Low-dose Heparin Research Articles

Bloodless lung transplantation: Comparison between 2 central venoarterial extracorporeal membrane oxygenation anticoagulation strategies and their impact on lung transplant outcomes

ObjectiveTo report differences between 2 anticoagulation protocols during venoarterial extracorporeal membrane oxygenation (VA-ECMO) intraoperative support and their effects on outcomes after lung transplantation. MethodsWe performed a retrospective analysis of patients undergoing double-lung transplantation with intraoperative VA-ECMO from January 1, 2016, to December 30, 2023. Two distinct anticoagulation protocols were in place during this period. One included targeted activated clotting time >180 seconds at all times with protamine reversal after decannulation. The second included 75 units per kilogram of heparin at the time of cannulation with no redosing plus a tranexamic acid infusion after ECMO initiation. ResultsA total of 116 patients (46 low heparin, 70 standard) were included in the analysis. Cannulation strategies and ECMO circuit were equivalent between the groups. The low-dose heparin protocol group had a shorter surgical time (7.28 hours vs 8.53 hours, P < .001) and required significantly less intraoperative packed red blood cells (median 0 vs 4.37 units, P < .001), fresh-frozen plasma (median 0 vs 2 units, P < .001), platelets (median 0 vs 1 units, P < .001), cryoprecipitate (median 0 vs 0 units, P < .001), and total blood products (median 0 vs 9 units, P < .001) compared with the standard group. There were no differences in rates of deep vein thrombosis (P = .13), airway dehiscence (P > .99), pneumonia (P = .38), or acute kidney injury requiring renal-replacement therapy (P = .59). There was no difference in rates of severe grade 3 primary graft dysfunction at 72 hours after transplant (P = .42). ConclusionsOur low-dose heparin VA-ECMO protocol for intraoperative support during lung transplantation led to a significant reduction of blood product use. Although this did not translate to a reduced rates of grade 3 primary graft dysfunction, the low-dose heparin protocol was associated with similar postoperative outcomes.

Consumptive coagulopathy: how low-dose unfractionated heparin can prevent bleeding complications during extracorporeal life support.

Consumptive coagulopathy: how low-dose unfractionated heparin can prevent bleeding complications during extracorporeal life support.

Citrate and low-dose heparin combined anticoagulation in pediatric continuous renal replacement therapy

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

Outcomes of different perioperative management strategies of patients on chronic anticoagulation in elective total hip and knee arthroplasty: a systematic review.

There are currently different management guidelines for patients undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) that are on long-term anticoagulation. The timing of discontinuation and restarting the anticoagulation is challenging during the postoperative care, which often involves general practitioners and physiotherapists. The systematic review followed the PRISMA guidelines and included 3 databases: PubMed/MEDLINE, EMBASE, and Web of Science Core Collection. It was registered in the International Prospective Register for Systematic Reviews and Meta-analysis (PROSPERO) under the registration number: CRD42023408906. The risk of bias assessment was performed using the Methodological index for non-randomized studies (MINORS) criteria. Six retrospective studies involving 727 patients with therapeutic anticoagulation (1,540 controls) for elective THA, TKA and revision arthroplasty have been included. The follow-up ranged from 30 days to 1 year postoperatively. All studies evaluated outcomes of warfarin therapeutic anticoagulation versus prophylactic dosages of one or more of the following: warfarin, aspirin, low-molecular-weight heparin (LMWH) and unfractionated low-dose heparin (UFH). One study did not discontinue therapeutic anticoagulation. Two studies reported no significant differences in complications between groups, whilst 3 studies had significantly higher rates of superficial wound infections, revision surgeries, postoperative haematomas, and prosthetic joint infections (PJI). Different anticoagulation-related perioperative management strategies achieve different outcomes following elective arthroplasty in patients with therapeutic chronic anticoagulation. There is contradictory evidence regarding the need for the discontinuation of therapeutic warfarin. Retrospective data showed that individual risk stratification with multi-modal prophylaxis resulted in minimal complications. Systematic Review of Level III studies.

