Age-Related Differences in the Time Course of Coagulation and Fibrinolytic Parameters in Patients with Traumatic Brain Injury

Coagulopathy and older age are common and well-recognized risk factors for poorer outcomes in traumatic brain injury (TBI) patients; however, the relationships between coagulopathy and age remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more pronounced in older patients and may be a factor in poorer outcomes. We retrospectively evaluated severe TBI cases in which fibrinogen and D-dimer were measured on arrival and 3–6 h after injury. Propensity score-matched analyses were performed to adjust baseline characteristics between older patients (the “elderly group,” aged ≥75 y) and younger patients (the “non-elderly group,” aged 16–74 y). A total of 1294 cases (elderly group: 395, non-elderly group: 899) were assessed, and propensity score matching created a matched cohort of 324 pairs. Fibrinogen on admission, the degree of reduction in fibrinogen between admission and 3–6 h post-injury, and D-dimer levels between admission and 3–6 h post-injury were significantly more abnormal in the elderly group than in the non-elderly group. On multivariate logistic regression analysis, independent risk factors for poor prognosis included low fibrinogen and high D-dimer levels on admission. Posttraumatic coagulation and fibrinolytic abnormalities are more severe in older patients, and fibrinogen and D-dimer abnormalities are negative predictive factors.

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Time course of coagulation and fibrinolytic parameters in pediatric traumatic brain injury

Journal of Neurosurgery Pediatrics ◽

10.3171/2021.5.peds21125 ◽

2021 ◽

pp. 1-7

Author(s):

Ryuta Nakae ◽

Yu Fujiki ◽

Yasuhiro Takayama ◽

Takahiro Kanaya ◽

Yutaka Igarashi ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Propensity Score ◽

Pediatric Patients ◽

Prognostic Significance ◽

Multivariate Logistic Regression Analysis ◽

Adult Patients ◽

Fibrinogen Concentration ◽

Fibrinolytic Parameters ◽

D Dimer

OBJECTIVE Coagulopathy is a well-recognized risk factor for poor outcomes in patients with traumatic brain injury (TBI). Differences in the time courses of coagulation and fibrinolytic parameters between pediatric and adult patients with TBI have not been defined. METHODS Patients with TBI and an Abbreviated Injury Scale of the head score ≥ 3, in whom the prothrombin time (PT)–international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration, and plasma D-dimer levels were measured on arrival and at 3, 6, and 12 hours after injury, were retrospectively analyzed. Propensity score–matched analyses were performed to adjust baseline characteristics between pediatric patients (aged < 16 years) and adult patients (aged ≥ 16 years). RESULTS A total of 468 patients (46 children and 422 adults) were included. Propensity score matching resulted in a matched cohort of 46 pairs. Higher PT-INR and APTT values at 1 to 12 hours after injury and lower fibrinogen concentrations at 1 to 6 hours after injury were observed in the pediatric group compared with the adult group. Plasma levels of D-dimer were elevated in both groups at 1 to 12 hours after injury, but no significant differences were seen between the groups. Multivariate logistic regression analysis of the initial coagulation and fibrinolytic parameters in the pediatric group revealed no prognostic significance of the coagulation parameter values, but elevation of the fibrinolytic parameter D-dimer was an independent negative prognostic factor. CONCLUSIONS In the acute phase of TBI, pediatric patients were characterized by prolongation of PT-INR and APTT and lower fibrinogen concentrations compared with adult patients, but these did not correlate with outcome. D-dimer was an independent prognostic outcome factor in terms of the Glasgow Outcome Scale in pediatric patients with TBI.

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A-126 Clinical Utility of Risk Factors to Predict Self-reported Neurobehavioral Outcome Following Traumatic Brain Injury: PTSD, Sleep, Resilience, and Lifetime Blast Exposure

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acaa068.126 ◽

2020 ◽

Vol 35 (6) ◽

pp. 919-919

Author(s):

Lange R ◽

Lippa S ◽

Hungerford L ◽

Bailie J ◽

French L ◽

...

