMO patients, our meta-analysis found a weak correlation between ACT and UFH infusion dose. New trials are required to investigate the role of emerging tools and to clarify the most appropriate monitoring strategy for patients receiving ECMO support.

Assessment of the effect of unfractionated heparin administered either by intravenous infusion vs. subcutaneous injection on heparin-binding protein, and plasminogen activator inhibitor-1 in critically ill septic patients: a randomized controlled trial.

The study compared the impact of unfractionated heparin (UFH) administered via two routes (infusion and subcutaneous injection) on heparin-binding protein (HBP) and plasminogen activator inhibitor-1 (PAI-1) levels in critically ill sepsis patients. Forty critically ill sepsis patients were randomly assigned to receive either a low-dose intravenous infusion of UFH (500 units/hour) or subcutaneous UFH (5,000 units/8 hours) for seven days. HBP and PAI-1 were measured at baseline and on days one, two, and seven. Intravenous administration of UFH showed a significant reduction in percentage change of HBP compared to subcutaneous administration on days one [(-35% vs. -13%, p = 0.03*) (*indicates a significant result *p < 0.05, relative to the subcutaneous group)] and seven (-62% vs. -39%, p = 0.02*). Also, the percentage change of PAI-1 was significantly reduced in the infusion group compared to the subcutaneous group on days one (-28% vs. -3%, p = 0.008*), two (-42% vs. -3%, p = 0.001*), and seven (-62% vs. 27%, p = 0.001*), respectively. Furthermore, a significant improvement in the 14-day survival was observed in the infusion group compared to the subcutaneous group (p = 0.008*). Intravenous infusion was the route of choice for UFH administration in critically ill septic patients, with a promising effect on HBP, PAI-1, and survival.

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15units/kg/h for infants with CRT and 2 to 3units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001). With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

Fibromuscular Dysplasia: Renal Artery Dissection and Infarction in a Young Male

Fibromuscular dysplasia is an abnormal cell growth of the arterial wall that usually affects the renal and carotid arteries. It may lead to stenosis, tortuosity, aneurysm, or dissection of the artery and can potentially compromise the circulation from ensuing total occlusion and infarction of the recipient area. We report a case of a young male who presented with severe acute abdominal pain in the right side of the abdomen associated with nausea, vomiting, and constipation. Computed tomography of the abdomen with intravenous contrast showed acute renal infarction of a focal area at the lower pole of the right kidney, subsequent computed angiography showed dissection of a segmental branch of the right renal artery associated with fibromuscular dysplasia and beading appearance of the right renal artery. The renal function test and urinalysis were both normal. The patient was treated with unfractionated heparin infusion, with the resolution of abdominal pain, he was subsequently discharged home uneventfully on oral aspirin.

Improving Compliance with a Nurse-Driven Protocol for Unfractionated Heparin Infusions in Patients with Venous Thromboembolism.

Unfractionated heparin (UFH) is a high-risk medication that can cause bleeding and/or thrombotic complications if not managed appropriately. Between January and July 2019, our institution experienced a high number of patient safety events related to UFH infusion for the treatment of venous thromboembolism (VTE). The aim of this quality improvement (QI) initiative was to prevent these safety events by improving compliance with our institution's nurse-driven VTE UFH infusion protocol. Baseline data for patients on the VTE UFH protocol were collected to identify improvement opportunities. Compliance with eight standards of care related to the VTE UFH infusion protocol was measured. Time to first therapeutic activated partial thromboplastin time (aPTT) was recorded to assess the benefit of improved compliance. Institutional policy updates were made to clarify the management of UFH infusions and documentation in the electronic health record. A multidisciplinary workgroup implemented order set changes, nursing communication orders, UFH infusion reports, and a nursing education module to promote compliance with the protocol. The overall rate of compliance with the VTE UFH infusion protocol increased from 79.4% at baseline to 85.2% following implementation of the QI initiative, and the median time to first therapeutic aPTT decreased from 831.5 minutes to 808 minutes over the same period. A multidisciplinary initiative to address improvement opportunities in a nurse-driven UFH protocol for VTE treatment increased compliance with the protocol and decreased the time to first therapeutic aPTT.

To Compare the Effectiveness of Low-Molecular-Weight Heparin and Unfractionated Heparin in Reducing Lower Limb Girth in Deep Vein Thrombosis.

