Outcome of Intracranial Bleed in Patients on Antiplatelet and Anticoagulant Therapy: A Retrospective Cohort Study

Shetty, Raghav; D, Souza

doi:10.65188/nurexus.1069

Shetty R et al | DOI: 10.65188/nurexus.1069

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Journal of MedVerse Research & Practice

ISSN: 3107-4278

Outcome of Intracranial Bleed in Patients on Antiplatelet and Anticoagulant

Therapy: A Retrospective Cohort Study

Dr. Raghav Shetty, Dr. Souza D

Assistant Professor, Professor

Department of Neurosurgery, Kasturba Medical College, Mangalore.

Email ID: raghavshetty44@gmail.com

Submission Date: 24.01.2026

Accepted Date:21.02.2026

Published Date: 28.02.2026

DOI: 10.65188/nurexus.1069

article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted

use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Abstract

Background: Intracranial hemorrhage (ICH) in patients receiving antiplatelet and anticoagulant therapy represents

a major clinical challenge due to increased bleeding risk, hematoma expansion, and adverse neurological outcomes.

With the growing use of oral anticoagulants and antiplatelet agents, understanding prognosis and determinants of

outcome in this population is essential.

Methods: A retrospective cohort study was conducted in the Department of Neurosurgery at Kasturba Medical

College, Mangalore. A total of 189 patients aged 18–75 years with imaging-confirmed traumatic intracranial bleed

and documented use of antiplatelet or anticoagulant therapy within 10 days of presentation were included. Clinical

characteristics, comorbidities, type and duration of anticoagulant therapy, Modified Rankin Score, radiological

findings, management strategies, and short-term outcomes were analyzed. Statistical analysis was performed using

SPSS. Chi-square and independent t-tests assessed associations, and multivariate logistic regression identified

independent predictors of composite poor outcome. A p-value <0.05 was considered statistically significant.

Results: Intracerebral hemorrhage was the most common subtype (41.3%). Poor outcome occurred in 36.5% of

patients. Significant predictors of adverse outcome included age >65 years (p=0.003), hypertension (p=0.041),

diabetes (p=0.006), atrial fibrillation (p=0.002), warfarin use (p=0.028), anticoagulant duration >3 years (p=0.033),

and poor medication compliance (p=0.001). Multivariate analysis identified intracerebral hemorrhage (AOR 4.6;

p<0.001) and poor compliance (AOR 2.8; p=0.001) as strongest independent predictors.

Conclusion: Intracranial bleeding in patients on blood thinners is associated with significant morbidity and mortality.

Early risk stratification, optimized anticoagulant selection, and strict monitoring may improve neurological

outcomes.

Keywords: Intracranial hemorrhage; Anticoagulants; Antiplatelet therapy; Warfarin; Traumatic brain injury;

Modified Rankin Score; Prognosis.

Introduction

Intracranial hemorrhage (ICH) is a life-threatening neurological emergency associated with high morbidity

and mortality. The risk becomes significantly greater in patients receiving antiplatelet or anticoagulant

therapy, as these medications impair normal hemostatic mechanisms and predispose to hematoma

expansion following trauma [1]. With the increasing global burden of cardiovascular disease and

thromboembolic disorders, the use of oral anticoagulants and antiplatelet agents has risen substantially in

recent years [2,3].

ORIGINAL ARTICLE

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Warfarin has long been the most commonly prescribed oral anticoagulant, but direct oral anticoagulants

(DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used because of

their predictable pharmacokinetics and lower incidence of spontaneous intracranial hemorrhage compared

to warfarin [4,5]. Nevertheless, bleeding events continue to occur in patients on DOAC therapy. Antiplatelet

agents such as aspirin and clopidogrel further increase hemorrhagic risk by inhibiting platelet aggregation

[6]. In elderly individuals and patients with multiple comorbidities, combined antithrombotic therapy may

significantly worsen bleeding severity and clinical outcomes [7]. Trauma-related intracranial hemorrhage

in anticoagulated patients poses unique neurosurgical challenges. Studies have shown that anticoagulated

individuals experience higher rates of hematoma expansion, neurological deterioration, and mortality

compared to non-anticoagulated patients [8,9]. Broderick et al. [10] identified hematoma volume and

anticoagulation status as strong predictors of mortality in intracerebral hemorrhage. Clinical severity at

presentation, radiological findings, and underlying comorbidities further influence prognosis [11].

