Anticoagulant Reversal Agents Research Articles

PB0033 Validated in vivo Model to Assess Direct Oral Anticoagulant Reversal Agents

PB0033 Validated in vivo Model to Assess Direct Oral Anticoagulant Reversal Agents

Standardizing periprocedural anticoagulation management: a stewardship initiative.

Study data indicates anticoagulant interruption peri-procedurally can increase the risk of anticoagulation-related bleeding and thrombosis. Management of anticoagulated patients during the peri-procedural period poses clinical challenges given the potential for thrombosis and bleeding in this complex, high risk population. As such, there is a need for enhanced emphasis on anticoagulated patient care throughout the peri-procedural period with the goal of optimizing patient safety and efficacy. To operationalize an effective, efficient, comprehensive, and standardized anticoagulation management peri-procedural process housed within the electronic health record (EHR). The IPRO-MAPPP clinical decision support logic was adapted into a nurse-managed protocol to guide anticoagulation therapy use during the elective peri-procedural period at Bassett Medical Center, an Anticoagulation Forum Center of Excellence. A second phase of this initiative endorsed peri-procedural warfarin and bridging management by the Anticoagulation Management Service. Outcomes revealed 30-day hospital or emergency department admissions remained at or below 1% of the surgical patient population, and below the published national standards for both phases of implementation. Further, no emergent anticoagulation reversal agent use was attributed to peri-procedural care during the assessment period. The phased implementation of this Anticoagulation Stewardship initiative in elective peri-procedural anticoagulation management successfully describes the operationalization and demonstration of high-quality care and low provider practice variation from policy. The integration of clinical decision support systems, in consort with effective communication, via the EHR, provides stability, sustainability, and drives high quality care to optimize patient outcomes.

P65: Predictors of Bleeding with Rotational Thromboelastometry in Patients with a Left Ventricular Assist Device

Purpose: Bleeding events are a significant source of morbidity and mortality in patients with left ventricular assist devices (LVAD). Rotational thromboelastometry (ROTEM) is a form of viscoelastographic testing that provides a real-time analysis of clot initiation, clot strength, and fibrinolysis. There is limited data regarding the use of ROTEM in predicting bleeding events in patients with LVADs post-implantation. Therefore, the purpose of this study is to determine if any component in ROTEM is associated with bleeding events in LVAD patients. Methods: This was a retrospective, single-centered, cohort study of LVAD patients implanted between January 2013 to December 2022 that compared ROTEM values between patients admitted due to bleeding and non-bleeding controls. ROTEM values drawn within 24 hours of separate hospitalizations were included. Patient encounters were excluded for the following reasons: ROTEM drawn after receiving blood or anticoagulant reversal agent, parenteral anticoagulation, or direct oral anticoagulants, and admission related to thrombotic events, index implantation, or device exchange. The primary outcome was to determine if ROTEM values were associated with bleeding events. Results: Of the 327 patient admissions evaluated, 266 patient encounters met inclusion criteria with 59 (22.2%) bleeding events and 207 (77.2%) controls. Of the excluded patients, 28 patients were excluded due to ROTEM drawn after receiving blood or an anticoagulant reversal agent. Baseline characteristics including age, gender, race, ethnicity, device type, last ejection fraction, and indication for implant were similar between groups. Patients admitted for a bleeding event were more likely to have a history of any bleeding event (p=0.01). There was no significant difference seen in the regression analysis evaluating INTEM clot time (p=0.55), INTEM clotting formation time (p=0.45), EXTEM clotting time (p=0.72), FIBTEM clot formation time (p=0.78), and FIBTEM clotting time (p=0.78) for patients experiencing a bleeding event vs those without a bleeding event (table 1). Conclusion: There are no differences in ROTEM values in LVAD patients admitted for bleeding events compared to non-bleeding admissions. Table 1.

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited.

Major Drivers of Increased Cost of Inpatient Stroke Care in the Wake of the COVID-19 Pandemic (P3-7.001)