Keyword(s):

Risk Factors ◽

Traumatic Brain Injury ◽

Risk Factor ◽

Brain Injury ◽

Clinical Utility ◽

Poor Sleep ◽

Post Injury ◽

Poor Outcome ◽

Blast Exposure ◽

Neurobehavioral Outcome

Abstract Objective To examine the clinical utility of PTSD, Sleep, Resilience, and Lifetime Blast Exposure as ‘Risk Factors’ for predicting poor neurobehavioral outcome following traumatic brain injury (TBI). Methods Participants were 993 service members/veterans evaluated following an uncomplicated mild TBI (MTBI), moderate–severe TBI (ModSevTBI), or injury without TBI (Injured Controls; IC); divided into three cohorts: (1) < 12 months post-injury, n = 237 [107 MTBI, 71 ModSevTBI, 59 IC]; (2) 3-years post-injury, n = 370 [162 MTBI, 80 ModSevTBI, 128 IC]; and (3) 10-years post-injury, n = 386 [182 MTBI, 85 ModSevTBI, 119 IC]. Participants completed a 2-hour neurobehavioral test battery. Odds Ratios (OR) were calculated to determine whether the ‘Risk Factors’ could predict ‘Poor Outcome’ in each cohort separately. Sixteen Risk Factors were examined using all possible combinations of the four risk factor variables. Poor Outcome was defined as three or more low scores (< 1SD) on five TBI-QOL scales (e.g., Fatigue, Depression). Results In all cohorts, the vast majority of risk factor combinations resulted in ORs that were ‘clinically meaningful’ (ORs > 3.00; range = 3.15 to 32.63, all p’s < .001). Risk factor combinations with the highest ORs in each cohort were PTSD (Cohort 1 & 2, ORs = 17.76 and 25.31), PTSD+Sleep (Cohort 1 & 2, ORs = 18.44 and 21.18), PTSD+Sleep+Resilience (Cohort 1, 2, & 3, ORs = 13.56, 14.04, and 20.08), Resilience (Cohort 3, OR = 32.63), and PTSD+Resilience (Cohort 3, OR = 24.74). Conclusions Singularly, or in combination, PTSD, Poor Sleep, and Low Resilience were strong predictors of poor outcome following TBI of all severities and injury without TBI. These variables may be valuable risk factors for targeted early interventions following injury.

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Self-Reported Complaints as Prognostic Markers for Outcome After Mild Traumatic Brain Injury in Elderly: A Machine Learning Approach

Frontiers in Neurology ◽

10.3389/fneur.2021.751539 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mayra Bittencourt ◽

Sebastián A. Balart-Sánchez ◽

Natasha M. Maurits ◽

Joukje van der Naalt

Keyword(s):

Machine Learning ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Elderly Patients ◽

Neck Pain ◽

Functional Outcome ◽

Mild Traumatic Brain Injury ◽

Prognostic Markers ◽

The Elderly ◽

Post Injury

Self-reported complaints are common after mild traumatic brain injury (mTBI). Particularly in the elderly with mTBI, the pre-injury status might play a relevant role in the recovery process. In most mTBI studies, however, pre-injury complaints are neither analyzed nor are the elderly included. Here, we aimed to identify which individual pre- and post-injury complaints are potential prognostic markers for incomplete recovery (IR) in elderly patients who sustained an mTBI. Since patients report many complaints across several domains that are strongly related, we used an interpretable machine learning (ML) approach to robustly deal with correlated predictors and boost classification performance. Pre- and post-injury levels of 20 individual complaints, as self-reported in the acute phase, were analyzed. We used data from two independent studies separately: UPFRONT study was used for training and validation and ReCONNECT study for independent testing. Functional outcome was assessed with the Glasgow Outcome Scale Extended (GOSE). We dichotomized functional outcome into complete recovery (CR; GOSE = 8) and IR (GOSE ≤ 7). In total 148 elderly with mTBI (median age: 67 years, interquartile range [IQR]: 9 years; UPFRONT: N = 115; ReCONNECT: N = 33) were included in this study. IR was observed in 74 (50%) patients. The classification model (IR vs. CR) achieved a good performance (the area under the receiver operating characteristic curve [ROC-AUC] = 0.80; 95% CI: 0.74–0.86) based on a subset of only 8 out of 40 pre- and post-injury complaints. We identified increased neck pain (p = 0.001) from pre- to post-injury as the strongest predictor of IR, followed by increased irritability (p = 0.011) and increased forgetfulness (p = 0.035) from pre- to post-injury. Our findings indicate that a subset of pre- and post-injury physical, emotional, and cognitive complaints has predictive value for determining long-term functional outcomes in elderly patients with mTBI. Particularly, post-injury neck pain, irritability, and forgetfulness scores were associated with IR and should be assessed early. The application of an ML approach holds promise for application in self-reported questionnaires to predict outcomes after mTBI.

