Rapid detection of platelet inhibition and dysfunction in traumatic brain injury: A prospective observational study.

BACKGROUND: Rapid platelet function testing is frequently used to determine platelet function in patients with traumatic intracranial hemorrhage (tICH). Accuracy and clinical significance of decreased platelet response detected by these tests is not well understood. We sought to determine whether VerifyNow and whole blood aggregometry (WBA) can detect poor platelet response and to elucidate its clinical significance for tICH patients. METHODS: We prospectively enrolled patients with isolated tICH between 2018 and 2020. Demographics, medical history, injury characteristics, and patient outcomes were recorded. Platelet function was determined by VerifyNow and WBA testing at the time of arrival to the trauma bay and 6 hours later. RESULTS: A total of 221 patients were enrolled, including 111 patients on no antiplatelet medication, 78 on aspirin, 6 on clopidogrel, and 26 on aspirin and clopidogrel. In the trauma bay, 29.7% and 67.7% of patients on no antiplatelet medication had poor platelet response on VerifyNow and WBA, respectively. Among patients on aspirin, 72.2% and 82.2% had platelet dysfunction on VerifyNow and WBA. Among patients on clopidogrel, 67.9% and 88.9% had platelet dysfunction on VerifyNow and WBA. Patients with nonresponsive platelets had similar in-hospital mortality (3 [3.0%] vs. 6 [6.3%], p = 0.324), tICH progression (26 [27.1%] vs. 24 [26.1%], p = 0.877), intensive care unit admission rates (34 [34.3%] vs. 38 [40.0%), p = 0.415), and length of stay (3 [interquartile range, 2-8] vs. 3.2 [interquartile range, 2-7], p = 0.818) to those with responsive platelets. Platelet transfusion did not improve platelet response or patient outcomes. CONCLUSION: Rapid platelet function testing detects a highly prevalent poor platelet response among patients with tICH, irrespective of antiplatelet medication use. VerifyNow correlated fairly with whole blood aggregometry among patients with tICH and platelet responsiveness detectable by these tests did not correlate with clinical outcomes. In addition, our results suggest that platelet transfusion may not improve clinical outcomes in patients with tICH. LEVEL OF EVIDENCE: Diagnostic tests, level II.

Coagulopathy and its effect on treatment and mortality in patients with traumatic intracranial hemorrhage.

BACKGROUND: The role of coagulopathy in patients with traumatic brain injury has remained elusive. In the present study, we aim to assess the prevalence of coagulopathy in patients with traumatic intracranial hemorrhage, their clinical features, and the effect of coagulopathy on treatment and mortality. METHODS: An observational, retrospective single-center cohort of consecutive patients with traumatic intracranial hemorrhage treated at Helsinki University Hospital between 01 January and 31 December 2010. We compared clinical and radiological parameters in patients with and without coagulopathy defined as drug- or disease-induced, i.e., antiplatelet or anticoagulant medication at a therapeutic dose, thrombocytopenia (platelet count < 100 E9/L), international normalized ratio > 1.2, or thromboplastin time < 60%. Primary outcome was 30-day all-cause mortality. Logistic regression analysis allowed to assess for factors associated with coagulopathy and mortality. RESULTS: Of our 505 patients (median age 61 years, 65.5% male), 206 (40.8%) had coagulopathy. Compared to non-coagulopathy patients, coagulopathy patients had larger hemorrhage volumes (mean 140.0 mL vs. 98.4 mL, p < 0.001) and higher 30-day mortality (18.9% vs. 9.7%, p = 0.003). In multivariable analysis, older age, lower admission Glasgow Coma Scale score, larger hemorrhage volume, and conservative treatment were independently associated with mortality. Surgical treatment was associated with lower mortality in both patients with and without coagulopathy. CONCLUSIONS: Coagulopathy was more frequent in patients with traumatic intracranial hemorrhage presenting larger hemorrhage volumes compared to non-coagulopathy patients but was not independently associated with higher 30-day mortality. Hematoma evacuation, in turn, was associated with lower mortality irrespective of coagulopathy.

