ORIGINAL ARTICLE Abnormal Coagulation Tests Are Associated With Progression of Traumatic Intracranial Hemorrhage Christopher B. Allard, MD, BSc, Sandro Scarpelini, MD, PhD, Shawn G. Rhind, PhD, Andrew J. Baker, MD, FRCPC, Pang N. Shek, PhD, Homer Tien, MD, MEpi, FRCSC, Michael Fernando, MBBS, Lorraine Tremblay, MD, PhD, FRCSC, FACS, Laurie J. Morrison, MD, MSc, FRCPC, Ruxandra Pinto, PhD, and Sandro B. Rizoli, MD, PhD, FRCSC, FACS Background: Intracranial hemorrhage (ICH) is common in traumatic brain injury (TBI) and a major determinant of death and disability. ICH commonly increases in size and coagulopathy has been implicated in such progression. We investigated the association between coagulopathy diagnosed by routine laboratory tests and ICH progression. Methods: Subgroup post hoc analysis from a randomized controlled trial including adult patients with blunt severe TBI (Glasgow Coma Scale score 8) and repeat computerized tomography scans in 48 hours. Coagulopathy was defined as international normalized ratio 1.3, activated partial throm- boplastin time 35, or platelet count (PLT) 100  10 9 /L any time in the first 24 hours. Progression was any size increase or new ICH. TBI-associated coagulopathy was investigated measuring soluble tissue factor (TF) and D-dimer. Results: The ICH progressed in 37 of 72 patients (51%), in 80% if any abnormal laboratory test (coagulopathic patients) versus 36% in noncoagu- lopathic (p = 0.0004). Abnormal international normalized ratio (odds ratio [OR] = 4.09; 95% confidence interval [CI] = 1.29 –12.95; p = 0.017), PLT (OR = 12.59; 95% CI = 1.52–108.57; p = 0.019), head Abbreviated Injury Scale (AIS) (OR = 1.82; 95% CI = 1.15–2.88; p = 0.011) were significantly associated with progression (univariate analysis). In a multiple logistic regression, only head AIS (OR = 1.81; 95% CI 1.10 –2.98; p = 0.0198) and PLT (OR = 11.8; 95% CI = 1.38 –101.23; p = 0.024) correlated with progression. All patients with abnormal partial thromboplastin time experi- enced progression. ICH progression carried a 5-fold higher odds of death; 32% with progression died versus 8.6% without. Age, head AIS, Injury Severity Score, and D-dimer were also associated with mortality. Tissue factor was not associated with progression or mortality. Conclusion: This study demonstrates an association between coagulopathy, diagnosed by routine laboratorial tests in the first 24 hours, with ICH progression; and ICH progression with mortality in patients with severe TBI. The causal relationship between coagulopathy and ICH progression will require further studies. Key Words: Intracerebral hemorrhage, Traumatic brain injury, INR, PTT, Platelet count. (J Trauma. 2009;67: 959 –967) I njury to the brain remains the leading cause of death and long-term disability after trauma. 1 At least one-fifth of the patients with severe traumatic brain injury (TBI) die from their injuries, making TBI the number one cause of death in people younger than 40 years. 2 Most deaths from TBI occur in the first 24 hours after injury, and therefore, any intervention aiming to reduce mortality must be ap- plied early. 3 Death and disability in patients with TBI are often caused by intraparenchymal and/or extra axial bleeding, com- monly referred to as “intracranial hemorrhage” or ICH. 4 Because many ICH lesions increase in size in the first hours after trauma, patients’ outcomes are often determined not by the initial hemorrhage but by its final size. In patients with traumatic ICH, studies using serial head computerized to- mography (CT) scans report ICH progression in about 50% of patients 5–7 reaching maximum size within 12 hours. New hemorrhagic lesions also appear within hours, making this acute period critical. 8,9 ICH progression is a strong predictor of mortality, and thus recognizing and addressing the factors associated with its progression may have an impact on mor- tality and disability from TBI. 10,11 Several factors have been implicated as determinants of ICH progression, including male gender, low initial level of consciousness, older age, volume of the initial hematoma, presence of the spot sign on CT angiography, and coagulopa- thy. 6,12–14 Coagulopathy is common in TBI and seems to have unique characteristics. It has been proposed that the injured brain releases tissue factor (TF) (or thromboplastin), trig- gering a consumptive coagulopathy and hyperfibrinolysis marked by high levels of D-dimers (DD). 11,15,16 Among patients with blunt TBI, 81% of those with Glasgow Coma Scale (GCS) score 6 and 100% with GCS score 5 are coagulopathic, which is independently associated with mortality. 17,18 Submitted for publication October 16, 2008. Accepted for publication May 1, 2009. Copyright © 2009 by Lippincott Williams & Wilkins From the Departments of Surgery and/or Critical Care Medicine (C.B.A., S.S., H.T., M.F., L.T., R.P., S.B.R.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Defence Research and Development Canada (DRDC) (S.G.R., P.N.S.), Toronto, Ontario, Canada; Cara Phelan Centre for Trauma Research (A.J.B.) and Pre-hospital and Transport Medicine Research Pro- gram, Keenan Research Centre (L.J.M.), Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada. This study was supported by the Defence Research and Development Canada (DRDC). Presented at the 67th Annual Meeting of the American Association for the Surgery of Trauma, September 24 –27, 2008, Maui, Hawaii. Address for reprints: Sandro Rizoli, MD, PhD, FRCSC, FACS, 2075 Bayview Avenue, Suite H1-71, Toronto, ON M4N 3M5, Canada; email: sandro. rizoli@sunnybrook.ca. DOI: 10.1097/TA.0b013e3181ad5d37 The Journal of TRAUMA ® Injury, Infection, and Critical Care • Volume 67, Number 5, November 2009 959