凝血分子标志物检测在脑梗死早期诊断中的应用

目的探讨血清凝血酶原片段1＋2(F_1＋2)、血小板球蛋白(β-TG)、血栓调节蛋白(TM)和D-二聚体(D-D)联合检测在脑梗死早期诊断中的临床应用。 方法采用病例-对照研究，病例组：选择2015年1月至2017年6月就诊于高唐县人民医院神经内科且诊断为脑梗死的患者，共125例。根据脑梗死患者颅脑CT或磁共振(MRI)病灶大小分组：大梗死组42例，中梗死组40例，小梗死组43例；按照美国国立卫生研究院卒中量表(NIHSS)评分分型：重度组26例，中度组55例，轻度组44例；对照组选择50例门诊健康体检者。采用双抗体夹心酶联免疫法(ELISA)测定F_1＋2、β-TG、TM、D-D水平。采用单因素方差分析比较各组间凝血分子水平差异，通过受试者工作特征(ROC)曲线下面积(AUC)比较各指标在脑梗死早期诊断中的价值。 结果对照组、小梗死组、中梗死组、大梗死组，各组间血清F_1＋2、β-TG、TM、D-D水平差异有统计学意义(F＝62.42，43.26，56.73，22.34；均P<0.01)。病例组血清F_1＋2小梗死组(2.67±0.24)nmol/L，中梗死组(2.84±0.26)nmol/L，大梗死组(3.19±0.30)nmol/L]、β-TG小梗死组(61.83±5.64)μg/L，中梗死组(73.68±6.47)μg/L，大梗死组(81.32±7.75)μg/L]、TM小梗死组(67.40±5.82)μg/L，中梗死组(74.84±6.37)μg/L，大梗死组(85.72±7.64)μg/L]、D-D水平小梗死组(2 541.10±226.24)μg/L,中梗死组(2 658.38±232.01)μg/L，大梗死组(2 724.47±256.35)μg/L]高于对照组(0.27±0.02)nmol/L, (3.74±0.32)μg/L，(5.75±0.45)μg/L, (106.10±81.24)μg/L]，差异有统计学意义小梗死组(q＝18.62，23.45，12.76，28.56；均P<0.01)，中梗死组(q＝19.59，25.67，13.83，31.21；均P<0.01)，大梗死组(q＝21.24，26.38，14.12，31.97；均P<0.01)]。病例组血清F_1＋2轻度组(2.42±0.21)nmol/L，中度组(2.77±0.25)nmol/L，重度组(2.98±0.27)nmol/L]、β-TG轻度组(62.34±6.02)μg/L，中度组(78.17±6.94)μg/L，重度组(80.76±7.62)μg/L], TM 轻度组(71.93±6.34)μg/L，中度组(76.72±7.18)μg/L，重度组(88.94±8.62)μg/L], D-D水平轻度组(2 583.37±237.04)μg/ L,中度组(2 667.46±249.33)μg/L，重度组(2 749.29±260.15)μg/L]高于对照组，差异有统计学意义轻度组(q＝16.58，21.22，12.37，21.64；均P<0.01)，中度组(q＝18.32，24.67，16.44，25.73；均P<0.01)，重度组(q＝22.47，32.53，19.59，34.65；均P<0.01)]。病例组各组间血清F_1＋2、β-TG、TM、D-D水平比较差异无统计学意义(P>0.05)。F_1＋2、β-TG、TM、D-D诊断脑梗死的敏感度及特异度分别为78.51%、86.73%, 82.62%、85.74%, 92.84%、86.22%, 67.46%、80.81%；F_1＋2与β-TG、TM、D-D联合检测后敏感度及特异度为96.32%、98.63%。F_1＋2、β-TG、TM、D-D单项检测的ROC曲线AUC分别为0.854，0.823，0.876，0.781，TM曲线的AUC最大。 结论联合测定血清F_1＋2、β-TG、TM、D-D水平，有助于为脑梗死的早期诊断提供实验依据。

Application of detection of coagulation molecular markers in early diagnosis of cerebral infarction