Choosing the Best Approach to Warfarin Reversal After Traumatic Intracranial Hemorrhage.

BACKGROUND: Patients on warfarin with traumatic intracranial hemorrhage often have the warfarin effects pharmacologically reversed. We compared outcomes among patients who received 4-factor prothrombin complex concentrate (PCC), fresh frozen plasma (FFP), or no reversal to assess the real-world impact of PCC on elderly patients with traumatic intracranial hemorrhage (ICH). MATERIALS AND METHODS: This was a retrospective analysis of 150 patients on preinjury warfarin. Data were manually abstracted from the electronic medical record of an academic level 1 trauma center for patients admitted between January 2013 and December 2018. Outcomes were ICH progression on follow-up computed tomography scan, mortality, need for surgical intervention, and trends in the use of reversal agents. RESULTS: Of 150 patients eligible for analysis, 41 received FFP, 60 PCC, and 49 were not reversed. On multivariable analysis, patients not reversed [OR 0.25 95% CI (0.31-0.85)] and women [OR 0.38 95% CI (0.17-0.88)] were less likely to experience progression of their initial bleed on follow-up computed tomography while subdural hemorrhage increased the risk [OR 3.69 95% CI (1.27-10.73)]. There was no difference between groups in terms of mortality or need for surgery. Over time use of reversal with PCC increased while use of FFP and not reversing warfarin declined (P < 0.001). CONCLUSIONS: Male gender and using a reversal agent were associated with progression of ICH. Choice of reversal did not impact the need for surgery, hospital length of stay, or mortality. Some ICH patients may not require warfarin reversal and may bias studies, especially retrospective studies of warfarin reversal.

Platelet Transfusion After Traumatic Intracranial Hemorrhage in Patients on Antiplatelet Agents.

BACKGROUND: With an aging population, the number of patients on antiplatelet medications and traumatic brain injury (TBI) is increasing. Our study aimed to evaluate the role of platelet transfusion on outcomes after traumatic intracranial bleeding (IB) in these patients. METHODS: We analyzed our prospectively maintained TBI database from 2014 to 2016. We included all isolated TBI patients with an IB, who were on preinjury antiplatelet agents and excluded patients taking anticoagulants. Outcome measures included the progression of IB, neurosurgical intervention, and mortality. Regression analysis was performed. RESULTS: A total of 343 patients met the inclusion criteria. Mean age was 58 ± 11 y, 58% were men, and median injury severity score was 15 (10-24). Distribution of antiplatelet agents was as follows: aspirin (60%) and clopidogrel (35%). Overall, 74% patients received platelet transfusion after admission with a median number of two platelet units. After controlling for confounders, patients who received one unit of pooled platelets had no difference in progression of IB (odds ratio [OR]: 0.98, [0.6-1.9], P = 0.41), need for neurosurgical intervention (OR: 1.09, [0.7-2.5], P = 0.53), and mortality (OR: 0.84, [0.6-1.8], P = 0.51). However, patients who received two units of pooled platelets had lower rate of progression of IB (OR: 0.69, [0.4-0.8], P = 0.02), the need for neurosurgical intervention (OR: 0.81, [0.3-0.9], P = 0.03), and mortality (OR: 0.84, [0.5-0.9], P = 0.04). Both groups were compared with those who did not receive platelet transfusion. CONCLUSIONS: The use of two units of platelet may decrease the risk of IB progression, neurosurgical intervention, and mortality in patients on preinjury antiplatelet agents and TBI. Further studies should focus on developing protocols for platelet transfusion to improve outcomes in these patients. LEVEL OF EVIDENCE: Level III prognostic.

Newer and Better? Comparing Direct Oral Anticoagulants to Warfarin in Patients With Traumatic Intracranial Hemorrhage.

