RESUMO
BACKGROUND: The goal of this study is to determine the presence of platelet dysfunction in patients with traumatic brain injury (TBI). The mechanisms underlying the coagulopathy associated with TBI remain elusive. The question of platelet dysfunction in TBI is unclear. METHODS: This was a prospective observational study conducted at Memorial Hospital of South Bend, IN, and Denver Health Medical Center, CO. A total of 50 patients sustaining TBI, and not under treatment with anticoagulants or platelet inhibitors, were analyzed utilizing modified thromboelastography (TEG) with platelet mapping (TEG/PM), along with standard coagulation tests. RESULTS: Compared to normal controls, patients with severe TBI had a significantly increased percentage of platelet ADP and arachidonic acid (AA) receptor inhibition. Furthermore, the percentage of ADP inhibition distinguished between survivors and non-survivors in patients with TBI (Mann-Whitney test, P = 0.035). ADP inhibition correlates strongly with severity of TBI (Mann-Whitney test, P = 0.014), while AA inhibition did not. CONCLUSION: These data indicate that early platelet dysfunction is prevalent after severe TBI, can be measured in a point-of-care setting using TEG/PM, and correlates with mortality. The mechanism responsible for this platelet dysfunction and associated implications for TBI management remains to be defined.
Assuntos
Transtornos Plaquetários/sangue , Lesões Encefálicas/sangue , Tromboelastografia/métodos , Adulto , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Lesões Encefálicas/diagnóstico , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Estudos Prospectivos , Receptores Purinérgicos P2/metabolismo , Fatores de TempoAssuntos
Acidentes de Trânsito , Cervicalgia/diagnóstico , Neurilemoma/diagnóstico , Neoplasias da Medula Espinal/diagnóstico , Adulto , Vértebras Cervicais , Diagnóstico Diferencial , Seguimentos , Humanos , Laminectomia/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Neurilemoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Índice de Gravidade de Doença , Neoplasias da Medula Espinal/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Coagulopathy in traumatic brain injury (CTBI) is a well-established phenomenon, but its mechanism is poorly understood. Various studies implicate protein C activation related to the global insult of hemorrhagic shock or brain tissue factor release with resultant platelet dysfunction and depletion of coagulation factors. We hypothesized that the platelet dysfunction of CTBI is a distinct phenomenon from the coagulopathy following hemorrhagic shock. METHODS: We used thrombelastography with platelet mapping as a measure of platelet function, assessing the degree of inhibition of the adenosine diphosphate (ADP) and arachidonic acid (AA) receptor pathways. First, we studied the early effect of TBI on platelet inhibition by performing thrombelastography with platelet mapping on rats. We then conducted an analysis of admission blood samples from trauma patients with isolated head injury (n = 70). Patients in shock or on clopidogrel or aspirin were excluded. RESULTS: In rats, ADP receptor inhibition at 15 minutes after injury was 77.6% ± 6.7% versus 39.0% ± 5.3% for controls (p < 0.0001). Humans with severe TBI (Glasgow Coma Scale [GCS] score ≤ 8) showed an increase in ADP receptor inhibition at 93.1% (interquartile range [IQR], 44.8-98.3%; n = 29) compared with 56.5% (IQR, 35-79.1%; n = 41) in milder TBI and 15.5% (IQR, 13.2-29.1%) in controls (p = 0.0014 and p < 0.0001, respectively). No patient had significant hypotension or acidosis. Parallel trends were noted in AA receptor inhibition. CONCLUSION: Platelet ADP and AA receptor inhibition is a prominent early feature of CTBI in humans and rats and is linked to the severity of brain injury in patients with isolated head trauma. This phenomenon is observed in the absence of hemorrhagic shock or multisystem injury. Thus, TBI alone is shown to be sufficient to induce a profound platelet dysfunction.
Assuntos
Ácido Araquidônico/antagonistas & inibidores , Transtornos da Coagulação Sanguínea/etiologia , Lesões Encefálicas/sangue , Lesões Encefálicas/complicações , Antagonistas do Receptor Purinérgico P2Y/sangue , Choque Hemorrágico/sangue , Choque Hemorrágico/etiologia , Adulto , Animais , Ácido Araquidônico/sangue , Transtornos da Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea , Plaquetas/fisiologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Testes de Função Plaquetária , Estudos Prospectivos , Ratos , Ratos Sprague-Dawley , Valores de Referência , Medição de Risco , Estatísticas não Paramétricas , TromboelastografiaRESUMO
Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.