Pre-injury antithrombotic agents predict intracranial hemorrhagic progression, but not worse clinical outcome in severe traumatic brain injury

Abstract

Background The incidence of traumatic brain injury (TBI) patients of older age with comorbidities, who are pre-injury treated with antithrombotic agents (antiplatelets and/or anticoagulants), has increased. In this study, our aim was to investigate if pre-injury antithrombotic treatment was associated with worse intracranial hemorrhagic/injury progression and clinical outcome in patients with severe TBI. Methods In this retrospective study, including 844 TBI patients treated at our neurointensive care at Uppsala University Hospital, Sweden, 2008–2018, 159 (19%) were pre-injury treated with antithrombotic agents. Demography, admission status, radiology, treatment, and outcome variables were evaluated. Significant intracranial hemorrhagic/injury evolution was defined as hemorrhagic progression seen on the second computed tomography (CT), emergency neurosurgery after the initial CT, or death following the initial CT. Results Patients with pre-injury antithrombotics were significantly older and with a higher Charlson comorbidity index. They were more often injured by falls and more frequently developed acute subdural hematomas. Sixty-eight (8%) patients were pre-injury treated with monotherapy of antiplatelets, 67 (8%) patients with anticoagulants, and 24 (3%) patients with a combination of antithrombotics. Pre-injury anticoagulants, but not antiplatelets, were independently associated with significant intracranial hemorrhagic/injury evolution in a multiple regression analysis. However, neither anticoagulants nor antiplatelets were associated with mortality and unfavorable outcome in multiple regression analyses. Conclusions Only anticoagulants were associated with intracranial hemorrhagic/injury progression, but no antithrombotic agent correlated with worse clinical outcome. Management, including early anticoagulant reversal, availability of emergency neurosurgery, and neurointensive care, may be important aspects for reducing the adverse effects of pre-injury antithrombotics.

Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis

“…Grandhi et al 26 found that antiplatelet agents did not influence neurosurgical intervention rates or mortality in patients ≥65 years old after closed HI. A 2021 retrospective study of 844 neurointensive care patients in Sweden27 did not show an association between antiplatelet use and mortality or poor outcomes after multiple regression analysis. In terms of studies included in this systematic review, Gangavati et al 15 found a reduced rate of tICH in patients on pre-injury clopidogrel and as there is not a biologically plausible mechanism for this the difference is likely due to confounding or bias that cannot be identified from the published information.…”

Intracranial lesion features in moderate-to-severe traumatic brain injury: relation to neurointensive care variables and clinical outcome

“…tSAH volumes could not be calculated reliably and these lesions were only defined as present or absent. Hemorrhage progression of intracranial lesions was defined as an increase in EDH/ASDH/IVH/contusions with 6 mL or more, in accordance with previous studies [ 23 , 25 ]. Some patients received emergency neurosurgery immediately after the first CT and to take into account these different clinical trajectories of hemorrhage/injury evolution, the patients were divided into three groups: (1) stable intracranial hemorrhages on follow-up CT, (2) progression of intracranial hemorrhages on follow-up CT as defined above, (3) immediate intracranial surgery after the first CT. Midline shift (mm) and basal cisterns (open/compressed/obliterated) were assessed on both the 1st and 2nd CT.…”

“…Lastly, significant hemorrhage evolution has previously been defined in many different ways (e.g., absolute vs. relative increase in hemorrhage volume). We defined it as an absolute hemorrhagic increase with 6 mL, similar to Shin et al and a previous study by our group [ 23 , 25 ]. This threshold was set relatively high to really capture large and truly clinically significant hemorrhage progression.…”

The Impact of Preinjury Use of Antiplatelet Drugs on Outcomes of Traumatic Brain Injury: A Systematic Review and Meta-Analysis

“…Thirty-eight were selected for full-text analysis of which 19 were excluded as they did not fulfill the inclusion criteria. Finally, 20 studies were included in this review (16)(17)(18)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Characteristics of included studies are presented in Table 1.…”