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Abstract：
OBJECTIVE: To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome.
METHODS: A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People\'s Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis.
RESULTS: Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%.
CONCLUSIONS: TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.
METHODS: A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People\'s Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis.
RESULTS: Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%.
CONCLUSIONS: TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.
摘要：
目的：探讨新的血栓标志物四项联合常规凝血试验对抗磷脂综合征血栓形成的预测价值。
方法：选取2022年3月至2023年1月北京大学人民医院收治的抗磷脂综合征(APS)患者121例，根据是否发生血栓分为血栓组(50例)和非血栓组(71例)。比较了血栓性和非血栓性组之间的实验室特征，包括抗磷脂抗体的差异。化学发光免疫分析法用于检测血栓调节蛋白（TM），凝血酶-抗凝血酶复合物(TAT),纤溶酶-α2纤溶酶抑制剂复合物(PIC),静脉血浆中的组织纤溶酶原激活物抑制剂复合物（t-PAIC）。采用二元Logistic回归分析确定APS患者血栓形成的独立危险因素。采用受试者工作特征(ROC)曲线分析评价各指标对血栓形成的预测效果。
结果：与无血栓形成的患者相比，血栓形成患者年龄较大[49（32，64）岁与36(32,39)年,P<0.05]。男性的百分比，吸烟,高血压,而总的抗磷脂综合征评分(GAPSS)≥10分的血栓患者明显高于无血栓患者(P<0.05)。血栓组抗心磷脂抗体(aCL)和狼疮抗凝物(LA)阳性率明显高于非血栓组(P<0.05),和凝血酶原时间的水平，活化部分凝血活酶时间，纤维蛋白原，血栓性组纤维蛋白降解产物明显高于非血栓性组(P<0.05)。在血栓形成组中，静脉血栓形成占19（38.00%），其中深静脉血栓(16,84.21%)和肺栓塞(5,26.32%)占35(70.00%),其中心肌梗死(6,17.14%)脑梗死(30,85.71%)。血栓组患者的TM水平明显高于非血栓组（P<0.05）。两组患者的TAT差异无统计学意义(Z=-1.420,P=0.156)。PIC(Z=-0.064,P=0.949),t-PAIC(Z=-1.487,P=0.137)。相关变量的单因素和二元Logistic回归分析显示高龄[OR=1.126,P=0.002],TM升高[OR=1.325，P=0.048]，凝血酶原时间延长[OR=4.127,P=0.008]是APS患者血栓形成的独立危险因素。以上三个独立危险因素的ROC曲线分析显示,年龄、PT和TM的Yoden指数(0.727)和灵敏度(83.0%)最高，特异性为89.7%。
结论：TAT，PIC,TM,t-PAIC可以反映凝血系统的血栓形成，纤溶系统,和内皮系统。年龄TM和PT的组合优于单一标记的应用，对APS血栓的早期识别具有诊断价值。
方法：选取2022年3月至2023年1月北京大学人民医院收治的抗磷脂综合征(APS)患者121例，根据是否发生血栓分为血栓组(50例)和非血栓组(71例)。比较了血栓性和非血栓性组之间的实验室特征，包括抗磷脂抗体的差异。化学发光免疫分析法用于检测血栓调节蛋白（TM），凝血酶-抗凝血酶复合物(TAT),纤溶酶-α2纤溶酶抑制剂复合物(PIC),静脉血浆中的组织纤溶酶原激活物抑制剂复合物（t-PAIC）。采用二元Logistic回归分析确定APS患者血栓形成的独立危险因素。采用受试者工作特征(ROC)曲线分析评价各指标对血栓形成的预测效果。
结果：与无血栓形成的患者相比，血栓形成患者年龄较大[49（32，64）岁与36(32,39)年,P<0.05]。男性的百分比，吸烟,高血压,而总的抗磷脂综合征评分(GAPSS)≥10分的血栓患者明显高于无血栓患者(P<0.05)。血栓组抗心磷脂抗体(aCL)和狼疮抗凝物(LA)阳性率明显高于非血栓组(P<0.05),和凝血酶原时间的水平，活化部分凝血活酶时间，纤维蛋白原，血栓性组纤维蛋白降解产物明显高于非血栓性组(P<0.05)。在血栓形成组中，静脉血栓形成占19（38.00%），其中深静脉血栓(16,84.21%)和肺栓塞(5,26.32%)占35(70.00%),其中心肌梗死(6,17.14%)脑梗死(30,85.71%)。血栓组患者的TM水平明显高于非血栓组（P<0.05）。两组患者的TAT差异无统计学意义(Z=-1.420,P=0.156)。PIC(Z=-0.064,P=0.949),t-PAIC(Z=-1.487,P=0.137)。相关变量的单因素和二元Logistic回归分析显示高龄[OR=1.126,P=0.002],TM升高[OR=1.325，P=0.048]，凝血酶原时间延长[OR=4.127,P=0.008]是APS患者血栓形成的独立危险因素。以上三个独立危险因素的ROC曲线分析显示,年龄、PT和TM的Yoden指数(0.727)和灵敏度(83.0%)最高，特异性为89.7%。
结论：TAT，PIC,TM,t-PAIC可以反映凝血系统的血栓形成，纤溶系统,和内皮系统。年龄TM和PT的组合优于单一标记的应用，对APS血栓的早期识别具有诊断价值。
