Coagulopathy In Traumatic Brain Injury Research Articles

Abnormal serum Magnesium Level is Associated with the Coagulopathy in Traumatic Brain Injury Patients.

Coagulopathy is associated with poor prognosis of traumatic brain injury (TBI) patients. This study is performed to explore the association between serum magnesium level and the risk of coagulopathy in TBI. TBI patients from the Medical Information Mart for Intensive Care-III database were included for this study. Logistic regression analysis was performed to explore risk factors and develop a predictive model for coagulopathy in TBI. The restricted cubic spline (RCS) was utilized to analyze the association between serum magnesium level and the development of coagulopathy. Receiver operating characteristic curve was drawn to evaluate the performance of the predictive model for coagulopathy. The incidence of coagulopathy in TBI was 32.6%. The RCS indicated the association between magnesium and coagulopathy was U-shaped. Multivariate logistic regression confirmed age, coronary heart disease, cerebral vascular disease, chronic liver disease, GCS, ISS, epidural hematoma, hemoglobin, shock index and magnesium level were independently associated with the coagulopathy in TBI. Compared with patients of magnesium level between 1.7 and 2.3 mg/dL, those with magnesium level below 1.7 mg/dL or above 2.2 mg/dL had a higher risk of coagulopathy. Both hypermagnesemia and hypomagnesemia are associated with higher risk of coagulopathy in TBI patients. Physicians should pay more attention on preventing coagulopathy in TBI patients with hypomagnesemia or hypermagnesemia.

CLINICAL VALUE OF SYNDECAN-1 LEVELS IN TRAUMA BRAIN INJURY: A META-ANALYSIS.

Background: Traumatic brain injury (TBI) is a head trauma usually associated with death and endothelial glycocalyx damage. Syndecan-1 (SDC-1)-a biomarker of glycocalyx degradation-has rarely been reported in meta-analyses to determine the clinical prognostic value in TBI patients. Methods: We looked into PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 1, 1990, to May 1, 2023, to identify eligible studies. A meta-analysis was conducted using RevMan 5.4 and Stata 16.0 with the search terms "SDC-1" and "traumatic brain injury." Results: The present study included five studies with a total of 640 enrolled patients included. Syndecan-1 concentrations were higher in the isotrauma TBI group than in the non-TBI group (standardized mean difference [SMD] = 0.52; 95% CI: 0.03-1.00; P = 0.04). Subgroup analysis revealed statistical significance when comparing the SDC-1 level of multitrauma TBI (TBI + other injuries) group with the isotrauma TBI group (SMD = 0.74; 95% CI: 0.42-1.05; P < 0.001), and the SDC-1 level of the TBI coagulopathy (+) group (TBI with early coagulopathy) with the TBI coagulopathy (-) group (SMD = 1.75; 95% CI: 0.41-3.10; P = 0.01). Isotrauma TBI patients with higher SDC-1 level were at a higher risk of 30-day in-hospital mortality (odds ratio = 3.32; 95% CI: 1.67-6.60; P = 0.0006). Conclusion: This meta-analysis suggests that SDC-1 could be a biomarker of endotheliopathy and coagulopathy in TBI, as it was increased in isotrauma TBI patients and was higher in multitrauma TBI patients. There is a need for additional research into the use of SDC-1 as a prognostic biomarker in TBI, especially in isotrauma TBI patients.

Neutrophil extracellular traps contribute to coagulopathy after traumatic brain injury.

Coagulopathy contributes to the majority of deaths and disabilities associated with traumatic brain injury (TBI). Whether neutrophil extracellular traps (NETs) contribute to an abnormal coagulation state in the acute process of TBI remains unknown. Our objectives were to demonstrate the definitive role of NETs in coagulopathy in TBI. We detected NET markers in 128 TBI patients and 34 healthy subjects. Neutrophil-platelet (PLT) aggregates were detected in blood samples from TBI patients and healthy subjects using flow cytometry and staining with CD41 and CD66b. Endothelial cells (ECs) were incubated with isolate NETs and detected the expression of vascular endothelial (VE)-cadherin, syncanden-1, thrombomodulin, von Willebrand factor (VWF), phosphatidylserine (PS) and and tissue factor (TF). In addition, we established a TBI mouse model to detect the potential role of NETs in TBI associated coagulopathy. NETs generation was mediated by High Mobility Group Box 1(HMGB1) from activated platelets and contribute to procoagulant activity in TBI. Furthermore, coculture experiments indicated that NETs damaged the endothelial barrier and caused these cells to assume a procoagulant phenotype. Moreover, the administration of DNase I before or after brain trauma markedly reduced coagulopathy and improved the survival and clinical outcome of mice with TBI.

