Progression Of Intracranial Hemorrhage Research Articles

Predicting Progression of Intracranial Hemorrhage in the Prehospital TXA for TBI Trial.

Progression of intracranial hemorrhage is a common, potentially devastating complication after moderate/severe traumatic brain injury (TBI). Clinicians have few tools to predict which patients with traumatic intracranial hemorrhage on their initial head computed tomography (hCT) scan will progress. The objective of this investigation was to identify clinical, imaging, and/or protein biomarkers associated with progression of intracranial hemorrhage (PICH) after moderate/severe TBI and to create an accurate predictive model of PICH based on clinical features available at presentation. We analyzed a subset of subjects from the phase II double-blind, multi-center, randomized "Prehospital Tranexamic Acid Use for TBI" trial. This subset was limited to the placebo arm of the parent trial with evidence of hemorrhage on the initial hCT and a follow-up hCT 6 h after. PICH was defined as an increase in hemorrhage size by 30% or more, or the development of new hemorrhage in the intra- and extra-axial intracranial vault between the initial and the follow-up hCT. Two independent radiologists evaluated each hCT, and conflicts were adjudicated by a third. Clinical and radiographic characteristics were collected, along with plasma protein biomarkers at admission. Principal component analysis (PCA) was performed, and each principal component (PC) was interrogated for its association with PICH. Finally, expert opinion and recursive feature extraction (RFE) were used to select input features for the construction of several supervised classification models. Their ability to predict PICH was quantified and compared. In this subset of subjects (n = 104), 46% (n = 48) demonstrated PICH. Univariate analyses showed no association between PICH and age, sex, admission Glasgow Coma Scale (GCS), GCS motor subscore, presence of midline shift, admission platelet count or admission INR. Radiographic severity scores (Marshall score [p = 0.007], Rotterdam score [p = 0.004]), and initial hematoma volume [p = 0.005] were associated with PICH. Higher levels of admission glial fibrillary acidic protein (p < 0.001) and MAP (p = 0.011) were also associated with PICH. Of the PCs, PC1 was significantly associated with PICH (p = 0.0125). Using multimodal data input, machine learning classifiers successfully discriminated patients with or without PICH. Models composed of machine-selected features performed better than models composed of expert-selected variables (reaching an average of 77% accuracy, AUC = 0.78 versus AUC = 0.68 for the expert-selected variables). Predictive models utilizing variables measured at admission can accurately predict PICH, confirmed by the 6-hour follow-up hCT. Our best-performing models must now be externally validated in a separate cohort of TBI patients with low GCS and initial hCT positive for hemorrhage.

Reducing Low-Value Interhospital Transfers for Mild Traumatic Brain Injury.

The modified Brain Injury Guidelines (mBIG) were developed to stratify traumatic brain injuries (TBI) and improve healthcare utilization by selectively requiring repeat imaging, ICU admission, and neurosurgical (NSG) consultation. The goal of this study is to assess safety and potential resource savings associated with the application of mBIG on interhospital patient transfers for TBI. Adult patients with TBI transferred to our Level I trauma center from 01/2017 to 12/2022 meeting mBIG inclusion criteria were retrospectively stratified into mBIG1, mBIG2, and mBIG3 based on initial clinicoradiological factors. At the time, our institution routinely admitted patients with TBI and intracranial hemorrhage to the ICU and obtained a repeat head CT with NSG consultation, independent of TBI severity or changes in neurological exam. The primary outcome was progression of intracranial hemorrhage (ICH) on repeat imaging and/or NSG intervention. Secondary outcomes included length of stay (LOS) and financial charges. Subgroup analysis on isolated TBI without significant extracranial injury was performed. Over the 6-year study period, 289 patients were classified into mBIG1 (61; 21.1%), mBIG2 (69; 23.9%), and mBIG3 (159; 55.0%). Of mBIG1 patients, 2 (2.9%) had radiological progression to mBIG2 without clinical decline, and none required NSG intervention. Of mBIG2, 2 (3.3%) patients progressed to mBIG3 and both required NSG intervention. Over 35% of transferred patients had minor isolated TBI. For mBIG1 and mBIG2, the median hospitalization charges per patient were $152,296 and $149,550 respectively, and the median LOS was 4 and 5 days respectively with the majority downgraded from the ICU within 48 hours. Clinically significant progression of ICH occurred infrequently in 1.5% of patients with mBIG1-2 injuries. Over 35% of interfacility transfers for minor isolated TBI meeting mBIG1 and 2 criteria are low-value and may potentially be safely deferred in an urban healthcare setting.