Treating deep vein thrombosis (DVT) using a once-daily dose of enoxaparin offers greater convenience and the possibility of home-based care for certain patients, as opposed to a continuous infusion of unfractionated heparin (UFH). The study aimed to determine the most cost-effective thromboprophylaxis between low-molecular-weight heparin (LMWH) and UFHfor hospitalized patients. After obtaining clearance from the institutional ethical committee, the study was conducted in the Departmentof General Surgery, Sri Devaraj Urs Medical College, over a period of six months. Informed consent was obtained from all 46 patients included in this study. The participants were divided into two groups: group A received LMWHand group B received UFH. The mean age in group A was 59.8 + 10.6 years and in group B was 54.9 + 12.3 years. There was no significant difference in the girth of the lower limb between the groups during the follow-up period (p > 0.05). In group A, there was a highly significant reduction in lower limb girth from day one to day five (p < 0.0001), day five to day 10 (p < 0.0001), and day one to day 10 (p < 0.0001).In group B, there was no significant reduction from day one to day five (p = 0.06), but there was a significant reduction from day five to day 10 (p = 0.001) and day one to day 10 (p = 0.001). Treatment with LMWH as an anticoagulant significantly reduced the lower extremity girth and thrombus thickness in cases of DVT when compared to UFH.

Management of prosthetic valve thrombosis with unfractionated heparin

BackgroundProsthetic valve thrombosis (PVT) is a severe and life-threatening complication. Surgery and thrombolytic therapy (TT) carry a high risk, and in several circumstances, optimal anticoagulation with unfractionated heparin (UFH) infusion may be an alternative treatment. This study aimed to assess the results of UFH in patients diagnosed with both obstructive and non-obstructive PVT. MethodsThis observational retrospective study enrolled patients who had contraindications for TT and surgery underwent UFH therapy. ResultsA total of 136 patients were enrolled [male: 55 (40.4%), mean age: 50.3 ± 14.6 years] in the study. In the successful group, 66 patients (48,5%) showed >75% regression in the thrombus burden without facing death or major non-fatal complications.In the unsuccessful group, 56 had less than a 50% reduction in thrombus load and 14 (10.3%) suffered major complications. The presence of obstruction (27.1% vs. 12.1%; p = 0.028), thrombus area 1.1 cm2 vs. 0.8 cm2; p = 0.005] and the duration of UFH treatment (15.1 vs. 11.8 (days); p = 0.005) were significantly higher in the unsuccessful UFH group.In multivariate regression analyses the presence of obstruction (RR: 3.088, p = 0.020), increased thrombus area (RR: 2.400; p = 0.015), and increased duration of UFH therapy (RR: 1.073 95%, p = 0.012) were identified as independent predictive parameters for a failed UFH therapy. ConclusionsThis study suggests that UFH therapy may be considered a relatively beneficial treatment strategy for some patients with PVT. The most significant factors affecting success are the obstructive nature and area of the thrombus.

Pilot study examining anti-factor Xa levels for heparin monitoring and outcomes in patients with cerebral venous thrombosis.

There are no studies to date that examine the association between anti-factor-Xa (AFXa)-based heparin monitoring and clinical outcomes in the setting of cerebral venous thrombosis (CVT). This pilot study included adults aged ≥18 admitted with CVT between 1 January 2018 and 1 January 2021, who were treated with unfractionated heparin (UFH) and were monitored via AFXa-based nomogram within 24 h of arrival. Comparisons were made between patients with AFXa levels within the target therapeutic range (0.25-0.5 IU/mL) and patients whose levels were not within the therapeutic range within 24 h of arrival; the time (hours) from arrival to reach the therapeutic range was also examined. Outcomes were length of stay (LOS) in the hospital, major (actionable) bleeding events, and discharge home (vs. higher acuity location). Continuous data are reported in the form of the median (interquartile range). Among 45 patients, treatment with UFH was initiated 2 (1-11) h after arrival, and the majority (84%) of UFH infusions did not need dose adjustment. AFXa assays were conducted every 6 (5.5-7) h. Thirty patients (67%) fell within the therapeutic range. Outcomes were similar for patients with levels within the therapeutic range vs. not: major bleeding events, 10% vs. 0% (p = 0.54); discharge home, 77% vs. 80% (p = 1.0); LOS, 5 days in each group (p = 0.95). There was also no association between outcomes and time to reach the therapeutic range. Our findings demonstrate the practicability of monitoring UFH based on AFXa values in this population of patients with CVT, but reaching target AFXa levels within 24 h of arrival may not necessarily be prognostic.

