摘要目的:探讨骨折患者凝血因子Ⅻ（coagulation factor Ⅻ，FⅫ）活性水平、凝血功能指标、 F12基因位点rs17876030和rs1801020多态性的关系，以及与下肢深静脉血栓形成（deep venous thrombosis，DVT）之间的相关性。 方法:采用病例对照研究方法，纳入2015年9月至2023年9月200例于天津市天津医院创伤骨科诊治的骨折患者，常规抗凝预防DVT治疗，仍在住院期间发生了DVT（血栓组）；匹配100例同期住院的骨折患者，同样的抗凝策略下住院期间未发生DVT（非血栓组）；匹配100例同期在天津医院门诊进行体检的健康人群（正常组）。收集所有受试者的血浆标本，实验室测定活化部分凝血活酶时间（activated partial thromboplastin time，APTT）、凝血酶原时间（prothrombin time，PT）、凝血酶时间（thrombin time，TT）、纤维蛋白原含量（fibrinogen，Fg）、D-二聚体（D-Dimer）。采用一期固定法检测FⅫ活性水平，酶联免疫法检测FⅫ抗原，直接测序法检测 F12基因位点rs17876030和rs1801020基因多态性，分析各检测指标间的关系以及与DVT的相关性。 结果:血栓组、非血栓组、正常组APTT、PT、TT的差异无统计学意义（ F=0.748， P=0.483； F=0.092， P=0.840； F=0.031， P=0.660）；血栓组Fg为（4.5±2.4） g/L、D-Dimer为（786.2±234.9） mg/L，大于非血栓组的（2.9±1.8） g/L和（261.3±165.5） mg/L、正常组的（2.2±1.1） g/L和（198.1±96.4） mg/L，差异均有统计学意义（ F=3.473， P=0.046； F=34.960， P<0.001； P<0.05）。血栓组FⅫ活性为78.3%±21.9%，与非血栓组的97.8%±31.4%、正常组的94.5%±35.7%的差异均有统计学意义（ F=3.581， P=0.032； P<0.05）。FⅫ活性与APTT呈负相关（ r=-0.149， P=0.035）。血栓组rs17876030 TT、CC、CT基因型分别为122、58、20例，非血栓组分别为34、27、39例，正常组分别为30、42、28例，组间差异有统计学意义（χ 2=12.630， P=0.002）；血栓组rs1801020 TT、CC、CT基因型分别为42、115、43例，非血栓组分别为37、25、38例，正常组分别为40、16、44例，组间差异有统计学意义（χ 2=26.820， P<0.001）。血栓组、非血栓组、正常组rs17876030 TT基因型的FⅫ活性水平较CC、CT基因型低，差异均有统计学意义（ F=27.130， P<0.001； F=18.384， P<0.001； F=12.830， P=0.001； P<0.05）；三组rs1801020 CC基因型FⅫ活性水平较TT、CT基因型低，差异均有统计学意义（ F=38.631， P<0.001； F=23.562， P<0.001； F=25.829， P<0.001； P<0.05）。血栓组中rs17876030 TT基因型构成比最高，且该型患者FⅫ活性水平更低，rs17876030 TT基因型与DVT相关（ r=-0.831， P=0.043）；血栓组中rs1801020 CC基因型构成比最高，且该型患者FⅫ活性水平更低，rs1801020 CC基因型与DVT相关（ r=-0.784， P=0.040）。 结论:Fg、D-Dimer与DVT相关，FⅫ活性水平与APTT负相关，APTT延长提示FⅫ缺陷症的可能，且FⅫ活性水平降低可能与DVT相关。

abstractsObjective:To explore the relationships among the activity level of coagulation factor XII (FXII), coagulation function indexes, polymorphisms of F12 gene loci rs17876030 and rs1801020, as well as their correlations with deep venous thrombosis (DVT) in fracture patients. Methods:A case-cohort control study was conducted. 200 fracture patients diagnosed and treated in the Department of Traumatic Orthopedics of Tianjin Hospital from September 2015 to September 2023 were included. They received routine anticoagulant prophylaxis for DVT treatment but still developed DVT during hospitalization (thrombus group). 100 fracture patients hospitalized during the same period without DVT under the same anticoagulant strategy were matched (non-thrombus group). 100 healthy people who underwent physical examinations in the outpatient department of Tianjin Hospital during the same period were also matched (normal group). Plasma samples of all subjects were collected. Laboratory tests were performed to measure activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), D-Dimer. The activity level of FXII was detected by the one-stage fixation method, the antigen of FXII was detected by enzyme-linked immunosorbent assay, and the polymorphisms of F12 gene loci rs17876030 and rs1801020 were detected by direct sequencing method. The relationships among various detection indexes and their correlations with DVT were analyzed. Results:There were no statistically significant differences in APTT, PT, and TT among the thrombus group, non-thrombus group, and normal group ( F=0.748, P=0.483; F=0.092, P=0.840; F=0.031, P=0.660). The Fg in the thrombus group was 4.5±2.4 g/L and D-Dimer was 786.2±234.9 mg/L, which were statistically different from 2.9±1.8 g/L and 261.3±165.5 mg/L in the non-thrombus group and 2.2±1.1 g/L and 198.1±96.4 mg/L in the normal group respectively ( F=3.473, P=0.046; F=34.960, P<0.001; P<0.05). The activity of FⅫ in the thrombus group was 78.3%±21.9%, which was statistically different from 97.8%±31.4% in the non-thrombus group and 94.5%±35.7% in the normal group ( F=3.581, P=0.032; P<0.05). The activity of FXII was negatively correlated with APTT ( r=-0.149, P=0.035). In the thrombus group, there were 122 cases (61.0%) with the TT genotype of rs17876030, which was statistically different from 34 cases (34.0%) in the non-thrombus group and 30 cases (30.0%) in the normal group (χ 2=12.630, P=0.002). In the thrombus group, there were 115 cases (57.5%) with the CC genotype of rs1801020, which was statistically different from 25 cases (25.0%) in the non-thrombus group and 16 cases (16.0%) in the normal group (χ 2=26.820, P<0.001). The activity levels of FXII of the TT genotype of rs17876030 in the thrombus group, non-thrombus group, and normal group were lower than those of the CC and CT genotypes, and the differences were statistically significant ( F=27.130, P<0.001; F=18.384, P<0.001; F=12.830, P=0.001; P<0.05). The activity levels of FXII of the CC genotype of rs1801020 in the three groups were lower than those of the TT and CT genotypes, and the differences were statistically significant ( F=38.631, P<0.001; F=23.562, P<0.001; F=25.829, P<0.001; P<0.05). The proportion of the TT genotype of rs17876030 was the highest in the thrombus group, and the activity level of FⅫ in patients with this genotype was lower. The TT genotype of rs17876030 was related to DVT ( r=-0.831, P=0.043). The proportion of the CC genotype of rs1801020 was the highest in the thrombus group, and the activity level of FⅫ in patients with this genotype was lower. The CC genotype of rs1801020 was related to DVT ( r=-0.784, P=0.040). Conclusion:Fg and D-Dimer are related to DVT. The activity level of FXII is negatively correlated with APTT. Prolonged APTT suggests the possibility of FⅫ deficiency, and the decreased activity level of FXII may be related to DVT.