The Role Of Coagulation Factor â…¦ In The Occurrence And Treatment Of Craniocerebral Traumatic Related Coagulation Dysfunction

[Part I]ObjectiveThe target population of this study was patients with acute isolated miedium to severe traumatic brain injury. The relationship between TBI-associated-coagulopathy and activity of FVII was studied by monitoring the changes of serum FVII level during the acute phase.MethodsDuring2010and2012, patients with acute isolated medium to severe traumatic brain injury admitted at Huashan hospital were screened and enrolled into the study. Blood samples within24hours after injury were collected and activity of FVII was measured by ELISA diagnostic kit for each sample. Coagulation parameters such as PT, aPTT, thrombin time, FDP, D-dimer and INR were also recorded respectively.TBI-associated-coagulopathy was defined as decreased platelet count <120000/mm3), or elevated INR (>1.2), or prolonged PT (>40s). Series CTs were performed to identify hemorrhagic lesions. A stepwise Logistic regression model was used to evaluate the relationship between coagulopathy and hemorrhage progression.ResultsThe activity of FVII in patients with and without coagulopathy were85.69±34.88%and99.57%±29.37%respectively, the difference was statistically significant. Patient with FVII activity level lower than75%suffered an increased risk of developing coagulopathy (0R=5.52,95%CI1.82~16.68, p=0.03). The activity of FVII was105.76±32.27%in patients without hemorrhage progression, which was substantially lower than that of patient with hemorrhage progression (70.76±18.21%, p<0.001). Stepwise Logistic regression model showed FVII activity<77.5%was an independent risk factor for hemorrhage progression (OR=4.53,95%CI1.62～12.67, p=0.004). The mortality in all patients was7.4%. The plasma FVII in death patients (91.44±47.19%) was slightly lower than that in survival patients (92.01±32.04%). But, there was no statistical difference between two groups (p=0.949).ConclusionIn patients with acute isolated traumatic brain injury, FVII activity-was closely related with the coagulation function. [Part Ⅱ]ObjectiveThe relationship between TBI-associated-coagulopathy and its genetic polymorphism was also evaluated by the investigation of6genetic locations of FVII by PCR-RFLP.MethodsStandardized data collection were carried out for each patient’s age, gender, height, weight, injury type, GCS, blood pressure, triglycerides, blood glucose, ICP, hospital-stay length, in-hospital mortality, diagnosis, therapy used and type of operation. Individual DNA was obtained from peripheral venous blood using a DNA extraction kit. The DNA amount was tested by2ul electrophoresis (2%agarose gel,120v,20minutes), and concentration and purity was detected by ultra violet photometry. Phenotype of FVII gene-323P0/P10、R353Q、-401G/T、-402G/A、-670A/C and IVS7was analyzed using PCR-RFLP technique. The relationship between FVII polymorphism and TBI-associated-coagulopathy was evaluated.ResultsThe length of the amplification product of FVII gene phenotype-323P0/P10by PCR were214bp and24bp,239bp for R353Q,467bp for both-401G/T and-402G/A,192bp for-670A/C,443bp and480bp for IVS7. Genetic equilibrium test showed that the distribution of phenotype polymorphism of FVII gene-323P0/P10, R353Q,-401G/T,-402G/A and-670A/C matched the Hardy-Weinberg equilibrium. The phenotype polymorphism-402G/A was associated with increased risk of coagulopathy, and-402G/A and-670A/C were associated with lower GCS at discharge.ConclusionPolymorphism study showed that-402G/A was associated with increased risk of developing coagulopathy. [Part III]ObjectiveA prospective cohort studied was also carried out to assess the effect and safety of low dose rFVIIa (20mcg/kg) for pataients with TBI-associated-coagulopathy in the acute phase.MethodsThe patients meeting the inclusion/exclusion criteria were enrolled into a prospective cohort study. Patients in the control group accepted only standard transfusion to normalize coagulopathy, while the treatment group accepted an addition low dose rFVIIa (20mcg/kg) in the acute phase. The observation window was72hours for change of coagulation parameters and adverse events. In-hospital costs were evaluated at discharge. The time for patient follow-up was90days. The two groups were compared to evaluated the effect and safety of low dose rFVIIa in TBI patients with coagulopathy.ResultsThe preliminary clinical study showed that INR was normalized by0.29±0.23in the treatment group, while by0.11±0.39in the control group, p=0.01. The incidence of brain infarction within72hours was7.2%and8.5%in the treatment and control group respectively. DVT were not recorded in both groups. The30-day mortality was22.2%and32.2%respectively, which was not statistically significant.ConclusionLow dose rFVII for patients with TBI-associated-coagulopathy was safe and could rapidly normalize INR. Our study indicated that FVII played an important role in the development and treatment of TBI-associated-coagulopathy.Further research focusing on the individual genetic susceptibility is warranted.