Platelet Reactivity Testing for Aspirin Patients Who Sustain Traumatic Intracranial Hemorrhage.

BACKGROUND: Patients who take aspirin and sustain traumatic intracranial hemorrhage (tICH) are often transfused platelets in an effort to prevent bleeding progression. The efficacy of platelet transfusion is questionable, however, and some medical societies recommend that platelet reactivity testing (PRT) should guide transfusion decisions. The study hypothesis was that utilization of PRT to guide platelet transfusion for tICH patients suspected of taking aspirin would safely identify patients who did not require platelet transfusion. METHODS: This was a retrospective study of patients with blunt tICH who received PRT for known or suspected aspirin use between June 2014 and December 2017 at a level I trauma center. Chart abstraction was conducted to determine home aspirin status, and PRT values were used to classify patients as therapeutic or nontherapeutic on aspirin. Differences were assessed with Kruskal-Wallis and chi-square tests. RESULTS: 157 patients met study inclusion criteria, and 118 (75%) patients had documented prior aspirin use. PRT results were available approximately 1.7 h (IQR: 0.9, 3.2) after arrival. Upon initial PRT, 70% of patients were considered inhibited and 88% of those patients had aspirin documented as a home medication. Conversely, 18% of patients with home aspirin use had normal platelet reactivity. Clinically significant worsening of the tICH did not significantly differ when comparing those who received platelet transfusion with those who did not (8% versus 7%, P = 0.87). CONCLUSIONS: Platelet reactivity testing can detect platelet inhibition related to aspirin and should guide transfusion decisions for head injured patients in the initial hours after trauma.

Procalcitonin is a Poor Predictor of Non-Infectious Fever in the Neurocritical Care Unit.

BACKGROUND: Fever is a common occurrence in the Neurocritical Care Unit (NCCU). It is reported that up to 50 % of these fevers are associated with a non-infectious source. As this is a diagnosis of exclusion, a complete fever evaluation must be done to rule out infection. Procalcitonin (PCT) has been identified as a possible biomarker to distinguish infectious from non-infectious etiologies of fever. We hypothesized that PCT could be used as a predictor of infectious fever in febrile patients with intracranial hemorrhage admitted to the NCCU. METHODS: A prospective observational cohort of patients admitted to a 12-bed NCCU in a tertiary-care university hospital from January 1, 2014, to October 1, 2014, was studied. Patients with intracranial hemorrhage (aneurismal subarachnoid hemorrhage, traumatic brain injury, intracerebral hemorrhage, or non-traumatic subdural hemorrhage) and fever defined as ≥101.4 °F were included. All patients had a urinalysis, chest X-ray, two sets of blood cultures, and PCT as part of their fever evaluation. Patients also had urine, sputum, CSF cultures, and Clostridium difficile toxin PCR as clinically indicated. Patients with incomplete fever evaluations were excluded. RESULTS: Seventy-three patients met inclusion criteria: 36 had infections identified and 37 did not. Type of intracranial hemorrhage was similar between groups. For those with identified infection, median PCT was 0.15 ng/mL (IQR 0.06-0.5 ng/mL). For those without identified infection, median PCT was 0.09 ng/mL (IQR 0.05-0.45 ng/mL), p = 0.30. Analyzing subgroups of intracranial hemorrhage patients revealed no group with a significant difference in PCT values. Patients with identified infection did have higher white blood cell counts (median 14.1 × 109/L (11.6-17.4 × 109/L) compared to those without identified infection 12 × 109/L (9.9-14.1 × 109/L), p = 0.02. CONCLUSION: Among patients with intracranial hemorrhage, PCT did not differentiate infectious fever from non-infectious fever.

Platelet dysfunction in patients with traumatic intracranial hemorrhage: Do desmopressin and platelet therapy help or harm?