BACKGROUND: Direct oral anticoagulants (DOACs) have overtaken warfarin as the preferred anticoagulants for stroke prevention with atrial fibrillation and for treatment of venous thromboembolism. Despite the increased prevalence of DOACs, literature studying their impact on trauma patients with intracranial hemorrhage (ICH) remains limited. Most DOAC reversal agents have only been recently available, and concerns for worse outcomes with DOACs among this population remain. This study aims to assess the outcomes of patients with traumatic ICH taking DOACs compared with those taking warfarin. METHODS: A retrospective analysis of patients with traumatic ICH over a 5-year period was conducted. Demographics, injury severity, medication, and outcome data were collected for each patient. Patients taking warfarin and DOACs were compared. RESULTS: 736 patients had traumatic ICH over the study period, 75 of which were on either DOACs (25 patients) or warfarin (50 patients). The median age of the anticoagulated patients was 78 years; 52% were female, and 91% presented secondary to a fall. DOACs were reversed at close to half the rate of warfarin (40% vs 77%; P = .032). Despite this, the 2 groups had similar rates of worsening examination, need for operative intervention, and in-hospital mortality. In the follow-up, fewer patients taking DOACs had died at 6-months postinjury compared with those taking warfarin (8% vs 30%; P = .041). DISCUSSION: Despite DOACs being reversed at nearly half the rate of warfarin, patients presenting with traumatic ICH on warfarin had higher 6-month mortality suggesting a potential survival advantage for DOACs over warfarin in this population.

A systematic review and meta-analysis of traumatic intracranial hemorrhage in patients taking prehospital antiplatelet therapy: Is there a role for platelet transfusions?

BACKGROUND: Platelet transfusion has been utilized to reverse platelet dysfunction in patients on preinjury antiplatelets who have sustained a traumatic intracranial hemorrhage (tICH); however, there is little evidence to substantiate this practice. The objective of this study was to perform a systematic review on the impact of platelet transfusion on survival, hemorrhage progression and need for neurosurgical intervention in patients with tICH on prehospital antiplatelet medication. METHODS: Controlled, observational and randomized, prospective and retrospective studies describing tICH, preinjury antiplatelet use, and platelet transfusion reported in PubMed, Embase, Cochrane Reviews, Cochrane Trials and Cochrane DARE databases between January 1987 and March 2019 were included. Investigations of concomitant anticoagulant use were excluded. Risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled estimates of relative effect of platelet transfusion on the risk of death, hemorrhage progression and need for neurosurgical intervention using the methods of Dersimonian-Laird random-effects meta-analysis. Sensitivity analysis established whether study size contributed to heterogeneity. Subgroup analyses determined whether antiplatelet type, additional blood products/reversal agents, or platelet function assays impacted effect size using meta-regression. RESULTS: Twelve of 18,609 screened references were applicable to our questions and were qualitatively and quantitatively analyzed. We found no association between platelet transfusion and the risk of death in patients with tICH taking prehospital antiplatelets (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.76-2.18; p = 0.346; I = 32.5%). There was no significant reduction in hemorrhage progression (OR, 0.88; 95% CI, 0.34-2.28; p = 0.788; I = 78.1%). There was no significant reduction in the need for neurosurgical intervention (OR, 1.00; 95% CI, 0.53-1.90, p = 0.996; I = 59.1%; p = 0.032). CONCLUSION: Current evidence does not support the use of platelet transfusion in patients with tICH on prehospital antiplatelets, highlighting the need for a prospective evaluation of this practice. LEVEL OF EVIDENCE: Systematic Reviews and Meta-Analyses, Level III.

Clinical role of low hemoglobin ratio in poor neurologic outcomes in infants with traumatic intracranial hemorrhage.