Advanced age, hypertension, diabetes mellitus, and atrial fibrillation are frequently observed among

patients on long-term anticoagulation [12]. These conditions not only increase bleeding risk but also

diminish physiological reserve, thereby worsening neurological recovery. Wilson et al. [13] reported that

anticoagulant exposure combined with underlying cerebral microvascular pathology markedly elevates the

risk of intracranial bleeding. Furthermore, delayed presentation, prolonged duration of anticoagulant

therapy, and poor medication compliance may contribute to unfavorable outcomes [14-16]. Despite

growing international literature, limited data are available from tertiary neurosurgical centers in India

focusing specifically on traumatic intracranial hemorrhage in patients on antiplatelet and anticoagulant

therapy. Regional prescribing patterns, monitoring practices, and patient demographics may influence

outcomes. Therefore, the present study conducted at Kasturba Medical College, Mangalore, aimed to

evaluate clinical outcomes, identify risk factors associated with poor neurological prognosis, compare

outcomes across anticoagulant types, and determine independent predictors of adverse events in this high-

risk population.

Materials and Methods

Study Design

This retrospective cohort study was conducted to evaluate the clinical characteristics, management

strategies, and neurological outcomes of patients presenting with traumatic intracranial hemorrhage while

receiving antiplatelet or anticoagulant therapy. The study assessed the impact of pre-injury blood thinner

use on patient outcomes and identified factors associated with poor neurological prognosis.

Study Setting and Duration

The study was carried out in the Department of Neurosurgery at Kasturba Medical College, Mangalore, a

tertiary care referral center specializing in the management of complex neurotrauma cases. Consecutive

eligible patients presenting during the predefined study period were identified through hospital medical

records and included in the analysis.

Study Population

A total of 189 patients aged between 18 and 75 years with trauma-related intracranial hemorrhage

confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) were included in the

study. Eligible patients had documented use of antiplatelet or anticoagulant medication within 10 days prior

to sustaining the traumatic brain injury.

Inclusion and Exclusion Criteria

Patients aged 18–75 years with radiologically confirmed traumatic intracranial hemorrhage and

documented use of anticoagulant agents, including warfarin, heparin, low-molecular-weight heparin

(clexane), dabigatran, rivaroxaban, apixaban, and edoxaban, or antiplatelet agents such as aspirin and

clopidogrel within 10 days before injury were included. Patients younger than 18 years or older than 75

Shetty R et al | DOI: 10.65188/nurexus.1069

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years, those with non-traumatic intracranial hemorrhage, individuals not receiving blood-thinning

medications, pregnant women, patients who left the hospital against medical advice, and those with

incomplete medical records were excluded from the study.

Data Collection

Data were retrospectively extracted from hospital medical records, neuroimaging reports, operative notes,

and discharge summaries using a structured data collection form. Demographic information including age

and gender was recorded. Clinical variables collected included comorbidities such as hypertension, diabetes

mellitus, atrial fibrillation, previous stroke, myocardial infarction, deep vein thrombosis, and pulmonary

thromboembolism. Details regarding the type of anticoagulant or antiplatelet therapy, duration of treatment,

and medication compliance were documented. Clinical presentation at admission, including headache,

vomiting, seizures, altered sensorium, and focal neurological deficits, was also recorded. Radiological

findings included the type of intracranial hemorrhage (subarachnoid hemorrhage, subdural hematoma,

epidural hematoma, or intracerebral hemorrhage), anatomical location of the bleed, hematoma size, and

associated imaging characteristics.

Data tool

Neurological outcome was evaluated using the Modified Rankin Scale (mRS) at the time of hospital

discharge. A composite poor outcome was defined as death during hospitalization, permanent neurological

disability indicated by an mRS score of 3 or higher, or recurrent intracranial bleeding occurring during the

hospital stay. Information regarding management strategies, including temporary discontinuation or

modification of anticoagulant therapy, administration of reversal agents, conservative treatment, and

neurosurgical intervention, was also documented.

Ethical Considerations

The study protocol was reviewed and approved by the Institutional Ethics Committee of Kasturba Medical

College, Mangalore (Reference No. KMC/IEC/2023/1011). As this was a retrospective record-based study,

informed consent for the use of anonymized clinical data for research purposes had been obtained from

patients or their legally authorized representatives at the time of hospital admission. Strict confidentiality

was maintained throughout the study by assigning unique identification numbers to all participants and

ensuring that no personally identifiable information was disclosed during data collection or analysis.