Safety and Effectiveness of an Anti-Xa-based Unfractionated Heparin Protocol for Impella Percutaneous Ventricular Assist Devices.

Background: Impella devices are used for mechanical circulatory support in patients with cardiogenic shock or those undergoing high-risk percutaneous coronary intervention (PCI). Anticoagulation protocols in this population are not well established and are complicated by concomitant use of purge solutions containing unfractionated heparin (UFH) and intravenous UFH continuous infusion (CI) for systemic anticoagulation. Objectives: To evaluate thrombotic and bleeding complications when using a novel UFH protocol with a reduced initial UFH CI dose of 6 units/kg/hour targeting an anti-Xa goal of 0.3 to 0.5 units/mL in patients receiving Impella support. Methods: This single-center, retrospective study included 41 patients on Impella support who received an UFH purge solution and/or an IV UFH infusion. The primary outcome was overall composite bleeding. Secondary outcomes included thrombotic events and systemic UFH exposure. An exploratory analysis was performed to identify risk factors for bleeding. Results: Anti-Xa values were in therapeutic range 46% of the time while on support (interquartile range 16.6%-75%), with a median IV UFH dose of 6 units/kg/hour. The overall bleeding rate was 29.2%, with 6 minor bleeds and 2 major bleeds with no fatal bleeding or intracranial hemorrhage. Rate of overall thrombosis was 4.9%, including 1 ischemic stroke and 1 occurrence of limb ischemia. Conclusion: Use of a modified UFH protocol to target an anti-Xa goal of 0.3 to 0.5 units/mL resulted in bleeding and thrombotic event rates similar to previous literature. This protocol utilizing an initial rate of 6 units/kg/hour may be a useful approach to achieve therapeutic anticoagulation while accounting for UFH exposure from the purge solution and minimizing need for frequent calculations.

Implementation of a Heparin Infusion Calculator in the Electronic Health Record System as a Risk-Mitigation Strategy in a Community Teaching Hospital Emergency Department

IntroductionAccording to the Institute for Safe Medication Practices, unfractionated heparin is a high-risk medication due to the potential for medication errors and adverse events. Unfractionated heparin is often started in the emergency department for patients with acute coronary syndromes or coagulopathies. Risk-mitigation strategies should be implemented to ensure appropriate initiation and monitoring of this high-risk medication. In 2019, an unfractionated heparin calculator was built into the electronic health record at a community medical center. The purpose of this study was to evaluate the impact of the calculator as a risk-mitigation strategy. MethodsPatients ≥18 years old admitted between January 1, 2020, and December 31, 2020, were included if they were administered an unfractionated heparin infusion in the emergency department. Patient encounters were excluded if unfractionated heparin order was discontinued before administration. Patient encounters were classified into the unfractionated heparin calculator arm if the unfractionated heparin calculator was used to determine initial dosing, and the remaining patient encounters were classified into the unfractionated heparin no calculator arm. Unfractionated heparin orders were reviewed if a baseline activated partial thromboplastin time was collected and if the correct initial bolus dose and infusion rate were administered. The primary objective is to determine whether the use of unfractionated heparin initiation calculator reduced the rate of medication administration errors. Medication administration errors are defined as baseline activated partial thromboplastin time not collected or incorrectly collected or the administration of incorrect initial bolus dose and infusion rate. ResultsA total of 356 patient encounters with unfractionated heparin orders were included in the primary analysis. There were 13.9% errors (39 of 279) present when the calculator was used and 23.3% (18 of 77) when the calculator was not used (P = .046). There was 86% correct administration of heparin (240 of 279) when the calculator was used and 76% correct administrations (59 of 77) when the calculator was not used. DiscussionThe use of the unfractionated heparin infusion calculator in the emergency department led to decrease in medication administration errors. This is the first study to evaluate the integration of an unfractionated heparin calculator into the electronic health record.