Predictors of direct oral anticoagulant concentrations in the trauma population.

Direct oral anticoagulant (DOAC) use is becoming more prevalent in patients presenting after trauma. We sought to identify the prevalence and predictors of subtherapeutic and therapeutic DOAC concentrations and hypothesized that increased anti-Xa levels would correlate with increased risk of bleeding and other poor outcomes. A retrospective cohort study of all trauma patients on apixaban or rivaroxaban admitted to a level 1 trauma center between January 2015 and July 2021 was performed. Patients were excluded if they did not have a DOAC-specific anti-Xa level at presentation. Therapeutic levels were defined as an anti-Xa of 50 ng/mL to 250 ng/mL for rivaroxaban and 75 ng/mL to 250 ng/mL for apixaban. Linear regression was used to identify correlations between study variables and anti-Xa level, and binomial logistic regression was used to test the association of anti-Xa level with outcomes. There were 364 trauma patients admitted during the study period who were documented to be on apixaban or rivaroxaban. Of these, 245 patients had anti-Xa levels measured at admission. The population was 53% woman, with median age of 78 years, and median Injury Severity Score of 5. In total, 39% of patients had therapeutic and 20% had supratherapeutic anti-Xa levels. Female sex, increased age, decreased height and weight, and lower estimated creatinine clearance were associated with higher anti-Xa levels at admission. There was no correlation between anti-Xa level and the need for transfusion or reversal agent administration, admission diagnosis of intracranial hemorrhage (ICH), progression of ICH, hospital length of stay, or mortality. Anti-Xa levels in trauma patients on DOACs vary widely; female patients who are older, smaller, and have decreased kidney function present with higher DOAC-specific anti-Xa levels after trauma. We were unable to detect an association between anti-Xa levels and clinical outcomes. III-Prognostic and Epidemiological.

Modified Brain Injury Guidelines for preinjury anticoagulation in traumatic brain injury: An opportunity to reduce health care resource utilization.

The Brain Injury Guidelines (BIG) stratify patients by traumatic brain injury (TBI) severity to provide management recommendations to reduce health care resource burden but mandates that patients on anticoagulation (AC) are allocated to the most severe tertile (BIG 3). We sought to analyze TBI patients on AC therapy using a modified BIG model to determine if this population can offer further opportunity for safe reductions in health care resource utilization. Patients 55 years or older on AC with traumatic intracranial hemorrhage (ICH) from two centers were retrospectively stratified into BIG 1 to 3 risk groups using modified BIG criteria excluding AC as a criterion. Intracranial hemorrhage progression, neurosurgical intervention (NSI), death, and worsened discharge status were compared. A total of 221 patients were included, with 23%, 29%, and 48% classified as BIG 1, BIG 2, and BIG 3, respectively. The BIG 3 cohort had a higher rate of AC reversal agents administered (66%) compared with the BIG 1 (40%) and BIG 2 (54%) cohorts ( p < 0.01), as well as ICH progression discovered on repeat head computed tomography (56% vs. 38% vs. 26%, respectively; p < 0.001). No patients in the BIG 1 and 2 cohorts required NSI. No patients in BIG 1 and 3% of patients in BIG 2 died secondary to the ICH. In the BIG 3 cohort, 16% of patients required NSI and 26% died. Brain Injury Guidelines 3 patients had 15 times the odds of mortality compared with BIG 1 patients ( p < 0.01). The AC population had higher rates of ICH progression than the BIG literature, but this did not lead to more NSI or mortality in the lower tertiles of our modified BIG protocol. If the modified BIG used the original tertile management on our population, then NS consultation may have been reduced by up to 52%. These modified criteria may be a safe opportunity for further health care resource and cost savings in the TBI population. Prognostic and Epidemiological; Level IV.

Early Venous Thromboembolism Prophylaxis in Patients with Trauma Intracranial Hemorrhage: Analysis of the Prospective Multicenter CLOTT Study.