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A prospective examination of Axis I psychiatric disorders in the first 5 years following moderate to severe traumatic brain injury

Psychological Medicine ◽

10.1017/s0033291715002986 ◽

2016 ◽

Vol 46 (6) ◽

pp. 1331-1341 ◽

Cited By ~ 41

Author(s):

Y. Alway ◽

K. R. Gould ◽

L. Johnston ◽

D. McKenzie ◽

J. Ponsford

Keyword(s):

Risk Factors ◽

Traumatic Brain Injury ◽

Substance Use ◽

Brain Injury ◽

Anxiety Disorders ◽

Psychiatric Disorders ◽

Substance Use Disorders ◽

First Year ◽

Post Injury ◽

Over Time

BackgroundPsychiatric disorders commonly emerge during the first year following traumatic brain injury (TBI). However, it is not clear whether these disorders soon remit or persist for long periods post-injury. This study aimed to examine, prospectively: (1) the frequency, (2) patterns of co-morbidity, (3) trajectory, and (4) risk factors for psychiatric disorders during the first 5 years following TBI.MethodParticipants were 161 individuals (78.3% male) with moderate (31.2%) or severe (68.8%) TBI. Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV, administered soon after injury and 3, 6 and 12 months, and 2, 3, 4 and 5 years post-injury. Disorder frequencies and generalized estimating equations were used to identify temporal relationships and risk factors.ResultsIn the first 5 years post-injury, 75.2% received a psychiatric diagnosis, commonly emerging within the first year (77.7%). Anxiety, mood and substance-use disorders were the most common diagnostic classes, often presenting co-morbidly. Many (56.5%) experienced a novel diagnostic class not present prior to injury. Disorder frequency ranged between 61.8 and 35.6% over time, decreasing by 27% [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.65–0.83] with each year post-injury. Anxiety disorders declined significantly over time (OR 0.73, 95% CI 0.63–0.84), whilst mood and substance-use disorder rates remained stable. The strongest predictors of post-injury disorder were pre-injury disorder (OR 2.44, 95% CI 1.41–4.25) and accident-related limb injury (OR 1.78, 95% CI 1.03–3.07).ConclusionsFindings suggest the first year post-injury is a critical period for the emergence of psychiatric disorders. Disorder frequency declines thereafter, with anxiety disorders showing greater resolution than mood and substance-use disorders.

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A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.788055 ◽

2022 ◽

Vol 13 ◽

Author(s):

Samuel Houle ◽

Olga N. Kokiko-Cochran

Keyword(s):

Risk Factors ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Inflammatory Response ◽

Genetic Risk ◽

Traumatic Injury ◽

Genetic Risk Factors ◽

Post Injury ◽

Immune Stress ◽

Age Related

Increasing evidence demonstrates that aging influences the brain's response to traumatic brain injury (TBI), setting the stage for neurodegenerative pathology like Alzheimer's disease (AD). This topic is often dominated by discussions of post-injury aging and inflammation, which can diminish the consideration of those same factors before TBI. In fact, pre-TBI aging and inflammation may be just as critical in mediating outcomes. For example, elderly individuals suffer from the highest rates of TBI of all severities. Additionally, pre-injury immune challenges or stressors may alter pathology and outcome independent of age. The inflammatory response to TBI is malleable and influenced by previous, coincident, and subsequent immune insults. Therefore, pre-existing conditions that elicit or include an inflammatory response could substantially influence the brain's ability to respond to traumatic injury and ultimately affect chronic outcome. The purpose of this review is to detail how age-related cellular and molecular changes, as well as genetic risk variants for AD affect the neuroinflammatory response to TBI. First, we will review the sources and pathology of neuroinflammation following TBI. Then, we will highlight the significance of age-related, endogenous sources of inflammation, including changes in cytokine expression, reactive oxygen species processing, and mitochondrial function. Heightened focus is placed on the mitochondria as an integral link between inflammation and various genetic risk factors for AD. Together, this review will compile current clinical and experimental research to highlight how pre-existing inflammatory changes associated with infection and stress, aging, and genetic risk factors can alter response to TBI.

