Immediate and Delayed Traumatic Intracranial Hemorrhage in Patients With Head Trauma and Preinjury Warfarin or Clopidogrel Use

Study objective

Patients receiving warfarin or clopidogrel are considered at increased risk for traumatic intracranial hemorrhage after blunt head trauma. The prevalence of immediate traumatic intracranial hemorrhage and the cumulative incidence of delayed traumatic intracranial hemorrhage in these patients, however, are unknown. The objective of this study is to address these gaps in knowledge.

Methods

A prospective, observational study at 2 trauma centers and 4 community hospitals enrolled emergency department (ED) patients with blunt head trauma and preinjury warfarin or clopidogrel use from April 2009 through January 2011. Patients were followed for 2 weeks. The prevalence of immediate traumatic intracranial hemorrhage and the cumulative incidence of delayed traumatic intracranial hemorrhage were calculated from patients who received initial cranial computed tomography (CT) in the ED. Delayed traumatic intracranial hemorrhage was defined as traumatic intracranial hemorrhage within 2 weeks after an initially normal CT scan result and in the absence of repeated head trauma.

Results

A total of 1,064 patients were enrolled (768 warfarin patients [72.2%] and 296 clopidogrel patients [27.8%]). There were 364 patients (34.2%) from Level I or II trauma centers and 700 patients (65.8%) from community hospitals. One thousand patients received a cranial CT scan in the ED. Both warfarin and clopidogrel groups had similar demographic and clinical characteristics, although concomitant aspirin use was more prevalent among patients receiving clopidogrel. The prevalence of immediate traumatic intracranial hemorrhage was higher in patients receiving clopidogrel (33/276, 12.0%; 95% confidence interval [CI] 8.4% to 16.4%) than patients receiving warfarin (37/724, 5.1%; 95% CI 3.6% to 7.0%), relative risk 2.31 (95% CI 1.48 to 3.63). Delayed traumatic intracranial hemorrhage was identified in 4 of 687 (0.6%; 95% CI 0.2% to 1.5%) patients receiving warfarin and 0 of 243 (0%; 95% CI 0% to 1.5%) patients receiving clopidogrel.

Conclusion

Although there may be unmeasured confounders that limit intergroup comparison, patients receiving clopidogrel have a significantly higher prevalence of immediate traumatic intracranial hemorrhage compared with patients receiving warfarin. Delayed traumatic intracranial hemorrhage is rare and occurred only in patients receiving warfarin. Discharging patients receiving anticoagulant or antiplatelet medications from the ED after a normal cranial CT scan result is reasonable, but appropriate instructions are required because delayed traumatic intracranial hemorrhage may occur.

Introduction

The use of anticoagulant and antiplatelet medications, specifically warfarin and clopidogrel, is steadily increasing.1, 2, 3 Previous studies suggest that patients receiving either of these medications are at increased risk for traumatic intracranial hemorrhage after blunt head trauma, but the risk in a large, generalizable cohort is unknown.4, 5, 6

The majority of patients with traumatic intracranial hemorrhage are identified on initial cranial computed tomographic (CT) scan. Limited data, however, suggest that patients receiving warfarin are at increased risk for delayed traumatic intracranial hemorrhage (traumatic intracranial hemorrhage diagnosed within 2 weeks of injury after an initially normal cranial CT scan result).7, 8, 9 The concern for delayed traumatic intracranial hemorrhage is highlighted by the not uncommon practice of reversing warfarin anticoagulation in patients with head trauma and a normal cranial CT scan result.¹⁰ The potential risk for both immediate and delayed traumatic intracranial hemorrhage has generated guidelines recommending routine cranial CT imaging and hospital admission for neurologic observation in head-injured patients receiving warfarin.11, 12, 13, 14 These recommendations, however, are not informed by rigorous, prospective, multicenter studies identifying the prevalence and incidence of immediate traumatic intracranial hemorrhage and delayed traumatic intracranial hemorrhage in patients receiving warfarin.

The evidence supporting an increased risk of traumatic intracranial hemorrhage in patients receiving clopidogrel is more limited,¹¹ despite this drug being one of the most commonly prescribed worldwide.¹⁵ Although small retrospective studies suggest an increased risk of traumatic intracranial hemorrhage and mortality in head trauma patients receiving clopidogrel,6, 16, 17 current guidelines do not explicitly recommend routine CT imaging for these patients after blunt head trauma.11, 12, 13 In addition, the risk of delayed traumatic intracranial hemorrhage in patients receiving clopidogrel is entirely unknown.

Knowledge of the true prevalence and incidence of immediate and delayed traumatic intracranial hemorrhage in patients receiving warfarin or clopidogrel would allow clinicians to make evidence-based decisions about their initial patient evaluation and disposition. Therefore, we assessed the prevalence and incidence of immediate and delayed traumatic intracranial hemorrhage in patients with blunt head trauma who were receiving either warfarin or clopidogrel. Warfarin and clopidogrel cohorts were compared. We hypothesized that the prevalence for immediate traumatic intracranial hemorrhage was similar between patients receiving clopidogrel and those receiving warfarin and that the cumulative incidence of delayed traumatic intracranial hemorrhage in both groups was less than 1%.