The optimal time to initiate venous thromboembolism prophylaxis (VTEp) for patients with intracranial hemorrhage (ICH) is controversial and must balance the risks of VTE with potential progression of ICH. We sought to evaluate the efficacy and safety of early VTEp initiation after traumatic ICH. This is a secondary analysis of the prospective multicenter Consortium of Leaders in the Study of Thromboembolism (CLOTT) study. Patients with head AIS > 2 and with immediate VTEp held due to ICH were included. Patients were divided into VTEp ≤ or > 48 hours and compared. Outcome variables included overall VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), progression of ICH (pICH), or other bleeding events. Univariate and multivariate logistic regressions were performed. There were 881 patients in total, 378 (43%) started VTEp ≤48 hours (early). Patients starting VTEp >48 hours (late) had higher VTE (12.4% vs 7.2%, p = .01) and DVT (11.0% vs 6.1%, p = .01) rates than the early group. The incidence of PE (2.1% vs 2.2%, p = .94), pICH (1.9% vs 1.8%, p = .95) or any other bleeding event (1.9% vs 3.0%, p = .28) were equivalent between early and late VTEp groups. On multivariate logistic regression analysis, VTEp >48 hours (OR 1.86), ventilator days >3 (OR 2.00), and risk assessment profile score ≥ 5 (OR 6.70) were independent risk factors for VTE (all p < 0.05), while VTEp with enoxaparin was associated with decreased VTE (OR 0.54, p < 0.05). Importantly, VTEp ≤48 hours was not associated with pICH (OR 0.75) or risk of other bleeding events (OR 1.28) (both p = NS). Early initiation of VTEp (≤48 h) for patients with ICH was associated with decreased VTE/DVT rates without increased risk of pICH or other significant bleeding events. Enoxaparin is superior to unfractionated heparin as VTE prophylaxis in patients with severe TBI. Level IV; Therapeutic/Care management.

Safety of the Trauma Quality Improvement Program Guideline for Venous Thromboembolism Prophylaxis in Traumatic Brain Injury.

The American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) provides a guideline for when to initiate pharmacologic venous thromboembolism (VTE) prophylaxis in traumatic brain injury (TBI) patients. We hypothesized that implementation of the guideline would not result in progression in intracranial hemorrhage. The TBI TQIP guideline was implemented at a Level I Trauma Center. Patients with a stable Computerized tomography (CT) of the brain were started on chemical prophylaxis per the Modified Berne-Norwood Criteria. CT scans before and after initiation of treatment were retrospectively reviewed by one board-certified radiologist to determine if there was progression of hemorrhage. Patients without a follow-up CT scan were evaluated for progression of bleed/neurologic deterioration by review of physician notes, nursing documentation, and Glasgow coma scale (GCS). From July 2017 to December 2020, 12,922 patients were admitted to the trauma service. A total of 552 of these patients had TBI and 269 met inclusion criteria. 55 patients had at least one CT of the brain after initiation of prophylaxis. None of these 55 patients had progression of hemorrhage. 214 patients did not have a CT of the brain after prophylaxis. Chart review showed that none of these patients had a clinical decline. Overall, there was no progression of hemorrhage in the 269 patients that met inclusion criteria. Initiation of the TQIP TBI VTE prophylaxis guideline was found to be safe with no progression of intracranial hemorrhage.

The Use of Andexanet Alfa Vs. Four-Factor Prothrombin Complex Concentrates in the Reversal of Life-Threatening Intracranial Hemorrhage

