• Human brain
• Natural extracts
• Neurotrauma
• Pharmacotherapy
• Phytochemicals
• Secondary injury

• Brain Injuries, Traumatic/drug therapy
• Brain Injuries, Traumatic/metabolism
• Brain Injuries, Traumatic/diet therapy
• Humans
• Neuroprotective Agents/therapeutic use
• Neuroprotective Agents/pharmacology
• Dietary Supplements
• Animals
• Biological Products/therapeutic use
• Biological Products/pharmacology

• DOAC
• ICH
• TBI
• VKA
• oral anticoagulant
• traumatic brain injury

• Humans
• Brain Injuries, Traumatic
• Anticoagulants/therapeutic use
• Anticoagulants/administration & dosage
• Aged
• Administration, Oral
• Treatment Outcome
• Aged, 80 and over

• Humans
• Dabigatran/adverse effects
• Anticoagulants/adverse effects
• Rivaroxaban/adverse effects
• Hemorrhage/drug therapy
• Thromboembolism
• Administration, Oral

• Anticoagulants
• blood coagulation tests
• critical care

• critical care
• general surgery
• intensive care unit
• pharmacy
• trauma

• Humans
• United States/epidemiology
• Adolescent
• Anticoagulants/therapeutic use
• Platelet Aggregation Inhibitors/therapeutic use
• Warfarin/therapeutic use
• Clopidogrel
• Retrospective Studies
• Aspirin/therapeutic use
• Brain Injuries, Traumatic/complications
• Brain Injuries, Traumatic/surgery

• Anticoagulants
• atrial fibrillation
• bleeding
• fall
• safety

• Humans
• Atrial Fibrillation/complications
• Atrial Fibrillation/drug therapy
• Atrial Fibrillation/chemically induced
• Stroke/etiology
• Stroke/prevention & control
• Hemorrhage/chemically induced
• Anticoagulants/adverse effects
• Thromboembolism/prevention & control
• Administration, Oral

• Anticoagulants
• atrial fibrillation
• frailty
• multimorbidity
• non-vitamin K antagonist oral anticoagulants
• older people
• stroke
• vitamin K antagonists

• Humans
• Aged
• Atrial Fibrillation/complications
• Atrial Fibrillation/drug therapy
• Anticoagulants/adverse effects
• Administration, Oral
• Frailty/complications
• Multiple Chronic Conditions/drug therapy
• Stroke/etiology
• Stroke/prevention & control
• Stroke/drug therapy
• Risk Factors

• Acute subdural hematoma
• Anticoagulant
• Antiplatelet
• Moderate and severe traumatic brain injury (TBI)

There is an increasing number of trauma patients presenting on pre-injury antiplatelet (AP) agents attributable to an aging population and expanding cardio- or cerebrovascular indications for antithrombotic therapy. The effects of different AP regimens on outcomes after traumatic brain injury (TBI) have yet to be elucidated, despite the implications on patient/family counseling and the potential need for better reversal strategies. The goal of this systematic review and meta-analysis was to assess the impact of different pre-injury AP regimens on outcomes after TBI. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the OVID Medline, Embase, BIOSIS, Scopus, and Cochrane databases were searched from inception to February 2022 using a combination of terms pertaining to TBI and use of AP agents. Baseline demographics and study characteristics as well as outcome data pertaining to intracerebral hematoma (ICH) progression, need for neurosurgical intervention, hospital length of stay, mortality, and functional outcome were extracted. Pooled odds ratios (ORs) and mean differences comparing groups were calculated using random-effects models. Thirteen observational studies, totaling 1244 patients receiving single AP therapy with acetylsalicylic acid or clopidogrel, 413 patients on dual AP therapy, and 3027 non-AP users were included. No randomized controlled trials were identified. There were significant associations between dual AP use and ICH progression (OR, 2.81; 95% confidence interval [CI], 1.19–6.61; I², 85%; p = 0.02) and need for neurosurgical intervention post-TBI (OR, 1.61; 95% CI, 1.15–2.28; I², 15%; p = 0.006) compared to non-users, but not between single AP therapy and non-users. There were no associations between AP use and hospital length of stay or mortality after trauma. Pre-injury dual AP use, but not single AP use, is associated with higher rates of ICH progression and neurosurgical intervention post-TBI. However, the overall quality of studies was low, and this association should be further investigated in larger studies.