BACKGROUND: Pre-injury anti-platelet use has been associated with increased risk of progression of traumatic intracranial hemorrhage (TICH) and worse outcomes. VerifyNow® assays assess platelet inhibition due to aspirin/clopidogrel. This study assesses the outcomes of patients with TICH and platelet dysfunction treated with desmopressin and/or platelets. METHODS: We performed a retrospective chart review of patients with mild TICH at a level 1 trauma center 1/1/2013-6/1/2016. Patients with documented platelet dysfunction who received desmopressin and/or platelets were compared to those who were untreated. Primary outcomes were progression of TICH and neurologic outcomes at discharge. RESULTS: Of 565 patients with a mild TICH, 200 patients had evidence of platelet dysfunction (a positive VerifyNow® assay). Patients had similar baseline demographics, injury characteristics, and rate of TICH progression; but patients who received desmopressin and/or platelets had worse Glasgow Outcomes Score at discharge. CONCLUSION: Treatment of patients with mild TICH and platelet dysfunction with desmopressin and/or platelets did not affect TICH progression but correlated with worse neurologic status at discharge.

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.

ABO blood groups do not predict progression of traumatic intracranial hemorrhage.

ABO blood groups are associated with genetically predisposed variations in von Willebrand factor (VWF) resulting in higher risks of thrombotic events in non-O blood types and bleeding complications in blood type O. The role of ABO blood groups in progression of traumatic intracranial hemorrhage (TICH) is unknown. Given statistically lower VWF levels in blood type O in the general population, we hypothesized that blood type O patients have a higher risk of such progression. A retrospective review of adult trauma patients with isolated TICH admitted to a Level 1 trauma center over eight years was conducted. Patients were categorized with blood type O and non-O (types A, B, AB) delineation. The primary outcome was radiological progression of TICH during the first 24 h. Secondary outcomes included surgical intervention after follow-up computed tomography (CT), complications, days on mechanical ventilation (DMV), intensive care unit (ICU) length of stay (LOS), hospital LOS, and mortality. Of 949 patients, 432 (45.5%) had blood type O. When comparing O and non-O groups, no significant differences were found in gender, age, race, admission vital signs, Glasgow Coma Scale, coagulation profile, TICH type, or Injury Severity Score. No difference in TICH progression was found between O and non-O groups: 73 (17%) vs 80 (15%), respectively, p = 0.55. Blood type O mortality was 12 (3% vs. 23 (4%), p = 0.174). Rate of TICH surgical intervention after follow-up CT, DMV, complications, and ICU and hospital LOS did not differ. No association between ABO blood types and radiological progression of TICH was identified.

The impact of platelets on the progression of traumatic intracranial hemorrhage.

BACKGROUND: The purpose of this study was to analyze the association of the initial platelet count with mortality and progression of intracranial hemorrhage (ICH) in blunt traumatic brain injured (TBI) patients. METHODS: All blunt trauma patients with severe TBI admitted from January 2006 to December 2007 were retrospectively identified. Patients with a chest, abdomen, or extremity AIS score >3 were excluded to minimize the impact of concomitant injuries on the outcomes of the patients. All brain computed tomography scans were reviewed to analyze ICH progression. Discrete platelet cutoff values were entered into a multiple regression model to detect critical thresholds associated with ICH progression and mortality. RESULTS: Of 626 TBI patients, 310 (49.5%) had a minimum of two brain computed tomography scans and were able to have ICH progression evaluated. Patients with platelets <175,000/mm3 had a significantly increased risk for ICH progression (OR [95% CI]: 2.09 [1.07-4.37]; adjusted p = 0.043). ICH progression was associated with increased need for craniotomy (OR [95% CI]: 3.27 [1.28-8.33]; adjusted p = 0.013) and mortality (OR [95% CI]: 3.41 [1.11-10.53]; adjusted p = 0.033). A platelet count <100,000/m3 was an independent predictor for mortality (OR [95% CI]: 9.5 [1.3-71.4]; adjusted p = 0.029). CONCLUSION: A platelet count <100,000/mm3 is associated with a ninefold adjusted risk of death, and a platelet count <175,000/mm3 is a significant predictor of ICH progression. The impact of early correction of the admission platelet count warrants further validation.

Prothrombin complex concentrate for vitamin K antagonist reversal in traumatic intracranial hemorrhage.