Statistical Analysis

Data were entered into Microsoft Excel for coding and cleaning before statistical analysis using the

Statistical Package for the Social Sciences (SPSS) software. Continuous variables were expressed as mean

± standard deviation, while categorical variables were summarized as frequencies and percentages.

Associations between clinical variables and neurological outcomes were analyzed using the Chi-square test

or Fisher's exact test for categorical variables and the independent sample t-test for continuous variables.

Variables demonstrating statistical significance in univariate analysis were included in multivariate logistic

regression analysis to identify independent predictors of poor neurological outcome. Adjusted odds ratios

(AORs) with 95% confidence intervals (CIs) were calculated, and a p-value of less than 0.05 was considered

statistically significant.

Results

A total of 189 patients with traumatic intracranial hemorrhage on antiplatelet or anticoagulant therapy were

analyzed.

Table 1: Baseline Demographic Characteristics (n = 189)

Variable

Frequency (%)

Age >65 years

78 (41.3%)

Age ≤65 years

111 (58.7%)

Male

122 (64.6%)

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Female

67 (35.4%)

Mean age

61.8 ± 11.4 years

The majority of patients were males (64.6%), with a mean age of 61.8 ± 11.4 years. A substantial proportion

(41.3%) were older than 65 years, indicating that elderly patients represent a significant high-risk group.

Advanced age showed significant association with poor outcome in later analysis (p = 0.003), suggesting

reduced physiological reserve and increased vulnerability to hematoma expansion.

Table 2: Medical Comorbidities

Comorbidity

Frequency (%)

Hypertension

98 (51.9%)

Diabetes Mellitus

74 (39.2%)

Atrial Fibrillation

52 (27.5%)

Previous Stroke

29 (15.3%)

Hypertension (51.9%) was the most prevalent comorbidity, followed by diabetes (39.2%) and atrial

fibrillation (27.5%). Diabetes (p = 0.006) and atrial fibrillation (p = 0.002) were significantly associated

with poor outcome. These comorbidities may contribute to microvascular fragility and impaired

autoregulation, thereby worsening hemorrhagic severity.

Figure 1: Type of Anticoagulant / Antiplatelet Therapy

Warfarin was the most common anticoagulant (30.7%). Warfarin use showed significant association with

poor outcome (p = 0.028). DOAC users demonstrated comparatively better outcomes. The increased risk

with warfarin may be related to variability in INR control and delayed reversal.

Table 3: Type of Intracranial Hemorrhage

Type of Bleed

Frequency (%)

Intracerebral Hemorrhage (ICH)

78 (41.3%)

Subdural Hematoma

52 (27.5%)

Subarachnoid Hemorrhage

36 (19.0%)

Epidural Hematoma

23 (12.2%)

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Intracerebral hemorrhage (41.3%) was the most common subtype and demonstrated strong association with

poor outcome (p <0.001). ICH patients showed higher mortality and disability rates compared to other

hemorrhage types, likely due to parenchymal damage and hematoma expansion.

Table 4: Duration and Compliance of Anticoagulant Therapy

Variable

Frequency (%)

Duration >3 years

69 (36.5%)

Duration ≤3 years

120 (63.5%)

Poor compliance

54 (28.6%)

Good compliance

135 (71.4%)

Long-term anticoagulant use (>3 years) was significantly associated with poor outcome (p = 0.033). Poor

medication compliance showed strong association with adverse prognosis (p = 0.001). Non-adherence may

lead to unstable anticoagulation levels, increasing risk of severe bleeding.

Figure 2: Clinical Outcomes

Overall mortality was 18.0%, and 18.5% developed permanent neurological disability. Composite poor

outcome occurred in 36.5% of patients.

Discussion

The present study evaluated clinical outcomes of traumatic intracranial hemorrhage in patients receiving

antiplatelet and anticoagulant therapy and identified key determinants influencing mortality and

neurological disability. Composite poor outcome occurred in 36.5% of patients, with an overall mortality

rate of 18.0%. These findings are consistent with prior international reports demonstrating that

anticoagulated patients experiencing intracranial hemorrhage have significantly higher morbidity and

mortality compared to non-anticoagulated individuals [17]. Steiner et al. [17] emphasized that

anticoagulation status independently worsens early hematoma expansion and short-term neurological

outcome, particularly in elderly populations.

Advanced age was significantly associated with adverse outcomes in our study (AOR 2.1; p = 0.009).