Utility of Thromboelastography in Detecting NOAC-Related Coagulopathy in Traumatic Brain Injury

IntroductionNovel oral anticoagulants (NOACs) have gained popularity as a vitamin K antagonist alternative without regular monitoring. There has been an increase in elderly patients on NOACs admitted for traumatic brain injury (TBI). The aim of this study is to determine the efficacy of thromboelastography (TEG) in detecting NOAC-related coagulopathy among TBI patients. MethodsA retrospective chart review of 456 TBI patients admitted to Sentara Norfolk General Hospital from 2015 to 2020 was performed. Inclusion criteria comprised patients on NOACs with a TEG performed at presentation (66 patients). Analysis included TEG values, use of prothrombin complex concentrate factor 4 (PCC4), increased intracranial hemorrhage on repeat head computed tomography within 24 h of admission, and mortality. ResultsTEG results showed 0% elevated reaction time, 1.5% elevated kinetics time, 1.5% low alpha angle, 4.5% low max amplitude, and 3.0% elevated clot lysis percent at 30 min in our cohort. Despite overwhelmingly normal TEG results, 42.42% of patients received PCC4. A subset analysis of these patients compared to those who did not receive PCC4, revealed a higher frequency of increased intracranial hemorrhage on repeat head computed tomography within 24 h of admission (42.86% versus 18.42%, P = 0.03), and increased mortality (25.0% versus 5.26%, P = 0.0219). Patients who did not receive PCC4 had no increased frequency of operative intervention or worsening of Glasgow Coma Score. ConclusionsResults suggest that TEG does not reliably assess NOAC-related coagulopathy in TBI patients. Caution must be used when interpreting TEG data to determine reversal strategies in TBI patients on NOACs.

Neutrophil to lymphocyte ratio in the prediction of coagulopathy in traumatic brain injury.

Aim: Traumatic brain injury (TBI) is a public health issue of increasing incidence. Coagulopathy after TBI is a frequent event, associated with a poor prognosis, and biomarkers that could predict coagulopathy occurrence are needed. The neutrophil-to-lymphocyte ratio (NLR) is useful as a cost-effective biomarker to assess prognosis and the need for cranial computed tomography in patients with mild TBI. As no study has yet evaluated the association of NLR with coagulopathy, we investigated whether the NLR at presentation could predict coagulopathy occurrence after TBI. Materials & methods: A retrospective study was conducted of patients aged >18years who attended the emergency department (ED) with TBI, over a 3-year period. We included all patients for whom the NLR at presentation was available, and who underwent a brain CT scan. Results: The study included 173 patients (mean age 57.4±21.1years) with TBI, the most frequent cause of which was a fall. According to the Glasgow Coma Scale, 37 patients had severe TBI, 19 moderateand 117 mild TBIand 40 patients (23.1%) developed coagulopathy. Their mean NLR was 7.5±6.7. Using receiver operating characteristic curve analysis, a cut-off value of 4.2 for NLR had 87.5% sensitivity and 52.9% specificity for predicting coagulopathy occurrence. Conclusion: Coagulopathy occurs frequently after TBI. This study investigated the value of NLR as a biomarker to predict coagulopathy occurrence, and concluded that NLR might be a novel and inexpensive biomarker for decision making in the management of TBI. Combination of NLR with other low-cost biomarkers and the clinical findings might further increase accuracy in the prediction of coagulopathy.

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.

Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury.

A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays—such as prothrombin time, partial thromboplastin time, and international normalized ratio—have historically been utilized to assess hemostasis and guide treatment following traumatic brain injury. However, these plasma-based assays alone often lack the sensitivity to diagnose and adequately treat coagulopathy associated with traumatic brain injury. Here, we review the whole blood coagulation assays termed viscoelastic tests and their use in traumatic brain injury. Modified viscoelastic tests with platelet function assays have helped elucidate the underlying pathophysiology and guide clinical decisions in a goal-directed fashion. Platelet dysfunction appears to underlie most coagulopathies in this patient population, particularly at the adenosine diphosphate and/or arachidonic acid receptors. Future research will focus not only on the utility of viscoelastic tests in diagnosing coagulopathy in traumatic brain injury, but also on better defining the use of these tests as evidence-based and/or precision-based tools to improve patient outcomes.

