Changes in Coagulation following Brain Injury

Abstract

Traumatic brain injury (TBI) is a worldwide public health concern due to increasing mortality, affecting around 10 million patients per year. A wide variety of clinical presentations are a function of the magnitude of injury and the anatomical perturbation of the brain parenchyma, supporting structures, and cerebral vasculature, with subsequent alteration of the blood–brain barrier. These disturbances correspond with the evolution of intracerebral hemorrhage and clinical outcomes. The associated hemostatic alterations associated with TBI are caused by the disruption of the delicate balance between bleeding and thrombosis formation, which can exacerbate initial injury. TBI-associated coagulopathy is a function of a cross-talk between coagulation and inflammation, with varying influences on the immunomodulation and regulation of coagulation that occur on platelets and the endothelium of injured TBI patients. In addition to the severity of initial injury, the following factors modulate the hemocoagulative response to TBI: time from the onset of injury to treatment, age, gender, catecholamine secretion, platelet dysfunction, endotheliopathy, premorbid anticoagulation, fibrinolysis, tissue factor, and activated protein C contribution. All these entities are intertwined and influence the pathologic evolution of TBI. These factors have implications for therapeutic options such as the choice of blood components for transfusion and hemostatic agents such as tranexamic acid. Monitoring hemostatic changes of TBI patients requires an understanding of these interactions between immunology and coagulation, which can be discerned by point-of-care viscoelastic testing with specific limitations. This review considers the implications of these interrelated influences on the evaluation of coagulopathy in TBI.

Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury

“…In addition to its fluctuant frequency, CTBI is defined by variable cut-off values when using common coagulation assays (CCAs), such as platelet count, prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), and fibrinogen levels. CCAs are also limited to detecting the initiation of clot formation and fail to provide information regarding the strength and integrity of the clot formed [4,6,23,[42][43][44][45][46][47][48]. Furthermore, CCAs are not sensitive detectors of hemostatic integrity in patients with multiple systemic polytrauma, including TBI, and fail to predict coagulopathy in patients on pre-injury anticoagulant medications, particularly antiplatelet drugs.…”

“…Published in 2019, the 5th edition of the European guideline on management of major bleeding and coagulopathy following trauma changed their recommendations to include the use of VETs such as thromboelastography (TEG ® ) and rotational thromboelastometry (ROTEM ® ) for patients with systematic multiple trauma and with TBI [47]. There are many advantages in using VETs to detect CTBI [4,6,23,48,58]. For example, VETs provide real-time coagulation information on the presence of anticoagulation or antiplatelet medications and the patient's initial coagulation profile, allowing for the monitoring of therapeutic interventions such as hemostatic adjuncts or blood component transfusion [23,47,[58][59][60][61][62][63].…”

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

“…24,25 The posttraumatic coagulopathy driving this phenomenon is attributed to increased fibrinolysis following an increase in the release of tPA and uPA from brain tissue, along with an upregulation of activated protein C and depletion of α2-PI. 3,62 In patients with mild TBI, D-dimer levels have been associated with the pres-ence of structural lesions on computed tomography (CT) 38 and elevated FDPs have been associated with delayed and recurrent ICH. 63 Fibrinolytic dysregulation has been repeatedly shown to contribute to ICH progression, which is associated with a fivefold increase in mortality.…”

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Although posttraumatic dysregulation of fibrinolysis has repeatedly been associated with increased morbidity and mortality, the factors underlying this process remain poorly understood. [1][2][3][4][5] However, a significant body of research on this subject has revealed a complex interplay of biologic mediators, physiologic processes, and iatrogenic effects that collectively contribute to local and systemic dysregulation of the fibrinolytic cascade. 6 Tissue injury results in activation of the coagulation cascade, beginning with local release of tissue factor (TF) and terminating in the deposition of fibrin polymers at the site of vascular endothelial disruption.

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The Complexity of Trauma-Induced Coagulopathy

“…The similarity and differences between adults and pediatric trauma patients are presented by Lucisano et al 4 Emerging literature also supports a link between changes in coagulation and fibrinolysis, and the central nervous, cardiovascular, and innate immune systems. The changes in traumatic brain injury are reviewed by Maegele et al, 5 whereas Zhao et al discuss the role of mitochondria in brain injury. 6 There are also differences in organ-specific contributions to coagulopathy, requiring ongoing investigation to better understand the pathophysiology of TIC.…”