Optimal Timing of Anticoagulation in Traumatic Brain Injury

A multidisciplinary research team faced the complex clinical challenge of determining the optimal timing for initiating anticoagulation in patients with traumatic brain injury (TBI). Clinicians must carefully balance the risks of intracranial haemorrhagic progression against the dangers of thromboembolic events, both of which significantly impact patient mortality and outcomes. Current guidelines provide only Level III evidence, with conflicting research findings creating uncertainty in clinical practice.

• Identify the optimal timing window for initiating anticoagulation in TBI patients

• Evaluate the relationship between anticoagulation timing and patient outcomes

• Assess the impact of different anticoagulant agents on treatment effectiveness

• Account for patient-specific factors influencing coagulation dynamics

• Develop a predictive model to support personalised clinical decision-making

1. Data Architecture Analysis

• Extracted comprehensive patient data from the National Trauma Data Bank®

• Implemented rigorous data cleaning protocols for missing values

• Applied standardised mean difference analysis to identify clinically meaningful imbalances

• Developed systematic categorisation based on timing of anticoagulation initiation

2. Technical Implementation

• Constructed propensity score modelling with Gradient Boosting Machines

• Implemented Cox proportional hazards model with time-dependent splines

• Applied restricted cubic splines to model non-linear effects of prophylaxis timing

• Developed cross-validation framework with multiple machine learning algorithms

3. Solution Delivery

• Created an interactive Shiny web application for clinicians

• Developed personalised risk prediction based on patient characteristics

• Enabled visualisation of optimised prophylaxis timing

Quantitative Outcomes

• Identified non-linear relationship between prophylaxis timing and adverse outcomes

• Found very early prophylaxis (<12 hours) associated with hazard ratios below 1

• Discovered elevated risk windows at 12-24 hours and after several days

• Determined unfractionated heparin had 34% higher hazard ratio compared to reference group

Qualitative Benefits

• Enhanced understanding of complex coagulation dynamics following TBI

• Revealed "sweet spot" timing for initiating prophylaxis

• Identified patient-specific risk factors influencing outcomes

• Provided evidence-based framework for guideline development

"The analysis from Umbizo offer new insights into the challenging decision of when to initiate anticoagulation in TBI patients. The complex, non-linear relationship between prophylaxis timing and outcomes highlights why a one-size-fits-all approach is unlikely to be optimal. This research supports the notion of a 'sweet spot' for starting pharmacologic prophylaxis, balancing the need to mitigate VTE risk while avoiding exacerbation of intracranial bleeding."

• Initial Data Extraction and Analysis: 1 week

• Model Development and Validation: 1 week

• Manuscript Preparation: 1 week

Future research will incorporate dynamic, patient-level markers of both thrombotic and bleeding risk to enable more precise tailoring of prophylaxis timing. Prospective studies with repeated imaging and standardised thresholds for anticoagulation initiation will further strengthen the evidence base. Additionally, exploration of specific subgroups—such as those with mild versus severe TBI or established coagulopathy—will help determine whether particular populations derive specific benefits or face heightened risks from earlier versus later prophylaxis.