Basic And Clinical Research About Treatment Of Traumatic Brain Injury Which Has Effect On Coagulation Function

Objective: Traumatic brain injury(TBI) is the most common cause of death and permanent disability in people younger than 45 years of age. Hemocoagulative disorders may occur in >60% of patients with severe TBI, and it is associated with worsening secondary brain injury, bleed progression, and increased morbidity and mortality. The mechanisms involved in pathophysiology of TBI induced coagulopathy remain not fully understood, but it is increasingly evident that TBI elicits interdependent CNS and systemic inflammatory and coagulation cascades that contribute to secondary neuropathological sequelae. These innate host defence responses to cerebral insults are characterized by rapid activation of resident microglia and astrocytes, brain microvascular Ecs and peripheral blood leukocytes(PMNs, monocytes). A monocyte is a unique blood cell that expresses tissue factorand(TF) and Thrombomodulin(TM) thus plays an essential role in the coagulation process. Inflammatory cytokines upregulate the expression of monocyte TF, which results in hypercoagulable diathesis. With regard to monocyte surface expression of TM, it is reported that TM expression on a small subset of inflammatory monocytes increases in patients with overt DIC. Resuscitation with hypertonic saline, alone or combined with dextran(HS/D), is emerging as effective first-line osmotherapeutic alternative for treatment of intracranial hypertension and cerebral edema. HSD can reduce TBI-induced increases in s TF and D-D levels by half, while maintaining s TM levels near control values. we hypothesized that prehospital resuscitation of head injury patients using 7.5% hypertonic saline would prevent derangements of hemostasis and fibrinolysis, which may be regulated by surface phenotype of monocyte. However, there is a paucity of information on what effect monocyte has on coagulopathy. Long noncoding RNA(lnc RNA) is now emerging as important regulators of immune cell differentiation and activation. Whether hypertonic saline improve coagulofibrinolytic balance that is regulated by lnc RNA which may alter monocyte phenotype? In this study, we identified the effects of these seven Lnc RNAs, lnc RNA4916 、 lnc RNA7406-2 、 lnc RNA1403 、lnc RNA2448-11、lnc RNA7411-2、lnc RNA4551-1、lnc RNA5189-2, in regulating monocyte subset which is associated with coagulopathy after TBI.Methods: 34 patients of moderate-to-Severe traumatic brain injury enrolled in this study according the designed inclusion criteria and exclusion criteria. They were divided into two groups randomly by random number table method: group A was 7.5% hypertonic saline group(HS 7.5%; 4m L/kg) and group A was 3% hypertonic saline group(HS 3%; 4m L/kg). Patients in both groups were treated with conventional treatment according to the diagnostic and treatment practices of TBI. The changes of intracranial pressure(ICP) and indexes of coagulation and fibrinolysis in plasma were observed during the course of illness. Blood samples were collected before, and 6 hours and 24 hours following infusion. Peripheral blood mononuclear Cell(PBMC) was purified by density-gradient centrifugation. Monocyte phenotype was analyzed by flow cytometry. Candidate lnc RNAs which is expressed only or mostly in monocyte were identified by real-time q PCR from human monocytic THP1 cells, human B lymphocyte cell lines Raji cells and human T lymphocyte cell lines A3 cells which were cultured in vitro. Then real-time q PCR was used to analyze the expression of candidate lnc RNAs and their target genes, including tumor necrosis factor-α(TNF-α)、interleukin-6(IL-6)、IL-1β、transforming growth factor-β(TGF-β) and TM.Results: We found that 7.5%HS can decreas raising intracranial pressure and improve coagulofibrinolytic homeostasis. Analysis of the monocyte subsets has revealed significant supression of the CD14++CD16+ inflammatory monocytes in 7.5% HS group. The 7.5%HS exerted significant influence on the downregulation of lnc RNA2448-11 and lnc RNA1403 from PBMC cells of moderate-to-severe traumatic brain injury patients. And 7.5%HS functionally regulated expression of TNF-α、IL-1β 、 TGF-β and TM which is the target genes of lnc RNA2448-11 and lnc RNA1403.Conclusions: this study of traumatic brain injury patients demonstrates that prehospital treatment with 7.5% HD improve ICP and coagulofibrinolytic homeostasis by modulating phenotype of monocyte which is regulated by lnc RNA2448-11 and lnc RNA1403. These findings provide direct evidence that initial resuscitation with HSD imparts functional changes to inflammatory cells after TBI, thereby reducing potential neuroinflammatory events associated with secondary brain injury.Objective: To study the effect of limited fluid resuscitation(LFR) on coagulation in patients with severe traumatic brain injury(s TBI) and investigate its clinical significance.Methods: All 79 patients were randomly assigned into two groups by completely random method, 40 patients with low volume treatment(low volume group), and 39 cases with high volume treatment(high volume group). Patients in both groups were treated with LFR. The levels of PT, APTT, TT and FIB were measured at different time points. The average heart rate, blood pressure, blood gas analysis and blood electrolytes were also measured. Meantime, we counted the ICU-Days, the days of hospitalization and the incidence of multiple organ failure(MODS). According to Glasgow Outcome Scale(GOS), the prognosis was evaluated.Results: Compared with high volume group, the levels of PT, APTT and TT were lower, but the level of FIB was higher(P<0.05) in the low volume group, and there were no significant difference in the ICU-Days(13.84±3.02 d VS. 15.28±3.79 d,P﹥0.05), the days of hospitalization(36.85±6.73 d VS. 40.01±7.21 d,P﹥0.05), the incidence of MODS(15.0% VS. 17.9%,P﹥0.05) and the mortality(27.5% VS. 38.5%,P﹥0.05)of both groups. The incidence of good recovery in low volume group was higher than that of high volume group(22.5% VS. 7.3%,P<0.05). The average heart rate, blood pressure, blood electrolytes, and blood gas values were not significantly changed(P﹥0.05).Conclusions: In the patients with s TBI, high volume LFR will aggravate the coagulation disorders, and low volume LFR will improve the coagulation disorders, it also can improve the prognosis, and it is a safe and effective therapy.Objective: To study the effects of hypothermia on coagulation in patients with severe traumatic brain injury(s TBI) and investigate the clinical significance of thromboelastography(TEG) monitoring.Methods: All 75 patients were randomly assigned into two groups, 37 patients with hypothermia treatment(hypothermia group), and 38 cases with routine treatment(control group). Hypothermia was induced within 24 hours after brain injury. Patients in both groups were treated with conventional treatment according to the diagnostic and treatment practices of s TBI. The levels of R, K,α,MA and LY30 were measured. Meantime, the intracranial pressure(ICP), vital sign, blood gas values, blood electrolytes and oxygen saturation were also measured. According to Glasgow Outcome Scale(GOS), the prognosis was evaluated.Results: All the date were compared between two groups. the levels of R, K,α,MA and LY30 were no significant difference(P>0.05), while there were statistically significant at 1 d, 2 d, 3 d and 7 d after the hypothermia therapy(P<0.05). And ICP was significantly decreased(P<0.01) in hypothermia group. The vital sign, blood gas values, blood electrolytes and oxygen saturation were not significantly changed. No severe complications were found. The mortality was lower and GOS of the patients discharge was improved in hypothermia group than that of control group.Conclusions: In the patients with s TBI, hypothermia may improve the hypercoagulability, and will not increase the risk of hyperfibrinolysis, it can protect brain tissue through decreasing ICP, and it is a safe and effective therapy.