Traumatic brain injury (TBI) is the leading cause of pediatric morbidity and mortality worldwide, and half of all fatalities occur in infants aged less than 1 year. We analyzed 129 infants diagnosed with TBI complicated with intracranial hemorrhage confirmed by brain computed tomography. We defined delta hemoglobin (ΔHB) as nadir HB - age specific mean HB, and the ratio of HB (%) as ΔHB/age specific mean HB x 100. Infants with poor neurologic outcomes had a lower admission HB and ΔHB (p < 0.05). The in-hospital mortality rate was 10.1% (13 infants), and the infants who died had a significantly lower ΔHB ratio compared to the survivors. The area under the receiving operating characteristic curve (AUC) of initial Glasgow Coma Score (GCS) in predicting neurologic outcomes was higher than that of ratio of ΔHB (0.881 v.s 0.859). In multivariate logistic regression analysis with the optimal cutoff ratio of ΔHB, it remained an independent predictor for in-hospital mortality and poor neurologic outcomes at discharge and at 6 months. AUC analysis for the ratio of ΔHB for poor neurologic outcomes in infants aged from 0-6 months was 0.85 and the optimal cutoff was -30.7% (sensitivity, 69%; specificity, 92%; positive likelihood ratio (LR+), 8.24; negative likelihood ratio (LR-), 0.34); the AUC was 0.88 in infants aged from 6-12 months and the optimal cutoff was -20.6% (sensitivity, 89%; specificity, 79%; LR+, 4.13; LR-, 0.15).

Traumatic Parafalcine Subdural Hematoma: A Clinically Benign Finding.

BACKGROUND: Guidelines for management of intracranial hemorrhage do not account for bleed location. We hypothesize that parafalcine subdural hematoma (SDH), as compared to convexity SDH, is a distinct clinical entity and these patients do not benefit from critical care monitoring or repeat imaging. METHODS: We identified patients presenting to a single level I trauma center with isolated head injuries from February 2016 to August 2017. We identified 88 patients with isolated blunt traumatic parafalcine SDH and 228 with convexity SDH. RESULTS: Demographics, comorbidities, and use of antiplatelet and anticoagulant agents were similar between the groups. As compared to patients with convexity SDH, patients with parafalcine SDH had a significantly lower incidence of radiographic progression, and had no cases of neurologic deterioration, neurosurgical intervention, or mortality (all P < 0.005). Compared to patients admitted to the intensive care unit, patients with parafalcine SDH admitted to the floor had a shorter length of stay (2.0 ± 1.6 versus 3.8 ± 2.9 d, P < 0.005) with no difference in outcomes. CONCLUSIONS: Patients presenting with a parafalcine SDH are a distinct and relatively benign clinical entity as compared to convexity SDH and do not benefit from repeat imaging or intensive care unit admission.

Updating the risk profile of fatal head trauma: an autopsy study with focus on age- and sex-dependent differences.

Fatal head trauma (FHT) represents one of the most frequent causes of death diagnosed in forensic pathology. However, profound statistic autopsy data on FHT is still sparse. Therefore, the purpose of this study was to investigate the circumstances and injury patterns of FHT with particular focus on age and sex, and additionally, to describe a recent risk profile of FHT. To this end, the forensic autopsy records of each FHT case at a large German university hospital during a 10-year period (2006-2015) were analyzed retrospectively (n = 372). The male-female ratio was 2.6:1. Regarding median age, females were 12.5 years older than males. Traffic-associated FHT represents the major mechanism of death, followed by fall-associated FHT. While accident was the major manner of death and presented a similar distribution of age and sex, homicides were the only subgroup with a significantly lower ratio between males and females. Skull fractures occurred in 78.2% and intracranial hemorrhages in 80.6% of all cases. In summary and partly in contrast to clinical data on head trauma, FHT still occurs predominantly in male individuals under the age of 45 years, in the context of traffic accidents and affected by alcohol intake. Improvements in traffic security as well as continuing surveillance of the incidence of FHT by forensic autopsies are necessary to further reduce the incidence of FHT.

