Intravenous Unfractionated Heparin Research Articles

Acetylsalicylic acid alone or in combination with either enoxaparin or unfractionated heparin for postoperative thromboprophylaxis in coronary artery bypass surgery patients. A randomised clinical trial assessing surrogate outcomes

IntroductionCoronary artery bypass graft surgery has considerable effects on patient haemostasis. Heparins as thromboprophylaxis may be beneficial but may also increase the risk of bleeding complications. ObjectivesTo assess the effects of heparins on haemostasis in post-coronary artery bypass graft patients. MethodsAcross one year, we randomised 60 participants scheduled for an elective coronary artery bypass graft-procedure with or without aortic valve replacement. The trial was a prospective, open-label (though blinded for the laboratory), randomised, single-centre trial with three intervention groups (n = 20 in each): group 1 received acetylsalicylic acid, group 2 received subcutaneous low molecular weight heparin and acetylsalicylic acid, and group 3 received intravenous unfractionated heparin and acetylsalicylic acid. Primary outcomes were platelet activation (Multiplate® ASPI-test) and time to clot initiation (TEG® R-time). We secondly assessed several additional Multiplate® and TEG® parameters. ResultsGroup 3 (intravenous unfractionated heparin) compared with group 1 (acetylsalicylic acid alone) showed evidence of 1) increased clot initiation time (R-time + 0.9 min; 95 % CI: +0.4 to +1.4 min; P = 0.009), and 2) decreased 30-min lysis (−1.3 %; 95 % CI: −2.1 to −0.5 %; P = 0.02). The remaining analyses of primary and secondary outcomes showed no evidence of a difference between the three groups. DiscussionIntravenous unfractionated heparins may increase the clot initiation time post-operatively after coronary artery bypass graft surgery and reduce lysis. Otherwise, there seems to be no effect of low molecular weight or unfractionated heparin on haemostatic parameters after coronary artery bypass surgery patients.

Evaluation of anti-XA-guided versus APTT-guided management of intravenous unfractionated heparin in patients requiring a durable ventricular assist device

ObjectiveThe objective of this study was to compare the effectiveness and safety of anti-Xa-guided management versus aPTT-guided management of intravenous (IV) unfractionated heparin (UFH) in patients with a durable ventricular assist device (VAD). Materials and methodsThis was a retrospective study conducted at a single academic medical center. Patients were included if they had a durable VAD and were managed using aPTT-guided UFH management from May 2019 to May 2020 or were managed using anti-Xa-guided UFH management from May 2021 to December 2021. The primary outcome of the study was the median time to goal anticoagulation post-initiation of UFH. Secondary outcomes included the percentage of time within the therapeutic range and the incidence of thromboembolic and bleeding complications. ResultsThe study included 23 patients, 12 of whom were managed using anti-Xa-guided UFH, and 11 were managed using aPTT-guided UFH. The treatment arm using anti-Xa-guided UFH demonstrated a faster time to therapeutic anticoagulation goal range with a median time of 21.3 h [IQR = 12.2–34.8] compared to 37.3 h [IQR = 41–74] in the aPTT-guided UFH treatment arm (P = 0.03). In addition, the anti-Xa-guided UFH arm had a higher percentage of time within the therapeutic range, 76 % [IQR = 64.25–96.25] compared to 53 % [IQR = 41–74] in the aPTT-guided UFH arm (P = 0.04). Both arms had no significant differences in major bleeding events (P = 0.59) or clinically relevant minor bleeding events (P = 0.60) among patients. There was no incidence of thromboembolic events in either treatment arm. ConclusionBased on this single-center experience, anti-Xa-guided UFH management resulted in a faster time to therapeutic anticoagulation and a longer time within the desired therapeutic range. The results suggest that anti-Xa-guided monitoring may be superior to UFH-guided monitoring in patients with a durable VAD.