The incidence of venous thromboembolism after curative colon cancer surgery within an enhanced recovery after surgery programme

AimBased on three randomised controlled trials performed more than a decade ago, several national guidelines recommend prolonged venous thromboprophylaxis for 28 days following elective surgery for colon cancer. None of these studies were conducted within enhanced recovery after surgery setting. Newer studies indicate that prolonged prophylaxis might not be necessary with enhanced recovery after surgery. We aimed to provide further evidence to this unresolved discussion. MethodRetrospective study of patients undergoing elective surgery for colon cancer stage I-III with enhanced recovery after surgery in the Capital Region of Denmark from 2014 to 2017. Patients were excluded if discharged on postoperative day 28 or later, dying before discharge, undergoing concomitant rectum resection, or discharged with vitamin K antagonists, direct-oral anticoagulants, or low molecular weight heparin treatment. All patients received only low-dose low molecular weight heparin as prophylaxis during their admission.The primary endpoint was symptomatic lower limb deep venous thrombosis or pulmonary embolism diagnosed within 60 days postoperatively. ResultsOut of the included population of 1806 patients, only three experienced a symptomatic venous thromboembolic event; none was fatal. Two had pulmonary embolism associated with pneumonia, while one patient was diagnosed with lower limb deep venous thrombosis at postoperative day 15 after an uncomplicated course with first discharge at postoperative day 2. ConclusionThe risk of symptomatic venous thromboembolism after elective surgery for colon cancer with enhanced recovery after surgery seems negligible even without prolonged prophylaxis. The current guidelines need to be reconsidered.

Heparin Dosing During Percutaneous Coronary Intervention and Obesity.

Unfractionated heparin is the most common anticoagulant used during percutaneous coronary intervention. Practice guidelines recommend an initial weight-based heparin bolus dose between 70 and 100 U/kg to achieve target activated clotting time (ACT) of 250-300 seconds. The impact of severe obesity on weight-based heparin dosing is not well studied. We performed a retrospective analysis of 424 patients undergoing percutaneous coronary intervention who received heparin for anticoagulation. We collected detailed data on cumulative heparin administration and measured ACT values in this cohort. We performed separate analyses to identify clinical predictors that may affect dose-response curves. There was significant variability in dosing with mean dose of 103.9 ± 32-U/kg heparin administered to achieve target ACT ≥ 250 seconds. Women received higher initial heparin doses when adjusted for weight than men (97.6 ± 31 vs. 89 ± 28 U/kg, P = 0.004), and only 49% of patients achieved ACT ≥ 250 s with the initial recommended heparin bolus dose (70-100 U/kg). Lower heparin dose (U/kg) was required in obese patients to achieve target ACT. In multivariate linear regression analysis with ACT as dependent variable, after inclusion of weight-based dosing for heparin, body mass index was the only significant covariate. In conclusion, there is significant variability in the therapeutic effect of heparin, with a lower weight-adjusted heparin dose required in obese patients.

Low-dose aspirin and heparin treatment improves pregnancy outcome in recurrent pregnancy loss women with anti-β2-glycoprotein I/HLA-DR autoantibodies: a prospective, multicenter, observational study.

Anti-β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA)-DR antibodies may be a risk factor for recurrent pregnancy loss (RPL). The therapeutic modality for women with RPL and anti-β2GPI/HLA-DR antibody positivity has not been evaluated. This prospective, multicenter, observational study aimed to assess whether low-dose aspirin (LDA) and/or heparin therapies improve pregnancy outcomes in women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies. Between August 2019 and December 2021, 462 women with RPL underwent anti-β2GPI/HLA-DR antibody measurements and risk assessments for RPL. Each attending physician decided the treatment modality for women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-β2GPI/HLA-DR antibody positivity were included in the analysis and were divided into two groups regarding whether they were treated with LDA and/or unfractionated heparin (UFH) (LDA/UFH group, n = 39) or with neither of them (non-LDA/non-UFH group, n = 8). The rates of live birth and pregnancy complications (i.e., preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency) were compared between the two groups. The live birth rate in the LDA/UFH group was higher than that in the non-LDA/non-UFH group (87.2% vs 50.0%, p = 0.03). The pregnancy complication rate in the LDA/UFH group was significantly lower than that in the non-LDA/non-UFH group (5.9% vs 50.0%, p = 0.048). Among 21 women who tested positive for anti-β2GPI/HLA-DR antibodies and had no other risk factors for RPL, the live birth rate in the LDA/UFH group (n = 14) was much higher than that in the non-LDA/non-UFH group (n = 7) (92.9% vs 42.9%, p = 0.03). This study, for the first time, demonstrated that LDA and/or UFH therapies are effective in improving pregnancy outcomes in women with RPL and aβ2GPI/HLA-DR antibody positivity.