Consequences of pre-injury utilization of direct oral anticoagulants in patients with traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: The rapid adoption and widespread use of direct oral anticoagulants (DOACs) has outpaced research efforts to establish their effects in bleeding trauma patients. In patients with complicated traumatic brain injury (TBI) caused by intracranial hemorrhage, DOAC use may be associated with higher bleeding volume and potentially more disastrous sequelae than use of vitamin K antagonists (VKAs). In the current systematic review and meta-analysis we set out to evaluate the literature on the relationship between preinjury DOAC use and course of the intracranial hemorrhage. (ICH), its treatment and mortality rates in TBI patients, and to compare these outcomes to those of patients with preinjury VKA use. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched using a search strategy including three main terms: "traumatic brain injury," "direct oral anticoagulants," and "vitamin K antagonists." There were 1,446 abstracts screened, and ultimately, six included articles. Random effects modeling meta-analysis was performed on in-hospital mortality, ICH progression and neurosurgical intervention rate. RESULTS: All cohorts had similar baseline and emergency department parameters. Within individual studies surgery rate, reversal agents used, ICH progression and in-hospital mortality differed significantly between DOAC and VKA cohorts. Meta-analysis showed no significant difference in in-hospital mortality (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.23-4.06; I = 76%; p = 0.97), neurosurgical interventions (OR, 0.48; 95% CI, 0.14-1.63; p = 0.24), or ICH progression rates (OR, 1.86; 95% CI, 0.32-10.66; p = 0.49) between patients that used preinjury DOACs versus patients that used VKAs. CONCLUSION: Direct oral anticoagulant-using mild TBI patients do not appear to be at an increased risk of in-hospital mortality, nor of increased ICH progression or surgery rates, compared with those taking VKAs. LEVEL OF EVIDENCE: Systematic review, level III.

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.

BACKGROUND: Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. METHODS: This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). RESULTS: Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]). INTERPRETATION: Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. FUNDING: National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme). TRANSLATIONS: For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material.

Mortality After Traumatic Brain Injury in Elderly Patients: A New Scoring System.

BACKGROUND: Traumatic brain injury (TBI) remains a life-threatening condition characterized by growing incidence worldwide, particularly in the aging population, in which the primary goal of treatment appears to be avoidance of chronic institutionalization. METHODS: To identify independent predictors of 30-day mortality or vegetative state in a geriatric population and calculate an intuitive scoring system, we screened 480 patients after TBI treated at a single department of neurosurgery over a 2-year period. We analyzed data of 214 consecutive patients aged ≥65 years, including demographics, medical history, cause and time of injury, neurologic state, radiologic reports, and laboratory results. A predictive model was developed using logistic regression modeling with a backward stepwise feature selection. RESULTS: The median Glasgow Coma Scale (GCS) score on admission was 14 (interquartile range, 12-15), whereas the 30-day mortality or vegetative state rate amounted to 23.4%. Starting with 20 predefined features, the final prediction model highlighted the importance of GCS motor score (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.09-0.32); presence of comorbid cardiac, pulmonary, or renal dysfunction or malignancy (OR, 2.86; 9 5% CI, 1.08-7.61); platelets ≤100 × 109 cells/L (OR, 13.60; 95% CI, 3.33-55.49); and red blood cell distribution width coefficient of variation ≥14.5% (OR, 2.91; 95% CI, 1.09-7.78). The discovered coefficients were used for nomogram development. It was further simplified to facilitate clinical use. The proposed scoring system, Elderly Traumatic Brain Injury Score (eTBI Score), yielded similar performance metrics. CONCLUSIONS: The eTBI Score is the first scoring system designed specifically for older adults. It could constitute a framework for clinical decision-making and serve as an outcome predictor. Its capability to stratify risk provides reliable criteria for assessing efficacy of TBI management.

Improving Survival with Tranexamic Acid in Cerebral Contusions or Traumatic Subarachnoid Hemorrhage: Univariate and Multivariate Analysis of Independent Factors Associated with Lower Mortality.