Safety and Efficacy of Enoxaparin During Low-Risk Elective Percutaneous Coronary Intervention

Intravenous unfractionated heparin (UFH) is the most frequently used anticoagulant for percutaneous coronary intervention (PCI). Intravenous enoxaparin, a low-molecular weight heparin, has superior pharmacokinetic and pharmacodynamic properties compared with UFH. Multiple trials have shown enoxaparin to be safe and effective in PCI. However, there has not been a contemporary study evaluating its safety and efficacy. To assess its efficacy and safety, intravenous enoxaparin during PCI via radial artery access was evaluated in PCI patients from Jan 2015 to Dec 2019. Outcomes included procedural success, all-cause mortality, ischemic complications, and bleeding complications from the time of the procedure until hospital discharge. 1,019 consecutive eligible patients were identified. Median age was 63 years, and 70% were males. The indication for PCI was stable and unstable angina in two thirds of cases (77%). Few patients had myocardial infarction (MI) (2.2%) as the indication for intervention. The procedure was successful in 98.2% of cases. There were no deaths. Procedural MI occurred in 0.3% of patients. Acute stent thrombosis occurred in 0.4%. Urgent revascularization and stroke occurred in 0.1% each. Small wrist hematomas occurred in 0.3% and all were managed conservatively. There was one radial artery pseudoaneurysm. There were no cases of major bleeding. In conclusion, this single-center study showed that intravenous enoxaparin is a reasonable alternative anticoagulant for use in low-risk and elective non-myocardial infarction percutaneous coronary intervention via radial artery access.

Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study.

Unfractionated heparin, administered during venoarterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depends on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation; however, its association with acquired antithrombin deficiency is poorly understood. The objective of this study was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. The hypothesis was that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. Adults receiving venoarterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3 to 0.5 IU/ml). For each patient, arterial blood was withdrawn into citrate-containing tubes at 11 time points (from hour 0 up to day 7). Anti-Xa (without dextran or antithrombin added) and antithrombin levels were measured. The primary outcome was the antithrombin plasma level. In the absence of consensus, antithrombin deficiency was defined as a time-weighted average of antithrombin less than or equal to 70%. Data regarding clinical management and heparin dosage were collected. Fifty patients, including 42% postcardiotomy, were included between April 2020 and May 2021, with a total of 447 samples. Median extracorporeal membrane oxygenation duration was 7 (interquartile range, 4 to 12) days. Median antithrombin level was 48% (37 to 60%) at baseline. Antithrombin levels significantly increased throughout the follow-up. Time-weighted average of antithrombin levels was 63% (57 to 73%) and was less than or equal to 70% in 32 (64%) of patients. Overall, 45 (90%) patients had at least one antithrombin value less than 70%, and 35 (70%) had at least one antithrombin value less than 50%. Antithrombin levels were not significantly associated with heparin responsiveness evaluated by anti-Xa assay or heparin dosage. Venoarterial extracorporeal membrane oxygenation support was associated with a moderate acquired antithrombin deficiency, mainly during the first 72 h, that did not correlate with heparin responsiveness.

Evaluation of Safety of Spinal Anaesthesia in Patients Receiving Perioperative Antithrombotic Therapy Undergoing Infrainguinal Revascularisation Surgeries: A One-Year Prospective Clinical Research

Objective: To evaluate anaesthetic outcome, patient outcome and timing of perioperative antithrombotic therapy in relation to intrathecal injection in patients undergoing infrainguinal revascularisation surgery, for peripheral artery disease (PAD) in spinal anaesthesia.Material and Methods: A one-year prospective observational study was conducted; from May 2019 to May 2020, in a tertiary care centre. This included all consecutive patients undergoing infrainguinal revascularisation surgery for PAD under spinal anaesthesia. Preoperative antithrombotics were stopped, as per standard guidelines, to achieve a normal coagulation profile before spinal anaesthesia. Perioperative data related to the patients, antithrombotics, anaesthesia, surgery, and complications were recorded. Primary outcomes measured were anaesthetic outcome in terms of spinal success and spinal safety. Secondary outcomes measured were timing of perioperative antithrombotic therapy in relation to intrathecal injection and patient outcomes defined as: good, morbidity or mortality.Results: A total of 102 patients were evaluated, with a mean age of 54.69±16.36 years (91% males, 9% females): 58% had medical comorbidities. A single dose of intravenous (IV) unfractionated heparin (5,000-7,500 IU) was given intraoperatively at 24.97±3.69 minutes after intrathecal injection. Anaesthetic outcome was good in all patients; in terms of spinal safety (100%), as none of the patients developed spinal related complications. All had spinal success (100%), as no patient required conversion to general anaesthesia. Postoperatively, 98% (100) of patients had good outcomes, and mortality only occurred in 2% (2) of patients.Conclusion: Spinal anaesthesia is safe and effective for infrainguinal revascularisation surgery. If the patient has a normal preoperative coagulation profile, and the timeline to stop antithrombotic therapy is strictly followed, administration of IV unfractionated heparin (5,000-7,500 IU); at approximately 25 minutes after intrathecal injection, was found to be safe.