Thromboelastography is a Marker for Clinically Significant Progressive Hemorrhagic Injury in Severe Traumatic Brain Injury.

Coagulopathy in traumatic brain injury (TBI) is associated with increased risk of poor outcomes, but accurate prediction of clinically significant progressive hemorrhagic injury (PHI) in patients with severe TBI remains a challenge. Thromboelastography (TEG) is a real-time test of whole blood coagulation that provides dynamic information about global hemostasis. This study aimed to identify differences in TEG values between patients with severe TBI who did or did not experience clinically significant PHI. This was a single-center retrospective cohort study of adult patients with severe TBI. Patients were eligible for inclusion if initial Glasgow coma scale (GCS) was ≤ 8 and baseline head computed tomography (CT) imaging and TEG were available. Exclusion criteria included receipt of hemostatic agents prior to TEG. PHI was defined as bleeding expansion on CT within 24h associated with 2-point drop in GCS, neurosurgical intervention, or mortality within 24h. The primary endpoint was TEG value differences between patients with and without PHI. Secondary endpoints included differences in conventional coagulation tests (CCTs) between groups. Of the 526 patients evaluated, 141 met inclusion criteria. The most common reason for exclusion was lack of baseline TEG and receipt of reversal product prior to TEG. Sixty-four patients experienced PHI in the first 24h after presentation. K time (2.03min vs. 1.33min, P = 0.035) and alpha angle (65° vs. 69°, P = 0.015) were found to be significantly different in patients experiencing PHI. R time (5.25min vs. 4.71min), maximum amplitude (61mm vs. 63mm), and clot lysis at 30min after maximum clot strength (3.5% vs. 1.7%) were not significantly different between groups. Of the CCTs, only activated partial thromboplastin time (30.3s vs. 27.6s, P = 0.014) was found to be different in patients with PHI. Prolonged K time and narrower alpha angle were found to be associated with developing clinically significant PHI in patients with severe TBI. Despite differences detected in alpha angle, median values in both groups were within normal reference ranges. These abnormalities may reflect pathologic hypoactivity of fibrinogen, and further study is warranted to evaluate TEG-guided cryoprecipitate administration in this patient population.

Global Characterisation of Coagulopathy in Isolated Traumatic Brain Injury (iTBI): A CENTER-TBI Analysis

BackgroundTrauma-induced coagulopathy in patients with traumatic brain injury (TBI) is associated with high rates of complications, unfavourable outcomes and mortality. The mechanism of the development of TBI-associated coagulopathy is poorly understood.MethodsThis analysis, embedded in the prospective, multi-centred, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, aimed to characterise the coagulopathy of TBI. Emphasis was placed on the acute phase following TBI, primary on subgroups of patients with abnormal coagulation profile within 4 h of admission, and the impact of pre-injury anticoagulant and/or antiplatelet therapy. In order to minimise confounding factors, patients with isolated TBI (iTBI) (n = 598) were selected for this analysis.ResultsHaemostatic disorders were observed in approximately 20% of iTBI patients. In a subgroup analysis, patients with pre-injury anticoagulant and/or antiplatelet therapy had a twice exacerbated coagulation profile as likely as those without premedication. This was in turn associated with increased rates of mortality and unfavourable outcome post-injury. A multivariate analysis of iTBI patients without pre-injury anticoagulant therapy identified several independent risk factors for coagulopathy which were present at hospital admission. Glasgow Coma Scale (GCS) less than or equal to 8, base excess (BE) less than or equal to − 6, hypothermia and hypotension increased risk significantly.ConclusionConsideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management.

Bloodletting Puncture at Hand Twelve Jing-Well Points Improves Neurological Recovery by Ameliorating Acute Traumatic Brain Injury-Induced Coagulopathy in Mice.

