Reversal Of Oral Anticoagulants Research Articles

Assessment of Oral Anticoagulant Reversal Strategies in Emergency Surgery: Insights from a Prospective Study

Introduction: The management of thrombotic risk in clinical medicine has been a longstanding challenge. Oral anticoagulants, specifically vitamin K antagonists (VKAs) like warfarin, have been used for over fifty years. However, VKAs present significant challenges such as frequent monitoring and dietary interactions. Direct oral anticoagulants (DOACs) were developed to address these limitations, offering simplified dosing and fewer interactions. Both VKAs and DOACs, however, pose challenges in managing major bleeding and urgent surgical interventions. Methods: This prospective study, conducted at Mohammed V Military Hospital in Rabat from January 2022 to January 2023, examined the clinical practice, efficacy, and safety of different treatment strategies in patients on oral anticoagulants (VKAs and DOACs) requiring emergency surgery within 24 hours of hospital admission. Inclusion criteria included being over 18 years of age, on anticoagulant therapy, and requiring emergency surgery. Patients were evaluated for bleeding before and after surgery, use of hemostatic agents, blood loss, transfusions, and adverse events. Results: A total of 69 patients were included, with 48 treated with VKAs and 21 with DOACs. The mean age was 63.8 years (range 36-78), with a mean age of 62.5 years (±10.2) for the VKA group and 66.7 years (±9.1) for the DOAC group (p = 0.44). There was no significant difference in delays to surgery between the VKA (68%) and DOAC (66.6%) groups for surgeries performed within 24 hours. Hemostatic treatment varied significantly, with more VKA patients receiving resh frozen plasma (77% vs. 52%) and more DOAC patients receiving prothrombin complex concentrates (48% vs. 23%). Bleeding complications were observed in 12.5% of VKA patients and 9.5% of DOAC patients. Thromboembolic events were observed in one patient within 30 days, specifically, a pulmonary embolism occurring on day 3 in a patient who underwent surgery for a hip fracture. The mortality rate ...

Troubleshooting heparin resistance.

The term heparin resistance is likely best defined as the failure of an appropriate dose of unfractionated heparin (UFH) to achieve a predetermined level of anticoagulation. Unfortunately, and despite many prior reports, there is no established consensus as to what either the appropriate dose or the predetermined level should be. Traditionally, assays used to monitor anticoagulation with UFH have been clot based, including the activated partial thromboplastin time, used for patients on the ward or intensive care unit, and the activated clotting time, used for patients undergoing vascular interventions and cardiopulmonary bypass. Unfortunately, these tests may be highly influenced by other factors occurring in many patients, especially those with inflammation or acute infection, as noted during the COVID-19 pandemic. Many hospitals have thus moved to anti-Xa testing for heparin monitoring. Another important factor in defining heparin resistance includes dosing, whether weight-based or total daily dosing is used, as initial reports of heparin resistance described daily doses independent of body weight. Multiple causes of apparent heparin resistance include hypercoagulability, antithrombin deficiency, andexanet alfa used for direct oral anticoagulant reversal, thrombocytosis, and antiphospholipid antibody syndromes. Treatment options for managing patients with heparin resistance include weight-based dosing and administration of additional UFH, antithrombin supplementation, or the use of an alternative anticoagulant such as the direct thrombin inhibitors bivalirudin or argatroban.

Incidence of Venous Thromboembolism Post-Oral Anticoagulation Reversal in Intracranial Hemorrhage Patients.