Direct thrombin inhibitors fail to reverse the negative effects of heparin on lung growth and function after murine left pneumonectomy.

Neonates with congenital diaphragmatic hernia (CDH) frequently require cardiopulmonary bypass and systemic anticoagulation. We previously demonstrated that even subtherapeutic heparin impairs lung growth and function in a murine model of compensatory lung growth (CLG). The direct thrombin inhibitors (DTIs) bivalirudin and argatroban preserved growth in this model. Although DTIs are increasingly used for systemic anticoagulation clinically, patients with CDH may still receive heparin. In this experiment, lung endothelial cell proliferation was assessed following treatment with heparin-alone or mixed with increasing concentrations of bivalirudin or argatroban. The effects of subtherapeutic heparin with or without DTIs in the CLG model were also investigated. C57BL/6J mice underwent left pneumonectomy and subcutaneous implantation of osmotic pumps. Pumps were preloaded with normal saline, bivalirudin, or argatroban; treated animals received daily intraperitoneal low-dose heparin. In vitro, heparin-alone decreased endothelial cell proliferation and increased apoptosis. The effect of heparin on proliferation, but not apoptosis, was reversed by the addition of bivalirudin and argatroban. In vivo, low-dose heparin decreased lung volume compared with saline-treated controls. All three groups that received heparin demonstrated decreased lung function on pulmonary function testing and impaired exercise performance on treadmill tolerance testing. These findings correlated with decreases in alveolarization, vascularization, angiogenic signaling, and gene expression in the heparin-exposed groups. Together, these data suggest that bivalirudin and argatroban fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of low-dose heparin with DTIs on CDH outcomes are warranted.NEW & NOTEWORTHY Infants with pulmonary hypoplasia frequently require cardiopulmonary bypass and systemic anticoagulation. We investigate the effects of simultaneous exposure to heparin and direct thrombin inhibitors (DTIs) on lung growth and pulmonary function in a murine model of compensatory lung growth (CGL). Our data suggest that DTIs fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of heparin with DTIs on clinical outcomes are thus warranted.

Management of cardiopulmonary bypass in patients with ischemic and hemorrhagic strokes in surgery for active infective endocarditis.

Stroke and intracranial hemorrhage (ICH) are serious complications that are difficult to manage during surgery for active infectious endocarditis (AIE). Relevant society guidelines still recommend delaying the cardiac surgery for AIE with ICH for 4weeks. Some early studies indicated that the mortality rate decreases when cardiac surgery for ICH is delayed. In contrast, some reported that surgical intervention should not be delayed if an early operation is demanded, even in patients with ICH. The current literature on early vs. late surgery for infectious endocarditis (IE) with ICH is conflicting. Changing the cardiopulmonary bypass (CPB) strategy might be necessary to improve the surgical outcomes of IE with ICH. Some studies reported that cardiac surgery using nafamostat mesylate (NM) as an alternative anticoagulant during CPB was performed successfully. The combination of NM and low-dose heparin was beneficial for early surgery in patients with AIE complicated by cerebral infarction and ICH, without worsening cerebral lesions. In this report, we review and discuss the management of CPB in patients with ischemic and hemorrhagic stroke during surgery for AIE.

When HIT Testing Hurts- the Financial and Clinical Repercussions of Heparin Induced Thrombocytopenia Testing: A Single Center Analysis