OBJECTIVE: Administration of prothrombin complex concentrate (PCC) is recommended for vitamin K antagonist (VKA) reversal in patients with severe bleeding complications. However, there are only limited data available on its use for VKA reversal in patients with traumatic intracranial hemorrhage (ICH). METHODS: Data from all anticoagulated patients referred to our hospital for treatment of traumatic ICH and who received PCC for anticoagulation reversal were retrospectively analysed with specific focus on bleeding and thromboembolic complications during the further in-hospital course. RESULTS: A total of 142 patients were included in the present study. The median age was 78 years (Interquartile range [IQR]: 72-84) and the median Glasgow Coma Scale (GCS) score on admission was 12 (IQR: 7-14). Median International Normalized Ratio (INR) on admission was 2.5 [IQR: 2.0-3.3] and decreased to 1.2 [IQR: 1.1-1.3] following administration of a median dose of 2000 I.U. PCC [IQR: 1500-2625]. The in-hospital mortality rate was 13% and the median GCS of survivors at discharge was 14 [IQR: 12-15]. Thromboembolic events after PCC administration occurred in 4 patients (2.8%). The overall one-year mortality rate in this patient cohort was 49%. CONCLUSIONS: PCC administration rapidly normalises INR and facilitates urgent neurosurgical procedures in anticoagulated patients with traumatic ICH.

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).

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.

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.

Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) is common in traumatic brain injury (TBI) and a major determinant of death and disability. ICH commonly increases in size and coagulopathy has been implicated in such progression. We investigated the association between coagulopathy diagnosed by routine laboratory tests and ICH progression. METHODS: Subgroup post hoc analysis from a randomized controlled trial including adult patients with blunt severe TBI (Glasgow Coma Scale score or=1.3, activated partial thromboplastin time >or=35, or platelet count (PLT)

Changes in serum levels of receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, IL-6 and TNF-alpha in patients with a concomitant head injury and fracture.

INTRODUCTION: Several reports indicated that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF- alpha) play important regulatory roles in bone remodeling and homeostasis. In addition, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) have been shown to be important regulators of osteoclastogenesis during bone remodeling, and their expressions were examined during fracture healing in a mouse model of tibial fracture. However, studies linking RANKL, OPG, IL-6 and TNF-alpha in patients with head injury and fracture are lacking. PATIENTS AND METHODS: Within the first few hours of admission to hospital and at 4, 8, and 12 weeks after the injury, we evaluated changes in serum levels of RANKL, OPG, IL-6 and TNF-alpha in 24 male patients with a concomitant head injury and fracture and in 26 male patients with fracture only. These levels were compared with those found in 36 healthy controls. RESULTS: The RANKL/OPG ratios were found to significantly lower in patients with a concomitant head injury and fracture than in the controls immediately after admission and at 4, 8, and 12 weeks after the injury. In addition, RANKL/OPG ratios were significantly lower in patients with a concomitant head injury and fracture than in those with fracture at 8 and 12 weeks after the injury. The serum IL-6 levels were significantly higher in patients with a concomitant head injury and fracture than in the controls upon admission, and at 4, 8, and 12 weeks after the injury. Moreover, the serum IL-6 levels were significantly higher in patients with a head injury and fracture than in those with just a fracture at 4, 8, and 12 weeks after the injury. CONCLUSIONS: Based on these changes in the profiles of RANKL, OPG, and IL-6 and the RANKL/OPG ratio, altered repair of a fracture can occur in patients with a concomitant head injury and fracture.

The role of thromboelastometry and recombinant factor VIIa in trauma.

PURPOSE OF REVIEW: Recombinant factor VIIa (rFVIIa) and thromboelastography have acquired increasing importance in patients with severe bleeding and coagulopathy. This article reviews the current opinions regarding their use, with the purpose of clarifying the ambiguities that exist in dealing with trauma patients. RECENT FINDINGS: Recent evidence encourages the early use of rFVIIa and thromboelastography in the severe trauma patient with hemorrhagic shock, as a component of the damage control strategy. rFVIIa may decrease short-term mortality and the rate of required blood components during resuscitation, with no apparent increase in thromboembolic complications. Thromboelastometry enables better and earlier recognition of the coagulopathy accompanying such trauma patients. In patients with traumatic brain injury and coagulopathy, rFVIIa may delay or even halt the need for surgery, with no proven decrease in mortality. In those who needed urgent neurosurgical intervention, rFVIIa may rapidly correct the coagulopathy, enabling earlier and safer surgical intervention. SUMMARY: Thromboelastometry may guide the medical staff when and to whom rFVIIa could be administered. Evidence also encourages the use of rFVIIa in traumatic brain injury. More research is required to prove decreases in mortality using both thromboelastography and rFVIIa in trauma, with a focus on clear end points and goal-directed therapy.

