Explore the vast range of titles available.

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

Limited data exist regarding the use of hemostatic adjuncts on the progression of traumatic intracranial hemorrhage (tICH). The objective of this study was to examine the impact of platelet transfusion and desmopressin (DDAVP) administration on hemorrhage progression following tICH. We hypothesized that platelet and DDAVP administration would not result in decreased early hemorrhagic progression. We performed a three-year retrospective analysis of a Level 1 trauma center database to identify all adult patents with blunt tICH. The primary outcome was early (≤4 hours) radiographic hemorrhagic progression. Secondary outcomes included mortality, frequency of operative interventions, and complications. Multiple logistic regression analysis was performed to identify predictors for hemorrhage progression and mortality. A propensity score analysis also was performed to minimize differences and improve comparability between patients who received platelets and DDAVP and those who did not. Of 408 patients with tICH meeting the inclusion criteria, 126 received platelets and DDAVP (P/D [+]) and 282 did not (P/D [−]). Overall, 37% of patients demonstrated early radiographic hemorrhage progression. On univariate analysis, there was no difference in the incidence of hemorrhage progression between groups (43.7% [P/D (+)] vs. 34.2% [P/D (−)]; p = 0.07). On multivariate analyses, platelet and DDAVP administration was not associated with either a decreased risk of hemorrhage progression (odds ratio [OR] = 1.40, confidence interval [CI] = 0.80–2.40; p = 0.2) or mortality (OR = 1.50, CI = 0.60–4.30; p = 0.4). The administration of platelets and DDAVP is not associated with a decreased risk for early radiographic hemorrhage progression in patients with tICH. Further prospective study of these potentially hemostatic adjuncts in patients with tICH is potentially warranted.

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

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.

Abstract BACKGROUND 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. OBJECTIVE To review frequencies, patterns, mechanisms, novel approaches to diagnostics, treatment, and outcomes of hemorrhagic progression and coagulopathy after TBI. METHODS Selective review of the literature in the databases Medline (PubMed) and Cochrane Reviews using different combinations of the relevant search terms was conducted. RESULTS 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. CONCLUSION 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.

•Repeat imaging has limited utility in low-risk, mild traumatic brain injury patients.•No patient with low-risk, mild traumatic brain injury had neurosurgical intervention.•Performing serial neurological examinations may be a safe, cost-effective alternative.•Transferring low-risk, mild traumatic brain injury patients may be unnecessary. Intracranial hemorrhage (ICH) is frequently found on computed tomography (CT) after mild traumatic brain injury (mTBI) prompting transfer to centers with neurosurgical coverage and repeat imaging to confirm hemorrhage stability. Studies suggest routine repeat imaging has little utility in patients with minimal ICH, no anticoagulant/antiplatelet use, and no neurological decline. Additionally, it is unclear which mTBI patients benefit from transfer for neurosurgery consultation. The authors sought to assess the clinical utility and cost effectiveness of routine repeat head CTs and transfer to tertiary centers in patients with low-risk, mTBI. Retrospective evaluation of patients receiving a neurosurgical consultation for TBI during a 4-year period was performed at a level 1 trauma center. Patients were stratified according to risk for neurosurgical intervention based on their initial clinical evaluation and head CT. Only patients with low-risk, mTBI were included. Of 531 patients, 119 met inclusion criteria. Eighty-eight (74.0 %) received two or more CTs. Direct cost of repeat imaging was $273,374. Thirty-seven (31.1 %) were transferred to our facility from hospitals without neurosurgical coverage, costing $61,384. No patient had neurosurgical intervention or mTBI-related in-hospital mortality despite enlarging ICH on repeat CT in three patients. Two patients had mTBI related 30-day readmission for seizure without ICH expansion. Routine repeat head CT or transfer of low-risk, mTBI patients to a tertiary center did not result in neurosurgical intervention. Serial neurological examinations may be a safe, cost-effective alternative to repeat imaging for select mTBI patients. A large prospective analysis is warranted for further evaluation.