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.

Role of Anticoagulation in Nonagenarian Patients with Acute Limb Ischemia

Preoperative anticoagulant therapy is known to have a positive impact on the prognosis of patients with acute limb ischemia (ALI). However, little is known about its efficacy in elderly patients. We aimed to investigate the potential effect of anticoagulation in nonagenarian patients managed for ALI. Between January 2015 and December 2021, we identified all nonagenarian patients managed for ALI at a single center. Long-term anticoagulation and hemostasis parameters (prothrombin rate, activated partial thromboplastin time [APTT], platelet count) measured on admission were reviewed. The primary end point was mortality at 30-day mortality (D30) in patients with or without long-term anticoagulation therapy. We also studied the effect of these factors on the occurrence of revascularization failure in operated patients (initial failure, ischemic recurrence during hospitalization, necrosis requiring major amputation). A total of 68 nonagenarian patients were managed for ALI, with a mean age of 93.8years (from 90-107years), 76.5% of whom were women. Of these patients, 47 (69%) were managed surgically. Long-term anticoagulation therapy was associated with better survival at D30, both in nonoperated (P<0.01) and operated (P<0.05) patients. In operated patients, the absence of long-term anticoagulation therapy was associated with the occurrence of revascularization failure (P<0.05). In operated patients, survival to D30 and successful revascularization were associated with a longer APTT (P<0,05). We were able to observe the survival of 4 patients contraindicated for surgery and treated with a single medical therapy (intravenous unfractionated heparin). Anticoagulation appears to have an impact on the survival and postoperative prognosis of nonagenarian patients with ALI. In addition, curative anticoagulation therapy may be an alternative treatment when surgery is contraindicated in this frail population.

PB1138 The Impact of Switching from Anti-Factor Xa (anti-Xa) Assays to APTT to Monitor Intravenous (IV) Unfractionated Heparin (UFH) at a Quaternary Care Academic Centre

PB1138 The Impact of Switching from Anti-Factor Xa (anti-Xa) Assays to APTT to Monitor Intravenous (IV) Unfractionated Heparin (UFH) at a Quaternary Care Academic Centre

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.

P115 "WHEN THE GOING GETS TOUGH, THE TOUGH GET GOING": LARGE THROMBOSIS ASPIRATION DURING PERCUTANEOUS APPENDAGE OCCLUSION

