Application of a TEG-Platelet Mapping Algorithm to Guide Reversal of Antiplatelet Agents in Adults with Mild-to-Moderate Traumatic Brain Injury: An Observational Pilot Study.

BACKGROUND: Traumatic intracranial hemorrhages expand in one third of cases, and antiplatelet medications may exacerbate hematoma expansion. However, the reversal of an antiplatelet effect with platelet transfusion has been associated with harm. We sought to determine whether a thromboelastography platelet mapping (TEG-PM)-guided algorithm could limit platelet transfusion in patients with hemorrhagic traumatic brain injury (TBI) prescribed antiplatelet medications without a resultant clinically significant increase in hemorrhage volume, late hemostatic treatments, or delayed operative intervention. METHODS: A total of 175 consecutive patients with TBI were admitted to our university-affiliated, level I trauma center between March 2016 and December 2019: 54 preintervention patients (control) and 121 patients with TEG-PM (study). After exclusion for anticoagulant administration, availability of neuroimaging and emergent neurosurgery, 62 study patients and 37 control patients remained. Intervention consisted of administration of desmopressin (DDAVP) for nonsurgical patients with significant inhibition at the arachidonic acid or adenosine diphosphate receptor sites. For surgical patients with significant inhibition, dual therapy with DDAVP and platelet transfusion was employed. Study patients were compared with a group of historical controls, which were identified from a prospectively maintained registry and typically treated with empiric platelet transfusion. RESULTS: Median age was 75 years (interquartile range 85-67) and 77 years (interquartile range 81-65) in the TEG-PM and control patient groups, respectively. Admission hemorrhage volumes were similar (10.7 cm3 [20.1] in patients with TEG-PM vs. 14.1 cm3 [19.7] in controls; p = 0.41). There were no significant differences in admission Glasgow Coma Scale, mechanism of trauma, or baseline comorbidities. A total of 57% of controls versus 10% of patients with TEG-PM (p < 0.001) were transfused platelets; 52% of intervention patients and 0% controls were treated with DDAVP. Expansion hemorrhage volumes were not significantly different (14.0 cm3 [20.2] patients with TEG-PM versus 13.6 cm3 [23.7] controls; p = 0.93). There was no significant difference in rates of clinical deterioration, delayed neurosurgical intervention, or late platelet transfusion between groups. CONCLUSIONS: Among patients with hemorrhagic TBI prescribed preinjury antiplatelet therapy, our study suggests that the use of a TEG-PM algorithm may reduce platelet transfusions without a concurrent increase in clinically significant hematoma expansion. Further study is required to prove a causative relationship.

Beta blockade in TBI: Dose-dependent reductions in BBB leukocyte mobilization and permeability in vivo.

BACKGROUND: Traumatic brain injury (TBI) is accompanied by a hyperadrenergic catecholamine state that can cause penumbral neuroinflammation. Prospective human studies demonstrate improved TBI survival with beta blockade (bb), although mechanisms remain unclear. We hypothesized that deranged post-TBI penumbral blood brain barrier (BBB) leukocyte mobilization and permeability are improved by bb. METHODS: CD1 male mice (n = 64) were randomly assigned to severe TBI-controlled cortical impact: 6 m/s velocity, 1 mm depth, 3 mm diameter-or sham craniotomy, and IP injection of either saline or propranolol (1, 2, or 4 mg/kg) every 12 hours for 2 days. At 48 hours, in vivo pial intravital microscopy visualized live endothelial-leukocyte (LEU) interactions and BBB microvascular leakage. Twice daily clinical recovery was assessed by regaining of lost body weight and the Garcia Neurological Test (motor, sensory, reflex, balance assessments). Brain edema was determined by hemispheric wet-to-dry ratios. RESULTS: Propranolol after TBI reduced both in vivo LEU rolling and BBB permeability in a dose-dependent fashion compared with no treatment (p < 0.001). Propranolol reduced cerebral edema (p < 0.001) and hastened recovery of lost body weight at 48 hours (p < 0.01). Compared with no treatment (14.9 ± 0.2), 24-hour Garcia Neurologic Test scores were improved with 2 (15.8 ± 0.2, p = 0.02) and 4 (16.1 ± 0.1, p = 0.001) but not with 1 mg/kg propranolol. CONCLUSION: Propranolol administration reduces post-TBI LEU mobilization and microvascular permeability in the murine penumbral neurovasculature and leads to reduced cerebral edema. This is associated with hastened recovery of post-TBI weight loss and neurologic function with bb treatment. Dose-dependent effects frame a mechanistic relationship between bb and improved human outcomes after TBI.

Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients. DATA SOURCES: MEDLINE, PubMed Central, Embase, and CENTRAL. STUDY SELECTION: Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021. DATA EXTRACTION: Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison. DATA SYNTHESIS: Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; p = 0.030). CONCLUSIONS: Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.

Neurosurgical applications of viscoelastic hemostatic assays.

Patients taking antithrombotic agents are very common in neurosurgical practice. The perioperative management of these patients can be extremely challenging especially as newer agents, with poorly defined laboratory monitoring and reversal strategies, become more prevalent. This is especially true with emergent cases in which rapid reversal of anticoagulation is required and the patient's exact medical history is not available. With an aging patient population and the associated increase in diseases such as atrial fibrillation, it is expected that the use of these agents will continue to rise in coming years. Furthermore, thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and myocardial infarction are common complications of major surgery. These trends, in conjunction with a growing understanding of the hemostatic process and its contribution to the pathophysiology of disease, stress the importance of the complete evaluation of a patient's hemostatic profile in guiding management decisions. Viscoelastic hemostatic assays (VHAs), such as thromboelastography and rotational thromboelastometry, are global assessments of coagulation that account for the cellular and plasma components of coagulation. This FDA-approved technology has been available for decades and has been widely used in cardiac surgery and liver transplantation. Although VHAs were cumbersome in the past, advances in software and design have made them more accurate, reliable, and accessible to the neurosurgeon. VHAs have demonstrated utility in guiding intraoperative blood product transfusion, identifying coagulopathy in trauma, and managing postoperative thromboprophylaxis. The first half of this review aims to evaluate and assess VHAs, while the latter half seeks to appraise the evidence supporting their use in neurosurgical populations.

Temporal dynamics of microparticle elevation following subarachnoid hemorrhage.

OBJECT: Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH. METHODS: On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden. RESULTS: When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)-, CD66b+(neutrophil)-, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])-associated MPs and CD146+(endothelial cell)-associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH. CONCLUSIONS: Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)-associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.

Anti-N-methyl-D-aspartate receptor encephalitis during pregnancy.

OBJECTIVE: To report 3 patients who developed anti-N-methyl-d-aspartate receptor encephalitis during pregnancy. DESIGN: Case reports. SETTING: University hospitals. Patients Three young women developed at 14, 8, and 17 weeks of gestation acute change of behavior, prominent psychiatric symptoms, progressive decrease of consciousness, seizures, dyskinesias, and autonomic dysfunction. MAIN OUTCOME MEASURES: Clinical, radiological, and immunological findings. RESULTS: The 3 patients had cerebrospinal fluid pleocytosis, normal magnetic resonance imaging, and electroencephalogram showing slow activity. All had higher antibody titers in cerebrospinal fluid than in serum and 2 had ovarian teratomas that were removed. The pregnancy was terminated in 1 patient with recurrent bilateral teratomas. All patients had substantial neurological recoveries, and the 2 newborns were normal. Results of extensive antibody testing in 1 of the babies were negative. CONCLUSION: The current study shows that anti-NMDAR encephalitis during pregnancy can have a good outcome for the mother and newborn.