Reversal of dabigatran-associated major bleeding with activated prothrombin concentrate: A prospective cohort study

Schulman, Sam; Ritchie, Bruce; Nahirniak, Susan; Gross, Peter L.; Carrier, Marc; Majeed, Ammar; Hwang, Hun Gyu; Zondag, Michelle

doi:10.1016/j.thromres.2017.02.010

Cited by 51 publications

(41 citation statements)

References 25 publications

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“…Activated PCCs were associated with an incidence of thrombotic events of approximately 4:100 000 FEIBA infusions when used in hemophiliacs . The thrombotic risk associated with the use of FEIBA in patients for VKA/DOAC reversal or PCC for DOAC reversal remains unclear, although a few small prospective cohort studies, as well as a small retrospective review revealed relatively low 30‐day thrombotic complication rates …”

Section: Nonspecific Prohemostatic Agents—pcc Apcc and Recombinant mentioning

confidence: 99%

“…Thus far, the majority of this evidence is limited to studies in which PCC, aPCC, or rVIIa were added in vitro to plasma from healthy volunteers receiving DOACs, as well as animal models evaluating hemostatic efficacy using various bleeding models. In vivo use of these prohemostatic agents in bleeding patients has been limited to case reports/series, as well as two small prospective cohort studies …”

Section: Nonspecific Prohemostatic Agents—pcc Apcc and Recombinant mentioning

confidence: 99%

“…45 The thrombotic risk associated with the use of FEIBA in patients for VKA/DOAC reversal or PCC for DOAC reversal remains unclear, although a few small prospective cohort studies, as well as a small retrospective review revealed relatively low 30-day thrombotic complication rates. [50][51][52] A growing body of evidence reviewed herein suggests that PCCs and aPCC may be useful adjunctive therapies to promote hemostasis for DOAC-associated life-threatening bleeding. However, there is a lack of high-quality evidence for hemostatic efficacy and safety of PCC, aPCC, and rVIIa in patients requiring urgent DOAC reversal for bleeding or urgent surgery.…”

Section: Nonspecific Prohemostatic Agents-pcc Apcc and Recombinanmentioning

confidence: 99%

“…In vivo use of these prohemostatic agents in bleeding patients has been limited to case reports/series, as well as two small prospective cohort studies. 50,51 When assessing the potential benefits and harms of these treatments, it is important to recognize that results from in vitro studies may not necessarily reflect hemostasis in vivo, and therefore, these studies should be interpreted with caution. Further, coagulation assays have variable sensitivity and reproducibility in the presence of DOACs as discussed above.…”

Section: Nonspecific Prohemostatic Agents-pcc Apcc and Recombinanmentioning

confidence: 99%

“…A small prospective cohort study evaluated the use of aPCC (FEIBA) in 14 patients with dabigatran-associated bleeding. 50 Hemostasis was assessed by the treating physician, and arterial/ venous thrombotic events were evaluated up to 30 days post-aPCC administration. The hemostatic efficacy of aPCC was rated as "good" in 64% of patients and "moderate" in 36% of patients.…”

Section: Dabigatran-treated Patients With Bleedingmentioning

confidence: 99%

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Pharmacological reversal of the direct oral anticoagulants—A comprehensive review of the literature

Shaw

Siegal

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials There remains clinical concern regarding the optimal management of direct oral (DOAC) anticoagulant effect for emergencies such as bleeding or urgent surgery/procedures.Idarucizumab is the preferred agent for urgent reversal of dabigatran for severe bleeding or urgent surgeries/procedures.There are currently no commercially available specific reversal agents for direct Xa inhibitors.Evidence for prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant VIIa (rVIIa) is limited primarily to animal bleeding models and studies in human volunteer subjects.PCC, aPCC, or rVIIa may contribute to hemostasis for severe bleeding or urgent surgery/procedures in patients receiving factor Xa inhibitors, or dabigatran if idarucizumab is unavailable but benefits and harms are uncertain. The direct oral anticoagulants (DOACs) are used for stroke prevention in atrial fibrillation (SPAF) and the prevention and treatment of venous thromboembolic disease (VTE). Although DOAC‐associated bleeding events are less frequent as compared to vitamin K antagonists, there is significant concern surrounding physicians’ ability to evaluate and manage DOAC‐associated bleeding when it does occur. Idarucizumab is a specific reversal agent for dabigatran and is the agent of choice for dabigatran reversal in the setting of major bleeding or urgent surgery/procedures. There are no commercially available specific reversal agents for the direct Xa inhibitors. Although they have not been rigorously studied in DOAC‐treated patients requiring urgent anticoagulant reversal, limited evidence from in vitro studies, animal bleeding models, human volunteer studies (in vivo and in vitro) and case series suggest that coagulation factor replacement with prothrombin complex concentrate (PCC) and activated PCC (FEIBA) may contribute to hemostasis. However, the safety and efficacy of these agents and the optimal dosing strategies remain uncertain.

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Section: Nonspecific Prohemostatic Agents—pcc Apcc and Recombinant mentioning

confidence: 99%

Section: Nonspecific Prohemostatic Agents—pcc Apcc and Recombinant mentioning

confidence: 99%

Section: Nonspecific Prohemostatic Agents-pcc Apcc and Recombinanmentioning

confidence: 99%

Section: Nonspecific Prohemostatic Agents-pcc Apcc and Recombinanmentioning

confidence: 99%

Section: Dabigatran-treated Patients With Bleedingmentioning

confidence: 99%

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Pharmacological reversal of the direct oral anticoagulants—A comprehensive review of the literature

Shaw

Siegal

2018

Research and Practice in Thrombosis and Haemostasis

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Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

et al. 2022

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ImportanceDirect 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.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data SourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study SelectionThe 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.Data Extraction and SynthesisPreferred 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.Main Outcomes and MeasuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA 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.Conclusions and RelevanceIn 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.

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Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

Cuker

Burnett

Triller³

et al. 2019

American J Hematol

258

263

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Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non‐specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.

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Reversal of dabigatran-associated major bleeding with activated prothrombin concentrate: A prospective cohort study

Cited by 51 publications

References 25 publications

Pharmacological reversal of the direct oral anticoagulants—A comprehensive review of the literature

Pharmacological reversal of the direct oral anticoagulants—A comprehensive review of the literature

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

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