Abstract Background An 83–year–old woman with permanent atrial fibrillation was referred for percutaneous left atrial appendage closure (LAAC) following a spontaneous intracranial hemorrhage caused by pituitary macroadenomas that the patient refused to excise. Pre–procedural EET revealed no formed thrombus. Intravenous unfractionated heparin (UFH) was administered. After multiple attempts, the device (Amplatzer Amulet) was correctly positioned but before final release, a large thrombus was noted within the left atrium, attached to delivery system. A further 4000 IU of UFH and 300 mg of salicylic acid were administrated, and a subsequent 300 s activated clotting time was recorded. Under continuous negative pressure in the delivery sheath via a 50 mL Luer–Lock syringe, suction of the thrombus was performed. Similarly, the device was released and the delivery system withdrawn into the delivery sheath and removed. Final EET revealed no residual thrombus within the left atrium with adequate device compression and no peri–device leaks. No further aspiration through the sheath was possible, indicating successful thrombus retrieval into the delivery sheath. Discussion Device–related thrombus (DRT) is a possible and terrible complication of percutaneous LAAC due to patient–specific (hypercoagulability disorders, renal insufficiency, nonparoxysmal AF) and/or procedural factors (LAAO depth of implantation &amp;gt;10 mm from the pulmonary vein limbus, pericardial effusion). For this patient, potential causes could be both the long intervention time required for correct positioning of the device and non–optimal pre interventional medical therapy and procedural options included either recapturing the device into the delivery sheath and abandoning the procedure or surgical thrombectomy. Both options would increase the risk of clot dislodgement and embolization. An off–label device deployment under continuous negative pressure was performed reducing embolic risk by minimizing both mechanical forces on the thrombus as well as procedural time. Conclusion Therefore, shorter procedural times and optimized preoperative medical therapy could reduce DRT risk. The evidence for the use of cerebral protection devices in the setting of LAAO insertion is limited to a small single case series. Randomized multicentric studies are necessary to approve routine use of these devices when the patient is deemed to be at high risk of thromboembolism based on clinical or intraprocedural factors.

No Association Between Outcomes And Anti-Factor Xa Levels For Heparin Monitoring In Patients With Cerebral Venous Thrombosis (P14-5.012)

<h3>Objective:</h3> We sought to determine whether Anti-factor-Xa (AFXa) values are associated with outcomes in cerebral venous thrombosis (CVT). <h3>Background:</h3> Intravenous unfractionated heparin (UFH) is a cornerstone of anticoagulant therapy for patients with CVT, but frequent monitoring is needed because of dose-response variability. The AFXa assay is used to monitor UFH treatment. <h3>Design/Methods:</h3> This pilot study included adults (≥18y) admitted to a comprehensive stroke center from 2018 through 2020 who were initially treated for CVT with low-intensity UFH drip and had at least one AFXa assay. AFXa therapeutic values were defined as 0.25 – 0.5 IU/mL. We examined percent of patients who became therapeutic within 24h of arrival, and time (hours, h) to reach therapeutic range. Outcomes included hospital LOS, bleeding event, and discharge disposition. Continuous data are presented as median (interquartile range). <h3>Results:</h3> There were 51 CVT patients included. The time to start UFH was 2h (1–6) from arrival and the time to the first AFXa assay was 8h (4–11) from arrival. AFXa were drawn 4 (2–8) times per patient. AFXa assays were performed within 24h for 45 (88%) patients and 30(67%) patients were in the therapeutic range. There was no association between study outcomes and AFXa being therapeutic or not: bleeding events were 17.2% and 13.3%, respectively (p=1.0), discharge to home was 77% vs. 80% (p=1.0), and hospital LOS was 5 days for each group (p=0.95). There was also no association between study outcomes and the time (h) to reach therapeutic range: discharge home vs. other location (11h vs. 14h, p=0.49), development of a bleed vs. no bleed (9h vs. 12h, p=0.44), and no correlation with hospital LOS (p=0.55). <h3>Conclusions:</h3> The time to achieve therapeutic AFXa was not associated with outcomes, although most patients were within the target AFXa range within 24h of arrival and had favorable outcomes. <b>Disclosure:</b> Dr. Pirahanchi has nothing to disclose. Ms. Salottolo has nothing to disclose. Dr. Burrell has nothing to disclose. Dr. Tang has nothing to disclose. Dr. DiSalvo has nothing to disclose. David Bar-Or has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Ampio Pharmaceuticals. David Bar-Or has stock in Ampio Pharmaceuticals. Dr. Bartt has nothing to disclose.