Background/objective Andexanet alfa (AA) is a novel reversal agent for life threatening bleeding associated with oral Xa inhibitors, but there is uncertainty regarding the benefit compared to 4-factor prothrombin complex concentrate (4F-PCC). We investigated the clinical outcomes and cost differences between these two reversal agents in life threatening intracranial hemorrhage (ICH). Methods We retrospectively reviewed patients at our institution who received anticoagulation reversal for life-threatening ICH with either AA or 4F-PCC between 9/1/2013 - 4/20/2020 and had an anti-Xa level greater than 0.6 IU/L. The primary outcome was 30-day mortality after administration of either 4F-PCC or AA. Secondary outcomes included progression of ICH based on imaging, ICU length of stay, hospital length of stay, disposition at discharge, functionality at discharged, and financial cost. Safety outcomes evaluated included thrombosis after administration of reversal agent. Results 89 patients were included in this study. There were no differences in 30-day mortality (p = 0.14, Figure 1), radiographic resolution of ICH (p = 0.93), objective volume change in ICH(p = 0.18), progression of ICH (p = 0.74), hospital and ICU length of stay (p=0.66, 0.50), discharge disposition (p=0.40), or thrombosis after administration of reversal agent (p=0.17) between the two groups. Modified Rankin at discharge was slightly higher for the AA group (p=0.02), while cost was 2.8 times higher for AA. Conclusion Given the lack of statistically significant differences in clinical outcomes and the high cost of AA, the results validate the use of 4F-PCCs as an alternative to AA, based on similar efficacy and safety. Multi-center prospective studies are needed to further evaluate novel anticoagulation reversal agents. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The impact of low-dose aspirin in the Brain Injury Guidelines on outcomes in traumatic brain injury: A retrospective cohort study.

Current Brain Injury Guidelines (BIG) characterize patients with intracranial hemorrhage taking antiplatelet or anticoagulant agents as BIG 3 (the most severe category) regardless of trauma severity. This study assessed the risk of in-hospital mortality or need for neurosurgery in patients taking low-dose aspirin who otherwise would be classified as BIG 1. This was a retrospective study at an academic level 1 trauma center. Patients were included if they were admitted with traumatic intracerebral hemorrhage and were evaluated by the BIG criteria. Exclusion criteria included indeterminate BIG status or patients with missing primary outcomes documentation. Patients were categorized as BIG 1, BIG 2, BIG 3, or BIG 1 on aspirin (patients with BIG 1 features taking low-dose aspirin). The primary endpoint was a composite of neurosurgical intervention and all-cause in-hospital mortality. Key secondary endpoints include rate of intracranial hemorrhage progression, and intensive care unit- and hospital-free days. A total of 1,520 patients met the inclusion criteria. Median initial Glasgow Coma Scale was 14 (interquartile range [IQR], 12-15), Injury Severity Scale score was 17 (IQR, 10-25), and Abbreviated Injury Scale subscore head and neck (AIS Head ) was 3 (IQR, 3-4). The rate of the primary outcome for BIG 1, BIG 1 on aspirin, BIG 2, and BIG 3 was 1%, 2.2%, 1%, and 27%, respectively; the difference between BIG 1 on aspirin and BIG 3 was significant ( p < 0.001). Patients taking low-dose aspirin with otherwise BIG 1-grade injuries experienced mortality and required neurosurgery significantly less often than other patients categorized as BIG 3. Inclusion of low-dose aspirin in the BIG criteria should be reevaluated. Therapeutic/Care Management; Level IV.

Acute myocardial infarction and concomitant acute intracranial hemorrhage: clinical characteristics and outcomes

This study aimed to evaluate the demographic and clinical characteristics, treatments and outcomes of concomitant acute myocardial infarction (AMI) and acute intracranial hemorrhage (ICH). All patients diagnosed with concomitant AMI...

Outcomes of elderly patients with traumatic brain injury associated with the pre-injury antithrombotic prophylaxis type - A systematic review and meta-analysis.

Our review aims at comparing the morbidity and mortality-related risks associated with the pre-injury administration of VK-antagonists or DOACs in elderly patients with TBI. We performed a systematic search of the academic literature across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE), following PRISMA guidelines. We conducted a random-effect meta-analysis to compare the influence of pre-injury VK-antagonists or DOACs administration on the overall intensive care unit and hospital stays of patients with TBI. We also evaluated the overall risks associated with VK-antagonists and with DOACs for intracranial hemorrhage progression, surgical intervention, and overall mortality in patients with TBI. From 973 studies, we found 11 eligible with 4,991 patients with traumatic brain injury (mean age, 77.82 ± 6.76 years). Our meta-analysis revealed insignificantly higher odds of surgical intervention (OR=1.72) and mortality (OR=1.07) associated with VK-antagonists administration than with DOACs administration. Similarly, we found that the intensive care unit (Hedge's g, 0.13) and hospital (g, 0.26) stays were insignificantly longer for individuals on VK-antagonists than for those on DOAC. Moreover, we observed insignificantly higher intracranial hemorrhage progression risks (OR=1.22) for individuals receiving DOACs than for those receiving VK-antagonists. This study provides evidence on the morbidity and mortality-related outcomes associated with the pre-injury administration of VK-antagonists or DOACs in patients with TBI. We found no significant differences between VK-antagonists and DOACs on the overall morbidity (hospital and intensive care unit stays, intracranial hemorrhage, and surgical intervention frequency) and mortality outcomes in elderly patients with TBI.

