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Age-related differences in fibrinolytic parameters in patients with acute traumatic brain injury.

ABSTRACT: Coagulopathy and old age have been associated with poor outcomes in traumatic brain injury (TBI) patients; however, the relationships of coagulopathy and age with the acute phase of TBI remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more severe in older patients in the acute phase of TBI and may explain, in part, their poor outcome.We analyzed the relationship between coagulation/fibrinolytic parameters and age in the acute phase of TBI by retrospectively evaluating 274 patients with initial blood samples obtained no more than 1 hour after injury. Measurement of platelet count, prothrombin time, activated partial thromboplastin time, plasma levels of fibrinogen, and D-dimer was done in the emergency department on arrival as well as 3, 6, and 12 hours following injury. Values were compared between patients aged 16-55 years (group 1) and those aged older than 55 years (group 2) with an Abbreviated Injury Score (AIS)-head of 3-5 to identify any relationship between these parameters and age.When groups 1 and 2 were matched for AIS-head, plasma levels of D-dimer in group 2 were significantly higher than those in group 1 from hospital admission to 12 hours after injury. The Glasgow Outcome Scale scores at 3 months post-injury of group 2 with AIS 4 and 5 were significantly lower than those of group 1 (both P < 0.0001).Fibrinolytic abnormalities are more severe in older acute-phase TBI patients, which may be a factor associated with their poor prognosis.

SUBMITTER: Nakae R

PROVIDER: S-EPMC5609444 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Age-related differences in fibrinolytic parameters in patients with acute traumatic brain injury.

Nakae Ryuta R Yokobori Shoji S Takayama Yasuhiro Y Kuwamoto Kentaro K Naoe Yasutaka Y Yokota Hiroyuki H

Surgical neurology international 20170906

<h4>Background</h4>Coagulopathy and old age have been associated with poor outcomes in traumatic brain injury (TBI) patients; however, the relationships of coagulopathy and age with the acute phase of TBI remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more severe in older patients in the acute phase of TBI and may explain, in part, their poor outcome.<h4>Methods</h4>We analyzed the relationship between coagulation/fibrinolytic parameters and age in the acute phas ...[more]

PMID: 28966820

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Project description:BackgroundAmong the many factors that may influence traumatic brain injury (TBI) progression, sex is one of the most controversial. The objective of this study was to investigate sex differences in TBI-associated morbidity and mortality using data from the largest trauma registry in Japan.MethodsThis retrospective, population-based observational study included patients with isolated TBI, who were registered in a nationwide database between 2004 and 2018. We excluded patients with extracranial injury (Abbreviated Injury Scale score ≥ 3) and removed potential confounding factors, such as non-neurological causes of mortality. Patients were stratified by age and mortality and post-injury complications were compared between males and females.ResultsA total of 51,726 patients with isolated TBI were included (16,901 females and 34,825 males). Mortality across all ages was documented in 12.01% (2030/16901) and 12.76% (4445/34825) of males and females, respectively. The adjusted odds ratio (OR) of TBI mortality for males compared to females was 1.32 (95% confidence interval [CI], 1.22-1.42]. Males aged 10-19 years and ≥ 60 years had a significantly higher mortality than females in the same age groups (10-19 years: adjusted OR, 1.97 [95% CI, 1.08-3.61]; 60-69 years: adjusted OR, 1.24 [95% CI, 1.02-1.50]; 70-79 years: adjusted OR, 1.20 [95% CI, 1.03-1.40]; 80-89 years: adjusted OR, 1.50 [95% CI, 1.31-1.73], and 90-99 years: adjusted OR, 1.72 [95% CI, 1.28-2.32]). In terms of the incidence of post-TBI neurologic and non-neurologic complications, the crude ORs were 1.29 (95% CI, 1.19-1.39) and 1.14 (95% CI, 1.07-1.22), respectively, for males versus females. This difference was especially evident among elderly patients (neurologic complications: OR, 1.27 [95% CI, 1.14-1.41]; non-neurologic complications: OR, 1.29 [95% CI, 1.19-1.39]).ConclusionsIn a nationwide sample of patients with TBI in Japan, males had a higher mortality than females. This disparity was particularly evident among younger and older generations. Furthermore, elderly males experienced more TBI complications than females of the same age.

