Delayed Intracranial Hemorrhage after Blunt Head Trauma while on Direct Oral Anticoagulant: Systematic Review and Meta-Analysis.
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SUBMITTER: Puzio TJ
PROVIDER: S-EPMC8722268 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Delayed Intracranial Hemorrhage after Blunt Head Trauma while on Direct Oral Anticoagulant: Systematic Review and Meta-Analysis.
Puzio Thaddeus J TJ Murphy Patrick B PB Kregel Heather R HR Ellis Ryan C RC Holder Travis T Wandling Michael W MW Wade Charles E CE Kao Lillian S LS McNutt Michelle K MK Harvin John A JA
Journal of the American College of Surgeons 20210322 6
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Project description:Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.
| S-EPMC6057345 | biostudies-literature
Project description: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.
| S-EPMC9636520 | biostudies-literature
Project description:Study objectiveWe determine the prevalence of significant intracranial injury among adults with blunt head trauma who are receiving preinjury anticoagulant or antiplatelet medications.MethodsThis was a multicenter, prospective, observational study conducted from December 2007 to December 2015. Patients were enrolled in 3 emergency departments (EDs) in the United States. Adults with blunt head trauma who underwent neuroimaging in the ED were included. Use of preinjury aspirin, clopidogrel, and warfarin was recorded. Data on direct oral anticoagulants were not specifically recorded. The primary outcome was prevalence of significant intracranial injury on neuroimaging. The secondary outcome was receipt of neurosurgical intervention.ResultsAmong 9,070 patients enrolled in this study, the median age was 53.8 years (interquartile range 34.7 to 74.3 years) and 60.7% were men. A total of 1,323 patients (14.6%) were receiving antiplatelet medications or warfarin, including 635 receiving aspirin alone, 109 clopidogrel alone, and 406 warfarin alone. Compared with that of patients without any coagulopathy, the relative risk of significant intracranial injury was 1.29 (95% confidence interval [CI] 0.88 to 1.87) for patients receiving aspirin alone, 0.75 (95% CI 0.24 to 2.30) for those receiving clopidogrel alone, and 1.88 (95% CI 1.28 to 2.75) for those receiving warfarin alone. The relative risk of significant intracranial injury was 2.88 (95% CI 1.53 to 5.42) for patients receiving aspirin and clopidogrel in combination.ConclusionPatients receiving preinjury warfarin or a combination of aspirin and clopidogrel were at increased risk for significant intracranial injury, but not those receiving aspirin alone. Clinicians should have a low threshold for neuroimaging when evaluating patients receiving warfarin or a combination of aspirin and clopidogrel.
| S-EPMC7039766 | biostudies-literature
Project description:Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.
| S-EPMC10249073 | biostudies-literature
Project description:Background and purposeThe safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism.MethodsWe searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes.ResultsEight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25-0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58-1.77; Q=24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses.ConclusionsIn observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk-benefit profile of anticoagulation resumption after ICH.
| S-EPMC5699447 | biostudies-literature
Project description:Direct oral anticoagulants (DOACs) are increasingly prescribed in treatment of cancer-associated thrombosis, but limited data exist regarding safety of DOACs in patients with brain metastases. We aimed to determine the incidence of intracranial hemorrhage (ICH) in patients with brain metastases receiving DOACs or low-molecular-weight heparin (LMWH) for venous thromboembolism or atrial fibrillation. An international 2-center retrospective cohort study was designed. Follow-up started on the first day of concomitant anticoagulation and brain tumor diagnosis. At least 2 brain imaging studies were mandated. The primary outcome was the cumulative incidence of any spontaneous ICH at 12-month follow-up with death as a competing risk. Major ICH was defined as spontaneous, ≥10 mL in volume, symptomatic, or requiring surgical intervention. Imaging studies were centrally reviewed by a neuroradiologist blinded for anticoagulant type. PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke) score for prediction of ICH was calculated. We included 96 patients with brain metastases (41 DOAC, 55 LMWH). The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.09-2.21). When anticoagulation was analyzed as a time-varying covariate, the risk of any ICH did not differ between DOAC- and LMWH-treated patients (HR, 0.98; 95% CI, 0.28-3.40). PANWARDS score was not associated with ICH risk. This international 2-center study suggests comparable safety of LMWH and DOACs in patients with brain metastases.
| S-EPMC7756985 | biostudies-literature
Project description:AbstractNonadherence to direct oral anticoagulant (DOAC) pharmacotherapy may increase the risk of thromboembolism or bleeding, and delayed or missed doses are the most common types of nonadherence. Current recommendations from regulatory agencies or guidelines regarding this issue lack evidence and fail to consider individual differences. This study aimed to develop individual remedial dosing strategies when the dose was delayed or missed for DOACs, including rivaroxaban, apixaban, edoxaban, and dabigatran etexilate. Remedial dosing regimens based on population pharmacokinetic (PK)-pharmacodynamic (PD) modeling and simulation strategies were developed to expeditiously restore drug concentration or PD biomarkers within the therapeutic range. Population PK-PD characteristics of DOACs were retrieved from previously published literature. The effects of factors that influence PK and PD parameters were assessed for their impact on remedial dosing regimens. A web-based dashboard was established with R-shiny to recommend remedial dosing regimens based on patient traits, dosing schedules, and delay duration. Addressing delayed or missed doses relies on the delay time and specific DOACs involved. Additionally, age, body weight, renal function, and polypharmacy may marginally affect remedial strategies. The proposed remedial dosing strategies surpass current recommendations, with less deviation time beyond the therapeutic range. The online dashboard offers quick and convenient solutions for addressing missed or delayed DOACs, enabling individualized remedial dosing strategies based on patient characteristics to mitigate the risks of bleeding and thrombosis.
| S-EPMC11612359 | biostudies-literature
Project description:BackgroundAortic valve perforation is a rare complication of blunt chest trauma. We report a case of delayed aortic insufficiency presenting several months after trauma.Case presentationA 17-year-old male presented to the emergency department with traumatic brain injuries and blunt chest trauma, but no evidence of cardiac injuries. Three months later, he developed acute heart failure due to severe aortic valve regurgitation with left ventricular dysfunction. A sizable tear in the right coronary cusp caused aortic insufficiency. He was treated successfully by surgical replacement with an aortic bioprosthesis.ConclusionWe reported a successful surgical case of valve replacement for delayed aortic valve perforation. Delayed valve perforation should be kept in mind after blunt chest trauma.
| S-EPMC10866806 | biostudies-literature
Project description: Not available
| S-EPMC5991311 | biostudies-literature
Project description: Not available
| S-EPMC11210085 | biostudies-literature