• anticoagulant
• antiplatelet
• dosing
• obesity
• reversal

• Ethics
• Geriatrics
• Heart failure
• Hypertension
• Oral anticoagulation

• Aged
• Cardiovascular Diseases/drug therapy
• Cardiovascular Diseases/epidemiology
• Humans

Emergency physicians and trauma surgeons are increasingly confronted with pre-injury direct oral anticoagulants (DOACs). The objective of this study was to assess if pre-injury DOACs, compared to vitamin K antagonists (VKA), or no oral anticoagulants is independently associated with differences in treatment, mortality and inpatient rehabilitation requirement.

We performed a review of the prospectively maintained institutional trauma registry at an urban academic level 1 trauma center. We included all geriatric patients (aged ≥ 65 years) with tICH after a fall, admitted between January 2011 and December 2018. Multivariable logistic regression analysis controlling for demographics, comorbidities, vital signs, and tICH types were performed to identify the association between pre-injury anticoagulants and reversal agent use, neurosurgical interventions, inhospital mortality, 3-day mortality, and discharge to inpatient rehabilitation.

A total of 1453 tICH patients were included (52 DOAC, 376 VKA, 1025 control). DOAC use was independently associated with lower odds of receiving specific reversal agents [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.15–0.54] than VKA patients. DOAC use was independently associated with requiring neurosurgical intervention (OR 3.14, 95% CI 1.36–7.28). VKA use, but not DOAC use, was independently associated with inhospital mortality, or discharge to hospice care (OR 1.62, 95% CI 1.15–2.27) compared to controls. VKA use was independently associated with higher odds of discharge to inpatient rehabilitation (OR 1.41, 95% CI 1.06–1.87) compared to controls.

Despite the higher neurosurgical intervention rates, patients with pre-injury DOAC use were associated with comparable rates of mortality and discharge to inpatient rehabilitation as patients without anticoagulation exposure. Future research should focus on risk assessment and stratification of DOAC-exposed trauma patients.

• Anticoagulant reversal
• Direct oral anticoagulants
• Geriatric trauma
• Neurotrauma
• Vitamin K antagonists

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.

• adenosine diphosphate
• arachidonic acid
• blood platelets
• brain injuries
• cerebral hemorrhage
• critical care
• fibrinolysis
• mortality
• resuscitation
• thromboelastography
• traumatic

• DOACs
• NOACs
• apixaban
• dabigatran
• edoxaban
• rivaroxaban

• Administration, Oral
• Anticoagulants/adverse effects
• Atrial Fibrillation/complications
• Atrial Fibrillation/diagnosis
• Atrial Fibrillation/drug therapy
• Dabigatran/therapeutic use
• Humans
• Pyridones/therapeutic use
• Rivaroxaban/therapeutic use
• Stroke/diagnosis
• Stroke/etiology
• Stroke/prevention & control

• Unrestricted Educational Grant

Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, and the visco-elastic ClotPro^® ecarin clotting time (ECA-CT), we added the reversal agent Idarucizumab in vitro and these two analyses were repeated. Likewise, the baseline plasma concentration of apixaban, edoxaban, and rivaroxaban as well as ClotPro^® Russell’s viper venom test clotting time (RVV-CT) were measured and reanalyzed following Andexanet alfa spiking. We analyzed fifty blood samples from 37 patients and 10 healthy volunteers. Idarucizumab decreased the measured dabigatran plasma concentration from 323.9 ± 185.4 ng/mL to 5.9 ± 2.3 ng/mL and ECA-CT from 706.2 ± 344.6 s to 70.6 ± 20.2 s, (all, p < 0.001). Andexanet alfa decreased the apixaban concentration from 165.1 ± 65.5 ng/mL to 9.8 ± 8.1 ng/mL, edoxaban from 152.4 ± 79.0 ng/mL to 36.4 ± 19.2 ng/mL, and rivaroxaban from 153.2 ± 111.8 ng/mL to 18.1 ± 9.1 ng/mL (all p < 0.001). Andexanet alfa shortened the RVV-CT of patients with apixaban from 239.2 ± 71.7 s to 151.1 ± 30.2 s, edoxaban from 288.2 ± 65.0 s to 122.7 ± 37.1 s, and rivaroxaban from 225.9 ± 49.3 s to 103.7 ± 12.1 s (all p < 0.001). In vitro spiking of dabigatran-containing blood with Idarucizumab substantially reduced the plasma concentration and ecarin-test clotting time. Andexanet alfa lowered the concentration of the investigated factor Xa-inhibitors but did not normalize the RVV-CT. In healthy volunteers’ blood, Idarucizumab spiking had no impact on ECA-CT. Andexanet alfa spiking of non-anticoagulated blood prolonged RVV-CT (p = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa.