Traumatic brain injury (TBI) contributes to hypocoagulopathy associated with prolonged bleeding and hemorrhagic progression. Bloodletting puncture therapy at hand twelve Jing-well points (BL-HTWP) has been applied as a first aid measure in various emergent neurological diseases, but the detailed mechanisms of the modulation between the central nervous system and systemic circulation after acute TBI in rodents remain unclear. To investigate whether BL-HTWP stimulation modulates hypocoagulable state and exerts neuroprotective effect, experimental TBI model of mice was produced by the controlled cortical impactor (CCI), and treatment with BL-HTWP was immediately made after CCI. Then, the effects of BL-HTWP on the neurological function, cerebral perfusion state, coagulable state, and cerebrovascular histopathology post-acute TBI were determined, respectively. Results showed that BL-HTWP treatment attenuated cerebral hypoperfusion and improve neurological recovery post-acute TBI. Furthermore, BL-HTWP stimulation reversed acute TBI-induced hypocoagulable state, reduced vasogenic edema and cytotoxic edema by regulating multiple hallmarks of coagulopathy in TBI. Therefore, we conclude for the first time that hypocoagulopathic state occurs after acute experimental TBI, and the neuroprotective effect of BL-HTWP relies on, at least in part, the modulation of hypocoagulable state. BL-HTWP therapy may be a promising strategy for acute severe TBI in the future.

Coagulopathy in the Acute Phase of Traumatic Brain Injury

Acute traumatic brain injury (TBI) can be accompanied by coagulopathy. In TBI, when an increased risk of hemorrhagic lesions in the brain tissue exists, keeping the normal hemostasis is crucial.The aim: to determine the incidence of coagulopathy in the acute phase of isolated TBI and identify the correlation between the types of hemostasis disorders and the severity of TBI.Materials and methods. We analyzed 323 case records of patients with TBI hospitalized to the Neurosurgery Center ICU from 2008 to 2016, 118 of them were included in the study. Criteria for inclusion were acute isolated TBI, hospitalization in the first 72 hours after injury, young and middle-aged patients. On admission to the hospital, all patients were assessed according to the Glasgow Coma Scale (GCS) and divided into two groups: group I with severe TBI, group 2 with mild and moderate TBI. All patients underwent blood coagulation testing (APTT, PTI, fibrinogen concentration, platelet count).Results. In 63.6% of patients with acute TBI coagulopathy were found, most of them (55.1%) had hypocoagulability state and were observed in the group of severe PMT (62.5%). The most frequent signs of coagulopathy were reduced PTI of less than 70% and thrombocytopenia of less than 150×109/l. A weak correlation (R=0.276; P=0.002) was found between the development of thrombocytopenia and adverse outcomes (1–3 points according to GOS).Conclusion. on hospital admission coagulopathy was diagnosed in 63,6% of patients in the acute phase of TBI, hypocoagulability state prevailed. Coagulopathy was significantly more common in patients in the acute phase of severe TBI (GCS8 points).The mechanisms of TBI-associated coagulopathy have not yet been fully clarified. Further studies of the role of platelet, plasma and fibrinolytic components in the development of coagulopathy are warranted, which require more comprehensive methods of hemostasis investigation.

Severe traumatic brain injury is associated with a unique coagulopathy phenotype.

Traumatic brain injury (TBI) patients present on a spectrum from hypocoagulability to hypercoagulability, depending on the injury complexity, severity, and time since injury. Prior studies have found a unique coagulopathy associated with TBI using conventional coagulation assays such as INR; however, few studies have assessed the association of TBI and coagulopathy using viscoelastic assays that comprehensively evaluate the coagulation in whole blood. This study aims to reevaluate the TBI-specific trauma-induced coagulopathy using arrival thrombelastography. Because brain tissue is high in key procoagulant molecules, we hypothesize that isolated TBI is associated with procoagulant and hypofibrinolytic profiles compared with injuries of the torso, extremities, and polytrauma, including TBI. Data are from the prospective Trauma Activation Protocol study. Activated clotting time (ACT), angle, maximum amplitude (MA), 30-minute percent lysis after MA (LY30), and functional fibrinogen levels (FFLEV) were recorded. Patients were categorized into isolated severe TBI (I-TBI), severe TBI with torso and extremity injuries (TBI + TORSO/EXTREMITIES), and isolated torso and extremity injuries (I-TORSO/EXTREMITIES). Poisson regression was used to adjust for multiple confounders. Overall, 572 patients (48 I-TBI, 45 TBI + TORSO/EXTREMITIES, 479 I-TORSO/EXTREMITIES) were included in this analysis. The groups differed in INR, ACT, angle, MA, and FFLEV but not in 30-minute percent lysis. When compared with I-Torso/Extremities, after adjustment for confounders, severe I-TBI was independently associated with ACT less than 128 seconds (relative risk [RR], 1.5; 95% confidence interval [CI], 1.1-2.2), angle less than 65 degrees (RR, 2.2; 95% CI, 1.4-3.6), FFLEV less than 356 (RR, 1.7; 95% CI, 1.2-2.4) but not MA less than 55 mm, hyperfibrinolysis, fibrinolysis shutdown, or partial thromboplastin time (PTT) greater than 30. Severe I-TBI was independently associated with a distinct coagulopathy with delayed clot formation but did not appear to be associated with fibrinolysis abnormalities. Low fibrinogen and longer ACT values associated with I-TBI suggest that early coagulation factor replacement may be indicated in I-TBI patients over empiric antifibrinolytic therapy. Mechanisms triggering coagulopathy in TBI are unique and warrant further investigation. Retrospective cohort study, prognostic, level III.