BACKGROUND: Fall with head injury is a pervasive challenge, especially in the aging population. Contributing factors for mortality include the development of cerebral contusions and delayed traumatic intracerebral hematoma. Currently, there is no established specific treatment for these conditions. OBJECT: This study aimed to investigate the impact of independent factors on the mortality rate of traumatic brain injury with contusions or traumatic subarachnoid hemorrhage. METHODS: Data were collected from consecutive patients admitted for cerebral contusions or traumatic subarachnoid hemorrhage at an academic trauma center from 2010 to 2016. The primary outcome was the 30-day mortality rate. Independent factors for analysis included patient factors and treatment modalities. Univariate and multivariate analyses were conducted to identify independent factors related to mortality. Secondary outcomes included thromboembolic complication rates associated with the use of tranexamic acid. RESULTS: In total, 651 consecutive patients were identified. For the patient factors, low Glasgow Coma Scale on admission, history of renal impairment, and use of warfarin were identified as independent factors associated with higher mortality from univariate and multivariate analyses. For the treatment modalities, univariate analysis identified tranexamic acid as an independent factor associated with lower mortality (P = 0.021). Thromboembolic events were comparable in patients with or without tranexamic acid. CONCLUSION: Tranexamic acid was identified by univariate analysis as an independent factor associated with lower mortality in cerebral contusions or traumatic subarachnoid hemorrhage. Further prospective studies are needed to validate this finding.

Predicting mortality in traumatic intracranial hemorrhage.

OBJECTIVE: Traumatic intracranial hemorrhage (tICH) is a significant source of morbidity and mortality in trauma patients. While prognostic models for tICH outcomes may assist in alerting clinicians to high-risk patients, previously developed models face limitations, including low accuracy, poor generalizability, and the use of more prognostic variables than is practical. This study aimed to construct a simpler and more accurate method of risk stratification for all tICH patients. METHODS: The authors retrospectively identified a consecutive series of 4110 patients admitted to their institution's level 1 trauma center between 2003 and 2013. For each admission, they collected the patient's sex, age, systolic blood pressure, blood alcohol concentration, antiplatelet/anticoagulant use, Glasgow Coma Scale (GCS) score, Injury Severity Score, presence of epidural hemorrhage, presence of subdural hemorrhage, presence of subarachnoid hemorrhage, and presence of intraparenchymal hemorrhage. The final study population comprised 3564 patients following exclusion of records with missing data. The dependent variable under study was patient death. A k-fold cross-validation was carried out with the best models selected via the Akaike Information Criterion. These models risk stratified the study partitions into grade I (< 1% predicted mortality), grade II (1%-10% predicted mortality), grade III (10%-40% predicted mortality), or grade IV (> 40% predicted mortality) tICH. Predicted mortalities were compared with actual mortalities within grades to assess calibration. Concordance was also evaluated. A final model was constructed using the entire data set. Subgroup analysis was conducted for each hemorrhage type. RESULTS: Cross-validation demonstrated good calibration (p < 0.001 for all grades) with a mean concordance of 0.881 (95% CI 0.865-0.898). In the authors' final model, older age, lower blood alcohol concentration, antiplatelet/anticoagulant use, lower GCS score, and higher Injury Severity Score were all associated with greater mortality. Subgroup analysis showed successful stratification for subarachnoid, intraparenchymal, grade II-IV subdural, and grade I epidural hemorrhages. CONCLUSIONS: The authors developed a risk stratification model for tICH of any GCS score with concordance comparable to prior models and excellent calibration. These findings are applicable to multiple hemorrhage subtypes and can assist in identifying low-risk patients for more efficient resource allocation, facilitate family conversations regarding goals of care, and stratify patients for research purposes. Future work will include testing of more variables, validation of this model across institutions, as well as creation of a simplified model whose outputs can be calculated mentally.

Is There a Need for Platelet Transfusion After Traumatic Brain Injury in Patients on P2Y12 Inhibitors?