Introduction: Thrombocytopenia is a common inpatient hematologic concern. Most often, thrombocytopenia is a multifactorial phenomenon, without one clear cause. Heparin Induced Thrombocytopenia (HIT) is a rare but serious hematologic consequence of exposure to heparin. In many hospitalized patients, heparin is routinely used as venous thromboembolism (VTE) prophylaxis or for therapeutic anticoagulation. The incidence of HIT is approximately 0.5-1.0% in patients exposed to unfractionated heparin (UFH). Though rare, there seems to be over-testing of HIT antibody in the inpatient setting. As such, there is potential for high cost with low yield and false positives that alter patient management, resulting in prolonged hospital stays and further complications in patient care. Methods: This was a retrospective, observational study reviewing the indications, results, and patient characteristics of cases in which HIT testing was ordered. Indications for testing and influence of results on management were determined based on clinical documentation. The tests of interest included HIT antibody testing and Seratonin Release Assay (SRA). We analyzed how many times a HIT antibody was positive with a negative result in the SRA. We also determined whether there was an increased length of stay in patients who had HIT testing ordered. The study population included patients who were admitted to University of Florida Shands Medical Center, an academic institution in Jacksonville, FL in 2022. All patients were &amp;gt;18 years of age. Results: 190 patients were identified, for whom 190 HIT antibody tests were ordered and 75 SRAs. All patients who had a SRA performed had exposure to low dose heparin or therapeutic high dose heparin. Out of 190 patients, HIT testing was positive in 30 patients (15.8%). SRA testing was performed on 75 patients despite only 30 positive HIT tests. The true positives were 10 patients who had positive SRA confirmatory testing out of 190 patients with suspected HIT. Based on the results of confirmatory testing, the false positive fraction of HIT testing was 66%. When analyzing the 190 patients who underwent HIT testing, the average length of stay was 14 days. On average, a hospital stay in the US is 5.5 days and evaluation of HIT results in 8.5 additional days of hospital admission at our institution. The prolonged length of stay for HIT testing is likely impacted by awaiting SRA results along with other factors. Conclusion: This analysis examines the relative over-testing for HIT at a single institution. Compared with the known incidence of positive HIT tests, there is a significant number of positive HIT antibody tests at our hospital. The data further reveals a high probability of a false positive HIT antibody test results in the hospitalized patient, possibly due to immune reactivity. Of 190 patients suspected with HIT, only 10 patients had a positive confirmatory SRA, indicating that only 5% of suspected patients truly had HIT. This demonstrates that 95% of the time HIT assays ordered did not provide clinically useful information. From the time work up was initiated to the time of discharge, the average stay length was 14 days in a patient suspected with HIT. Cost burden of HIT testing was evaluated. Each HIT panel is $153.83 and each confirmatory SRA test is approximately $250, at a commercial laboratory. Taken together, the total average cost per patient with suspected HIT is $413.83 in diagnostic testing. Prolonged hospital stay contributes to approximately $25,000 increase in hospital stay per patient being evaluated for HIT. This does not include the cost of further work up or interventions. Changing to an alternate anticoagulant such as Argatroban increased costs by nearly $1,500 per case and this number increased further when adding the daily coagulation panel required while on this drug. In other studies, this cost has been estimated to add $90,000 to the hospital stay. Prolonged hospital stays are also associated with unintended incidents such as GI bleeding leading to blood transfusions, invasive testing (such as endoscopy/colonoscopy) and increased morbidity to the patient. We will use this information to implement a tool in our Electronic Medical Record (EMR) that will require answering the 4T score in order to establish high pre-test probability, prior to ordering HIT antibody testing at the University of Florida in Jacksonville.

Anti-PF4/Heparin Monoclonal Antibodies Induce Thrombus Formation in an Ex Vivo Endothelialized Microfluidic System