Expressions of plasma cystatin C, D-dimer and hypersensitive C-reactive protein in patients with intracranial progressive hemorrhagic injury after craniocerebral injury, and their clinical significance.

OBJECTIVE: To investigate the expressions of plasma cystatin C (Cys-C), D-dimer (D-D) and hypersensitive C-reactive protein (hs-CRP) in patients with intracranial progressive hemorrhagic injury (IPHI) after craniocerebral injury, and their clinical significance. METHODS: Forty-two IPHI patients and 20 healthy participants (control) were enrolled. The severity and outcome of IPHI were determined according to the Glasgow Coma Scale and Glasgow Outcome Scale, and the plasma Cys-C, hs-CRP and D-D levels were measured. RESULTS: The plasma Cys-C, D-D and hs-CRP levels in the IPHI group were significantly higher than those in the control group (p < 0.01). There were significant differences of plasma Cys-C, D-D and hs-CRP levels among different IPHI patients according to the Glasgow Coma Scale and according to the Glasgow Outcome Scale (all p < 0.05). In the IPHI patients, the plasma Cys-C, D-D and hs-CRP levels were positively correlated with each other (p < 0.001). CONCLUSION: The increase of plasma Cys-C, D-D and hs-CRP levels may be involved in IPHI after craniocerebral injury. The early detection of these indexes may help to understand the severity and outcome of IPHI.

A protocol for the rapid normalization of INR in trauma patients with intracranial hemorrhage on prescribed warfarin therapy.

Trauma patients on prescribed warfarin therapy sustaining intracranial hemorrhage can be difficult to manage. Rapid normalization of coagulopathy is imperative to operative intervention and may affect outcomes. To identify and expedite warfarin reversal, we designed a protocol to administer a prothrombin complex concentrate. A Proplex T protocol was instituted in May 2004. It dictated that trauma patients with an International Normalized Ratio (INR) greater than 1.5, history of prescribed warfarin therapy, and intracranial hemorrhage on CT scan receive a prothrombin complex concentrate for reversal of their coagulopathy. Neither the protocol nor the factor concentrate was validated for use in this subset of trauma patients; therefore, adherence to the protocol and use of the factor concentrate was not mandatory. Patients not administered the prothrombin complex concentrate received vitamin K and fresh-frozen plasma. The protocol resulted in an increased number of patients receiving Proplex T (54.3% vs 35.4%, P = 0.047). Protocol patients had improved times to normalization of INR (331.3 vs 737.8 minutes, P = 0.048), number of patients with reversal of coagulopathy (73.2% vs 50.9%, P = 0.026), and time to operative intervention (222.6 vs 351.3 minutes, P = 0.045) compared with control subjects. There were no differences in intensive care unit (ICU) days, hospital days, or mortality. The Proplex T protocol increased the number of patients who received prothrombin complex concentrate, provided rapid normalization of INR, and improved time to operative intervention.

Correlation of a high D-dimer level with poor outcome in traumatic intracranial hemorrhage.

The correlations between D-dimer and Glasgow Coma Scale (GCS), pupillary light reflex, distance of midline shift on brain computed tomography (CT), and Glasgow Outcome Score (GOS) in patients with trauma/non-trauma intracranial hemorrhage (ICH) are not consistent in studies. Ninety-eight traumatic and 59 non-traumatic ICH patients were studied. Pre-existing venous thrombosis, recent surgery, drug use (aspirin or coumadin), or malignancy, were excluded. D-dimer level was estimated within hours after acute insult, and statistical analyses were used for comparisons between groups. Traumatic ICH patients had higher D-dimer levels than controls (2984 vs. 256 microg/l; P = 0.001). The GCS, midline shift on brain CT, pupillary reflex, and GOS at 3 months were significantly correlated with high D-dimer value in traumatic patients (individual P < 0.001), but not in the non-traumatic group. Using receiver-operating characteristic curve (ROC), the cutoff point was 1496 microg/l, with sensitivity and specificity of 100% and 83%, respectively. D-dimer > or =1496 microg/l predicted a poor outcome [adjusted odds ratio (OR) 14.44, 95% CI 1.16-179.27; P = 0.038]. A high D-dimer level is associated with a poor outcome in patients with traumatic ICH. It can be used in addition to neurological assessment to predict the outcome.