Abstract TP12: No Association Between Outcomes And Anti-Factor Xa Levels For Heparin Monitoring In Patients With Cerebral Venous Thrombosis

Introduction: For patients with cerebral venous thrombosis (CVT), intravenous unfractionated heparin (UFH) is a cornerstone of anticoagulant therapy. Drawbacks of UFH include difficulty in reaching an optimal dose. Anti-factor-Xa (AFXa) assay is used to monitor UFH treatment. We sought to determine whether AFXa values are associated with outcomes in CVT. Methods: This pilot study included adults (≥18y) admitted to a CSC between 1/1/2018-12/31/2020 who were initially treated for CVT with low-intensity UFH drip and had at least one AFXa assay. AFXa therapeutic values were defined as 0.25 - 0.5 IU/mL. We examined percent of patients who became therapeutic within 24h of arrival, and time (hours) to reach therapeutic range. Outcomes included hospital LOS, bleeding event, and discharge disposition. Continuous data are presented as median (interquartile range). Significance was p&lt;0.20. Results: 51 CVT patients were included. The hospital LOS was 5 (4-9) days, 40 (78%) patients were discharged home, and 7 (14%) developed a bleed; 4 bleeds required no action. The time to start UFH was 2h (1-6) from arrival and the time to the first AFXa assay was 8h (4-11) from arrival. AFXa were drawn 4 (2-8) times per patient. AFXa assays were performed within 24h for 45 (88%) patients and 30 (67%) patients were in the therapeutic range. There was no association between study outcomes and therapeutic AFXa ( Table 1 ). There was also no association between study outcomes and the time (h) to reach therapeutic range: discharge home vs. other location (11h vs. 14h, p=0.49), development of a bleed vs. no bleed (9h vs. 12h, p=0.44), and no correlation with hospital LOS (p=0.55). Conclusions: Most CVT patients were within the target AFXa range within 24h of arrival. The time to achieve therapeutic AFXa was not associated with better outcomes, although most patients had a favorable disposition and bleeding complications were infrequent.

Effective, safe and efficient porcine model of Forrest Ib bleeding gastric and colonic ulcers.

Developing effective gastrointestinal (GI) bleeding animal models is necessary to advance endoscopic hemostasis methods and train endoscopists on their use. Our aim, therefore, was to develop an effective and safe porcine GI bleeding model in the stomach and colon of large and small-sized oozing-type ulcers. Gastric and colonic bleeding ulcers were created using either a hybrid endoscopic submucosal dissection (ESD) technique or a cap-assisted endoscopic mucosal resection (EMR-C) technique in 14 pigs. Prior to ulcer creation, animals were treated with either oral apixaban or intravenous (IV) unfractionated heparin anticoagulation in combination with clopidogrel and aspirin. The primary outcome was the technical success of inducing oozing-type Forrest Ib bleeding ulcers. Secondary outcomes included ulcer diameter, number, creation time and the number of complications associated with each technique. Using hybrid ESD and IV heparin anticoagulation, bleeding was observed in 21/23 (91.3%) gastric ulcers and 6/7 (85.7%) colonic ulcers created. The mean diameter and ulcer creation time were 2.3 ± 0.3cm and 5.3 ± 0.5min, respectively, for gastric ulcers and 2.2 ± 0.4cm and 4.06 ± 0.6min, respectively, for colonic ulcers. Using EMR-C and IV heparin anticoagulation, bleeding was observed in 14/15 (93.3%) gastric ulcers and 6/6 (100%) colonic ulcers created. The mean diameter and ulcer creation time were 0.8 ± 0.2cm and 2.1 ± 0.5min, respectively, for gastric ulcers and 0.7 ± 0.2cm and 1.7 ± 0.3min, respectively, for colonic ulcers. None of the ulcers created in animals anticoagulated with apixaban developed bleeding. None of the 14 pigs developed any complications. We have demonstrated the effectiveness and safety of a porcine GI bleeding model utilizing IV heparin anticoagulation and either hybrid ESD or EMR-C techniques to create oozing-type bleeding ulcers in the stomach and colon with customizable size.

Perioperative management in chronically anticoagulated children undergoing tonsillectomy.