<h3>Objective:</h3> To evaluate the impact of the COVID-19 pandemic on inpatient stroke care costs in a 23 hospital, integrated University Hospitals System Stroke Program (UHSSP). <h3>Background:</h3> Since 2008, the UHSSP implemented system-wide clinical practice guidelines and analytics to optimize high-value stroke care by improving quality and reducing unnecessary costs of care. <h3>Design/Methods:</h3> All stroke hospital discharges for DRGs 64–66 at 12 UHSSP hospitals were analyzed for volume, case mix index (CMI), inpatient total direct costs (TDC) including length of stay (LOS), ICU LOS, diagnostics, imaging, lab, OR, Pharmacy, supply and direct contribution margin (DCM) using EPSi™ and quality using <i>GWTG-</i>Stroke® and STATIT piMD™. The data encompassed three waves: 2017 (baseline), 2019 (2 years into a high-reliability initiative), and through 2q2022 (2 years into the pandemic). <h3>Results:</h3> For all medically managed stroke at the academic hub, the average TDC, CMI and positive DCM all increased (by +15%, +0.07, and +0.5% respectively) in 2019 over baseline in 2017. However, in 2q2002 over 2019, there was a significant increase in TDC, not scaled to the increase in CMI, and associated with a significant reduction in the positive DCM (by +63%, +0.06, and −61% respectively). The increased costs were driven by increased ICU LOS (ratio of ICU LOS vs non-ICU LOS +37%, from 2.05 to 2.8-fold) associated with nursing shortages and shifting step-down care to the ICU, and anticoagulant reversal agents accounting for a growth of 37% to 56% of all pharmacy costs. The same pattern was seen analyzing all hospitals in aggregate. <h3>Conclusions:</h3> The inpatient stroke costs have increased significantly since the pandemic, resulting in many health systems now operating in a deficit. Analyses have focused on pharmacy, labor and supply costs. This report identifies an unanticipated significant cost related to prolonged ICU LOS resulting from nursing staffing shortages. <b>Disclosure:</b> The institution of Dr. Sila has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Syntactx . Dr. Sila has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . Dr. Sila has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astrazeneca . Colin Beilman has nothing to disclose. Mr. Vincent has nothing to disclose. Dr. De Georgia has nothing to disclose. Dr. Sarraj has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AstraZeneca. Dr. Sarraj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stryker Neurovascular. Dr. Sarraj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Stryker Neurovascular. The institution of Dr. Sarraj has received research support from Stryker Neurovascular.

When and How to Use Reversal Agents for Direct Oral Anticoagulants?

Our objective is to describe currently available reversal agents for direct oral anticoagulants (DOACs), their target population, the available clinical practice recommendations and future directions. Specific (idarucizumab for dabigatran and andexanet alfa for direct factor Xa inhibitors) and non-specific (prothrombin complex concentrates) reversal agents are effective in neutralizing the anticoagulant effect of DOACs. New investigational antidotes such as ciraparantag and VMX-C001 offer an alternative to andexanet alfa in reversing the anticoagulant activity of direct oral factor Xa inhibitors, but more clinical data are needed before they could be licensed for use. Specific reversal agents are recommended for use in clinical situations within their licensed indications (i.e.: reversal of DOACs in patients with severe uncontrolled or life-threatening bleeding or in need of emergency surgery or other invasive procedures), while non-specific reversal agents may be used when specific antidotes are not available or indicated.

The Role of Thromboelastography in Identifying Coagulopathy Among Geriatric Traumatic Brain Injury Patients.

Background The geriatric population has the highest incidence of head injury, and those who are anticoagulated have an increased risk of traumatic intracranial hemorrhage (ICH). The availability of viscoelastic coagulation studies has coincided with the development of many anticoagulation reversal agents. In this study, our objective was to assess whether the thromboelastography (TEG) assay affected clinical decision-making regarding reversal agent administration among geriatric patients with ICH caused by blunt head trauma. Methodology We prospectively screened adults aged 65 and older with head trauma presenting to the emergency departments of two level-one trauma centers. International Classification of Diseases, Tenth Revision codes S00-09 were used to identify the diagnosis of head injury. Patients with CT head imaging positive for acute ICH were included. Each patient was assessed for home use of antiplatelet or anticoagulant medications, as well as in-hospital use of any reversal agents. Reversal agent administration and mortality were compared between patients who received TEG and those who did not. Results A total of 680 patients had acute ICH on head CT, and 324 (48%) patients received TEG. More patients screened with TEG were transfused platelets (30.2% vs. 10.7%, p < 0.001). This remained significant for patients taking anticoagulants, antiplatelets, or neither. There were no differences in the administration of other reversal agents (prothrombin complex concentrate or fresh frozen plasma) or mortality whether or not TEG was performed. Conclusions Patients who had TEG performed were more likely to receive platelet reversal agents, regardless of antiplatelet medication usage. Among elderly adults with ICH, TEG is a rapid screening test that may help identify patients with platelet function abnormalities requiring reversal.