• Andexanet alfa
• DOAC
• ECA-test
• Idarucizumab
• RVV-test
• reversal

• Anticoagulants
• direct oral anticoagulant
• head injury
• intracranial hemorrhage
• warfarin

Objective: Elderly patients are frequently in need of antithrombotic therapy for reducing thrombotic events. The association between antithrombotic drugs and survival after traumatic brain injury (TBI) is, nevertheless, unclear.

Methods: This retrospective study included patients ≥65 years admitted to a Norwegian Level 1 trauma center with TBI identified on cerebral computed tomography (cerebral-CT) during 2014–2019. Preinjury use of antiplatelets and anticoagulants was compared to the prescription rate in the general Norwegian population. The primary outcome was 30-day mortality. Uni- and multivariate logistic regression analyses estimated the association between the use of antithrombotic drugs and mortality.

Results: The study includes 832 consecutive TBI patients ≥65 years. The median age was 76 years, 58% were males, 51% had moderate or severe TBI, and 39% had multiple traumas. Preinjury use of antithrombotics was registered in 471/832 (55.6%) patients; antiplatelet therapy alone in 268, anticoagulant therapy alone in 172, and combined antiplatelet and anticoagulant therapy in 31. Antiplatelet use did not differ between the study cohort and the general Norwegian population ≥65 years (31 vs. 31%, p = 0.87). Anticoagulant therapy was used more commonly in the study cohort than in the general Norwegian population (24 vs. 19%, p = 0.04). Combined use of antiplatelet and anticoagulant therapy was significantly associated with 30-day mortality, while preinjury antiplatelet or anticoagulation treatment alone was not. No difference in 30-day mortality between patients using VKA, DOACs, or LMWH was encountered.

Conclusions: In this cohort, neither antiplatelet nor anticoagulant therapy alone was associated with increased 30-day mortality. Anticoagulant use was more prevalent among TBI patients than the general population, suggesting that anticoagulation might contribute to the initiation of intracranial bleeding after blunt head trauma. Combined antiplatelet and anticoagulant therapy posed increased risk of 30-day mortality.

• anticoagulant therapy
• antiplatelet therapy
• antithrombotic therapy
• elderly
• mortality
• traumatic brain injury

Falls from standing are common in the elderly and are associated with a significant risk of bleeding. We have compared the proportional incidence of bleeding complications in patients on either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA).

Our retrospective cohort study compared elderly patients (≥65 years) on DOAC or VKA oral anticoagulation who presented at the study site – a Swiss university emergency department (ED) – between 01.06.2012 and 01.07.2017 after a fall. The outcomes were the proportional incidence of any bleeding complication and its components (e.g. intracranial haemorrhage), as well as procedural and clinical parameters (length of hospital stay, admission to intensive care unit, in-hospital-mortality). Uni- and multivariable analyses were used to compare the studied outcomes.

In total, 1447 anticoagulated patients were included – on either VKA (n = 1021) or DOAC (n = 426). There were relatively more bleeding complications in the VKA group (n = 237, 23.2%) than in the DOAC group (n = 69, 16.2%, p = 0.003). The difference persisted in multivariable analysis with 0.7-fold (95% CI: 0.5–0.9, p = 0.014) lower odds for patients under DOAC than under VKA for presenting with any bleeding complications, and 0.6-fold (95% 0.4–0.9, p = 0.013) lower odds for presenting with intracranial haemorrhage. There were no significant differences in the other studied outcomes.