Abstract 18267: Successful C-Section Delivery at 36 Weeks in a Patient With a Heartmate 3 LVAD

Introduction: Pregnancy in patients with advanced heart failure requiring left ventricular assist device (LVAD) support is risky and discouraged, though there are cases of successful deliveries. Hypothesis: A 29-year-old G3P2002 female with history of embolic cerebrovascular accident, postpartum hemorrhage, peripartum cardiomyopathy status-post HeartMate 3 (HM3) LVAD, became pregnant after intrauterine device dislodgement. She elected to continue the pregnancy against the advice of maternal-fetal medicine (MFM). A multidisciplinary team convened to plan for delivery. Methods: Warfarin and sacubitril-valsartan were stopped due to teratogenicity. Therapeutic anticoagulation with enoxaparin injections was started. Aspirin was continued. Low-dose digoxin was added for right ventricular support. A multidisciplinary team involving anesthesiology, MFM, and advanced heart failure (AHF) was convened. Through patient-centered shared decision-making, cesarean delivery was planned for 36 weeks. She was seen by MFM and AHF every two weeks with LVAD speed optimization under transthoracic echocardiogram (TTE) guidance and anti-Xa monitoring. Results: The patient was electively admitted at 35 weeks for pre-delivery optimization. Enoxaparin was switched to an unfractionated heparin infusion. Betamethasone was administered to facilitate fetal lung maturation. Twice-daily fetal non-stimulation tests were performed. LVAD speed was optimized with TTE guidance. Continuous hemodynamic monitoring was performed perioperatively with a Swan-Ganz catheter and arterial line. Femoral veno-arterial sheaths were placed in case extracorporeal membrane oxygenation was needed. Anesthesia was administered via spinal-epidural approach. LVAD speed was modulated as needed. A healthy neonate was delivered by cesarean section without complication at 36 weeks and 3 days. Conclusions: Pregnancy during LVAD support remains an extremely high-risk clinical situation, though this case demonstrates that it is possible to carry such a pregnancy to near-term.

THU153 Deep Vein Thrombosis As The Presenting Symptom In An Adolescent With New-Onset Type 2 Diabetes

Abstract Disclosure: F.I. Cooper: None. S. Gurnurkar: None. M. Carakushansky: None. Introduction The prothrombin G20210A mutation occurs in a small portion of the population, but usually does not become apparent unless the individual exhibits another risk factor for clotting (such as diabetes in adulthood). In this case report, we discuss a 15-year-old male with extensive deep vein thrombosis (DVT) in the setting of hyperglycemia and a newly-discovered prothrombin G20210A mutation. Case Presentation A previously healthy, obese 15-year-old male presented to the emergency department with two days of left hip pain radiating down to the left calf, and one day of left calf swelling. The patient denied prolonged immobility, recent infections, or recent vaccinations. There was strong maternal family history of diabetes but no history of thrombosis. D-dimer was 2013 ng/mL (0-500 ng/mL). A Computed Tomography of the abdomen and pelvis with contrast revealed thrombi in the inferior vena cava, left common iliac, left external iliac, left internal iliac and left common femoral veins. Initial labs were remarkable for unexpected significant hyperglycemia-- random serum glucose 317 mg/dl (&amp;lt;140 mg/dl).He was started on unfractionated heparin infusion as well as Lantus and Humalog insulins. An echocardiogram did not reveal pulmonary embolism or right heart strain. Hemoglobin A1C was 11.8% (3.4-5.6%) and C-peptide was detectable at 1.2 ng/mL (1.1-4.4 ng/mL), suggesting type 2 diabetes (in addition to negative anti-GAD 65 and islet cell antibody titers, in this child with a BMI of 34 kg/m2). The patient underwent image-guided thrombolysis and thrombectomy from the popliteal vein to the left iliac vessels and received continuous infusion of heparin and tissue plasminogen activator (TPA). As the clot improved over the subsequent days, he underwent image-guided angioplasty and removal of the popliteal sheath. He was then transitioned to enoxaparin and discharged on day 10 of hospitalization. His blood sugars responded well to insulin therapy (85-308 mg/dl). The patient received a staged thrombophilia workup. A heterozygous mutation was found in factor II (prothrombin G20210A) gene which is associated with a 2-4 fold increased risk of venous thromboembolism. The patient was discharged on enoxaparin, as well as Lantus and Humalog. He is followed by the Hematology and Endocrinology departments. Conclusion In this case, we presented the first written occurrence of DVT in a pediatric patient with type 2 diabetes. Our patient’s hyperglycemia caused by his new onset type 2 diabetes may have led to onset of an extensive DVT thrombosis at an usually young age, since he had an underlying prothrombin G20210A mutation. Our case also illustrates the need for a multidisciplinary approach (involving endocrinology, hematology, pediatric intensive care, and interventional radiology) for successful outcomes in these patients. Presentation: Thursday, June 15, 2023