Contributing Factors for Coagulopathy in Traumatic Brain Injury.

Context:In traumatic brain injury patients, coagulation disorder causes secondary brain injury, thereby increasing mortality and morbidity.Aims:The aim of this study is to identify the factors responsible for coagulopathy in traumatic brain injury.Settings and Design:This prospective longitudinal study from June 2012 included 100 patients with moderate and severe head injury presenting to National Institute of Neurological and Allied Sciences, Kathmandu, over 1-year period.Subjects and Methods:Patients were evaluated for the development of coagulopathy, defined as collectively three abnormal hemostatic parameters, and associated risk factors for coagulopathy. They were then analyzed for correlation with coagulopathy.Statistical Analysis Used:SPSS version 16 was used for the analysis of data. For identification of contributing factors, a stepwise logistic regression analysis was performed, including the factors with P < 0.05 from the analysis.Results:Among the 100 patients, coagulopathy was present in 63% of cohort. Forty-three patients had severe head injury, and 76.7% (n = 33) of them had coagulopathy compared to 52.7% (n = 30) in 57 patients with moderate head injury (P = 0.013). Statistically significant correlation with coagulopathy was present with polytrauma, severity of head injury, blood transfusion, surgical intervention, and Marshall's classification of CT of the head; however, stepwise logistic regression analysis showed that blood transfusion, surgical intervention, polytrauma, and severity of head injury were significant independent variables responsible for the development of coagulopathy.Conclusions:Traumatic brain injury is complicated with coagulopathy in up to 63% of patients. Blood transfusion, surgical intervention, polytrauma, and severity of head injury are significant independent variables responsible for coagulopathy.

Coagulopathy in traumatic brain injury: Current concepts and controversies

Coagulopathy in traumatic brain injury: Current concepts and controversies

Coagulopathy and transfusion requirements in war related penetrating traumatic brain injury. A single centre study in a French role 3 medical treatment facility in Afghanistan

IntroductionTraumatic brain injury associated coagulopathy is frequent, either in isolated traumatic brain injury in civilian practice and in combat traumatic brain injury. In war zone, it is a matter of concern because head and neck are the second most frequent site of wartime casualty burden. Data focusing on transfusion requirements in patients with war related TBI coagulopathy are limited. Materials and methodsA descriptive analysis was conducted of 77 penetrating traumatic brain injuries referred to a French role 3 medical treatment facility in Kabul, Afghanistan, deployed on the Kabul International Airport (KaIA), over a 30 months period. ResultsOn 77 patients, 23 died during the prehospital phase and were not included in the study. Severe traumatic brain injury represented 50% of patients. Explosions were the most common injury mechanism. Extracranial injuries were present in 72% of patients. Traumatic brain injury coagulopathy was diagnosed in 67% of patients at role 3 admission. Red blood cell units (RBCu) were transfused in 39 (72%) patients, French lyophilized plasma (FLYP) in 41 (76%), and fresh whole blood (FWB) in 17 (31%). ConclusionThe results of this study support previous observations of coagulopathy as a frequent complication of traumatic brain injury. The majority of patients with war related penetrating traumatic brain injury presented with extracranial lesions. Most of them required a high level of transfusion capacity.