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. 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. 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. 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. [Display omitted] •Traumatic brain injury patients may have worse outcomes if on antiplatelet therapy.•Treating these patients with desmopressin and/or platelets may not improve outcomes.•Further studies to investigate optimal treatment strategies for these patients are warranted.

Background With increasing use of direct oral anticoagulants (DOACs) and availability of new reversal agents, the risk of traumatic intracranial hemorrhage (tICH) requires better understanding. We compared hemorrhage expansion rates, mortality, and morbidity following tICH in patients treated with vitamin k antagonists (VKA: warfarin) and DOACs (apixaban, rivaroxaban, dabigatran). Methods Retrospective chart review of patients from 2010 to 2017 was performed to identify patients with imaging diagnosis of acute traumatic intraparenchymal, subdural, subarachnoid, and epidural hemorrhage with preadmission use of DOACs or VKAs. We identified 39 patients on DOACs and 97 patients on VKAs. Demographic information, comorbidities, hemorrhage size, and expansion over time, as well as discharge disposition and Glasgow Outcome Scale (GOS) were collected. Primary outcome was development of new or enlargement of tICH within the first 48 h of initial CT imaging. Results Of 136 patients with mean (SD) age 78.7 (13.2) years, most common tICH subtype was subdural hematoma ( N  = 102/136; 75%), and most common mechanism was a fall ( N  = 130/136; 95.6%). Majority of patients in the DOAC group did not receive reversal agents (66.7%). Hemorrhage expansion or new hemorrhage occurred in 11.1% in DOAC group vs. 14.6% in VKA group ( p  = 0.77) at a median of 8 and 11 h from initial ED admission, respectively ( p  = 0.82). Patients in the DOAC group compared to VKA group had higher median discharge GOS (4 vs. 3 respectively, p  = 0.03), higher percentage of patients with good outcome (GOS 4–5, 66.7% vs. 40.2% respectively, p  = 0.005), and higher rate of discharge to home or rehabilitation ( p  = 0.04). Conclusions We report anticoagulation-associated tICH outcomes predominantly due to fall-related subdural hematomas. Patients on DOACs had lower tICH expansion rates although not statistically significantly different from VKA-treated patients. DOAC-treated patients had favorable outcomes versus VKA group following tICH despite low use of reversal strategies. DOAC use may be a safer alternative to VKA in patients at risk of traumatic brain hemorrhage.