When Apixaban and Rivaroxaban Interfere With Anti-Xa Assays: A Cohort Study

Background: The use of direct factor Xa inhibitors, such as apixaban and rivaroxaban, has improved medication adherence. However, in certain situations during hospital admission, patients on these medications may need to be transitioned to unfractionated heparin (UFH) infusions. This transition can skew results of anticoagulation monitoring, such as the anti-Xa assay, due to residual factor-Xa inhibitor activity. Methods: We conducted this retrospective chart among admitted patients to St. Vincent’s Medical Center in Bridgeport, CT between December 2020 till June 2022. Patients who were maintained on Apixaban or Rivaroxaban, factor-Xa inhibitors, and were transitioned to unfractionated intravenous drip were included. A baseline plasma anti-Xa level was noted. Assessment for thrombotic or bleeding events during hospitalization was performed. Results: A total of 48 patients were included in this study. The majority of patients were bridged to UFH for NSTEMI (31%) or pre-procedure (23%). The mean baseline anti-Xa for all patients was 0.92 U/mL. Twelve patients (25%) and one patient (2%) of patients had bleeding and thrombotic events, respectively. Although the mean baseline anti-Xa level was higher for patients who had an adverse event compared to no event, the difference was non-statistically significant. Fifty seven percent of patients who had an adverse event had a supratherapeutic plasma anti-Xa baseline level. A gastrointestinal bleed was the most common type of bleeding event. Conclusions: To prevent thrombotic or bleeding events, we suggest adopting a standard practice of obtaining a baseline anti-Xa level in patients with recent exposure to factor Xa inhibitors in order to guide the timing of UFH initiation, the dosing of heparin, and determine the need for alternative assays, such as the activated partial thromboplastin clotting time.

Therapeutic inefficacy of protocol driven intravenous unfractionated heparin infusion in the current era

Unfractionated heparin (UFH) is commonly used for several life-threatening conditions requiring anticoagulant therapy but failure to reach therapeutic levels in 24 h can be associated with adverse outcomes. Use of low molecular weight heparin (LMWH) may provide an alternative while providing superior outcomes as compared to UFH. We studied 100 patients who underwent UFH therapy for >24 h and found that theoretically 80 % were eligible for LMWH therapy. Only 29 % and 40 % of the total aPTT draws were in the therapeutic window within the first 24 h and at 25–48 h respectively. This study reports that a vast majority of patients remain outside of therapeutic aPTT within first 24–48 h when anticoagulated with UFH. With high eligibility for LMWH therapy, its substitution can potentially lead to better patient outcomes, higher levels of therapeutic efficacy, and decrease in hospital resources.

PULM4: Silicone-Based Hollow Fiber Membrane Lungs For Long-Term Extracorporeal Respiratory Supports: Initial Results From A Pilot Study Using A Goat Model

Background: There has been an increasing demand of organs for lung transplant to save those who suffer from end-stage lung disease. However, the number of organ donations have never matched that of candidate recipients, leading to a high mortality rate on the waiting period for transplant. One potential approach to decrease the wait-list mortality is to develop an artificial gas-exchange device that can support lung function until the time of transplantation. We’ve started to develop a gas-exchange system that consists of silicone-based membrane lungs with methacryloyloxyethyl phosphorylcholine (MPC) polymer coating and tubing system for a longer-term use. Objective: The purpose of this study was to evaluate the long-term durability, oxygenation, and pressure loss of newly developed artificial lungs using a large animal model. Materials and methods: The surface area of the membrane lung is approximately 2 m2. Central ECMO from the pulmonary artery to the left atrium was introduced to a healthy female goat via left thoracotomy under general anesthesia (N=3). Unfractionated heparin infusion was utilized for anticoagulation (target activating clotting time: 150-200 sec). After recovery from the surgery, blood gas and flow pressure before and after the artificial lung with flow rates of 1, 2, and 3 L/min were tested weekly. Daily physiological data, regular blood biochemistry and coagulation tests, and histopathological findings after autopsy were also evaluated. Thrombus adhesion to the silicone membrane was evaluated using an electron microscopy after the experiments. Results: Durations for testing the artificial lungs were 53, 58, and 100 days. The experiments were terminated due to an accidental tubing event, a sudden cardiac complication, and massive renal hemorrhage. Averages of oxygen transfer rates (ml/min) and oxygen pressure gradients (mmHg) at each flow rate were 63.3 and 466.5 at 1 L/min, 118.3 and 291.3 at 2 L/min, and 152.7 and 138.2 at 3 L/min. Averages of flow pressures through the artificial lungs at each flow rate were 21.7 mmHg at 1 L/min, 44.7 at 2 L/min, and 66.9 at 3 L/min. No significant increase of pressure loss or decrease of oxygenation was observed throughout the experimental periods. Thrombus at the inlet of the membrane was mainly observed, but those inside and near the outlet were minor, indicating the long-term antithrombotic property of the polymer coating. Electron microscopical examinations revealed minimal thrombus formation on the hollow fiber membrane inside the lung. At autopsy, although micro-infarction and thrombus were observed in the heart and kidney, native lungs were well maintained without appreciable congestion. Conclusion: The newly developed MPC polymer-coated silicone-based lungs could be used stably for more than 50 days. Improving the oxygenation in higher blood flow rates with reduced pressure loss is our ongoing subject to work on.