Rates of in-hospital venous thromboembolism (VTE) in the intracranial hemorrhage (ICH) population post oral anticoagulation (AC) reversal are as high as 10%. Guidelines recommend the initiation of prophylactic AC 24 to 48 hours post ICH; however, there is no guidance regarding optimal VTE prophylaxis post-reversal. This study aimed to identify the incidence of thromboembolism post oral AC reversal in patients presenting with ICH and describe VTE prophylaxis timing and agent selection. This was a retrospective, descriptive study conducted within a single health system. Patients on AC who received reversal agents 4-factor prothrombin complex concentrate (4F-PCC) with or without vitamin K, andexanet alfa, and/or idarucizumab for AC-associated ICH were included. The primary endpoint was incidence of in-hospital VTE post-reversal. Secondary endpoints included AC utilization specifications, length of stay, and in-hospital mortality. There were 118 patients (57%) who received 4F-PCC and 89 patients (43%) who received andexanet alfa for reversal post-ICH. Overall, 195 patients (94.2%) achieved hemostasis. Eight patients had incidence of VTE (3.9%), and of those, 6 patients (75%) were reinitiated on AC, all of which utilized prophylactic heparin. The median time from reversal to VTE was 55.9 days (interquartile range [IQR] = 21.2-72.4). For all patients on AC, the median time to initiation from reversal was 3.98 days (IQR = 2.5-6.01), and for those with incidence of thrombosis, the median time to AC initiation was 6.4 days (IQR = 2.6-13.1). Mortality occurred in 13 patients (6.3%). This patient population is complex in that the need to achieve hemostasis with AC reversal must be balanced with the risk of VTE. Further studies are needed to determine the ideal timing and agent selection for VTE prophylaxis initiation post ICH reversal.

Four-factor Prothrombin Complex Concentrate Use for Bleeding Management in Adult Trauma.

The clinical use of four-factor prothrombin complex concentrate in adult trauma patients at risk of bleeding is supported by evidence for urgent reversal of oral anticoagulants but is controversial in acquired traumatic coagulopathy.

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding.

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding.

Clinical guideline on reversal of direct oral anticoagulants in patients with life threatening bleeding.

Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding. A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process. So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%. DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given. In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings.

Time to oral anticoagulant reversal in intracranial hemorrhage with an emergency medicine pharmacist presence

PurposeIntracranial hemorrhage (ICH) is associated with high morbidity and mortality, with mortality rates up to 65%. Oral anticoagulants (OAC) are a major risk factor for ICH. Since these patients are usually diagnosed in the emergency department (ED), emergency medicine (EM) pharmacists can help ensure appropriate selection and delivery of medications in urgent situations including reversal agents for OAC-associated bleeding. The purpose of this study was to determine the impact EM pharmacist presence has on time to OAC reversal in patients presenting with an ICH. ProceduresThis was a retrospective, single-center cohort study evaluating time to reversal of OAC-associated ICH at a level one trauma center between November 2016 and September 2022. Patients 18 years or older who presented to the ED with an OAC-associated ICH and received at least one dose of an emergent reversal agent were included. Patients were excluded if their ICH was diagnosed at an outside facility, if they received emergent reversal agents for other indications, or if they had do not resuscitate orders upon admission. The primary outcome was time to administration of reversal agent with or without an EM pharmacist present, represented as median [interquartile range]. Secondary outcomes included hematoma expansion, hospital length of stay, intensive care unit LOS, and in-hospital mortality. ResultsOf the 157 patients evaluated, 83 met criteria for inclusion. Majority of patients presented with warfarin-associated ICH (55%) and the most common indication for OAC was atrial fibrillation (66%). The most common type of ICH was intracerebral hemorrhage (35%). The median time to emergent reversal agent administration was significantly shorter in the EM pharmacist group (50 min [31–65] vs. 85 min [51–121], p < 0.01). No significant differences in secondary outcomes existed. ConclusionsThe presence of an EM pharmacist at the bedside of patients who present to the ED with ICH was associated with a decrease in the time to OAC reversal by 36 min. Presence of an EM pharmacist was not associated with improved clinical outcomes for ICH in our study. Larger trials are warranted to determine whether the presence of an EM pharmacist is associated with improved functional and clinical outcomes in patients with OAC-associated ICH and whether time to newer reversal agents, other than 4F-PCC, has an effect on outcomes.

Abstract WP169: Thromboelastography as a Biomarker of Emergent Direct-Acting Oral Anticoagulant Reversal With Prothrombin Complex Concentrates for Intracranial Hemorrhage