Introduction: Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin. Antibodies against platelet factor 4 (PF4) or a heparin/PF4 complex have been reported to activate platelets, neutrophils and possibly endothelial cells, resulting in thrombocytopenia, hypercoagulability and thromboembolic complications. While the impact of anti-PF4/heparin antibodies on platelet, neutrophil and monocyte activation has been extensively studied, the role of endothelial cells in HIT-associated thrombosis remains underexplored. In particular, the interactions between HIT-induced procoagulancy and endothelial cells under dynamic conditions is not completely analyzed. In this report, we investigated how HIT antibodies induce thrombosis in an endothelialized microfluidic system. Methods: Fibrinogen microfluidic channels were coated with confluent monolayer of human umbilical vein endothelial cells (HUVECs). Cells were primed with low-dose TNF-α to induce a sub-thrombotic endothelial activation, prior to perfusion of whole blood. Recalcified unstimulated or Thrombin Receptor Activator Peptide 6 (TRAP-6) activated whole blood was perfused at a venous flow rate. HIT-thrombosis model was established and tested with monoclonal anti-PF4/heparin antibodies in whole blood. In brief, whole blood was pre-incubated with unfractionated heparin (UFH, 0.2 IU/mL and 100 IU/mL). Next, anti-PF4/heparin antibodies were introduced to the whole blood mixture and incubated for 30 minutes. Whole blood was recalcified and perfused over resting or primed endothelial cells at a venous shear stress. Thrombus formation was recorded over time. Results: The endothelialized microfluidic model successfully captures sub-thrombotic conditions under venous shear. Activated platelets induced a procoagulant shift and three-dimensional thrombi. We applied our thrombosis model to investigate thrombus formation induced by a HIT mimicking monoclonal antibody. We show that the heparin-dependent platelet activation predicts the thrombotic response in the microfluidic system: HIT antibodies in absence of heparin did not exert a pro-thrombotic effect on activated endothelial cells. Co-incubation with 0.2 IU/mL UFH induced thrombosis, embolization of thrombus material and channel occlusion only when endothelial cells were primed with TNF-α. The pro-thrombotic effect of HIT antibodies was fully reversed at the super-therapeutic dose of 100 IU/mL UFH. Conclusions: HIT antibodies induce thrombosis and embolization in a system emulating physiological environment. For the first time, we present a comprehensive thrombosis model that incorporates the established thrombogenicity of HIT-mimicking antibodies. We show that our thrombosis model incorporates both endothelial- and blood-based control of thrombosis. Primed endothelial cells and antibody-induced procoagulancy trigger thrombosis in a concerted fashion, allowing investigation of the underlying mechanisms and possible preclinical evaluation of potential inhibitors of HIT-thrombosis. Figure 1, upper panel: Maximal thrombus surface area coverage of TNF-α primed endothelial cells, perfused with unstimulated, TRAP-6 activated or HIT-like IgG/heparin challenged whole blood. HIT-like IgG did not increase thrombus formation in absence of heparin. Addition of low-dose heparin exerted a strong pro-thrombotic effect, that was fully reversible with a super-therapeutic concentration of heparin. Lower panel: representative images of thrombi formed by HIT-like IgG in absence and under low or high-dose heparin. Platelets: green, Calcein-AM. Scale bar: 200 µm.

Anti-Factor-Xa and Activated Partial Thromboplastin Time Concordance and Outcomes in Adults Undergoing Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Pilot Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation Randomized Trial.

To determine the concordance between activated partial thromboplastin time (aPTT) and anti-factor-Xa (anti-Xa) in adults undergoing extracorporeal membrane oxygenation (ECMO) and to identify the factors associated with discordant paired aPTT/anti-Xa. Pre-planned secondary analysis of the Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation pilot randomized unblinded, parallel-group controlled trial. Two ICUs in two university hospitals. Thirty-two critically ill patients who underwent ECMO and who had at least one paired aPTT and anti-Xa assay performed at the same time. We analyzed the concordance between aPTT and anti-Xa and identified factors associated with discordant paired aPTT/anti-Xa based on their respective therapeutic ranges. We also compared biological parameters between heparin resistance episode and no heparin resistance. Of the 32 patients who were included in this study, 24 (75%) had at least one discordant paired aPTT/anti-Xa. Of the 581 paired aPTT/anti-Xa that were analyzed, 202 were discordant. The aPTT was relatively lower than anti-Xa in 66 cases (32.7%) or relatively higher than anti-Xa in 136 cases (67.3%). Thirty-three heparin resistance episodes were identified in six patients (19%). In these critically ill patients undergoing ECMO, one third of paired aPTT/anti-Xa measures was discordant. Coagulopathy and heparin resistance might be the reasons for discordance. Our results support the potential importance of routinely monitoring both tests in this setting.

Abstract 109: Endonasal Endoscopic Approach Associated Cerebral Vasospasm and Management: A Case Report