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Longitudinal Analyses of the Reciprocity of Depression and Anxiety after Traumatic Brain Injury and Its Clinical Implications

Journal of Clinical Medicine ◽

10.3390/jcm10235597 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5597

Author(s):

Biyao Wang ◽

Marina Zeldovich ◽

Katrin Rauen ◽

Yi-Jhen Wu ◽

Amra Covic ◽

...

Keyword(s):

Risk Factors ◽

Traumatic Brain Injury ◽

Brain Injury ◽

First Year ◽

Depression And Anxiety ◽

Post Injury ◽

Related Factors ◽

Cross Domain ◽

Psychiatric Disturbances ◽

Patient Reported

Depression and anxiety are common following traumatic brain injury (TBI). Understanding their prevalence and interplay within the first year after TBI with differing severities may improve patients’ outcomes after TBI. Individuals with a clinical diagnosis of TBI recruited for the large European collaborative longitudinal study CENTER-TBI were screened for patient-reported major depression (MD) and generalized anxiety disorder (GAD) at three, six, and twelve months post-injury (N = 1683). Data were analyzed using autoregressive cross-lagged models. Sociodemographic, premorbid and injury-related factors were examined as risk factors. 14.1–15.5% of TBI patients reported moderate to severe MD at three to twelve months after TBI, 7.9–9.5% reported GAD. Depression and anxiety after TBI presented high within-domain persistency and cross-domain concurrent associations. MD at three months post-TBI had a significant impact on GAD at six months post-TBI, while both acted bidirectionally at six to twelve months post-TBI. Being more severely disabled, having experienced major extracranial injuries, an intensive care unit stay, and being female were risk factors for more severe MD and GAD. Major trauma and the level of consciousness after TBI were additionally associated with more severe MD, whereas being younger was related to more severe GAD. Individuals after TBI should be screened and treated for MD and GAD early on, as both psychiatric disturbances are highly persistent and bi-directional in their impact. More severely disabled patients are particularly vulnerable, and thus warrant timely screening and intensive follow-up treatment.

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Age-related differences in the impact of coagulopathy in patients with isolated traumatic brain injury: an observational cohort study

10.21203/rs.2.19876/v1 ◽

2020 ◽

Author(s):

Wataru Takayama ◽

Akira Endo ◽

Hazuki Koguchi ◽

Kiyoshi Murata ◽

Yasuhiro Otomo

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hospital Mortality ◽

The Elderly ◽

International Normalized Ratio ◽

Elderly Group ◽

Age Related ◽

Correlation Degree ◽

Observational Cohort ◽

The Impact

Abstract Background Although age and trauma-induced coagulopathy (TIC) are well-known predictors of poor outcome after traumatic brain injury (TBI), the interaction effect of these two predictors remains unclear.Objectives We assessed age-related differences in the impact of TIC on the outcome following isolated TBI.Methods We conducted a retrospective observational study in two tertiary emergency critical care medical centers in Japan from 2013 to 2018. A total of 1036 patients with isolated TBI [head abbreviated injury scale (AIS) ≥3, and other AIS <3] were selected, and divided into the non-elderly (n = 501, 16-64 years) and elderly group (n = 535, age ≥65 years). We further evaluated the impact of coagulopathy (international normalized ratio ≥1.2, and/or platelet count <120 × 10 9 /L, and/or fibrinogen ≤150 mg/dL) on TBI outcomes [Glasgow Outcome Scale-Extended (GOS-E) scores, in-hospital mortality, and ventilation-free days (VFD)] in both groups using univariate and multivariate models. Further, we conducted an age-based assessment of the impact of coagulopathy on GOS-E using a generalized additive model.Results The multivariate model showed a significant association of age and coagulopathy with lower GOS-E scores, in-hospital mortality, and shorter VFD in the non-elderly group; however, significant impact of coagulopathy was not observed for all the outcomes in the elderly group. There was a decrease in the correlation degree between coagulopathy and GOS-E scores decreased with age over 65 years old.Conclusions There was a low impact of coagulopathy on functional and survival outcomes in geriatric patients with isolated TBI.