Project description:Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week. At each time-point, gene expression profiles, and imaging findings from both magnetic resonance imaging (MRI) and computed tomography were obtained and compared. The young group was found to have greater gene expression of inflammatory regulatory genes at 48 h and 1-week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine-rich repeat neuronal 3 (LRRN3), and lymphoid enhancer-binding factor 1 (LEF1) compared to the old group. In the old group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The old group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-? superfamily and is linked to neurorecovery and neuroregeneration compared to the young group. We link these gene expression findings that were validated to neuroimaging, reporting that in the old group with a MRI finding of TBI-related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the young group. Together, these data indicate that age impacts gene activity following a TBI, and suggest that this differential activity related to immune regulation and neurorecovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging.

Project description:See Schiff (doi:10.1093/awx209) for a scientific commentary on this article. Patients with acute severe traumatic brain injury may recover consciousness before self-expression. Without behavioural evidence of consciousness at the bedside, clinicians may render an inaccurate prognosis, increasing the likelihood of withholding life-sustaining therapies or denying rehabilitative services. Task-based functional magnetic resonance imaging and electroencephalography techniques have revealed covert consciousness in the chronic setting, but these techniques have not been tested in the intensive care unit. We prospectively enrolled 16 patients admitted to the intensive care unit for acute severe traumatic brain injury to test two hypotheses: (i) in patients who lack behavioural evidence of language expression and comprehension, functional magnetic resonance imaging and electroencephalography detect command-following during a motor imagery task (i.e. cognitive motor dissociation) and association cortex responses during language and music stimuli (i.e. higher-order cortex motor dissociation); and (ii) early responses to these paradigms are associated with better 6-month outcomes on the Glasgow Outcome Scale-Extended. Patients underwent functional magnetic resonance imaging on post-injury Day 9.2 ± 5.0 and electroencephalography on Day 9.8 ± 4.6. At the time of imaging, behavioural evaluation with the Coma Recovery Scale-Revised indicated coma (n = 2), vegetative state (n = 3), minimally conscious state without language (n = 3), minimally conscious state with language (n = 4) or post-traumatic confusional state (n = 4). Cognitive motor dissociation was identified in four patients, including three whose behavioural diagnosis suggested a vegetative state. Higher-order cortex motor dissociation was identified in two additional patients. Complete absence of responses to language, music and motor imagery was only observed in coma patients. In patients with behavioural evidence of language function, responses to language and music were more frequently observed than responses to motor imagery (62.5-80% versus 33.3-42.9%). Similarly, in 16 matched healthy subjects, responses to language and music were more frequently observed than responses to motor imagery (87.5-100% versus 68.8-75.0%). Except for one patient who died in the intensive care unit, all patients with cognitive motor dissociation and higher-order cortex motor dissociation recovered beyond a confusional state by 6 months. However, 6-month outcomes were not associated with early functional magnetic resonance imaging and electroencephalography responses for the entire cohort. These observations suggest that functional magnetic resonance imaging and electroencephalography can detect command-following and higher-order cortical function in patients with acute severe traumatic brain injury. Early detection of covert consciousness and cortical responses in the intensive care unit could alter time-sensitive decisions about withholding life-sustaining therapies.