Correlation between heparin anti-Xa activity and thromboelastography in adult critically ill COVID-19 patients.

Severe coronavirus disease 2019 (COVID-19) increases the risk of thrombotic complications with unfractionated heparin (UFH) as a commonly used agent in managing venous thromboembolism (VTE). The optimal anticoagulation intensity and monitoring parameters in intensive care unit (ICU) COVID-19 patients remains controversial. The primary study aim was to evaluate the relationship between anti-Xa and thromboelastography (TEG) reaction (R) time in patients with severe COVID-19 receiving therapeutic UFH infusions. Single-center, retrospective study conducted over a 15-month period (2020-2021). Academic medical center (Banner University Medical Center Phoenix). Adult patients with severe COVID-19 administered therapeutic UFH infusions with one or more corresponding TEG, and anti-Xa assessments drawn within ≤2 hours of each other were included. The primary end point was the correlation between anti-Xa and TEG R time. Secondary aims were to describe the correlation between activated partial thromboplastin time (aPTT) and TEG R time, as well as clinical outcomes. Pearson's coefficient was used to evaluate the correlation using a kappa measure of agreement.

P209 HUGE AND OCCLUDING LAA THROMBUS DISSOLUTION IN A CASE OF SEVERE TACHI–CARDIOMYOPATHY

Abstract A 62–year–old man was admitted to our emergency department for worsening nocturnal dyspnea and orthopnea for 15 days. Finding of Acute Pulmonary Edema in a setting of non datable high ventricular response atrial fibrillation (AF) associated with severe LV dysfunction. NT–proBNP 8.252 pg/ml. ECG: atrial fibrillation with high ventricular response (120/bpm). TTE: Severe left ventricular systolic disfunction (EF 20%). TOE/3D TOE: evidence of voluminous oval–shaped thrombotic formation (10 x 17 mm) protruding in LA and completely occluding the left atrial appendage (LAA). LA thrombosis in patients with AF is relatively rare and represents a contraindication to rhythm control strategies. Once an LAA thrombus is identified, effective anticoagulation is recommended for at least three weeks or until LAA thrombus resolution is detected. Available evidence on left atrial thrombus dissolution largely refers to the use of vitamin K antagonist oral anticoagulant (VKAs), but their effectiveness may be influenced by variability in the level of anticoagulant activity obtained, wich may be suboptimal. In a recent prospective observational study has been evaluated the effectiveness of Edoxaban for the resolution of LA thrombosis in 25 patients with AF: it has been demonstrated a complete thrombus resolution in 56% of patients at 4 weeks, similar to studies using VKAs and the other NOACs. Use of NOACs in this setting represents a great field of interest for the near future. In our experience, indeed, after confirmed diagnosis of LAA thrombus, we started anticoagulant therapy with warfarin (currently the first choice), however due to poor INR control, we switched to continuous infusion of unfractionated heparin (UFH), wich represents, in a hospital setting, a safe and effective method for thrombus dissolution, allowing continuous monitoring of efficacy and a rapid cessation of effect in case of major bleeding. In this way we obtained complete thrombus dissolution in about 3 weeks. At the meantime we initiate a rate control therapy, an optimized treatment for HFrEF and intravenous diuretics. Our experience highlights the need of great ductility in the choice of anticoagulant therapy in patients with evidence of voluminous LAA thrombus, monitoring treatment’s efficacy parameters and being ready to change strategy if necessary and it reminds that auricular thrombosis is often inserted in a wider picture of heart disease wich requires multiple other specifics treatments.