Elderly patients often demonstrate reduced cerebral autoregulatory capacity and increased vascular

fragility, predisposing them to larger hematoma volumes and poorer recovery. Broderick et al. [18]

identified age as a major prognostic determinant in intracerebral hemorrhage, while Hemphill et al. [19]

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incorporated age into validated ICH severity scoring systems predicting mortality. Our findings reinforce

the need for age-adjusted risk stratification in anticoagulated trauma patients.

Hypertension and diabetes mellitus were common comorbidities, with diabetes independently predicting

poor outcome (p = 0.022). Chronic metabolic disorders contribute to endothelial dysfunction and

microangiopathy, increasing susceptibility to hemorrhagic injury. Wilson et al. [20] reported that

underlying microvascular pathology combined with anticoagulation exposure markedly increases

hemorrhagic severity. Similarly, January et al. [21] highlighted that atrial fibrillation patients requiring

anticoagulation frequently possess multiple cardiovascular risk factors that influence bleeding prognosis.

Atrial fibrillation itself was independently associated with poor outcome (AOR 2.3; p = 0.004). This

association likely reflects both the underlying cardiac pathology necessitating anticoagulation and the

systemic inflammatory and thromboembolic milieu contributing to vascular instability. Hart et al. [22]

demonstrated that anticoagulated atrial fibrillation patients with intracranial hemorrhage exhibit higher

mortality compared to non-AF patients. Our results align with these observations, emphasizing that AF

represents not only a thromboembolic risk but also a hemorrhagic vulnerability factor.

Although direct oral anticoagulants (DOACs) have demonstrated lower spontaneous ICH rates compared

to warfarin [23], trauma-related bleeding remains clinically significant across all anticoagulant classes. Ruff

et al. [23] showed that DOACs reduce relative risk of intracranial hemorrhage compared to vitamin K

antagonists; however, once hemorrhage occurs, severity and outcomes depend on rapid reversal and

hematoma control. Variability in international normalized ratio (INR) control and delayed reversal therapy

may explain poorer outcomes among warfarin users in our cohort. Intracerebral hemorrhage was the

strongest independent predictor of poor outcome (AOR 4.6; p <0.001). Parenchymal bleeding directly

disrupts neuronal tissue and frequently results in mass effect and midline shift. Broderick et al. [18]

identified hematoma volume as the most powerful predictor of mortality in ICH. Similarly, Law et al. [24]

demonstrated that patients with antiplatelet-associated intracerebral hemorrhage have increased rates of

early neurological deterioration and disability. Our findings confirm that hemorrhage subtype significantly

influences prognosis, with intracerebral bleeds demonstrating markedly worse outcomes than subdural or

epidural hematomas.

Duration of anticoagulant therapy exceeding three years was associated with poor outcome (p = 0.033).

Long-term anticoagulation may reflect chronic cardiovascular disease burden and cumulative vascular

injury. Additionally, prolonged therapy increases the likelihood of microbleeds and cerebral amyloid

angiopathy in elderly patients, further predisposing to severe hemorrhage [20]. Non-adherence also reflects

inadequate monitoring and suboptimal patient education. Camm et al. [25] emphasized the importance of

regular follow-up and adherence monitoring in patients on anticoagulation to reduce adverse events. Our

findings highlight compliance as a modifiable determinant of outcome.

Strengths

This study provides real-world evidence on the outcomes of traumatic intracranial hemorrhage in patients

receiving antiplatelet and anticoagulant therapy using a relatively large cohort from a tertiary care

neurotrauma center. Comprehensive clinical, radiological, and treatment-related data were analyzed, and

multivariate logistic regression was employed to identify independent predictors of poor neurological

outcomes, thereby strengthening the validity of the findings.

Limitations

The retrospective single-center study design may limit the generalizability of the findings and is subject to

potential selection and information bias. Additionally, reliance on medical records may have resulted in

incomplete documentation of certain clinical variables, and long-term functional outcomes beyond hospital

discharge could not be assessed.

Shetty R et al | DOI: 10.65188/nurexus.1069

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Conclusion

This study assessed outcomes of traumatic intracranial hemorrhage in patients on antiplatelet and

anticoagulant therapy and found poor outcomes in over one third of cases, with intracerebral hemorrhage

as the strongest independent predictor. Advanced age, atrial fibrillation, diabetes, warfarin use,

prolonged therapy, and poor compliance were significantly associated with adverse prognosis. These

findings emphasize careful anticoagulant selection, strict monitoring, early reversal, and improved

patient compliance to reduce morbidity and mortality.

Declaration

Conflict of interest: Nil

Funding: Nil

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