Systematic Review and Meta-Analysis: Is Pre-Injury Antiplatelet Therapy Associated with Traumatic Intracranial Hemorrhage?

The objective of this systematic review and meta-analysis is to evaluate whether the pre-injury use of antiplatelet therapy (APT) is associated with increased risk of traumatic intracranial hemorrhage (tICH) on CT scan. PubMed, Medline, Embase, Cochrane Central, reference lists, and national guidelines on traumatic brain injury were used as data sources. Eligible studies were cohort studies and case-control studies that assessed the relationship between APT and tICH. Studies without control group were not included. The primary outcome of interest was tICH on CT. Two reviewers independently selected studies, assessed methodological quality, and extracted outcome data. This search resulted in 10 eligible studies with 20,247 patients with head injury that were included in the meta-analysis. The use of APT in patients with head injury was associated with significant increased risk of tICH compared with control (odds ratio [OR] 1.87, 95% confidence interval [CI]1.27-2.74). There was significant heterogeneity in the studies (I2 84%), although almost all showed an association between APT use and tICH. This association could not be established for patients receiving aspirin monotherapy. When considering only patients with mild traumatic brain injury (mTBI), the OR is 2.72 (95% CI 1.92-3.85). The results were robust to sensitivity analysis on study quality. In summary, APT in patients with head injury is associated with increased risk of tICH; this association is most relevant in patients with mTBI. Whether this association is the result of a causal relationship and whether this relationship also exists for patients receiving aspirin monotherapy cannot be established with the current review and meta-analysis.

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.

Coagulation Parameters and Risk of Progressive Hemorrhagic Injury after Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Intracranial hemorrhage (ICH) after traumatic brain injury (TBI) commonly increases in size and coagulopathy has been implicated in such progression. Our aim is to perform a meta-analysis to assess their relationship. Cochrane library, PubMed, and EMBASE were searched for literatures. Pooled effect sizes and 95% confidential intervals (CIs) were calculated using random-effects model. We included six studies, involving 1700 participants with 540 progressive hemorrhagic injuries (PHIs). Our findings indicate that PT, D-dimer level, and INR value are positively associated with the risk of PHI. Higher level of PLT and Fg seemed to suggest a lower risk of PHI. Among these parameters, higher D-dimer level and INR value would possess more powerful strength in predicting PHI.

[A role of stress-induced neuroendocrine disorders and tissue hypoxia in the thanatogenesis of traumatic intracranial hematomas].

AIM: To study the dynamics of plasma concentration of stress hormones (ACTH and cortisol) and lactate as well as the integrative stress level indicator at neuroreanimation stage of severe cranial-brain injury. MATERIAL AND METHODS: Authors examined 34 patients with traumatic intracranial hematomas including 19 patients who died during the first two weeks after admission to the hospital and 15 patients who were discharged for outpatient treatment. To assess stress level, we used the indicator of stress level estimated as body mass x 1/3 x heart rate frequency x pulse pressure x 0,000126. Contents of blood plasma ACTH and cortisol were determined using radioimmune method, lactic acid was measured with enzyme colorimetric method. A control group included the indicators of 10 healthy people aged from 24 to 44 years. RESULTS AND CONCLUSION: In the first 24 h, the overstrain of the neuroendocrine system in response to strong stress influence of the trauma was noted in all patients. In patients with fatal outcome, an increase in cortisol in the first 24 h was excessive and lactate level was significantly higher during the observational period compared to the patients with favorable outcome. The peak of mortality was at 1-5 days when the stress level indicators, contents of ACTH, cortisol and lactate reached maximal values indicating the stress-induces overstrain of the hypothalamic- pituitary-adrenal axis and promoting the development of brain tissue hypoxia.