Introduction Endoscopic endonasal approach(EEA) techniques have been increasingly utilized and have been associated with development of cerebrospinal fluid(CSF) leak, meningitis, diabetes insipidus post‐operatively. Cerebral vasospasm following EEA has rarely been described. Here, we describe the clinical course and management of a patient who underwent EEA for encephalocele repair whose course was complicated by postoperative subarachnoid hemorrhage(SAH) and cerebral vasospasm. Methods n/a Results Case Presentation: 40 year old female with past medical history significant for cerebral venous sinus stent on aspirin, CSF rhinorrhea secondary to right nasal encephalocele s/p endoscopic transnasal transethmoidal repair with nasoseptal flap reconstruction and lumbar drain placement eleven days prior presented with speech difficulties and right sided weakness. On exam, patient was noted to have mild right hemiparesis and expressive aphasia. MRI brain showed subacute infarcts in left greater than right frontal lobes, corpus collosum and right anterior perforated substance. MRA head demonstrated multifocal arterial stenosis. In light of postoperative CT head showing SAH in the basilar, perimesencephalic, prepontine cisterns, interhemispheric fissure and right frontal sulci as well as intraventricular hemorrhage in fourth ventricle, her presentation was thought to be secondary to cerebral vasospasm in the setting of postoperative SAH. She was treated with intravenous hydration, permissive hypertension with head of bed in flat position and transferred for further evaluation. On arrival, she continued have mild right hemiparesis and aphasia. Repeat CTA head/neck and CT perfusion showed severe stenosis of bilateral M1 segments and left greater than right A1 segments as well as ischemic penumbra in left ACA/MCA watershed territory. Diagnostic cerebral angiogram showed bilateral severe A1 stenosis and mild to moderate bilateral M1 and supraclinoid ICA stenosis which improved with intra‐arterial verapamil. She was started on nimodipine. Systolic blood pressure was augmented with vasopressors for goal of 150‐180mmHg. Daily TCDs were followed. She developed worsening right leg weakness following day, thus she was taken for repeat diagnostic cerebral angiogram during which time she was re‐administered intra‐arterial verapamil with improvement in vasospasm. After the second treatment, she had improvement in speech and motor strength. Systolic blood pressure goal was gradually normalized. She was noted to have incidental left internal jugular (IJ) vein thrombosis for which anticoagulation was held in the setting of recent neurosurgical procedure and SAH. Workup for vasculitis and hypercoagulability was unrevealing. Lumbar puncture demonstrated 13 WBC/cu mm with lymphocytic predominance(90%), 23 RBC/cu mm, glucose 89mg/dl, protein 30mg/dl. CSF cultures were negative. Pleocytosis in CSF was attributed to recent neurosurgical procedure. Her neurological exam improved to baseline on hospital day(HD) 9.On HD12, she was found to have left common femoral deep venous thrombus in addition to the left IJ thrombus. Anticoagulation with low dose heparin infusion was started which was transitioned to apixaban on discharge. She was discharged home on HD20. Conclusion We report a case of EEA associated with severe multifocal cerebral vasospasm secondary to postoperative SAH that was successfully treated with induced hypertension, oral nimodipine and intra‐arterial verapamil as an adjunct therapy with an excellent outcome.

A Systematic Review of the Impact of Antibiotic and Antimicrobial Catheter Locks on Catheter-Related Infections in Adult Patients Receiving Hemodialysis.

Central venous catheter (CVC)-based hemodialysisis a major contributor to bacteremia in immunocompromised hosts. Heparin-locking CVCs is a frequent therapeutic procedure. However, it has not been shown to reduce catheter-related bloodstream infections (CRBSIs). For this systematic review, we searched PubMed, PubMed Central, ResearchGate, Science Direct, and Multidisciplinary Digital Publishing Institute (MDPI) for multiple articles published between January 2018 and January 2023 to determine how antimicrobial locking solutions affect CRBSIs, which could ultimately lower the risk of morbidity, mortality, and hospitalization costs. Antilocking products, catheter-related bacteremia, central-line associated bloodstream infections, tunneled dialysis catheter, hemodialysis, antibiotic, and antimicrobial catheter locks, and the Medical Subject Heading (MeSH) method for PubMed were used as the main keywords for searching publications. A pool of 13 studies with 46,139 individuals showed that the therapy group had a lower incidence of CRBSIs than the heparin-treated control group. Furthermore, it was discovered that bacteria were resistant to gentamicin, and the use of antibiotics had no discernible impact on catheter malfunction. In conclusion, the most effective locking solution to date is an antilocking solution made up of an antibiotic or antimicrobial agent combined with low-dose heparin (500-2,500 U/mL).