Tonsillectomy is a common procedure in children. Patients at high risk for thrombosis who require chronic anticoagulation therapy pose a special challenge when undergoing tonsillectomy, as bleeding may occur up to two weeks after surgery. Due to a lack of evidence-based data, there is no consensus on the best management for such patients. The objective of our manuscript is to review perioperative anticoagulation bridging strategies in children undergoing tonsillectomy. Retrospective case series of chronically anticoagulated patients at high risk for a thromboembolic event, who underwent tonsillectomy from 2010 to 2021. Patients whose anticoagulation treatment was discontinued due to a low risk of thromboembolic events were excluded. Four patients met inclusion criteria (age range 1.5-16.1 years). All patients were admitted prior to surgery for bridging therapy with intravenous unfractionated heparin (UFH) drip titrated to a therapeutic dose until 4-6 hours prior to surgery. The estimated blood loss during surgery was minimal in all surgeries. UFH was readministered per hospital protocol on the night of surgery and titrated to a therapeutic dose. Postoperative warfarin was restarted within 2 days for all patients. High-risk patients were kept in the hospital until postoperative day 6-8 due to concern for delayed bleeding. One patient was noticed to have blood-tinged sputum requiring no intervention, and none of the patients developed early or delayed hematemesis. Our data show that bridging therapy with UFH has been successful. Chronically anticoagulated patients undergoing tonsillectomy require multidisciplinary care for the management of their pre- and postoperative course.

177: SAFETY AND EFFECTIVENESS OF AN ANTI-XA-BASED UNFRACTIONATED HEPARIN PROTOCOL FOR IMPELLA DEVICES

Introduction: Impella® devices are used as a short-term form of mechanical circulatory support in patients with cardiogenic shock or high-risk percutaneous coronary intervention (PCI). Anticoagulation protocols in this population are not well established. The purpose of this study was to evaluate thrombotic and bleeding complications when using an unfractionated heparin (UFH) protocol with a reduced initial dose of 6 units/kg/hour targeting an anti-Xa goal of 0.3-0.5 units/mL. Methods: This single-center, retrospective study included patients on Impella® support who received an UFH purge solution and/or an intravenous UFH infusion. The primary outcome was overall composite bleeding including major or minor bleeding or bleeding requiring medical attention. Secondary outcomes included thrombotic events and systemic UFH exposure. Results: Forty-one patients met criteria for inclusion. Anti-Xa values were in therapeutic range 46% of the time while on Impella support (interquartile range 16.6-75), with a median IV UFH dose of 6 units/kg/hour. The overall bleeding rate was 29.2% (12 total events), of which six were minor bleeds and two were major bleeds. Rates of thrombosis were low with two events during the study period. Conclusions: Use of a modified UFH protocol to target an anti-Xa goal of 0.3-0.5 units/mL prevented thromboembolic events, demonstrating the efficacy of this strategy. The majority of bleeding events were minor with no cases of fatal bleeding or intracranial hemorrhage. Based on this study, an anti-Xa goal of 0.3-0.5 units/mL with an initial rate of 6 units/kg/hr may be a useful approach to minimize heparin exposure while preventing thrombotic complications.

Heparin Does Not Regulate Circulating Human PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) in a General Population-Brief Report.

PCSK9 (proprotein convertase subtilisin-kexin type 9) chaperones the hepatic LDLR (low-density lipoprotein receptor) for lysosomal degradation, elevating serum LDL (low-density lipoprotein) cholesterol and promoting atherosclerotic heart disease. Though the major effect on the hepatic LDLR comes from secreted PCSK9, the details of PCSK9 reuptake into the hepatocyte remain unclear. In both tissue culture and animal models, HSPGs (heparan sulfate proteoglycans) on hepatocytes act as co-receptors to promote PCSK9 reuptake. We hypothesized that if this PCSK9:HSPG interaction is important in humans, disrupting it with unfractionated heparin (UFH) would acutely displace PCSK9 from the liver and increase plasma PCSK9. We obtained remnant plasma samples from 160 subjects undergoing cardiac catheterization before and after administration of intravenous UFH. PCSK9 levels were determined using a commercial enzyme-linked immunosorbent assay. Median plasma PCSK9 was 113 ng/mL prior to UFH and 119 ng/mL afterward. This difference was not significant (P=0.83 [95% CI, -6.23 to 6.31 ng/mL]). Equivalence testing provided 95% confidence that UFH would not raise plasma PCSK9 by > 4.7%. Among all subgroups, only subjects with the lowest baseline PCSK9 concentrations exhibited a response to UFH (8.8% increase, adj. P=0.044). A modest correlation was observed between baseline plasma PCSK9 and the change in plasma PCSK9 due to UFH (RS=-0.3634; P<0.0001). Administration of UFH does not result in a clinically meaningful effect on circulating PCSK9 among an unselected population of humans. The results cast doubt on the clinical utility of disrupting the PCSK9:HSPG interaction as a general therapeutic strategy for PCSK9 inhibition. However, the observations suggest that in selected populations, disrupting the PCSK9:HSPG interaction could still affect PCSK9 reuptake and offer a therapeutic benefit.