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Traumatic Brain Injury in the Elderly: Can We Reduce Readmissions?

The American Surgeon ◽

10.1177/0003134820933560 ◽

2020 ◽

pp. 000313482093356

Author(s):

Tarik Wasfie ◽

Jordan Maxwell ◽

Andrea Parsons ◽

Jennifer Hille ◽

Raquel Yapchai ◽

...

Keyword(s):

Risk Factors ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Anticoagulant Therapy ◽

The Elderly ◽

Primary Diagnosis ◽

Trauma Patients ◽

Chi Square ◽

Home Setting ◽

Chi Square Analysis

Background Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity in trauma patients, with a growing incidence among the elderly. Injury-related disability has many costs, and rehospitalization is a significant part of that. The current study was carried out in an elderly population with TBI to identify risk factors and measures associated with rehospitalization. Methods We performed a retrospective analysis of 299 patients with a primary diagnosis of TBI admitted between 2016 and 2018. Variables selected for analysis encompassed the following: patient age, sex, comorbidities, diagnosis, length of stay, use of anticoagulants, 6-month readmission rate, and diagnosis for readmission. Chi-square analysis was used to identify potential risk factors, and multiple regression analysis was conducted to model the relationship. Results 209 patients met inclusion criteria, with a mean age of 69 years (SD ± 18.6 years), with (51.5%) males and (48.5%) females. 188 (62.9%) patients were on anticoagulant therapy. 120 patients were discharged to home (40.1%). 79 patients (26.4%) were readmitted within 6 months of discharge, the majority of whom (48 patients, 60.8%) presented with a subdural hematoma (SDH). 38 readmitted patients (49%) came from home, and 57 patients (80%) were on anticoagulant therapy. Conclusion In elderly patients with TBI, discharge to a home setting correlates with a higher risk of readmission within 6 months, a majority with a diagnosis of recurrent SDH. Anticoagulant therapy and frequent past readmissions also correlated with a higher risk of subsequent readmission.

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Suicidality after traumatic brain injury: demographic, injury and clinical correlates

Psychological Medicine ◽

10.1017/s0033291702005561 ◽

2002 ◽

Vol 32 (4) ◽

pp. 687-697 ◽

Cited By ~ 94

Author(s):

GRAHAME SIMPSON ◽

ROBYN TATE

Keyword(s):

Risk Factors ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Suicidal Ideation ◽

Suicide Ideation ◽

Suicide Attempts ◽

Post Injury ◽

Psychiatric Disturbance ◽

Clinical Correlates ◽

High Level

Background. In spite of the high frequency of emotional distress after traumatic brain injury (TBI), few investigations have examined the extreme of such distress, namely, suicidality, and no large scale surveys have been conducted. The current study examined both the prevalence and demographic, injury, and clinical correlates of hopelessness, suicidal ideation and suicide attempts after TBI.Methods. Out-patients (N = 172) with TBI were screened for suicidal ideation and hopelessness using the Beck Scale for Suicide Ideation and the Beck Hopelessness Scale. Data were also collected on demographic, injury, pre-morbid and post-injury psychosocial variables and included known risk factors for suicide.Results. A substantial proportion of participants had clinically significant levels of hopelessness (35%) and suicide ideation (23%), and 18% had made a suicide attempt post-injury. There was a high degree of co-morbidity between suicide attempts and emotional/psychiatric disturbance. Results from regression analyses indicated that a high level of hopelessness was the most significant association of suicide ideation and a high level of suicide ideation, along with occurrence of post-injury emotional/psychiatric disturbance, were the most significant associations of post-injury suicide attempts. Neither injury severity nor the presence of pre-morbid suicide risk factors contributed to elevated levels of suicidality post-injury.Conclusions. Suicidality is a common psychological reaction to TBI among out-patient populations. Management should involve careful history taking of previous post-injury suicidal behaviour, assessment of post-injury adjustment to TBI with particular focus on the degree of emotional/psychiatric disturbance, and close monitoring of those individuals with high levels of hopelessness and suicide ideation.

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