Impact of Pharmacist-Led Education on Proper Prophylactic Enoxaparin Dosing in Obese Patients

Background/Purpose: Venous thromboembolism (VTE) is a common cardiovascular complication in middle-aged adults. There is a likelihood a patient may experience VTE when admitted to a hospital. Prophylactic medications such as low-dose unfractionated heparin and enoxaparin are started to prevent VTE. A pharmacist-led health system-wide Grand Rounds promoted prophylactic enoxaparin 40 mg twice daily instead of once daily in patients with a body mass index (BMI) 40 kg/m2 or greater. Methodology: This case-control study was conducted at a Essentia Health – Fargo, in the Upper Midwest. Data of acute care patients were extracted from electronic health records 2 years before and after the pharmacist-led education. Patients in the study were 18 years old or older, hospitalized with a need for prophylactic anticoagulation receiving enoxaparin, and had a BMI 40 kg/m2 or greater. Patients with a diagnosis of COVID-19 and recent bleeding were excluded. Groups were compared to determine the effect of pharmacist-led education. The outcome was the number of patients who received enoxaparin 40 mg twice daily compared to once daily. Results: In the control group, 9 out of 15 hospitalizations received enoxaparin 40 mg subcutaneous twice daily and in the case group 34 out of 70 hospitalizations received the twice daily dosing. The odds ratio of receiving enoxaparin 40 mg twice daily after the pharmacist-led education compared to before the education was OR = .99, 95% CI = .96, 1.02. Conclusions: There was no difference in enoxaparin 40 mg once daily and twice daily dosing after the pharmacist-led education.

#5633 USE OF HEPARIN GRAFTED DIALYZER (EVODIAL) FOR HEMODIALYSIS IN PATIENTS WITH HIGH RISK OF BLEEDING: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims During hemodialysis exposure of the blood to the dialysis membrane and the tubing system can activate blood cells and promote clotting activation. So usually, some form of anticoagulation, most frequently heparin, is used to prevent blood coagulation. However, there are patients with increased risk for bleeding (patients with active bleeding, major surgery in past 72 hours, severe trombocytopenia) where use of heparin free regime is mandatory. Evodial dialyzer (Gambro-Hospal, France) [1] contains a heparin-grafted membrane aiming to provide a system with a low thrombogenicity that can be used without or with low dose heparin in order to reduce the patients' bleeding risk. As high-quality evidence of the optimal choice of anticoagulation in these patients is limited we wanted to show our experience with the use of Evodial dialyzer. Method During 12 months 106 dialysis sessions in 59 patients were performed. Reasons for using Evodial : active bleeding, hematological conditions, complications of vascular access. Changes in the dialyzer or the blood lines, or any aditional interventions were examined. Results Low dose unfractionated heparin (1250 IE total) was used in 10 (9,4%) sessions, and it was added in 15 (14%) more sessions because of problems with the coagulation. In 4 (2,8%) sessions we had to terminate dialysis because of clotting. Conclusion Heparin grafted dialyzers can be safely used in patients with high risk for bleeding. Although results are worse than the ones reported in literature [2] where regional citrate anticoagulation (RCA) is used, it can be reasonable alternative when RCA is unavailable.

Intermediate-Dose Versus Low-Dose Low-Molecular-Weight Heparin in Pregnant and Post-Partum Women with a History of Venous Thromboembolism (Highlow Study): An Open-Label, Multicentre, Randomised, Controlled Trial