The Use of Andexanet Alfa Vs. Four-Factor Prothrombin Complex Concentrates in the Reversal of Life-Threatening Intracranial Hemorrhage

Background/objective Andexanet alfa (AA) is a novel reversal agent for life threatening bleeding associated with oral Xa inhibitors, but there is uncertainty regarding the benefit compared to 4-factor prothrombin complex concentrate (4F-PCC). We investigated the clinical outcomes and cost differences between these two reversal agents in life threatening intracranial hemorrhage (ICH). Methods We retrospectively reviewed patients at our institution who received anticoagulation reversal for life-threatening ICH with either AA or 4F-PCC between 9/1/2013 - 4/20/2020 and had an anti-Xa level greater than 0.6 IU/L. The primary outcome was 30-day mortality after administration of either 4F-PCC or AA. Secondary outcomes included progression of ICH based on imaging, ICU length of stay, hospital length of stay, disposition at discharge, functionality at discharged, and financial cost. Safety outcomes evaluated included thrombosis after administration of reversal agent. Results 89 patients were included in this study. There were no differences in 30-day mortality (p = 0.14, Figure 1), radiographic resolution of ICH (p = 0.93), objective volume change in ICH(p = 0.18), progression of ICH (p = 0.74), hospital and ICU length of stay (p=0.66, 0.50), discharge disposition (p=0.40), or thrombosis after administration of reversal agent (p=0.17) between the two groups. Modified Rankin at discharge was slightly higher for the AA group (p=0.02), while cost was 2.8 times higher for AA. Conclusion Given the lack of statistically significant differences in clinical outcomes and the high cost of AA, the results validate the use of 4F-PCCs as an alternative to AA, based on similar efficacy and safety. Multi-center prospective studies are needed to further evaluate novel anticoagulation reversal agents. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited. To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH. PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022. The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model. The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent. A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events. In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Safety of Vitamin K in mechanical heart valve patients with supratherapeutic INR: A systematic review and meta-analysis.

Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR. CINAHL, Cochran Library, Clinical trial.gov, OpenGrey, PubMed, ScienceDirect, and Scopus were systematically searched from the inception up to October 2021 without language restriction. Studies comparing the safety of low-dose vitamin K1 treatment in patients with placebo or other anticoagulant reversal agents were included. We used a random-effect model for the meta-analysis. Publication bias was determined by a funnel plot with subsequent Begg's test and Egger's test. From 7529 retrieved studies, 3 randomized control trials were included in the meta-analysis. Pooled data demonstrated that low-dose vitamin K was not associated with thromboembolism rate (risk ratio [RR] = 0.94; 95% CI: 0.19-4.55) major bleeding rate (RR = 0.58; 95% CI: 0.07-4.82), and minor bleeding rate (RR = 0.60; 95% CI: 0.07-5.09). Subgroup and sensitivity analysis demonstrated the nonsignificant effect of low-dose vitamin K on the risk of thromboembolism. Publication bias was not apparent, according to Begg's test and Egger's test (P = .090 and 0.134, respectively). The current evidence does not support the role of low-dose vitamin K as a trigger of thromboembolism in supratherapeutic INR patients with mechanical heart valves. Nevertheless, more well-designed studies with larger sample sizes are required to justify this research question.

A short review of ciraparantag in perspective of the currently available anticoagulant reversal agents

Despite the improved safety-profile of direct oral anticoagulants (DOACs), bleeding complications remain an important side effect of anticoagulant treatment. Although anticoagulant-specific antidotes are available, an universal anticoagulant reversal agent in case of life-threatening bleeding or emergency surgery is not yet available. Ciraparantag, a synthetic small molecule that inactivates heparins and DOAC, is a promising new reversal agent that has been investigated in phase 2 trials. In this short review we provide an overview of the preclinical and clinical evidence of ciraparantag, and compare strengths and weaknesses of ciraparantag and the currently available anticoagulant reversal strategies.

Porous Polymers as Universal Reversal Agents for Heparin Anticoagulants through an Inclusion-Sequestration Mechanism.

Heparins are widely used anticoagulants for surgical procedures and extracorporeal therapies. However, all of them have bleeding risks. Protamine sulfate, the only clinically approved antidote for unfractionated heparin (UFH), has adverse effects. Moreover, protamine can only partially neutralize low-molecular-weight heparins (LMWHs) and is not effective for fondaparinux. Here, an inclusion-sequestration strategy for efficient neutralization of heparin anticoagulants by cationic porous supramolecular organic frameworks (SOFs) and porous organic polymers (POPs) is reported. Isothermal titration calorimetric and fluorescence experiments show strong binding affinities of these porous polymers toward heparins, whereas dynamic light scattering and zeta potential analysis confirm that the heparin sequences are adsorbed into the interior of the porous hosts. Activated partial thromboplastin time, anti-FXa, and thromboelastography assays indicate that their neutralization efficacies are higher than or as high as that of protamine for UFH and generally superior to protamine for LMWHs and fondaparinux, which is further confirmed by tail-transection model in mice and ex vivo aPTT or anti-FXa analysis in rats. Acute toxicity evaluations reveal that one of the SOFs displays outstanding biocompatibility. This work suggests that porous polymers can supply safe and rapid reversal of clinically used heparins, as protamine surrogates, providing an improved approach for their neutralization.