BACKGROUND: A significant portion of patients sustaining traumatic brain injury (TBI) are on antiplatelet medications. The reversal of P2Y12 agents after intracranial hemorrhage (ICH) remains unclear. The aim of our study is to evaluate outcomes after TBI in patients who are on preinjury P2Y12 inhibitors and received a platelet transfusion. METHODS: We analyzed our prospectively maintained TBI database from 2013 to 2016 and included all patients with isolated ICH who were on P2Y12 inhibitors (Clopidogrel, Prasugrel, Ticagrelor). Regression analysis was performed adjusting for demographics and injury parameters. Outcome measures included progression of ICH, adverse discharge disposition (skilled nursing facility), and mortality. RESULTS: A total 243 patients with ICH on preinjury P2Y12 inhibitor met our inclusion criteria and were analyzed. Mean age was 55 ± 18 y, 58% were males and 60% were white and median injury severity score was 13 [9-18]. 73.6% received platelet transfusion after admission. The median packs of platelet transfusion were 1 [1-2] units. After controlling for confounders, patients who received platelet transfusion had a lower rate of progression (OR: 0.68, P = 0.01) and decreased rate of neurosurgical intervention (OR: 0.80, P = 0.03). Overall mortality was 12.3%. Patients on P2Y12 inhibitors who received platelet transfusion had lower odds of discharge to a skilled nursing facility (OR: 0.75, P = 0.02) and mortality (OR: 0.85, P = 0.04). CONCLUSIONS: Platelet transfusion after isolated traumatic ICH in patients on P2Y12 inhibitors is associated with improved outcomes. Platelet transfusion was associated with decreased risk of progression of ICH, neurosurgical intervention, and mortality. Further randomized studies to validate the use of platelet transfusion and define the optimal dose in patients on P2Y12 inhibitors are warranted.

Four-factor prothrombin complex concentrate for the reversal of factor Xa inhibitors for traumatic intracranial hemorrhage.

OBJECTIVE: The objective of this study was to determine the effectiveness and safety of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitors in patients with traumatic intracranial hemorrhage (ICH). METHODS: This was a retrospective cohort study of patients taking factor Xa inhibitors with traumatic ICH between March 1, 2015 and August 31, 2017 at two trauma centers. The primary outcome was in-hospital mortality in patients who received 4F-PCC (4F-PCC group) compared to those who did not (no reversal group). Secondary outcomes included functional recovery, hospital and intensive care unit (ICU) length of stay (LOS), and thromboembolic complications. RESULTS: There were 62 patients included in the study. Injury Severity Score (ISS) was significantly higher in the 4F-PCC group (17.6 vs. 12.1, p = 0.019). The 4F-PCC group had a significantly higher mortality (22.9% vs. 3.7%, p = 0.034) and longer ICU LOS (2.5 vs. 1.4 days, p = 0.0024). The no reversal group had a significantly higher incidence of ischemic stroke/transient ischemic attack (TIA) (0% vs. 14.8%, p = 0.019). After controlling for ISS, there was no significant difference in mortality (p = 0.20), ICU LOS (p = 0.64), or ischemic stroke/TIA (p = 0.94). There was no difference in hospital LOS, discharge disposition, final Activity Measure for Post Acute Care daily activity score, VTE, or MI. CONCLUSION: Patients with a higher ISS received 4F-PCC preferentially, which led to an apparent mortality benefit the no reversal group. After adjusting for baseline differences between groups, there was no difference in mortality, functional recovery, hospital and ICU LOS, or thromboembolic complications.

Heads Up: Describing and Implementing a Time-Saving Head Strike Protocol at a Level II Trauma Center.