An Evaluation of Time to Therapeutic Range of Intravenous Unfractionated Heparin After Transitioning From Direct Oral Factor Xa Inhibitors.

Purpose: Direct oral factor Xa inhibitors (Xa inhibitor) may falsely elevate anti-Xa assays, creating a challenge when patients transition from Xa inhibitors to intravenous unfractionated heparin (IV UFH). This study compared the time to therapeutic anti-Xa range in patients transitioning from Xa inhibitors to IV UFH to those not previously anticoagulated and initiated on IV UFH. Methods: This single-center, retrospective study included adults receiving IV UFH from August 2018 through August 2019. The study group received apixaban or rivaroxaban prior to the initiation of IV UFH, and the control group was not previously anticoagulated. The primary outcome was the time to reach therapeutic range. Secondary outcomes included the number of anti-Xa levels drawn to reach therapeutic range, incidence of treatment failure, and incidence of major bleeding episodes. Categorical and continuous data were analyzed with chi-square and Mann-Whitney U tests, respectively. Results: The time to reach therapeutic range was a median of 18.5 hours in the study group (IQR 14.9-26.9) compared to 7.3 hours (IQR 5.9-14.7) in the control group (P < .001). Two anti-Xa levels were drawn in the study group (IQR 1-4) compared to 1 (IQR 1-2) in the control group (P < .001). There was no difference in the incidence of treatment failures (P = .981) or major bleeding episodes (P = .972). Conclusions: In patients transitioning from Xa inhibitors to IV UFH, the time to therapeutic range was longer and required additional laboratory tests compared to those not previously anticoagulated. Further research is needed to examine the incidence of treatment failures or major bleeding episodes.

Abstract 12891: Protocol Driven Therapeutic Efficacy of Intravenous Unfractionated Heparin in the Current Era

Introduction: Despite years of refining algorithms, intravenous (IV) unfractionated heparin (UFH) is associated with many limitations in the inpatient setting. Low-molecular-weight heparin (LMWH) has shown to be equivalent to UFH in the treatment of acute venous thromboembolic disease (VTE), and demonstrated superiority in acute coronary syndrome (ACS). LMWH has less pharmacokinetic variability, a longer plasma half-life, and is associated with fewer complications. UFH also requires frequent activated partial thromboplastin time (aPTT) monitoring, affecting hospital resources. The objectives of this study were to assess the real-word therapeutic impact of routine IV UFH use in the setting of a hospital-based algorithm, evaluate the number of patients eligible for substitution with LMWH, and estimate the cost differential. Hypothesis: Methods: Adult patients who received greater than 24 hours of IV UFH from 8/1/21 to 9/30/21 (n=174), were included in this retrospective evaluation. A random sample of 100 of these 174 patients was analyzed for aPTT results in hours 25-48. These 100 patients were also considered for theoretical substitution with LMWH. Ineligibility for substitution included intermittent and continuous renal replacement therapy (RRT), creatinine clearance less than 30 mL/min, and a planned invasive procedure within 24 hours. Fiscal analyses were also done. Results: Among 519 aPTTs drawn from these 100 patients, 348 (67%) were not within the hospital therapeutic range. The most common indications for anticoagulation were ACS and acute VTE. Eighty-one percent of patients on UFH were eligible for LMWH substitution. Ineligibility was most commonly secondary to renal dysfunction. Estimated drug acquisition costs were similar, but overall cost was lower with LMWH due to decreased laboratory testing, nurse/patient contact time, and infusion supplies. Conclusions: In spite of current hospital-based algorithms and electronic order sets to minimize variability, achieving a therapeutic aPTT during the day after UFH initiation, remained elusive. The majority of patients receiving IV UFH were eligible for substitution with LMWH. Patients who qualify, should be placed on the simpler and more reliable antithrombotic LMWH regimen.