Prothrombin complex concentrates (PCCs) are used to emergently reverse direct-acting oral anticoagulant (DOAC) activity. PCCs are recommended as an alternative to recombinant coagulation factor-Xa to reverse anticoagulation activity of apixaban or rivaroxaban. Measuring the degree of anticoagulation reversal in this population is limited. Thromboelastography (TEG) has been used to detect the presence of DOAC plasma levels in patients chronically taking a DOAC but has not been utilized to measure the effect on anticoagulant activity after PCC administration. We aimed to determine whether TEG R-time is useful in detecting the impact of PCC administration on anticoagulation activity in patients with anti-factor Xa-associated intracranial hemorrhage (ICH). We prospectively evaluated the utility of TEG to assess anticoagulation activity after factor Xa inhibitor reversal with 4-factor PCC. Adults with ICH taking apixaban or rivaroxaban were included. Patients were excluded if their last known dose of anticoagulation was &gt;48 hours prior to arrival, had known apixaban or rivaroxaban blood levels &lt;20 ng/mL, or had the following comorbidities: hepatic failure, hereditary disorders of hemostasis, polytrauma, or pregnancy. TEG samples were collected before PCC administration (if available), and 0.5, 12, and 24 hours after PCC administration. Thirty-one patients were enrolled between November 2022 and August 2023. The median PCC dose was 24.5 units/kg (IQR 20.3-26.9 units/kg; n=29). Nine patients received anticoagulation reversal after baseline TEG collection; the remainder received anticoagulation reversal at transferring facilities. Baseline R-time was negatively correlated with time since last dose of DOAC (n=9). A median decrease in R-time of 0.8 minutes after PCC (IQR -1.6 - 0.3; n=8) was found in patients with baseline TEG collection. R-time rebounded by a median of 0.75 minutes (IQR 0.2-2.0; n=8) from 0.5 hours to 12 hours after PCC administration (n=8). TEG R-time, a measure that inversely correlates with the degree of anticoagulant effect, rapidly decreases after PCC in patients taking DOACs that present with acute ICH. TEG R-time rebounds 12 hours after PCC administration. TEG-R time may be a useful biomarker in DOAC reversal with PCC.

Four-factor prothrombin complex concentrate versus andexanet alfa for the reversal of traumatic brain injuries

BackgroundAndexanet alfa was approved in 2018 for reversal of direct oral anticoagulants but due to issues of cost and access, four-factor prothrombin complex concentrate (4F-PCC) continues to be used for...

Basics for the Use of Andexanet

For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and for bleeding in association with the direct factor Xa inhibitors rivaroxaban or apixaban, the modified recombinant FXa protein andexanet is available for reversal. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures. An interdisciplinary group of experienced experts in the fields of angiology, hematology, internal medicine, clinical pharmacology, laboratory medicine, transfusion medicine, anesthesiology, intensive care, and hemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence. Reversal of oral anticoagulants should be considered for severe bleeding in the following situations: (1) life-threatening bleeding or refractory hemorrhagic shock, (2) intracerebral bleeding, or (3) endoscopically unstoppable gastrointestinal bleeding. After successful hemostasis, anticoagulation (e.g., direct oral anticoagulant, vitamin K antagonist, and heparin) should be resumed promptly, taking into account individual bleeding and thromboembolic risk. This article aims to facilitate the management of patients with andexanet by all medical disciplines involved, thereby ensuring optimal care of patients during bleeding episodes.

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

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

Propensity matched analysis examining the effect of passive reversal of direct oral anticoagulants on blood loss and the need for transfusions among traumatic geriatric hip fractures

BackgroundReversal of direct oral anticoagulants (DOACs) is currently recommended prior to emergent surgery, such as surgical intervention for traumatic geriatric hip fractures. However, reversal methods are expensive and timely, often delaying surgical intervention, which is a predictor of outcomes. The study objective was to examine the effect of DOAC reversal on blood loss and transfusions among geriatric patients with hip fractures.MethodsThis retrospective propensity-matched study across six level I trauma centers included geriatric patients on DOACs with isolated fragility hip fractures requiring surgical intervention (2014–2017). Outcomes included: intraoperative blood loss, intraoperative pRBCs, and hospital length of stay (HLOS).ResultsAfter matching there were 62 patients (31 reversed, 31 not reversed), 29 patients were not matched. The only reversal method utilized was passive reversal (waiting ≥ 24 hours for elimination). Passively reversed patients had a longer time to surgery (mean, 43 vs. 18 hours, p < 0.01). Most patients (92%) had blood loss (90% passively reversed, 94% not reversed); the median volume of blood loss was 100 mL for both those groups, p = 0.97. Thirteen percent had pRBCs transfused (13% passively reversed and 13% not reversed); the median volume of pRBCs transfused was 525 mL for those passively reversed and 314 mL for those not reversed, p = 0.52. The mean HLOS was significantly longer for those passively reversed (7 vs. 5 days, p = 0.001).ConclusionsPassive DOAC reversal for geriatric patients with isolated hip fracture requiring surgery may be contributing to delayed surgery and an increased HLOS without having a significant effect on blood loss or transfusions. These data suggest that passive DOAC reversal may not be necessary prior to surgical repair of isolated hip fracture.