Complications and Transfusions on Therapeutic Anticoagulation After Trauma

Trauma patients who develop indications for therapeutic anticoagulation (TAC) present a challenge due to concern for bleeding. Transfusion requirement has been described as a common complication of TAC after trauma but its clinical relevance is unclear. Determine risk factors for and clinical outcomes associated with transfusion requirement on TAC after trauma. All trauma patients admitted to an academic urban level I trauma center from January 2010 to August 2020 who received TAC were included in this retrospective cohort study. Data included injury characteristics; TAC indication and timing; transfusions; and interventions. Patients who required transfusion after TAC were compared to those who did not. Eighty-two patients were included. The most common reasons for TAC were deep vein thrombosis (67.1%) and pulmonary embolism (31.7%). Two (2.4%) patients developed gastrointestinal bleeding. One (1.2%) underwent endoscopic intervention. Two patients (4.9%) had intracranial hemorrhage progression. Blood transfusion after TAC initiation was required in 43.9% of patients. Patients who were transfused started TAC more quickly after traumatic injury (5.5 vs 10.0days, P = .03), had fewer hospital-free days (54 vs 64days, P < .01), ICU-free days (8.5 vs 16.5 days, P = .01), and higher mortality (13.9% vs 2.1%, P = .04). Transfusions are common after starting TAC in trauma patients. Requiring transfusion after starting TAC was associated with shorter time from injury to starting TAC, higher mortality, and fewer ICU and hospital-free days.

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): a pilot randomized trial.

The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We evaluated the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries. Severely injured children (0 up to 18th birthday) were randomized into a double-blind randomized trial of 1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/hr infusion over 8 hours, 2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/hr infusion over 8 hours, or 3) normal saline placebo bolus and infusion. The trial was conducted at 4 pediatric Level I trauma centers in the United States between June 2018 and March 2020. We enrolled patients under federal exception from informed consent (EFIC) procedures when parents were unable to provide informed consent. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The target enrollment rate was at least 1.25 patients per site per month. A total of 31 patients were randomized with a mean age of 10.7 years (standard deviation [SD] 5.0 years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (9 patients TXA 15 mg/kg bolus dose, 10 patients TXA 30 mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified. Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large-scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.

Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis

BackgroundTrauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury.MethodsResults from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick’s value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers.ResultsPatients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15–20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2.ConclusionsThis more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.

Are oral anticoagulants a risk factor for mild traumatic brain injury progression? A single-center experience focused on of direct oral anticoagulants and vitamin K antagonists.

Mild traumatic brain injury (TBI) in anticoagulated patients is a common challenge for emergency departments because of lack of appropriate epidemiological data and huge management variability for those under oral anticoagulation therapy. Given the discrepancies between guidelines, the aim of the present study was to quantify the association between oral anticoagulant therapy (either vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC)) and the post-traumatic intracranial hemorrhage worsening compared to admission CT scan. We included all consecutive records of patients admitted to our emergency department for mild TBI as chief complaint and with a positive admission CT scan. After statistical univariate comparison, cause-specific hazard ratio (HR) and 95% confidence interval (CI) were determined with the use of Cox proportional hazard model. In the study period, 4667 patients had a CT scan for mild TBI; 439 (9.4%) were found to have intracranial hemorrhage. Among these patients, 299 (68.1%) were prescribed observation and control CT: 46 (15.38%) were on anticoagulant therapy, 23 (50%) on VKA, and 23 (50%) on DOAC. In multivariate analysis, only oral anticoagulation therapy was significantly associated to an increased risk of intracranial hemorrhage progression (HR 2.58; 95% CI 1.411-4.703; p = .002 and HR 1.9; 95% CI 1.004-3.735; p = .0048 for VKA and DOAC, respectively). Surgery was due to isolated subdural hematoma in 87.5% of cases, to subdural hematoma associated with intraparenchymal hemorrhage in 9.38% and to intraparenchymal hemorrhage only in 3.12%; 13 cases (4.35%) deceased in intensive care unit. In our series, anticoagulation was associated to a significant increase in intracranial progression, leaving the question open as to what this implies in current clinical practice; subdural hematoma was the major finding associated to evolution and surgery. Against this background, further studies are needed to clarify patients' management and DOAC safety profile compared to VKA in mild TBI.

