RESUMEN
BACKGROUND: Upon cellular injury, damage-associated molecular patterns (DAMPs) are released into the extracellular space and evoke proinflammatory and prothrombotic responses in animal models of sterile inflammation. However, in clinical settings, the dynamics of DAMP levels after trauma and links between DAMPs and trauma-associated coagulopathy remain largely undetermined. METHODS: Thirty-one patients with severe trauma, who were transferred to Kagoshima City Hospital between June 2018 and December 2019, were consecutively enrolled in this study. Blood samples were taken at the time of delivery, and 6 and 12 h after the injury, and once daily thereafter. The time-dependent changes of coagulation/fibrinolysis markers, including thrombin-antithrombin complex, α2-plasmin inhibitor (α2-PI), plasmin-α2-PI complex, and plasminogen activator inhibitor-1 (PAI-1), and DAMPs, including high mobility group box 1 and histone H3, were analyzed. The relationship between coagulation/fibrinolysis markers, DAMPs, Injury Severity Score, in-hospital death, and amount of blood transfusion were analyzed. RESULTS: The activation of coagulation/fibrinolysis pathways was evident at the time of delivery. In contrast, PAI-1 levels remained low at the time of delivery, and then were elevated at 6-12 h after traumatic injury. Histone H3 and high mobility group box 1 levels were elevated at admission, and gradually subsided over time. PAI-1 levels at 6 h were associated with serum histone H3 levels at admission. Increased histone H3 levels and plasmin-α2-PI complex levels were associated with in-hospital mortality. α2-PI levels at admission showed the strongest negative correlation with the amount of blood transfusion. CONCLUSION: The elevation of histone H3 levels and fibrinolysis perturbation are associated with fatal outcomes in patients with traumatic injury. Patients with low α2-PI levels at admission tend to require blood transfusion.
RESUMEN
A 25-years-old man experienced fever and diarrhea. Ten days later he noticed difficulty walking (day 1). On admission neurological examination revealed lethargy, dysarthria and weakness of limbs. Oculocephalic response was not be elicited and extensor toe signs were positive. In spite of treatment with aciclovir and methylprednisolone, he continued to show progressive deterioration developing to coma with decorticate posture. Autonomic symptoms (hyperhidrosis, hypersalivation and fever) and groaning were observed. Brain magnetic resonance image and brainstem evoked potential presented no abnormality, but electroencephalographic study showed a spindle pattern indicating spindle coma. Laboratory tests including cerebrospinal fluids showed no specific results. High-dose immunoglobulin was administered from day 6, and his consciousness level improved. External ophthalomoplegia and ataxic gait were observed after he became more alert. Because he had IgG type anti-GQ1b antibodies in the serum, a diagnosis was made of Bickerstaff's brainstem encephalitis (BBE). Six months after discharge he had complete resolution of his symptoms. This is the first report of spindle coma observed in a case of serologically confirmed BBE.