Project description:BACKGROUND:Older-age individuals are at the highest risk for disability from a traumatic brain injury (TBI). Astrocytes are the most numerous glia in the brain, necessary for brain function, yet there is little known about unique responses of astrocytes in the aged-brain following TBI. METHODS:Our approach examined astrocytes in young adult, 4-month-old, versus aged, 18-month-old mice, at 1, 3, and 7?days post-TBI. We selected these time points to span the critical period in the transition from acute injury to presumably irreversible tissue damage and disability. Two approaches were used to define the astrocyte contribution to TBI by age interaction: (1) tissue histology and morphological phenotyping, and (2) transcriptomics on enriched astrocytes from the injured brain. RESULTS:Aging was found to have a profound effect on the TBI-induced loss of astrocyte function needed for maintaining water transport and edema-namely, aquaporin-4. The aged brain also demonstrated a progressive exacerbation of astrogliosis as a function of time after injury. Moreover, clasmatodendrosis, an underrecognized astrogliopathy, was found to be significantly increased in the aged brain, but not in the young brain. As a function of TBI, we observed a transitory refraction in the number of these astrocytes, which rebounded by 7?days post-injury in the aged brain. Transcriptomic data demonstrated disproportionate changes in genes attributed to reactive astrocytes, inflammatory response, complement pathway, and synaptic support in aged mice following TBI compared to young mice. Additionally, our data highlight that TBI did not evoke a clear alignment with the previously defined "A1/A2" dichotomy of reactive astrogliosis. CONCLUSIONS:Overall, our findings point toward a progressive phenotype of aged astrocytes following TBI that we hypothesize to be maladaptive, shedding new insights into potentially modifiable astrocyte-specific mechanisms that may underlie increased fragility of the aged brain to trauma.

Project description:Introduction:Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are two of the signature injuries in military service members who have been exposed to explosive blasts during deployments to Iraq and Afghanistan. Acute stress disorder (ASD), which occurs within 2-30 d after trauma exposure, is a more immediate psychological reaction predictive of the later development of PTSD. Most previous studies have evaluated service members after their return from deployment, which is often months or years after the initial blast exposure. The current study is the first large study to collect psychological and neuropsychological data from active duty service members within a few days after blast exposure. Materials and Methods:Recruitment for blast-injured TBI patients occurred at the Air Force Theater Hospital, 332nd Air Expeditionary Wing, Joint Base Balad, Iraq. Patients were referred from across the combat theater and evaluated as part of routine clinical assessment of psychiatric and neuropsychological symptoms after exposure to an explosive blast. Four measures of neuropsychological functioning were used: the Military Acute Concussion Evaluation (MACE); the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); the Headminder Cognitive Stability Index (CSI); and the Automated Neuropsychological Assessment Metrics, Version 4.0 (ANAM4). Three measures of combat exposure and psychological functioning were used: the Combat Experiences Scale (CES); the PTSD Checklist-Military Version (PCL-M); and the Acute Stress Disorder Scale (ASDS). Assessments were completed by a deployed clinical psychologist, clinical social worker, or mental health technician. Results:A total of 894 patients were evaluated. Data from 93 patients were removed from the data set for analysis because they experienced a head injury due to an event that was not an explosive blast (n = 84) or they were only assessed for psychiatric symptoms (n = 9). This resulted in a total of 801 blast-exposed patients for data analysis. Because data were collected in-theater for the initial purpose of clinical evaluation, sample size varied widely between measures, from 565 patients who completed the MACE to 154 who completed the CES. Bivariate correlations revealed that the majority of psychological measures were significantly correlated with each other (ps ? 0.01), neuropsychological measures were correlated with each other (ps ? 0.05), and psychological and neuropsychological measures were also correlated with each other (ps ? 0.05). Conclusions:This paper provides one of the first descriptions of psychological and neuropsychological functioning (and their inter-correlation) within days after blast exposure in a large sample of military personnel. Furthermore, this report describes the methodology used to gather data for the acute assessment of TBI, PTSD, and ASD after exposure to an explosive blast in the combat theater. Future analyses will examine the common and unique symptoms of TBI and PTSD, which will be instrumental in developing new assessment approaches and intervention strategies.

Dataset Information

Age-related differences in fibrinolytic parameters in patients with acute traumatic brain injury.

Publications

Age-related differences in fibrinolytic parameters in patients with acute traumatic brain injury.

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