Andexanet alfa and heparin resistance in cardiac surgery: Experiences and risks associated with the reversal of direct oral anticoagulants.

Journal Article Accepted manuscript Andexanet Alfa and Heparin Resistance in Cardiac Surgery: Experiences and risks associated with the reversal of direct oral anticoagulants Get access Daniel-Sebastian Dohle, Daniel-Sebastian Dohle Department of Cardiovascular Surgery, Johannes-Gutenberg University, Mainz, Germany Corresponding author: Daniel-Sebastian Dohle, MD, PhD, Department of Cardiovascular Surgery, Heart Center Mainz, University Hospital Mainz, Langenbeckstraße 1, 55122 Mainz, Germany, Tel: 0049 6131 17 2735 E-Mail: Daniel-Sebastian.Dohle@unimedizin-mainz.de Search for other works by this author on: Oxford Academic PubMed Google Scholar Philipp Pfeiffer, Philipp Pfeiffer Department of Cardiovascular Surgery, Johannes-Gutenberg University, Mainz, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Chris Probst, Chris Probst Department of Cardiovascular Surgery, Johannes-Gutenberg University, Mainz, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Hendrik Treede Hendrik Treede Department of Cardiovascular Surgery, Johannes-Gutenberg University, Mainz, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar European Journal of Cardio-Thoracic Surgery, ezad189, https://doi.org/10.1093/ejcts/ezad189 Published: 05 May 2023 Article history Received: 24 April 2023 Accepted: 04 May 2023 Published: 05 May 2023

Reversal of Oral Anticoagulants a Narrative Review

Reversal of Oral Anticoagulants a Narrative Review

Reversal of Oral Anticoagulants a Narrative Review

Anticoagulants have long been used for prevention and treatment of arterial and venous thromboembolism (VTE). Vitamin K antagonists (VKAs), especially warfarin, were used for decades as the only available oral anticoagulants.

Reversal of Oral Anticoagulants: A Survey of Contemporary Practice Trends (ReACT).

This study evaluated practice patterns and factors influencing treatment decisions regarding urgent or emergent reversal of oral anticoagulants (OACs). A 30-question survey was electronically distributed to anticoagulation members of the Anticoagulation Forum. Questions were designed to capture practice trends in the reversal of warfarin, factor Xa inhibitors, and factor IIa inhibitors. Continuous and categorical data were analyzed to generate descriptive statistics. Open-ended questions were summarized by thematic categories. 173 responses were collected most from US-based pharmacists with direct patient care responsibilities. The majority of the respondents' institutions (90.2%) utilized a guideline or protocol for OACs reversal. Vitamin K (91.3%), activated charcoal (80.4%), and fresh frozen plasma (72.8%) were the most common reversal agents on formulary without restrictions. Most institutions (87.0%) reported having 4-factor prothrombin complex concentrate (4F-PCC) and idarucizumab on formulary, but most commonly (52.2%) with restrictions. Andexanet alfa was only reported on formulary at 35.9% of institutions. In contrast to current guideline recommendations, vitamin K (98.8%) was preferred over 4F-PCC and 4F-PCC (71.6%) was preferred over andexanet alfa as first-line agents used to reverse warfarin and factor Xa inhibitors, respectively. Weight-based dosing strategies for 4F-PCC were commonly utilized for different reversals (41.2%-59.4%). Cost, efficacy, and safety of 4F-PCC were identified as top facilitators and barriers for 4F-PCC adoption in practice. Our findings revealed that guideline recommendations for reversal of warfarin and factor Xa and IIa inhibitors are not followed by a majority of institutions. Studies are needed to investigate strategies to overcome barriers for implementing and following guideline recommendations.

