Background: International Normalized Ratio (INR) is a measure of the extrinsic coagulation cascade. Elevated INR is associated with increased risk of bleeding and mortality after Traumatic Brain Injury (TBI). This study examines the relationship between magnitude of INR abnormality and outcomes in the ProTECTIII multi-center clinical trial.
Methods: Subjects with moderate-severe traumatic brain injury (TBI) were enrolled in ProTECTIII across 42 sites (n=882) between 2010 and 2013. Elevated INR (value >1.4) was documented per patient on electronic case report forms. Maximal value of INR (INRmax) during the first two weeks after enrollment was identified for each subject and grouped into quartiles (1.41-1.5, 1.51-1.6, 1.61-1.8, >1.8). Three outcome measures were examined: death, craniotomy (within 2 weeks of injury), and 6 month functional outcome. Functional outcome was measured by Glasgow Outcome Scale Extended (GOS-E, stratified dichotomy). The relationship between INRmax and outcome was assessed using the Wilcoxon Rank-Sum Test and logistic regression of the INRmax quartiles.
Results: INRmax was identified in 191 patients, from 491 instances of INR>1.4 in the two weeks after injury. Median INRmax=1.60 [95% CI:1.55,1.60]. INRmax was significantly related to both poor functional outcome (median 1.60 [95% CI:1.60,1.70] vs 1.50 [95% CI:1.50,1.55], p=0.0002) and mortality (median 1.70 [95% CI:1.60,1.90] vs 1.54 [95% CI:1.50,1.60], p<0.0001). The odds of poor outcome with INRmax>1.8 was 3.8 times greater than for INRmax 1.41-1.5 (OR: 4.8, 95% CI:2.08, 11.30). The odds of death for INRmax>1.8 was 8.3 times greater than that for INRmax 1.41-1.5 (OR:9.3, 95% CI:3.31, 25.96). Craniotomy was not associated with INRmax (p=0.81).
Conclusion: Maximum INR value is associated with six-month functional outcome and death within two weeks after traumatic brain injury. Future analyses will explore the area under the curve between INR value and outcome after traumatic brain injury.