Coagulopathy after hemorrhagic traumatic brain injury, an observational study of the incidence and prognosis

Abstract

Background Traumatic brain injury is associated with high rates of mortality and morbidity. Trauma patients with a coagulopathy have a 10-fold increased mortality risk compared to patients without a coagulopathy. The aim of this study was to identify the incidence of coagulopathy and relate early coagulopathy to clinical outcome in patients with traumatic intracranial hemorrhages. Methods Between September 2015 and December 2016, 108 consecutive cranial trauma patients with traumatic intracranial hemorrhages were included in this study. To assess the relationship between patients with a coagulopathy and outcome, a chisquared test was performed. Results A total of 29 out of the 108 patients (27%) with a traumatic intracranial hemorrhage developed a coagulopathy within 72 h after admission. Overall, a total of 22 patients (20%) died after admission of which ten were coagulopathic at emergency department presentation. Early coagulopathy in patients with traumatic brain injury is associated with progression of hemorrhagic injury (odds ratio 2.4 (95% confidence interval 0.8-8.0)), surgical intervention (odds ratio 2.8 (95% confidence interval 0.87-9.35)), and increased in-hospital mortality (odds ratio 23.06 (95% confidence interval 5.5-95.9)). Conclusion Patients who sustained a traumatic intracranial hemorrhage remained at risk for developing a coagulopathy until 72 h after trauma. Patients who developed a coagulopathy had a worse clinical outcome than patients who did not develop a coagulopathy. Keywords Traumatic brain injury. Coagulopathy. Progression of hemorrhagic injury. Time course. Mortality Jort A. N. van Gent and Thomas A. van Essen contributed equally to this work. This article is part of the Topical Collection on Brain trauma

Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations

“…hypocoagulable state reflected in prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) between 3 and 6 hours post-TBI. [15][16][17] The combination of fibrinolysis and consumptive coagulopathy increases the risk of delayed or progressive intracranial hemorrhage (ICH), [18][19][20][21][22][23] which has been associated with increased likelihood of neurosurgical intervention and increased mortality. 24,25 While the initial increase in D-dimer is part of the normal physiologic response to coagulation activation, D-dimer formation exceeds thrombin upregulation in patients with progressive ICH, suggesting excessive clot degradation rather than a complimentary response to increased fibrin generation.…”

“…63 Fibrinolytic dysregulation has been repeatedly shown to contribute to ICH progression, which is associated with a fivefold increase in mortality. [23][24][25] Increased levels of D-dimer and tPA, as well as decreased levels of α2-PI among polytrauma patients with severe TBI, have been associated with progression of ICH. 19 Evidence of this association between admission D-dimer levels and ICH progression has prompted consideration for its use as predictive biomarker for this outcome, although specific cut-off levels have yet to be defined.…”

“…68 In the late postinjury period, additional evidence of a systemic imbalance between procoagulant and fibrinolytic pathways is demonstrated by the development of venous thromboembolic events, including deep venous thrombosis and pulmonary embolism, which contribute significantly to morbidity and mortality after TBI. 23,69…”

Factors Associated with the Development of Coagulopathy after Open Traumatic Brain Injury

“…Coagulopathy can be divided into a hypocoagulable state characterized by prolonged bleeding and bleeding progression, and a hypercoagulable state characterized by an increased risk of thrombosis. Although both of these states can co-exist after TBI, a hypocoagulable state tends to be more common [ 6 ]; nevertheless, the clinical significance, pathophysiological mechanisms, and temporal relationship of these two phenotypes are unknown [ 6 , 7 ]. Several theories have been proposed to explain the underlying mechanism.…”

“…Several theories have been proposed to explain the underlying mechanism. One theory is based on the fact that brain tissue contains the highest prothrombin content in the human body, and TBI leads to the release of large amounts of the tissue factor from the microvessels of the damaged brain tissue into the bloodstream, resulting in activation of the coagulation cascade through the external coagulation pathway and insufficient consumption of coagulation factors [ 7 , 8 , 9 ]. In addition, the interaction between shock and hypoperfusion leads to the activation of protein C, which promotes apoptosis by inactivating proenzyme activator inhibitor-1 [ 7 ].…”