Acute Haemostatic Depletion and Failure in Patients with Traumatic Brain Injury (TBI): Pathophysiological and Clinical Considerations

Abstract

Background: Because of the aging population, the number of low falls in elderly people with pre-existing anticoagulation is rising, often leading to traumatic brain injury (TBI) with a social and economic burden. Hemostatic disorders and disbalances seem to play a pivotal role in bleeding progression. Interrelationships between anticoagulatoric medication, coagulopathy, and bleeding progression seem to be a promising aim of therapy.

Methods: We conducted a selective search of the literature in databases like Medline (Pubmed), Cochrane Library and current European treatment recommendations using relevant terms or their combination.

Results: Patients with isolated TBI are at risk for developing coagulopathy in the clinical course. Pre-injury intake of anticoagulants is leading to a significant increase in coagulopathy, so every third patient with TBI in this population suffers from coagulopathy, leading to hemorrhagic progression and delayed traumatic intracranial hemorrhage. In an assessment of coagulopathy, viscoelastic tests such as TEG or ROTEM seem to be more beneficial than conventional coagulation assays alone, especially because of their timely and more specific gain of information about coagulopathy. Furthermore, results of point-of-care diagnostic make rapid "goal-directed therapy" possible with promising results in subgroups of patients with TBI.

Conclusions: The use of innovative technologies such as viscoelastic tests in the assessment of hemostatic disorders and implementation of treatment algorithms seem to be beneficial in patients with TBI, but further studies are needed to evaluate their impact on secondary brain injury and mortality.

Keywords: coagulopathy; diagnostics; mechanisms; traumatic brain injury; treatment.

Figure 1

Trimodal age distribution of moderate to severe traumatic brain injury in men and women: 1. first peak: marked difference in incidence between the sexes, starting at puberty and rising until age 18 (driver’s license); “testosterone effect” > “young risk-takers”; male > female; 2. second peak: mid-fifties (“older risk-takers”; work accidents); 3. third peak: late seventies (incidence in the two sexes is now more nearly equal; mainly falls) and frequency of coagulopathy upon admission for three age groups according to the Berlin definition of coagulopathy, e.g., PTT ≥ 40 s and/or INR ≥ 1.4. First published by Maegele et al. [6], with permission from Deutscher Ärzteverlag GmbH; Reprinted from Maegele et al. [7], adapted with permission from Wolters Kluwer Health, Inc., Alphen aan den Rijn, The Netherlands.

Figure 2

Clinical example of a patient with severe TBI and initial coagulopathy who developed complicating subsequent hypotensive (multifactorial) coagulopathy with deteriorating ICH within three hours of hospital admission. Shown are cranial computed tomographies of the brain (CCTs), results from viscoelastic (ROTEM^®), and standard laboratory and conventional coagulation assays (CCAs) upon admission (A) and after three hours of admission (B). A normal reference condition is displayed for comparison (C). Viscoelastic assays after three hours of admission indicate delayed and insufficient clotting, as reflected by prolonged initiation times and reduced clot amplitudes. The flat line in the ROTEM^® FIBTEM channel reflects the complete absence of fibrin polymerization. Results from standard laboratory assays and CCAs three hours after admission display signs of shock with deranged coagulation along with hypofibrinogenemia and thrombocytopenia. aPTT = activated Partial Thromboplastin Time; BE = base excess; PT = Prothrombin Time; PTr = Prothrombin ratio. First published by Maegele et al. [3], with permission from Elsevier; Reprinted from Maegele et al. [7], with permission from Wolters Kluwer Health, Inc.

Figure 3

Conceptual timeline of hemostatic disruptions after TBI based upon changes in conventional coagulation assays (CCAs). Reprinted from Fletcher-Sandersjöö et al. [37], under CC BY-4.0, http://creativecommons.org/licenses/by/4.0/ (assessed on 3 January 2023).

Figure 4

Summary of potential interactions and pathways involved in the development of hemostatic failure and coagulopathy after TBI. The exact nature of hemostatic disruptions observed after TBI remains elusive, but current evidence suggests the presence of both a hyper- and hypocoagulable state with possible overlap and lack of distinction between phases and states. Arrows indicate activation; bold circles inhibition. Reprinted from Maegele et al. [7], with permission from Wolters Kluwer Health, Inc.

Figure 5

Exemplar algorithm to guide hemostatic therapies by the use of functional viscoelastic testing results (ROTEM^®) successfully implemented at centers formerly naïve to this technology. Test results were available for clinical decision-making within a median of 15 min of blood sampling. When the algorithm recommended specific interventions and was followed, thromboelastometric test results improved significantly by the second blood sampling performed 30–60 min after decision-making and at least 10 min after the intervention (adapted from [66]). A10 = Clot amplitude after 5 and 10 min (in mm); CT = Clotting time (in seconds); Ex = ROTEM^® EXTEM assay; FFP = Fresh Frozen Plasma; Fib = ROTEM^® FIBTEM assay; g = gram; IU = International Units; ML = Maximum lysis (in percent); PCC = Prothrombin Complex Concentrate.