Progression of Intracranial Hemorrhage After Chemical Prophylaxis Using Low-Molecular-Weight Heparin in Patients With Traumatic Brain Injury.

Chemical prophylaxis using low-molecular-weight heparin (LMWH) is considered a standard of care for venous thromboembolism in trauma patients. Our center performs a head computed tomography (CT) scan 24 hours after initiation with prophylactic LMWH in the setting of a known traumatic brain injury (TBI). The purpose was to determine the overall incidence of ICH progression after chemoprophylaxis in patients with a TBI. This retrospective study was performed at a Level I trauma center, from 1/1/2014 to 12/31/2017. Study patients were drawn from the institution's trauma registry based on Abbreviated Injury Score codes. 778 patients met all inclusion criteria after initial chart review. The proportion of patients with an observed radiographic progression of intracranial hemorrhage after LMWH was 5.8%. 3.1% of patients had a change in clinical management. Observed radiographic progression after LMWH prophylaxis and the presence of SDH on initial CT, the bilateral absence of pupillary response in the emergency department, and a diagnosis of dementia were found to have statistically significant correlation with bleed progression after LMWH was initiated. Over a 4-year period, the use of CT to evaluate for radiographic progression of traumatic intracranial hemorrhage 24 hours after receiving LMWH resulted in a change in clinical management for 3.1% of patients. The odds of intracranial hemorrhage progression were approximately 6.5× greater in patients with subdural hemorrhage on initial CT, 3.1× greater in patients with lack of bilateral pupillary response in ED, and 4.2× greater in patients who had been diagnosed with dementia.

Coagulopathy and Progression of Intracranial Hemorrhage in Traumatic Brain Injury: Mechanisms, Impact, and Therapeutic Considerations.

Traumatic brain injury (TBI) remains one of the most challenging health and socioeconomic problems of our times. Clinical courses may be complicated by hemostatic abnormalities either pre-existing or developing with TBI. To review frequencies, patterns, mechanisms, novel approaches to diagnostics, treatment, and outcomes of hemorrhagic progression and coagulopathy after TBI. Selective review of the literature in the databases Medline (PubMed) and Cochrane Reviews using different combinations of the relevant search terms was conducted. Of the patients, 20% with isolated TBI display laboratory coagulopathy upon hospital admission with profound effect on morbidity and mortality. Preinjury use of antithrombotic agents may be associated with higher rates of hemorrhagic progression and delayed traumatic intracranial hemorrhage. Further testing may display various changes affecting platelet function/numbers, pro- and/or anticoagulant factors, and fibrinolysis as well as interactions between brain tissues, vascular endothelium, mechanisms of inflammation, and blood flow dynamics. The nature of hemostatic disruptions 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. More "global" hemostatic assays, eg, viscoelastic and thrombin generation tests, may provide more detailed and timely information on the overall hemostatic potential thereby allowing early "goal-directed" therapies. Whether timely and targeted management of hemostatic abnormalities after TBI can protect against secondary brain injury and thereby improve outcomes remains elusive. Innovative technologies for diagnostics and monitoring offer windows of opportunities for precision medicine approaches to managing TBI.