ObjectiveTo explore the clinical significance of combined detection of serum prothrombin fragment 1+ 2 (F_{1+ 2}), beta-thromboboglobulin (β-TG), thrombomodulin (TM) and D-Dimer (D-D) in the early diagnosis of cerebral infarction. MethodsThe case group selected 125 cases from the patients who were diagnosed as cerebral infarction in neurology department of the Gaotang County People's Hospital from January 2015 to June 2017. The patients with cerebral infarction were grouped according to the sizes of head CT or MRI lesions. There were 42 cases in the large infarction group, 40 cases in the middle infarction group and 43 cases in the small infarction group. According to the National Institutes of Health (NIHSS) score on the degree of nerve function defect: there were 26 cases in the severe group, 55 cases in the moderate group and 44 cases in the mild group. Fifty cases of health check-up outpatient were selected as control group. The levels of F_{1+ 2}, β-TG, TM and D-D were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). A single factor variance analysis was used to compare the levels of coagulation molecules among different groups, and the values of each index in the early diagnosis of cerebral infarction were compared under the receiver operating characteristic (ROC) curve (AUC). ResultsThe serum levels of F_{1+ 2}, β-TG, TM and D-D were statistically significant in the coutrol group, small infarct group, middle infarct group and large infarct group (F=62.42, 43.26, 56.73, 22.34; P<0.01). The serum levels of F_{1+ 2} small infarct group (2.67±0.24)nmol/L, middle infarct group (2.84±0.26)nmol/L, large infarct group (3.19±0.30)nmol/L], β-TGsmall infarct group (61.83±5.64)μg/L, middle infarct group (73.68±6.47)μg/L, large infarct group (81.32±7.75)μg/L], TM small infarct group (67.40±5.82)μg/L, middle infarct group (74.84±6.37)μg/L, large infarct group (85.72±7.64)μg/L] and D-D small infarct group (2 541.10±226.24)μg/L, middle infarct group (2 658.38±232.01)μg/L, large infarct group (2 724.47±256.35)μg/L] in each group were higher than those in control group (0.27±0.02)nmol/L, (3.74±0.32)μg/L, (5.75±0.45)μg/L, (106.10±81.24)μg/L], the differences were statistically significant small infarct group (q=18.62, 23.45, 12.76, 28.56; P<0.01), middle infarct group(q=19.59, 25.67, 13.83, 31.21; P<0.01), large infarct group(q=21.24, 26.38, 14.12, 31.97; P<0.01)] .The serum levels of F_{1+ 2} mild group (2.42±0.21)nmol/L, moderate group (2.77±0.25)nmol/L, severe group (2.98±0.27)nmol/L], β-TG mild group (62.34±6.02)μg/L, moderate group (78.17±6.94)μg/L, severe group (80.76±7.62)μg/L], TM mild group (71.93±6.34)μg/L, moderate group (76.72±7.18)μg/L, severe group (88.94±8.62)μg/L], D-D mild group (2 583.37±237.04)μg/L, moderate group (2 667.46±249.33)μg/L, severe group (2 749.29±260.15)μg/L] were higher than those in the control group mild group (q=16.58, 21.22, 12.37, 21.64; P<0.01), moderate group (q=18.32, 24.67, 16.44, 25.73; P<0.01), severe group (q=22.47, 32.53, 19.59, 34.65; P<0.01)]. There were no significant differences in the levels of serum F_{1+ 2}, β-TG, TM and D-D in the case groups(P>0.05). The sensitivity and specificity of F_{1+ 2} were 78.51% and 86.73%. The sensitivity and specificity of β-TG were 82.62%, 85.74%. The sensitivity and specificity of TM were 92.84%, 86.22%. The sensitivity and specificity of D-D were 67.46%, 80.81%. The sensitivity and specificity of F_{1+ 2}, β-TG, TM and D-D were 96.32%, 98.63%. The ROC curves of the single item of F_{1+ 2}, β-TG, TM and D-D were 0.854, 0.823, 0.876, 0.781, and the AUC of TM curve was the largest. ConclusionThe combined determination of serum F_{1+ 2}, β-TG, TM and D-D levels can provide an experimental basis for early diagnosis of cerebral infarction.