Abstract 12956: Pulmonary Vein Thrombosis: A Rare Complication Following Infection With SARS-CoV-2

Case Presentation: 49 year old male with past medical history of hypertension who presented with dyspnea and nasal congestion of three days duration. Testing for SARS-CoV-2 was positive. ECG revealed sinus tachycardia with an incomplete right bundle branch block. D-dimer was elevated 3,388 ng/mL and CT pulmonary angiogram revealed thrombosis of a right lower lobe pulmonary vein extending to the posterior aspect of the left atrium along with consolidation in the right lower lobe concerning for pulmonary infarct versus congestion in the setting of pulmonary venous thrombosis. The patient was admitted and started on intravenous unfractionated heparin. Echocardiogram performed later in the day revealed left ventricular segmental wall motion to be globally hypokinetic with mildly reduced ejection fraction of 45%. Left atrium was severely enlarged. No thrombus could be seen in the left atrium or ventricle. Bubble study revealed no evidence of atrial septal defect or patent foramen ovale. The next day after admission, his symptoms had resolved and he was back to his baseline, so he was discharged. No supplemental oxygen was required. Heparin was transitioned to apixaban, and metoprolol succinate and lisinopril were initiated. Cardiac monitoring during the hospitalization did not demonstrate any arrhythmias. Etiology of his pulmonary vein thrombosis was ultimately felt to be due to coagulopathy secondary to COVID-19 given that the patient’s medical history was otherwise unremarkable. Discussion: This case describes a rare complication due to infection with SARS-CoV-2. Pulmonary artery thrombi are common with SARS-CoV-2 infection, but pulmonary vein thrombi are rare. With thrombus extending to the left atrium, cardiac monitoring was performed and did not reveal evidence of atrial fibrillation or atrial flutter. With no other identifiable cause of the thrombus, the etiology was likely due to SARS-CoV-2 infection.

Discordance among assays for monitoring? Anticoagulation during extracorporeal life support.

The optimal method for monitoring of anticoagulation in patients on extracorporeal life support (ECLS) is unknown. The objective of this study was to assess the relationship between anti-factor Xa level (anti-Xa; IU/mL) and activated partial thromboplastin time (aPTT; seconds) for monitoring intravenous unfractionated heparin anticoagulation in adult ECLS patients. Charts of all adult patients cannulated for ECLS from 2015 through 2017 were reviewed and laboratory and heparin infusion data were extracted for analysis. Time matched pairs of anti-Xa and aPTT were considered concordant if both laboratory values were within the same clinically utilized range. A hierarchical logistic regression model was used to determine factors associated with discordance while accounting for patient level effects. A total of 1016 paired anti-Xa and aPTT values from 65 patients were evaluated. 500 (49.2%) paired samples were discordant with a degree of variability on linear regression (r2 = 0.315). The aPTT fell into a higher therapeutic range compared to the anti-Xa in 31.6% and lower in 17.3%. Logistic regression demonstrated that discordance was independently associated with time from initiation of ECLS (OR 1.17 per day, p < 0.001), average heparin infusion rate (OR 1.25 per U/kg/hr, p < 0.001), and INR (OR 3.22, p < 0.001). Nearly half of all aPTT and anti-Xa values were in discordant ranges and discordance is more likely as the time on ECLS and the INR level increase. The use of either assay in isolation to guide heparin anticoagulation may lead to misestimation of the degree of anticoagulation in complex ECLS patients.