Among elderly, anticoagulated patients who had fallen from standing, those under DOACs had a lower proportional incidence of bleeding complications in general and an even lower incidence of intracranial haemorrhage than in patients under VKAs.

The online version contains supplementary material available at 10.1186/s13049-021-00866-6.

• Anticoagulants
• Bleeding
• Direct oral anticoagulants
• Fall
• Intra cranial bleeding
• Syncope
• Vitamin K antagonist

• direct oral anticoagulants
• traumatic intracranial hemorrhage
• warfarin

• Administration, Oral
• Aged
• Anticoagulants/administration & dosage
• Atrial Fibrillation/complications
• Atrial Fibrillation/drug therapy
• Blood Coagulation/drug effects
• Female
• Follow-Up Studies
• Humans
• Intracranial Hemorrhage, Traumatic/blood
• Intracranial Hemorrhage, Traumatic/complications
• Intracranial Hemorrhage, Traumatic/mortality
• Male
• Retrospective Studies
• Risk Factors
• Stroke/etiology
• Stroke/prevention & control
• Survival Rate/trends
• Time Factors
• United States/epidemiology
• Warfarin/administration & dosage

• Anticoagulants
• Mortality
• Preinjury
• Trauma

• DOAC
• ED revisit rates
• NOAC
• VKAs
• anticoagulated patients
• computed tomography
• direct anticoagulant drugs
• emergency department
• hemorrhage
• intracranial hemorrhage
• intrahospital mortality
• mild head injury
• mild head trauma
• minor head injury
• minor head trauma
• new anticoagulant drugs
• observation
• risk management
• surgery
• vitamin K antagonist anticoagulants

• Aged
• Aged, 80 and over
• Craniocerebral Trauma/complications
• Craniocerebral Trauma/epidemiology
• Emergency Service, Hospital/organization & administration
• Emergency Service, Hospital/statistics & numerical data
• Factor Xa Inhibitors/pharmacology
• Factor Xa Inhibitors/therapeutic use
• Female
• Humans
• Intracranial Hemorrhages/epidemiology
• Intracranial Hemorrhages/ethnology
• Male
• Retrospective Studies
• Tomography, X-Ray Computed/methods
• Vitamin K/antagonists & inhibitors
• Vitamin K/therapeutic use

• Evidence based Medicine
• Older adults
• anticoagulation
• hypertension
• osteoporosis

• Aged
• Evidence-Based Medicine
• Geriatrics
• Humans

As intracerebral hemorrahge becomes more frequent as a result of an aging population with greater comorbidities, rapid identification and reversal of precipitators becomes increasingly paramount. The aformentioned population will ever more likely be on some form of anticoagulant therapy. Understanding the mechanisms of these agents and means by which to reverse them early on is critical in managing the acute intracerebral hemorrhage.

• anticoagulation
• cerebral hemorrhage
• coagulopathy reversal
• hemorrhagic stroke

• Intracranial hemorrhages
• Oral anticoagulants
• Subdural hematoma
• Subdural hemorrhage
• Trauma

• Bleeding
• Direct-acting oral anticoagulant
• Hemorrhage
• Oral anticoagulant
• Warfarin

• Administration, Oral
• Anticoagulants/adverse effects
• Atrial Fibrillation/drug therapy
• Blood Component Transfusion
• Factor Xa Inhibitors/therapeutic use
• Hemorrhage/chemically induced
• Hemorrhage/drug therapy
• Humans
• Inpatients
• Plasma
• Retrospective Studies
• Stroke/drug therapy
• Warfarin/adverse effects

