System-Level Delays For Anticoagulation Reversal In Intracerebral Hemorrhage: Implications For Quality Improvement

Q: What are the key findings of this study?

Code Stroke activation reduced median door-to-treatment time for anticoagulation reversal from 277 to 64 minutes (p<0.001) compared to non-activation in anticoagulation-associated ICH.

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Anticoagulation-associated spontaneous intracerebral hemorrhage (ICH) (n=50). Intervention: Code Stroke activation vs. No Code Stroke activation. Primary outcome: Median door-to-treatment (DTT) time for anticoagulation reversal (minutes) (p=<0.001).

Q: What does this research mean for the field?

Code Stroke activation significantly reduces door-to-treatment time for anticoagulation reversal in patients with anticoagulation-associated intracerebral hemorrhage. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To investigate system-level delays in anticoagulation reversal among patients with anticoagulation-associated intracerebral hemorrhage and identify opportunities for quality improvement.

Heidi Tan; Michael Carrillo; Diana Dench; Ju Chen; Mohammad Shafie; Wengui Yu

doi:10.21203/rs.3.rs-11031585/v1

October 14, 2026Open Access

System-Level Delays For Anticoagulation Reversal In Intracerebral Hemorrhage: Implications For Quality Improvement

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Key result

Code Stroke activation linked to ~213-minute faster anticoagulation reversal in ICH.

P<0.001
n=50

Why the study?

Spontaneous intracerebral hemorrhage lacks the established time-critical treatment guidelines available for acute ischemic stroke. This study investigated system-level delays in anticoagulation reversal for patients with anticoagulation-associated ICH to identify opportunities for quality improvement.

Does Code Stroke activation reduce door-to-treatment time and system-level delays for anticoagulation reversal in patients with anticoagulation-associated intracerebral hemorrhage?

Key Points

To investigate system-level delays in anticoagulation reversal among patients with anticoagulation-associated intracerebral hemorrhage and identify opportunities for quality improvement.
Retrospective review of consecutive spontaneous intracerebral hemorrhage admissions between January 1, 2020, and December 31, 2025, identifying 50 confirmed anticoagulation-associated cases (N=50).
Assessed timing metrics among 34 patients reversed at the center, comparing outcomes by Code Stroke activation status and anticoagulant class (warfarin versus direct oral anticoagulants).
Code Stroke activation (n=24) significantly reduced median door-to-CT time (16.5 [12.8–22.0] vs 172.5 [49.0-261.5] minutes, p < 0.001), order-to-needle time (37.5 [24.7–56.9] vs 57.0 [39.0–85.0] minutes, p = 0.042), and door-to-treatment time (64 [48–98] vs 277 [159–305] minutes, p < 0.001) compared with non-activation (n=10).
Warfarin use was associated with higher INR levels (2.7 [2.2–3.6] vs 1.3 [1.2–1.9], p = 0.003) and significantly longer door-to-treatment times (95 [51–108] vs 64 [48–77] minutes, p = 0.007) driven by waiting for INR results (38 [36.5–57.0] minutes).
Primary treatment delays were attributed to the absence of a time-critical protocol, weight-based 4F-PCC dosing, waiting for INR lab results, and omitting Code Stroke activation in patients with mild symptoms or unresponsiveness.

Study Design

Type

Observational (n=50)

Multicenter

No

Structured PICO

Does Code Stroke activation reduce door-to-treatment time and system-level delays for anticoagulation reversal in patients with anticoagulation-associated intracerebral hemorrhage?

P

Population

50 patients with confirmed warfarin- or direct oral anticoagulant-associated spontaneous intracerebral hemorrhage admitted to a single medical center, of whom 34 underwent anticoagulation reversal directly in the emergency department and were evaluated through hospital discharge.

E

Exposure

Code Stroke activation upon emergency department arrival and anticoagulation reversal therapy per institutional protocol: intravenous (IV) four-factor prothrombin complex concentrates (4F-PCC; 25–50 units/kg) for factor Xa inhibitor–associated ICH, idarucizumab for dabigatran-associated ICH, and IV 4F-PCC (25–50 units/kg) combined with IV vitamin K (10 mg) for warfarin-associated ICH (or low-dose vitamin K alone for INR < 2.0, or 4F-PCC plus fresh frozen plasma).

C

Comparator

No Code Stroke activation upon emergency department arrival (n=10 among those reversed at the study center), or DOAC-associated ICH (n=27) versus warfarin-associated ICH (n=7) in subgroup analyses, or no anticoagulation reversal therapy (n=9).