Retrospective Analysis of the Real-World Utilization of 4-Factor Prothrombin Complex Concentrate and Plasma in Oral Anticoagulant-Associated Bleeding in US Hospitals.

Real-world utilization of 4-factor prothrombin complex concentrate (4F-PCC) and plasma for the management of oral anticoagulant (OAC)-associated bleeding in US trauma hospitals was described.This is amulticenter, retrospective chart review evaluating the use of 4F-PCC and plasma in OAC reversal across medical specialties. Physicians completed a survey and extracted data from 3 to 5 patient charts. Variables of interest included medical specialty, urgency, and bleed type. Two hundred and thirty-five physicians completed the survey, and 861 patient charts were included in the study. 4F-PCC was commonly used in life-threatening or emergent indications, whereas plasma was used in emergent and urgent indications. Plasma was used mostly for patients on warfarin (53% vs 47% 4F-PCC) and 4F-PCC for those on apixaban (82% vs 18% plasma) and rivaroxaban (77% vs 23% plasma). This retrospective analysis showed that 4F-PCC was predominantly used for OAC reversal despite available specific reversal agents for some of the OAC. Although it is not recommended by any reversal guidelines, plasma is still used for OAC reversal. Plasma should be avoided in the management of OAC-associated bleeding.

Pre-emptive intraoperative administration of PCC4 in cardiac surgery patients at high risk of bleeding: Apilot study.

Four-factor prothrombin complex (PCC4), a concentrate of factors II, VII, IX, and X and proteins C and S, has been used selectively for reversal of oral anticoagulation before surgery. There is data to support PCC4 as opposed to supplemental fresh frozen plasma (FFP) to manage postoperative bleeding following cardiac surgery. The preemptive, intraoperative use of PCC4 in cardiothoracic surgery has not been studied though it may prevent postoperative bleeding, the need for blood transfusion and the risk of transfusion-related acute lung injury, volume overload, and right ventricular (RV) heart failure. The purpose of this study is to evaluate the intraoperative administration of PCC4 to decrease bleeding and lower the rate of blood transfusion. A single institution retrospective chart review was conducted from May 2020 to November 2021 of patients who received PCC4 intraoperatively during cardiothoracic surgery of high-risk variety. Patients were evaluated for the type of surgery, demographics, baseline anticoagulation, PCC4 dose, type and quantity of blood transfusion within 72 hours (h) postoperatively, chest tube output, the incidence of RV failure, hypersensitivity reactions, acute kidney injury (AKI), thrombosis, acute lung injury, and mortality within 45 days of the operative dose of PCC4. Thirty-five patients received PCC4 at a mean dose of 2920 units (U). Sixty-fivepercent of cases were left ventricular assist devices(LVADs) or heart transplants. The protocol is to use PCC4 30 units (U)/kg immediately after the completion of protamine administration. Inclusion criteria are cardiothoracic surgery with increased risk of postoperative right heart failure commonly secondary to blood product transfusion, or cardiothoracic surgery associated with increased risk of bleeding, including heart transplant, LVAD implant, aortic dissection, and redo sternotomy (e.g., coronary artery bypass). Total chest tube output was recorded as a mean of 757 ml for 24 h after surgery (32 ml/h). Overall median event rates of FFPand red blood cell (RBC) transfusions were 0 (interquartile range [IQR]: 0-3 U) and 4 (IQR: 2-5 U). Overall, 43%and 89%of cases received FFP and RBC, respectively. There was one occurrence of RV failure, one occurrence of AKI requiring renal replacement therapy, one occurrence of venoarterial extracorporeal membrane oxygenation, one occurrence of venous thromboembolism related to a central venous access line, and one death unrelated to surgery or PCC4 that was attributed to advanced heart failure not amenable to advanced therapies. Overall patients received a low rate of blood transfusion, had minimal chest tube output, and there was a small incidence of right heart failure. Patients did not have an increased risk of adverse effects such as AKI or venous thromboembolism. A randomized controlled clinical trial comparing the observed dose and timing of PCC4 versus routine postoperative bleeding management with blood product transfusion is recommended.

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.

Direct Oral Anticoagulant Reversal in the Pediatric Emergency Department.

Direct Oral Anticoagulant Reversal in the Pediatric Emergency Department.