• HHSN268201100001C WHI NIH HHS
• HHSN268201100001I NHLBI NIH HHS
• HHSN268201100002I NHLBI NIH HHS

• Administration, Oral
• Anticoagulants/administration & dosage
• Anticoagulants/adverse effects
• Anticoagulants/classification
• Cardiology/education
• Cardiology/methods
• Cardiovascular Diseases/drug therapy
• Consensus
• Critical Pathways/organization & administration
• Emergency Medical Services/methods
• Hemorrhage/chemically induced
• Hemorrhage/therapy
• Humans
• Interdisciplinary Communication
• Patient Care Management/methods
• Patient Care Management/trends

• Anticoagulation
• falls
• frailty
• geriatric trauma
• traumatic brain injury

• Anticoagulation reversal
• Coagulation management
• Idarucizumab
• Intracranial hemorrhage
• Non-vitamin K antagonist oral anticoagulant (NOAC)
• Platelet inhibitors
• Prothrombin complex concentrate (PCC)
• Traumatic brain injury
• Vitamin K antagonist (VKA)

• Administration, Oral
• Anticoagulants/adverse effects
• Anticoagulants/therapeutic use
• Austria
• Brain Injuries, Traumatic/drug therapy
• Brain Injuries, Traumatic/physiopathology
• Consensus
• Dabigatran/adverse effects
• Dabigatran/therapeutic use
• Deamino Arginine Vasopressin/pharmacology
• Humans
• Interdisciplinary Communication
• Partial Thromboplastin Time/methods
• Pyrazoles/analysis
• Pyrazoles/blood
• Pyrazoles/therapeutic use
• Pyridines/analysis
• Pyridines/blood
• Pyridines/therapeutic use
• Pyridones/analysis
• Pyridones/blood
• Pyridones/therapeutic use
• Rivaroxaban/analysis
• Rivaroxaban/blood
• Rivaroxaban/therapeutic use
• Thiazoles/analysis
• Thiazoles/blood
• Thiazoles/therapeutic use
• Thromboembolism/prevention & control
• Tomography, X-Ray Computed/methods
• Tranexamic Acid/therapeutic use
• Treatment Outcome
• Vitamin K/antagonists & inhibitors
• Vitamin K/therapeutic use

Dabigatran is one of the four drugs currently used as a direct oral anticoagulant in Japan. Idarucizumab, which specifically targets dabigatran, was recently approved in Japan. We present a case of intracranial hemorrhage in a traumatic brain injury patient taking dabigatran who was treated by administering idarucizumab.

A 72-year-old man was injured in a traffic accident and was transferred to our emergency room. On arrival, his Glasgow Coma Scale score was 14 (eye, 3; verbal, 5; motor, 6), and his other vital signs were stable. Computed tomography (CT) imaging on arrival showed a small intracranial hematoma. A second CT 3 h later revealed expansion of the hematoma. We received information that he was taking dabigatran only after the second CT. Idarucizumab was then promptly administered, and emergency craniotomy for hematoma removal was performed. There was no tendency for bleeding during the operation, and blood transfusion was not required during the perioperative period. Although the patient underwent additional surgery for subdural effusion and hydrocephalus, his postoperative course was uneventful. He was transferred to a rehabilitation hospital on postoperative day 102.

We managed a patient taking dabigatran who suffered traumatic intracranial hemorrhage by administering idarucizumab preoperatively without the need for blood transfusion perioperatively. We suggest that idarucizumab could be a potent therapeutic bridge to definitive surgical management in such patients with traumatic brain injury who are taking dabigatran.

• Dabigatran
• Direct oral anticoagulants
• Idarucizumab
• Specific neutralizing drug
• Traumatic brain injury
• Traumatic intracranial hemorrhage

• Adult
• Aged
• Aged, 80 and over
• Anticoagulants/adverse effects
• Anticoagulants/therapeutic use
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Phlebography/methods
• Pregnancy
• Pulmonary Embolism/epidemiology
• Pulmonary Embolism/prevention & control
• Risk Factors
• Ultrasonography/methods
• Ultrasonography, Doppler, Duplex/methods
• United States/epidemiology
• Venous Thromboembolism/diagnosis
• Venous Thromboembolism/epidemiology
• Venous Thromboembolism/mortality
• Venous Thrombosis/diagnostic imaging
• Venous Thrombosis/epidemiology
• Venous Thrombosis/therapy