Head strikes can be fatal for patients taking blood thinners (anticoagulants or antiplatelets). Our trauma center instituted the "head strike protocol" to provide uniform and expedited care for adult trauma patients taking preinjury anticoagulants and antiplatelet medications with suspected head injury. The purpose of this article is to describe the development and implementation of the head strike protocol and compare time metrics and outcomes before and after implementing the protocol. Per the head strike protocol, patients with suspected traumatic intracranial hemorrhage (tICH) were screened for anticoagulants or antiplatelet medications by emergency medical service personnel/at first contact, activated as a Level II trauma and received a computed tomographic scan of the head within 30 min of arrival, and started reversal of blood products within 30 min of tICH confirmation. Compared with patients admitted before establishing the head strike protocol, patients treated postimplementation were significantly more likely to have trauma team activation (77% preprotocol vs. 89% postprotocol) and expeditious initiation of reversal agents (68 min preprotocol vs. 21 min postprotocol) and to survive their head injury for patients taking anticoagulants (42% preprotocol vs. 21% postprotocol). There were no differences in mortality for patients taking antiplatelet agents. This comprehensive nurse-driven reversal protocol presents an algorithm for managing patients with suspected tICH taking any preinjury blood thinners, allowing "ownership" by the nursing staff to ensure there are no delays in initiating blood products. This protocol may be particularly salient with the aging of the trauma population and parallel increase in the use of blood thinners.

Prognostic significance of optic nerve sheath diameter on computed tomography scan with severity of blunt traumatic brain injury in the emergency department.

Optic nerve sheath diameter measurement (ONSD) has been associated with identifying the prognosis of traumatic brain injury (TBI) patients. The study was planned to evaluate the prognostic value of ONSD measured on the initial brain computed tomography (CT) scan performed on patients with blunt TBI in the emergency department(ED). This retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of moderate and severe TBI patients from January to December 2014. ONSD for each eye on the initial CT scan and Glasgow Coma Scale (GCS) was measured upon patient presentation. Correlation between presentation GCS and ONSD was done through Pearson's correlation. Receiver operator curve (ROC) analysis was done to measure the predictive values of ONSD for mortality. Of the 276 patients, 211(76%) were males and 65(23%) females. ONSD was measured on 160(58%) patients. The mean ONSD measured on CT scan was 3.8±1. The Pearson's correlation between the severity of brain injury as per GCS at presentation and ONSD was not significant (-0.182). We concluded that ONSD measured on the initial CT brain scan had good association with the severity of blunt TBI in patients presenting to the ED.

SHORT-TERM OUTCOME OF OPERATED TRAUMATIC BRAIN INJURY PATIENTS FOR INTRACRANIAL HEMORRHAGE AT TIKUR ANBESSA SPECIALIZED TEACHING HOSPITAL (TASTH), ADDIS ABABA, ETHIOPIA.

Background: Traumatic brain injury is the leading cause of death and disability in people younger than 40 years of age worldwide. Objective: The study primarily aims at assessing the short-term outcome of patients operated for traumatic intracranial hemorrhage. Patients and Methods: This is a hospital based cross sectional study on patients with traumatic brain injury at Tikur Anbessa Specialized Teaching Hospital in Addis Ababa, Ethiopia, between February 2013 and February 2014. Standardized and structured questionnaire was used to collect sociodemographic data. All patients with traumatic brain injury operated following intracranial hemorrhage were included. Glasgow Coma Scale was used to determine the outcome. Difference in proportions was examined using Chi-square test. Results: The study reviewed 91 patients with traumatic brain injury. Their age ranged from 13 to 60 years with a mean (SD) of 32.3 (±12.1). Eighty-seven (95.6%) of the cases were males and 4(4.4%) females and 34(37.4%) of them cases had mild and 30(33%) had severe traumatic brain injury. Acute Epidural Hematoma was seen in 79(86.8%), Acute Subdural hematoma had the highest proportion, 4/11(36.4%), of deaths and it was also significantly associated with unfavorable Glasgow Outcoma Scale at 3 months (p=0.03). Overall, the proportion patients who died was 18.7% with older patients (>50 years) had a significantly higher proportion of death (p=0.01). Most of the patients had favorable Glasgow Outcoma Scale ,unfavorable was seen in 22/30 (73.3%) and 17/30 (56.7%) of patients with severe traumatic brain injury at 3 and 6 months, respectively. Conclusion: In conclusion, male predominance was substantially high. Acute Subdural hematoma and old patients had high death rates and unfavorable outcome. Overall the death rate was not different from global figures.

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

BACKGROUND: Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. METHODS: The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. DISCUSSION: The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. TRIAL REGISTRATION: The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).