Dabigatran Reversal: A Practical Approach

Dabigatran is a direct oral anticoagulant used to prevent stroke and systemic embolism in patients with atrial fibrillation. In situations that require the urgent reversal of its anticoagulant activity, such as in the case of severe bleeding that is life-threatening; urgent/ emergent surgery or invasive procedures with significant bleeding risk; and the need for thrombolysis in a patient with ischemic stroke, several measures can be taken, including the use of its specific reversal agent, idarucizumab. Based on the guidelines for the use of reversal agents for oral anticoagulants, and on the clinical experience of reversal of dabigatran, a practical guide is presented for use in clinical situations where reversal of dabigatran anticoagulation is required, including the use of idarucizumab. The adoption of this type of guideline contributes to therapeutic optimization and, consequently, greater reversal efficiency and a better resource management.

Outcomes of a Stroke Response Team on the Emergent Management of Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage results in high patient mortality or poor functional outcomes. Early access to specialty care allows for rapid implementation of evidence-based strategies that improve the patient's long-term outcomes. The aim of this study was to determine the impact of a dedicated stroke response team on timeliness of blood pressure control, administration of anticoagulation reversal agents, and emergency department arrival to a critical care bed. A stroke response team was developed from the neuro intensive care unit that compliments the hospital's current rapid response team. Development of an algorithm guides the implementation of key interventions for intracerebral hemorrhages. Widespread education targeting care of patients with hemorrhagic stroke provided the stroke response team and emergency department staff with knowledge to implement the plan of care. Baseline time interval data were collected on 70 consecutive patients with intracerebral hemorrhage. After implementation of a dedicated stroke response team, time interval data on 70 consecutive patients with intracerebral hemorrhage were collected for comparison with the baseline measurement. A significant decrease was seen in the time to control the patient's systolic blood pressure (median of 130 to 56 minutes, P = .000) and emergency department arrival to a critical care bed (240 to 132 minutes, P = .000). Patient arrival to anticoagulation reversal agent administration decreased from a mean of 98 to 72 minutes (P = .32). Implementation of a stroke response team increased the knowledge of the care team, improved the timeliness of blood pressure control, and decreased the time for emergency department arrival to a critical care bed, and to anticoagulation reversal agent administration.

Review of Target-Specific Anticoagulation Reversal Agents.

Bleeding related to direct oral anticoagulants accounts for nearly half of emergency department visits annually and until recently there were no reversal antidotes available. As there continues to be a shift in prescribing practices away from warfarin, it is essential to have these reversal agents readily available for the treatment of life-threatening bleeds associated with these anticoagulants. In addition, for agents that continue to lack a targeted reversal agent (eg, low-molecular-weight heparin, antiplatelets, and new antithrombotics), it is imperative that research continues to evaluate improved reversal strategies. This review focuses on target-specific anticoagulation reversal agents currently available in the United States (protamine, idarucizumab, and andexanet alfa) and summarizes agents that are in the pipeline for these anticoagulants and antiplatelets.

Neurosurgical Treatment of Patients with Posterior Fossa Acute Subdural Hematoma Right after Cardiac Surgery.

As posterior fossa acute subdural hematoma (ASDH) right after cardiac surgery is extremely rare, the clinical course and optimal treatment strategy remain undetermined. We performed a retrospective analysis of patients with posterior fossa ASDH right after cardiac surgery requiring neurosurgical treatment at our institution over a 7-year period and, in this study, discussed the neurosurgical strategy and clinical course. Collected data included clinical history, laboratory results, time course, symptoms, neurosurgical treatment, outcome at discharge, and imaging studies. All six patients were women who had no history of head trauma and had received antithrombotic therapy during the perioperative period of cardiac surgery. All patients showed lower platelets count and were diagnosed with ASDH within 3 days (longest time 64 h) right after cardiac surgery. After discontinuation of anticoagulation therapy and administration of reversal agents, they underwent emergency hematoma evacuation craniotomy (n = 5) or burr hole drainage surgery (n = 1), which were performed in the prone (n = 4) or lateral (n = 2) positions. Four of these patients showed favorable outcomes, and two showed poor outcomes. One of the poor-outcome patients received three antithrombotic therapies, and another developed rapidly progressive ASDH. Posterior fossa ASDH associated with antithrombotic therapy right after cardiac surgery is frequently found in women, and emergent neurosurgical treatment with anticoagulation discontinuation and reversal agent administration can be performed safely. Burr hole drainage surgery might be acceptable in nonsevere cases. By contrast, we must pay attention to cases receiving both anticoagulant and antiplatelet drugs and rapid progression cases.