ABSTRACT Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and mortality, but its prevention, medical thromboprophylaxis, can cause bleeding complications. Without thromboprophylaxis, up to 10% of women with a history of VTE are at risk of pregnancy-related recurrence. For those women with a history of VTE who are not on long-term anticoagulation medication, guidelines recommend subcutaneous low-molecular-weight heparin (LMWH) in all women in the postpartum stage. For those with moderate or high risk of recurrent VTE, antepartum thromboprophylaxis is recommended. In both cases, the optimal dose of heparin is unknown, and professional societies do not provide clear specific guidance often recommending multiple different dosing approaches without clear evidence to guide recommendations. The aim of this study was to assess the efficacy and safety of low- versus intermediate-dose LMWH in pregnant women with a history of VTE. This was an open-label, randomized controlled study conducted at 70 hospitals in the Netherlands, France, Belgium, Norway, Demark, Canada, the United States, and Russia. Included were adult pregnant women with a history of objectively confirmed VTE, either unprovoked or provoked by hormonal or minor risk factors, and a gestational age ≤14 weeks. Excluded were women with previous VTE related to a major risk factor, indication for therapeutic-dose anticoagulants, or contraindication to LMWH. Eligible women were randomly assigned to receive either weight-adjusted intermediate-dose heparin or fixed, low-dose heparin. Participants self-administered their allocated dose of heparin once daily and participated in in-person or telephone contacts 2 weeks after randomization; at 20 and 30 weeks of gestation; and 1 week, 6 weeks, and 3 months postpartum. The primary efficacy outcome was symptomatic VTE, and the primary safety outcome was major bleeding. A total of 1110 women were included in the analysis—555 were randomized to the intermediate-dose group and 555 to the low-dose group. Approximately 81% of women had a history of VTE related to hormone use, pregnancy, or the postpartum period. From randomization to 6 weeks postpartum, VTE occurred in 2% of women in the intermediate-dose group and 3% in the low-dose group (relative risk, 0.69; 95% confidence interval, 0.32–1.47; P = 0.33). Antepartum VTE occurred in 1% of women in each treatment group; postpartum VTE occurred in 1% in the intermediate-dose group and 2% in the low-dose group. These findings remained consistent up to 3 months postpartum. From randomization to 6 weeks postpartum, major bleeding occurred in 4% of women in the intermediate-dose group and 4% in the low-dose group (relative risk, 1.16; 95% confidence interval, 0.65–2.09; p = 0.63). Antepartum major bleeding occurred in &lt;1% of women in each treatment group. Early postpartum bleeding occurred in 4% in the intermediate-dose group and 3% in the low-dose group. Last postpartum bleeding occurred in &lt;1% in the intermediate-dose group and none in the low-dose group. In comparing weight-adjusted, intermediate-dose LMWH with fixed, low-dose LMWH, the risk of VTE was similar in pregnant women with a history of VTE in the antepartum and postpartum periods. Moreover, no differences were observed in the occurrence of major bleeding between the 2 treatment groups. These findings provide evidence-based guidance that low-dose heparin is appropriate for preventing pregnancy-related recurrent VTE.

WCN23-0388 Effect of Low-dose Heparin as an Anticoagulant Protocol on the Number of Dialyzer Reuses for Maintenance Hemodialysis

WCN23-0388 Effect of Low-dose Heparin as an Anticoagulant Protocol on the Number of Dialyzer Reuses for Maintenance Hemodialysis

Clinical practice of emergency department-initiated extracorporeal cardiopulmonary resuscitation for cardiac arrest in adults.

Clinical practice of emergency department-initiated extracorporeal cardiopulmonary resuscitation for cardiac arrest in adults.

Risk-Stratified Anticoagulation Protocol Increases Success of Lower Extremity Free Tissue Transfer in the Setting of Thrombophilia.

Optimal perioperative thromboprophylaxis is crucial to avoid flap thrombosis and achieve high rates of microsurgical success. At the authors' institution, implementation of a risk-stratified anticoagulation (AC) protocol preliminarily showed a reduction in postoperative thrombotic events and flap loss. The authors present an updated analysis of surgical outcomes using risk-stratified AC in thrombophilic patients who underwent free tissue transfer (FTT) reconstruction for nontraumatic lower extremity (LE) wounds. The authors retrospectively reviewed patients who underwent FTT to an LE from 2012 to 2021. Their risk-stratification AC protocol was implemented in July of 2015. Low-risk and moderate-risk patients received subcutaneous heparin. High-risk patients received heparin infusion titrated to a goal partial thromboplastin time of 50 to 70 seconds. Before July of 2015, nonstratified patients were treated with either subcutaneous heparin or low-dose heparin infusion (500 U/hour). Patients were divided into two cohorts (nonstratified and risk-stratified) based on date of FTT reconstruction. Primary outcomes included rates of postoperative complications, flap salvage, and flap success. Two hundred nineteen hypercoagulable patients who underwent FTT to an LE were treated with nonstratified ( n = 26) or risk-stratified ( n = 193) thromboprophylaxis. The overall flap success rate was 96.8% ( n = 212). Flap loss was lower among risk-stratified patients (1.6% versus 15.4%; P = 0.004), which paralleled a significant reduction in postoperative thrombotic events (2.6% versus 15.4%; P = 0.013). Flap salvage was accomplished more often in the risk-stratified cohort (80% versus 0%; P = 0.048). Intraoperative anastomotic revision (OR, 6.10; P = 0.035) and nonrisk stratification (OR, 9.50; P = 0.006) were independently associated with flap failure. Hypercoagulability can significantly affect microsurgical outcomes. Implementation of a risk-stratified AC protocol can significantly improve flap outcomes. Therapeutic, III.