Pre-injury chronic alcohol abuse predicts intracranial hemorrhagic progression, unfavorable clinical outcome, and mortality in severe traumatic brain injury

ABSTRACT Objective We aimed to determine the incidence of pre-injury alcohol abuse in TBI at our neurointensive care unit (NICU), the relation to intracranial hemorrhage evolution, and clinical outcome. Methods Patients with TBI treated at our NICU at Uppsala university hospital, Sweden, 2008–2018, were included. Clinical, radiological, and outcome variables were evaluated. Results Of 844 patients with TBI, 147 (17%) had a history of pre-injury alcohol abuse and these patients were slightly older, but had a similar Charlson co-morbidity index as the other patients. They were more often injured by falls and more frequently developed acute subdural hematomas and cerebral contusions. Their platelets were lower and their IVY bleeding time slightly longer. Patients with pre-injury alcohol abuse more often exhibited an intracranial hemorrhage progression on the second computed tomography. Pre-injury alcohol abuse was an independent predictor of increased mortality (odds ratio = 2.96, p-value = 0.001) and decreased favorable outcome (odds ratio = 0.46, p-value = 0.001) in multiple regression analyses. Conclusions Pre-injury alcohol abuse was common in severe TBI, associated with coagulopathy, worse intracranial hemorrhage/injury evolution, and independently predicted poor clinical outcome. These patients deserve more attention in care and research to address specific challenges including disturbed hemostasis.

Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations.

Posttraumatic coagulopathy involves disruption of both the coagulation and fibrinolytic pathways secondary to tissue damage, hypotension, and inflammatory upregulation. This phenomenon contributes to delayed complications after traumatic brain injury (TBI), including intracranial hemorrhage progression and systemic disseminated intravascular coagulopathy. Development of an early hyperfibrinolytic state may result in uncontrolled bleeding and is associated with increased mortality in patients with TBI. Although fibrinolytic assays are not routinely performed in the assessment of posttraumatic coagulopathy, circulating biomarkers such as D-dimer and fibrin degradation products have demonstrated potential utility in outcome prediction. Unfortunately, the relatively delayed nature of these tests limits their clinical utility. In contrast, viscoelastic tests are able to provide a rapid global assessment of coagulopathy, although their ability to reliably identify disruptions in the fibrinolytic cascade remains unclear. Limited evidence supports the use of hypertonic saline, cryoprecipitate, and plasma to correct fibrinolytic disruption; however, some studies suggest more harm than benefit. Recently, early use of tranexamic acid in patients with TBI and confirmed hyperfibrinolysis has been proposed as a strategy to further improve clinical outcomes. Moving forward, further delineation of TBI phenotypes and the clinical implications of fibrinolysis based on phenotypic variation is needed. In this review, we summarize the clinical aspects of fibrinolysis in TBI, including diagnosis, treatment, and clinical correlates, with identification of targeted areas for future research efforts.

Incorporating Immunoproteins in the Development of Classification Models of Progression of Intracranial Hemorrhage After Traumatic Brain Injury.

To define clinical, radiographic, and blood-based biomarker features to be incorporated into a classification model of progression of intracranial hemorrhage (PICH), and to provide a pilot assessment of those models. Patients with hemorrhage on admission head computed tomography were identified from a prospectively enrolled cohort of subjects with traumatic brain injury. Initial and follow-up images were interpreted both by 2 independent readers, and disagreements adjudicated. Admission plasma samples were analyzed and principal components (PCs) composed of the immune proteins (IPs) significantly associated with the outcome of interest were selected for further evaluation. A series of logistic regression models were constructed based on (1) clinical variables (CV) and (2) clinical variables + immune proteins (CV+IP). Error rates of these models for correct classification of PICH were estimated; significance was set at P < .05. We identified 106 patients, 36% had PICH. Dichotomized admission Glasgow Coma Scale (P = .004), Marshall score (P = .004), and 3 PCs were significantly associated with PICH. For the CV only model, sensitivity was 1.0 and specificity was 0.29 (95% CI, 0.07-0.67). The CV+IP model performed significantly better, with a sensitivity of 0.93 (95% CI, 0.64-0.99) and a specificity of 1.0 (P = .008). Adjustments to refine the definition of PICH and better define radiographic predictors of PICH did not significantly improve the models' performance. In this pilot investigation, we observed that composites of IPs may improve PICH classification models when combined with CVs. However, overall model performance must be further optimized; results will inform feature inclusion included in follow-up models.

Choosing the Best Approach to Warfarin Reversal After Traumatic Intracranial Hemorrhage

BackgroundPatients 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 MethodsThis 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. ResultsOf 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). ConclusionsMale 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.