Is reversal of anticoagulants necessary in neurologically intact traumatic intracranial hemorrhage?

Authors: Kelly Powell, William Curtiss III, Erin Sadek, Jason Hecht

Journal: Pharmacotherapy

Year: 2024

Volume: 44

Issue: 3

Type of Study: Retrospective Cohort Study

DOI: 10.1002/phar.2901

Quick Reference Summary

This study investigated whether reversing anticoagulation in neurologically intact patients with minor traumatic intracranial hemorrhage (ICH) affects in-hospital mortality or hospice rates. No significant difference was found between patients who received anticoagulant reversal (4.6%) and those who did not (4.9%) (p = 0.861).

Core Clinical Question

Does anticoagulant reversal improve in-hospital mortality or hospice rates in neurologically intact patients with minor traumatic intracranial hemorrhage compared to no reversal?

Background

Disease Overview:

Falls are the leading cause of injury in individuals aged ≥65, with traumatic brain injury (TBI) and intracranial hemorrhage (ICH) being common complications.

ICH includes subtypes such as intracerebral hemorrhage, subarachnoid hemorrhage (SAH), and subdural hemorrhage (SDH), each with unique prognoses based on hematoma location and severity.

Prior Data:

Anticoagulant reversal in TBI patients is complex and lacks consensus among authoritative organizations.

Previous studies suggest limited benefits of reversal in minor ICH cases, particularly with direct oral anticoagulants (DOACs).

Current Standard of Care:

Guidelines emphasize individualized treatment based on anticoagulant type, patient factors, and clinical status.

Reversal agents like andexanet alfa and 4-factor prothrombin complex concentrate (4F-PCC) are used for factor Xa inhibitors.

Knowledge Gaps Addressed:

Necessity of anticoagulant reversal in neurologically intact patients with minor traumatic ICH.

Study Rationale:

To identify a low-risk population where anticoagulant reversal may not improve outcomes, potentially reducing unnecessary interventions and associated costs.

Methods Summary

Study Design:

Retrospective cohort study

Setting and Time Period:

Data from 35 Level 1 and Level 2 trauma centers, Michigan and Minnesota, from February 14, 2018, to November 30, 2021.

Population Characteristics:

• Adults aged ≥18 years on preinjury anticoagulation (DOAC or VKA)
• Minor traumatic ICH defined by Glasgow Coma Scale (GCS) score of 15 and Abbreviated Injury Scale (AIS) head score of 2-4
• AIS ≤1 for non-head regions within 24 hours of hospital arrival

Inclusion Criteria:

• Age ≥18 years
• Preinjury oral anticoagulant use (DOAC or VKA)
• Minor ICH (GCS 15, AIS head 2-4, AIS ≤1 elsewhere)
• Blunt trauma mechanism

Exclusion Criteria:

• Emergent neurosurgical procedures
• Preinjury P2Y12 inhibitor use
• Concomitant DOAC and VKA use

Intervention Details:

Anticoagulant reversal using 4F-PCC, andexanet alfa, or fresh frozen plasma (FFP)

Control/Comparison Group Details:

Patients who did not receive anticoagulant reversal

Primary Outcome:

In-hospital mortality or hospice discharge

Secondary Outcomes:

• ICU length of stay
• Hospital length of stay
• Ventilator length of stay
• Composite of in-hospital serious complications

Statistical Analysis Approach:

• Descriptive statistics for baseline characteristics
• Comparisons using t-tests for continuous variables and chi-square tests for categorical variables
• p-value <0.05 considered statistically significant

Sample Size Calculations:

Not feasible due to exploratory nature

Ethics and Funding Information:

Exempt research status by Trinity Health Ann Arbor Institutional Review Board

Funded by Walter M Whitehouse Jr MD Endowed Chair of Surgery Fund

Detailed Results

Participant Flow and Demographics:

• Total Patients Included: 654
  • Reversed Group: 263 (120 DOAC, 143 VKA)
  • Not Reversed Group: 391 (287 DOAC, 104 VKA)
• Mean Age: 76.9 ± 11.3 years (Reversed) vs. 76.7 ± 12.4 years (Not Reversed), p = 0.840
• Majority White and Male; no significant differences in sex or race
• Significant differences in anticoagulant type (p < 0.001) and injury severity scores between groups

Primary Outcome Results:

• In-hospital mortality/hospice: 12 (4.6%) reversed vs. 19 (4.9%) not reversed, p = 0.861

Secondary Outcome Results:

• ICU Length of Stay: 1.4 ± 3.4 days (Reversed) vs. 1.1 ± 1.8 days (Not Reversed), p = 0.069
• Composite In-hospital Complications: 21 (8%) reversed vs. 34 (8.7%) not reversed, p = 0.748
• Hospital Length of Stay: 5.03 ± 5.29 days (Reversed) vs. 3.26 ± 3.11 days (Not Reversed), p < 0.001
• Ventilator Length of Stay: 1.14 ± 2.04 days (Reversed) vs. 1.12 ± 2.95 days (Not Reversed), p = 0.979

Subgroup Analyses:

• DOAC Group: No significant difference in mortality/hospice between reversed and not reversed (5.0% vs. 5.2%, p = 0.925)
• VKA Group: No significant difference in mortality/hospice between reversed and not reversed (4.2% vs. 3.8%, p = 0.891)

Adverse Events/Safety Data:

• No significant differences in adverse events between groups
• Types of reversal agents included 4F-PCC, vitamin K, and FFP

Results Tables

Authors’ Conclusions

Primary Conclusions:

No difference in hospital outcomes between patients with minor traumatic ICH on oral anticoagulants who were neurologically intact and either reversed or not reversed.

Interpretation of Results:

Anticoagulant reversal may not be necessary in this patient subset as it did not improve mortality or hospice rates.

Clinical Implications:

Potential to avoid unnecessary reversal procedures in low-risk patients, reducing exposure to adverse events and healthcare costs.

Future Research Recommendations:

Further studies to define subsets of traumatic ICH patients who may not require anticoagulation reversal.

Literature Review

A. Previous Studies and Meta-Analyses:

• Thompson et al., Neurocrit Care. 2020;32(2):407-418.

  Compared ICH expansion and outcomes in patients on DOACs vs. VKAs.

• Galgano et al., Cell Transplant. 2017;26(7):1118-1130.

  Reviewed traumatic brain injury treatment strategies.

B. Contrasting Methodological Quality:

Previous studies varied in reversing agents used and patient populations, impacting outcome comparability.

C. Comparisons with Guidelines:

American Heart Association/American Stroke Association guidelines emphasize individualized reversal strategies.

D. This Trial’s Contribution:

Adds evidence suggesting non-necessity of anticoagulant reversal in neurologically intact minor ICH patients, aligning with some previous findings but addressing specific patient subsets.

Critical Analysis

A. Strengths:

• Large, multicenter database (MTQIP) enhances generalizability within Level 1 and II trauma centers.
• Comprehensive inclusion/exclusion criteria ensure a homogeneous patient population.
• Inclusion of both DOAC and VKA users allows for subgroup analyses.
• Detailed data on reversal agents and outcomes supports robust analysis.

B. Limitations:

• Generalizability limited to Level 1 and II trauma centers; may not apply to other settings.
• Low granularity of data prevents analysis of dosing specifics and provider decision-making factors.
• Observational study design susceptible to residual confounding and selection bias.
• Potential underpowering to detect small effect sizes or benefits of reversal.
• Exclusion of patients on P2Y12 inhibitors and those requiring emergent neurosurgery limits applicability to broader populations.

C. Literature Context:

• Contradictions: While some studies suggest benefits of reversal in severe cases, this study focuses on minor ICH without neurological deficits, aligning with limited data questioning reversal necessity.
• Confirmations: Supports trends showing similar outcomes regardless of reversal in low-risk ICH scenarios.
• Guidelines Alignment: Reinforces individualized treatment approaches recommended by major organizations.

Clinical Application

Practice Change:

Findings suggest that routine reversal of anticoagulants in neurologically intact patients with minor traumatic ICH may be unnecessary.

Applicable Populations:

Elderly patients ≥65 years with minor ICH and no neurological deficits on anticoagulants.

Implementation Considerations:

Clinicians should assess individual risk factors and consider the absence of neurological deficits before deciding on reversal.

Integration with Existing Evidence:

Aligns with emerging data advocating for selective reversal based on clinical presentation rather than blanket protocols.

How to Use This Info in Practice

Practitioners should consider forgoing anticoagulant reversal in neurologically intact patients with minor traumatic ICH, evaluating each case individually based on patient-specific factors.