O

Outcome

Door-to-treatment (DTT) time for anticoagulation reversal

Main Result

Absolute Event Rate: 64% vs 277%

p-value: p=<0.001

In patients with anticoagulation-associated intracerebral hemorrhage, Code Stroke activation significantly reduces door-to-CT and door-to-treatment times for anticoagulation reversal, whereas waiting for INR results in warfarin-treated patients and weight-based 4F-PCC preparation cause substantial treatment delays.

Limitations

Small sample size and single-center design may limit generalizability to the broader population of patients with anticoagulation-associated ICH
Inherent risk of Type I or Type II errors in the interpretation of baseline demographics and clinical results due to small sample size
Multivariable regression modeling could not be performed due to sample size constraints, leaving potential unadjusted confounders
Retrospective design may have introduced selection bias
Small sample size and single-center design may limit generalizability to the broader population of patients with anticoagulation-associated ICH.
Inherent risk of Type I or Type II errors in the interpretation of baseline demographics and clinical results due to limited sample size.
Multivariable modeling could not be performed due to sample size constraints, and potential confounders (e.g., age, baseline NIHSS, or baseline ICH score) likely influenced the clinical decision to activate Code Stroke.
Retrospective design and relatively small sample size may have introduced selection bias.

Implication

Code Stroke activation was associated with shorter door-to-treatment times; hypothesis-generating for standardized protocols in anticoagulation-associated ICH.

Abstract

Background Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke but lacks the established time-critical treatment guidelines available for acute ischemic stroke. This study investigated the system-level delays in anticoagulation reversal for patients with anticoagulation-associated ICH to identify opportunities for quality improvement. Methods We conducted a retrospective study of patients with anticoagulation-associated ICH admitted to our medical center between January 1, 2020, and December 31, 2025. Patients with warfarin- or direct oral anticoagulant (DOAC)-associated ICH were identified from clinical trial screening log, Vizient, and AHA’s Get With The Guidelines-Stroke registry. Code Stroke activation, warfarin or DOAC use, door to CT, INR results or anticoagulation reversal times, and the causes of delay were analyzed. Results Of 892 ICH admissions, 50 patients had confirmed anticoagulation-associated ICH. Among those who underwent reversed at our center (n = 34), Code Stroke activation (n = 24) significantly reduced median door-to-CT time (16.5 [12.8–22.0] vs 172.5 [49.0-261.5] minutes, p < 0.001), anticoagulation reversal order-to-needle time (37.5 [24.7–56.9] vs 57.0 [39.0–85.0] minutes, p = 0.042), and door-to-treatment (DTT) time (64 [48–98] vs 277 [159–305] minutes, p < 0.001) compared to non-activation (n = 10). Conversely, warfarin use was associated with higher international normalized ratios (INR) (2.7 [2.2–3.6] vs 1.3 [1.2–1.9], p = 0.003) and significantly longer DTT time (95 [51–108] vs 64 [48–77] minutes, p = 0.007) due to waiting for INR results (38 [36.5–57.0] minutes). Primary DTT delays stemmed from the absence of a time-critical treatment protocol, weight-based dosing for 4F-PCC, waiting for INR results, and a lack of Code Stroke activation for patients with mild symptoms or unresponsiveness. Conclusions Our findings suggest that Code Stroke activation for all suspected cases of ICH, a time-critical ICH algorithm targeting a DTT time of less than 60 minutes, and immediate anticoagulation reversal with fixed-dose 4F-PCC without waiting for INR results may optimize the acute management of anticoagulation-associated ICH.

Discussion

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Cite This Study

Tan et al. (2026) conducted an observational in Anticoagulation-associated spontaneous intracerebral hemorrhage (ICH) (n=50). Code Stroke activation vs. No Code Stroke activation was evaluated on Median door-to-treatment (DTT) time for anticoagulation reversal (minutes) (p=<0.001). Code Stroke activation reduced median door-to-treatment time for anticoagulation reversal from 277 to 64 minutes (p<0.001) compared to non-activation in anticoagulation-associated ICH.

synapsesocial.com/papers/6ae682a3e432e7a5c4ef35ec https://doi.org/10.21203/rs.3.rs-11031585/v1

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System-Level Delays For Anticoagulation Reversal In Intracerebral Hemorrhage: Implications For Quality Improvement

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

System-Level Delays For Anticoagulation Reversal In Intracerebral Hemorrhage: Implications For Quality Improvement

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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