After a traumatic intracranial hemorrhage (tICH), patients often receive a platelet transfusion to reverse the effects of antiplatelet medication and to reduce neurologic complications. As platelet transfusions have their own risks, this study evaluated their effects on tICH progression, need for operations and mortality. In this retrospective study, we identified patients admitted to a level 1 trauma centre with a tICH from 2011 to 2015 who were taking acetylsalicylic acid (ASA) or clopidogrel, or both. We categorized patients into 2 groups: platelet transfusion recipients and nonrecipients. We collected data on demographic characteristics, changes in brain computed tomography findings, neurosurgical interventions, in-hospital death and intensive care unit (ICU) length of stay (LOS). We used multivariable logistic regression to compare outcomes between the 2 groups. We identified 224 patients with tICH, 156 (69.6%) in the platelet transfusion group and 68 (30.4%) in the no transfusion group. There were no between-group differences in progression of bleeds or rates of neurosurgical interventions. In the transfusion recipients, there was a trend toward increased ICU LOS (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 0.74–3.40) and in-hospital death (adjusted OR 3.23, 95% CI 0.48–21.74). There were no differences in outcomes between patients who received platelet transfusions and those who did not; however, the results suggest a worse clinical course, as indicated by greater ICU LOS and mortality, in the transfusion recipients. Routine platelet transfusion may not be warranted in patients taking ASA or clopidogrel who experience a tICH, as it may increase ICU LOS and mortality risk. Après une hémorragie intracrânienne traumatique, les patients reçoivent souvent une transfusion de plaquettes pour inverser les effets des médicaments antiplaquettaires et réduire les complications neurologiques. Les transfusions de plaquettes comportent des risques particuliers; l’étude portait sur leurs effets sur la progression de l’hémorragie intracrânienne traumatique, ainsi que sur la nécessité d’une opération et la mortalité. Dans cette étude rétrospective, nous avons ciblé des patients atteints d’une hémorragie intracrânienne traumatique admis dans un centre de traumatologie de niveau 1, de 2011 à 2015, qui prenaient de l’acide acétylsalicylique (AAS) ou du clopidogrel, ou les deux. Ces patients ont été classés en 2 catégories : ceux ayant reçu une transfusion de plaquettes et ceux n’ayant pas reçu de transfusion. Nous avons recueilli des données sur les caractéristiques démographiques, les changements des résultats de la tomodensitométrie cérébrale, les interventions neurochirurgicales, les décès à l’hôpital et la durée de séjour en unité de soins intensifs. Nous avons eu recours à une analyse de régression logistique multivariée pour comparer les résultats entre les 2 groupes. Nous avons ciblé 224 patients atteints d’une hémorragie intracrânienne traumatique : 156 (69,6 %) ayant reçu une transfusion de plaquettes et 68 (30,4 %) n’ayant pas reçu de transfusion. Il n’y avait aucune différence entre les groupes concernant la progression des saignements ou les taux d’interventions neurochirurgicales. Chez les patients ayant reçu une transfusion, on a observé une tendance à la hausse de la durée de séjour en unité de soins intensifs (rapport de cotes [RC] ajusté de 1,59; intervalle de confiance [IC] de 95 %, 0,74–3,40) et des décès à l’hôpital (RC ajusté de 3,23; IC de 95 % de 0,48–21,74). On n’a observé aucune différence au chapitre des résultats entre les patients ayant reçu une transfusion de plaquettes et les autres. Toutefois, les résultats suggèrent une évolution clinique défavorable chez les patients ayant reçu une transfusion, se traduisant par une durée de séjour en unité de soins intensifs plus longue et un taux de mortalité plus élevé. La transfusion plaquettaire systématique pourrait ne pas être avisée chez les patients prenant de l’AAS ou du clopidogrel qui souffrent d’une hémorragie intracrânienne traumatique, car elle pourrait faire augmenter la durée de séjour en unité de soins intensifs et exacerber le risque de mortalité.

Patients with traumatic intracranial hemorrhage and mild traumatic brain injury (mTIH) receive broadly variable care which often includes transfer to a trauma center, neurosurgery consultation and ICU admission. However, there may be a low risk cohort of patients who can be managed without utilizing such significant resources. Describe mTIH patients who are at low risk of clinical or radiographic decompensation and can be safely managed in an ED observation unit (EDOU). Retrospective evaluation of patients age≥16, GCS≥13 with ICH on CT. Primary outcomes included clinical/neurologic deterioration, CT worsening or need for neurosurgery. 1185 consecutive patients were studied. 814 were admitted and 371 observed patients (OP) were monitored in the EDOU or discharged from the ED after a period of observation. None of the OP deteriorated clinically. 299 OP (81%) had a single lesion on CT; 72 had mixed lesions. 120 patients had isolated subarachnoid hemorrhage (iSAH) and they did uniformly well. Of the 119 OP who had subdural hematoma (SDH), 6 had worsening CT scans and 3 underwent burr hole drainage procedures as inpatients due to persistent SDH without new deficit. Of the 39 OP who had cerebral contusions, 3 had worsening CT scans and one required NSG admission. No patient returned to the ED with a complication. Follow-up was obtained on 81% of OP. 2 patients with SDH required burr hole procedure >2weeks after discharge. Patients with mTIH, particularly those with iSAH, have very low rates of clinical or radiographic deterioration and may be safe for monitoring in an emergency department observation unit.