Relationship between tissue perfusion and coagulopathy in traumatic brain injury

BackgroundTraumatic brain injury (TBI)–related coagulopathy appears to be most prevalent in patients with tissue hypoperfusion, but evidence for this association is scarce. This study investigated the relationship between tissue perfusion and hemostatic derangements in TBI patients. Materials and methodsCoagulation parameters were measured on emergency department admission in patients with TBI (head abbreviated injury scale ≥ 3). The level of hypoperfusion was simultaneously assessed by near-infrared spectroscopy (NIRS) at the forehead and arm, and by base excess and lactate. Coagulopathy was defined as an international normalized ratio > 1.2 and/or activated partial thromboplastin time > 40 s and/or thrombocytopenia (<120 × 109/L). ResultsTBI patients with coagulopathy (42%) had more signs of tissue hypoperfusion as indicated by increased lactate levels (2.1 [1.1-3.2] mmol/L versus 1.2 [1.0-1.7] mmol/L; P = 0.017) and a larger base deficit (−3.0 [−4.6 to −2.0] mmol/L versus −0.1 [−2.5 to 1.8] mmol/L; P < 0.001). There was no difference in the cerebral or somatic tissue oxygenation index. However, there was a distinct trend toward a moderate inverse association between the cerebral tissue oxygenation index and D-dimer levels (r=−0.40; P = 0.051) as marker of fibrinolysis. The presence of coagulopathy was associated with an increased inhospital mortality rate (45.5% versus 6.7%; P = 0.002). ConclusionsThis is the first study to investigate the relationship between hemostatic derangements and tissue oxygenation using NIRS in TBI patients. This study showed that TBI-related coagulopathy is more profound in patients with metabolic acidosis and increased lactate levels. Although there was no direct relationship between tissue oxygenation and coagulopathy, we observed an inverse relationship between NIRS tissue oxygenation levels and fibrinolysis.

Coagulopathy in Traumatic Brain Injury and Its Correlation with Progressive Hemorrhagic Injury: A Systematic Review and Meta-Analysis.

The association between coagulopathy and either isolated traumatic brain injury (TBI) or progressive hemorrhagic injury (PHI) remains controversial. The aims of this study were to evaluate whether isolated TBI induces pronounced coagulopathy, in comparison with non-TBI or TBI in conjunction with other injuries (TBI + other injuries), and to examine whether there is any evidence of a relationship between coagulopathy and PHI in patients who have experienced TBI. The MEDLINE(®) and Embase databases, and the Cochrane Central Register of Controlled Trials (Central), were trawled for relevant studies. Searches covered the period from the inception of each of the databases to June 2015, and were conducted using appropriate combinations of terms and key words based on medical subject headings (MeSH). Studies were included if they compared isolated TBI with a similar severity of injury to other body regions, or compared PHI with non-PHI, with regard to coagulation tests and the prevalence of coagulopathy. We extracted the means and standard deviations (SD) of coagulation test levels, as well as their ranges or the percentage of abnormal coagulation tests, in both cases and controls. A total of 19 studies were included in our systematic review and meta-analysis. Only the mean fibrinogen (FIB) in isolated TBI was found to be significantly higher than in TBI + other injuries (pooled mean difference [MD] 32.09; 95% confidence interval [CI] 4.92-59.25; p = 0.02); in contrast, it was also significantly higher than in non-TBI (pooled MD 15.44; 95% CI 0.28-30.59; p = 0.05). We identified 15 studies that compared coagulopathy between a PHI group and a non-PHI group. The PHI group had a lower platelet count (PLT) value (pooled MD -19.21; 95% CI: -26.99 to -11.44, p < 0.001) and a higher international normalized ratio (INR) value (pooled MD 0.07; 95% CI: 0.02-0.13, p = 0.006) than the non-PHI group, but no differences were observed in the mean activated partial thromboplastin time (APTT) and prothrombin time (PT) between the PHI and non-PHI patients. In addition, PHI was significantly associated with a higher percentage of INR >1.2 (pooled OR 3.49 [95% CI 1.97-6.20], p < 0.001), PLT <100 × 109/L (pooled OR 4.74 [95% CI 2.44-9.20], p < 0.001), and coagulopathy (pooled OR 2.52; 95% CI 1.88- 3.38; p < 0.001), compared with non-PHI. The current clinical evidence does not indicate that the prevalence of coagulopathy in TBI is significantly higher than in injuries of similar severity to other areas of the body, or in multiple injuries with TBI. With respect to the association between coagulopathy and PHI, the occurrence of coagulopathy, INR, and PLT was significantly associated with PHI, but APTT and PT were not found to be associated with PHI. In the future, high quality research will be required to further characterize the effects of coagulopathy on TBI and subsequent PHI.