Abdominal Aortic Aneurysm with Persistent and Rebound Coagulopathy Despite Aggressive Corrective Treatment: A Case Report

Abdominal aortic aneurysm (AAA) is not uncommon to cause coagulopathy. Warfarin use in patients presented with ruptured AAA can further complicate the preparation for surgical intervention and affect prognosis. We reported a case of impending rupture AAA that progressed to contained leak AAA in a warfarin user, with persistent elevated and rebound international normalized ratio (INR) despite aggressive correction with fresh frozen plasma (FFP) and three-factor prothrombin complex concentrate (3F-PCC). Persistent and rebound coagulopathy is possible in AAA. Corrective treatment with FFP or 3F-PCC alone does not always guarantee the successful reversal of coagulopathy in AAA. Some cases, especially those that failed the initial corrective treatment, require more aggressive reversal with co-administration of vitamin K. This case described coagulopathy in AAA, anticoagulation reversal agents used and emphasized the importance of rigorous coagulation profile monitoring in managing AAA.

Porous dynamic covalent polymers as promising reversal agents for heparin anticoagulants.

Heparins are natural and partially degraded polyelectrolytes that consist of sulfated polysaccharide backbones. However, as clinically used anticoagulants, heparins are associated with clinical bleeding risks and thus require rapid neutralization. Protamine sulfate is the only clinically approved antidote for unfractionated heparin (UFH), which not only may cause severe adverse reactions in patients, but also is only partially effective against low molecular weight heparins (LMWHs). We here present the facile synthesis of four porous multicationic dynamic covalent polymers (DCPs) from the condensation of tritopic aldehyde and acylhydrazine precursors. We show that, as new water-soluble polymeric antidotes, the new DCPs can effectively include both UFH and LMWHs and thus reverse their anticoagulating activity, which is confirmed by the activated partial thromboplastin time and thromboelastographic assays as well as mouse tail transection assay (bleeding model). The neutralization activities of two of the DCPs were found to be overall superior to that of protamine and have wider concentration windows and good biocompatibility. This pore-inclusion neutralization strategy paves the way for the development of water-soluble polymers as universal heparin binding agents.

New agents for DOAC reversal: a practical management review.

Bleeding is the commonest and most concerning adverse event associated with anticoagulants. Bleeding, depending on the severity, is managed in various ways, and for severe or life-threatening bleeding, specific antidotes are indicated and recommended. This review provides guidance relating to specific direct oral anticoagulant (DOAC) reversal agents, the antidotes. We discuss their indications for use, dosing, and potential side effects.

Utilization of anti-factor Xa levels to guide reversal of oral factor Xa inhibitors in the emergency department.

PurposeOral factor Xa inhibitors (FXaIs) are increasingly utilized for outpatient anticoagulation therapy; however, laboratory monitoring is not routinely used to assess the safety and efficacy of these agents. We aimed to evaluate the role of chromogenic anti–factor Xa (anti-Xa) assays in the emergency department (ED) in the setting of patients with an acute bleed or requiring emergent procedures.MethodsA retrospective review of anti-Xa levels obtained in the ED between June 1, 2019, and April 30, 2020, was completed. Data were collected to describe the clinical setting of anti-Xa level collection, oral FXaIs used before admission, administration of reversal agents, and patient disposition to further characterize the role of anti-Xa levels in the management of rivaroxaban and apixaban reversal.ResultsThirty anti-Xa levels were included in the final analysis. The median time from sample collection to anti-Xa assay result was 45.9 minutes (interquartile range, 35.3-54.7 minutes). Eleven patients (37%) received anticoagulation reversal after their anti-Xa levels were determined. Anticoagulation reversal agents included either activated prothrombin complex concentrates (aPCCs) or prothrombin complex concentrates (PCCs). Anti-Xa levels were collected in 2 patients who had received PCCs before arrival at our ED. Of the patients with anti-Xa levels below 30 ng/mL, none received aPCCs or PCCs after their anti-Xa levels were determined. Anti-Xa assays were used to rule out the presence of FXaIs in 3 patients.ConclusionThis study illustrates the novel role of anti-Xa levels in managing patients with an emergent need for reversal in the ED. The assay may be used to rule out the presence of oral FXaIs and avoid unnecessary administrations of anticoagulation reversal agents.