Thromboelastography After Murine TBI and Implications of Beta-Adrenergic Receptor Knockout.

The source of coagulopathy in traumatic brain injury (TBI) is multifactorial and may include adrenergic stimulation. The aim of this study was to assess coagulopathy after TBI using thromboelastography (TEG), and to investigate the implications of β-adrenergic receptor knockout. Adult male wild type c57/bl6 (WT) and β1/β2-adrenergic receptor knockout (BKO) mice were assigned to either TBI (WT-TBI, BKO-TBI) or sham injury (WT-sham, BKO-sham). Mice assigned to TBI were subject to controlled cortical impact (CCI). At 24h post-injury, whole blood samples were obtained and taken immediately for TEG. At 24h after injury, a trend toward increased fibrinolysis was seen in WT-TBI compared to WT-sham although this did not reach significance (EPL 8.1 vs. 0%, p=0.18). No differences were noted in fibrinolysis in BKO-TBI compared to BKO-sham (LY30 2.6 vs. 2.5%, p=0.61; EPL 3.4 vs. 2.9%, p=0.61). In addition BKO-TBI demonstrated increased clot strength compared to BKO-sham (MA 76.6 vs. 68.6, p=0.03; G 18.2 vs. 11.3, p=0.03). In a mouse TBI model, WT mice sustaining TBI demonstrated a trend toward increased fibrinolysis at 24h after injury while BKO mice did not. These findings suggest β-blockade may attenuate the coagulopathy of TBI and minimize progression of intracranial hemorrhage by reducing fibrinolysis and increasing clot strength.

Traumatic brain injury advancements.

Traumatic brain injury (TBI) remains the leading cause of morbidity and mortality in the United States. Over the last decade, several advancements have been made in the field of TBI all aimed at improving outcomes. Advancements in the management of TBI have been made possible through improved understanding of basic pathophysiology associated with this condition. The aim of this review is to briefly highlight the underlying pathophysiology of TBI and the most recent advancements and novel strategies being used in its treatment. We also briefly discuss coagulopathy of TBI, clinical management of TBI and how it has evolved recently. The mortality associated with TBI continues to remain high and several novel strategies have emerged as potential candidates for the treatment of secondary brain injury. The clinical management of TBI and associated coagulopathy has evolved allowing for a more tailored approach toward its management.

Use of prothrombin complex concentrate as an adjunct to fresh frozen plasma shortens time to craniotomy in traumatic brain injury patients.

The use of prothrombin complex concentrate (PCC) to reverse acquired (coagulopathy of trauma) and induced coagulopathy (preinjury warfarin use) is well defined. To compare outcomes in patients with traumatic brain injury without warfarin therapy receiving PCC as an adjunct to fresh frozen plasma (FFP) therapy compared with patients receiving FFP therapy alone. All patients with traumatic brain injury coagulopathy without warfarin therapy who received PCC (25 IU/kg) in conjunction with FFP or FFP alone at our Level I trauma center were reviewed. Coagulopathy was defined as an international normalized ratio >1.5. The groups (PCC + FFP vs FFP alone) were matched using propensity score matching on a 1:2 ratio for age, sex, Glasgow Coma Scale score, Injury Severity Score, head Abbreviated Injury Scale score, and international normalized ratio (INR) on presentation. The primary outcome measure was time to craniotomy. Secondary outcome measures were blood product requirements, cost of therapy, and mortality. A total of 1641 patients were reviewed, 222 of whom were included (PCC + FFP, 74; FFP, 148). The mean ± standard deviation age was 46.4 ± 21.7 years, the median (range) Glasgow Coma Scale score was 8 (3-12), and the mean ± standard deviation INR on presentation was 1.92 ± 0.6. PCC + FFP therapy was associated with an accelerated correction of INR (P = .001) and decrease in overall pack red blood cell (P = .035) and FFP (P = .041) administration requirement. Craniotomy was performed in 26.1% of patients (n = 58). Patients who received PCC + FFP therapy had faster time to craniotomy (P = .028) compared with patients who received FFP therapy alone. PCC as an adjunct to FFP decreases the time to craniotomy with faster correction of INR and concomitant decrease in the need for blood product requirement in patients with traumatic brain injury exclusive of prehospital warfarin therapy.