TAT、TM、PIC、t-PAIC在弥散性血管内凝血中的临床应用价值分析

Clinical value of TAT, TM, PIC and t-PAIC in disseminated intravascular coagulation

摘要:

目的 探索凝血酶-抗凝血酶复合物（TAT）、纤溶酶-抗纤溶酶复合物（PIC）、血栓调节蛋白（TM）和组织型纤溶酶原激活物-纤溶酶原激活物抑制复合物（t-PAIC）4个血栓分子标志物在弥散性血管内凝血（DIC）中的临床应用价值。方法 选取2019年1月—2022年4月西安交通大学第二附属医院收治的261例疑似DIC患者，回顾性分析其临床资料。经临床确诊后分为DIC组93例和非DIC组168例，比较两组传统凝血指标和新型分子标志物的差异。通过绘制受试者工作特征（ROC）曲线评估分子标志物对DIC的诊断效能。分析不同疾病类型、临床表现的DIC组患者分子标志物的差异。同时比较住院期间不同生存状况的DIC患者其分子标志物的差异。结果 与非DIC组相比，DIC组凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）延长（P <0.05），血小板计数（PLT）、纤维蛋白原（FIB）水平降低（P <0.05），纤维蛋白原降解产物（FDP）、D-二聚体（D-D）水平升高（P <0.05）。与非DIC组比较，DIC组TAT、TM、PIC、t-PAIC及TAT/PIC均升高（P <0.05）。与血液系统肿瘤组比较，感染性疾病组PIC水平降低（P <0.05），TM、t-PAIC及TAT/PIC升高（P <0.05）。与无出血组比较，出血组t-PAIC、TAT/PIC降低（P <0.05），PIC水平升高（P <0.05）。Spearman相关性分析结果显示，中国弥散性血管内凝血诊断积分系统评分与TM、TAT、PIC、t-PAIC及TAT/PIC均呈正相关（P <0.05）；FDP与TM、TAT、PIC、t-PAIC均呈正相关（P <0.05）；D-D与TM、TAT、PIC、t-PAIC均呈正相关（P <0.05）。ROC曲线分析结果显示，TM、TAT、D-D、FDP联合检测诊断DIC的曲线下面积（AUC）为0.929（95% CI：0.899，0.959），敏感性为82.8%（95% CI：0.751，0.905），特异性为88.7%（95% CI：0.839，0.935）；TM、TAT、PIC、t-PAIC、D-D、FDP联合检测诊断DIC的AUC为0.944（95% CI：0.919，0.970），敏感性为87.1%（95% CI：0.803，0.939），特异性为89.9%（95% CI：0.853，0.944）。与非死亡组比较，死亡组年龄更高（P <0.05），TM水平更高（P <0.05），PIC水平更低（P <0.05）。多因素逐步Logistic回归分析结果显示，年龄增长［O^R=1.042（95% CI：1.017，1.068）］、TM水平升高［O^R=1.022（95% CI：1.001，1.044）］是DIC患者预后的独立危险因素（P <0.05）。结论 凝血标志物TAT、TM、PIC、t-PAIC在DIC患者的精准诊断、出血风险评估、不良结局预测等方面均具有重要意义。

Abstract:

Objective To explore the clinical value of four thrombotic molecular markers, including thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC), in disseminated intravascular coagulation (DIC).Methods A retrospective analysis was performed on the clinical data of 261 patients suspected of DIC admitted to the Second Affiliated Hospital of Xi'an Jiaotong University from January 2019 to April 2022. According to clinical confirmation, the patients were divided into the DIC group (93 cases) and the non-DIC group (168 cases). The differences in conventional coagulation indicators and novel molecular markers between the two groups were compared. The diagnostic efficacy of molecular markers for DIC was evaluated using the receiver operating characteristic (ROC) curves. The differences in molecular markers among DIC patients with distinct disease subtypes and clinical manifestations were analyzed. Meanwhile, the differences in molecular markers between DIC patients with different survival statuses during hospitalization were compared.Results Compared to the non-DIC group, the DIC group exhibited prolonged PT and APTT (P < 0.05), decreased levels of PLT and FIB (P < 0.05), and increased levels of FDP and D-D (P < 0.05). Compared with the non-DIC group, levels of TAT, TM, PIC, t-PAIC, and the TAT/PIC ratio were elevated in the DIC group (P < 0.05). Compared with the hematological tumor group, the infectious disease group showed lower PIC levels (P < 0.05), higher levels of TM and t-PAIC, and a higher TAT/PIC ratio (P < 0.05). Compared with the non-bleeding group, the bleeding group had lower t-PAIC levels and a lower TAT/PIC ratio (P < 0.05), but higher PIC levels (P < 0.05). Spearman correlation analysis revealed that CDSS scores were positively correlated with the levels and TM, TAT, PIC, and t-PAIC, and the TAT/PIC ratio (P < 0.05). The level of FDP was positively correlated with levels of TM, TAT, PIC, and t-PAIC (P < 0.05). The D-D level was positively correlated with levels of TM, TAT, PIC, and t-PAIC (P < 0.05). ROC curve analysis showed that the combined detection of TM, TAT, D-D, and FDP for diagnosing DIC yielded an area under the curve (AUC) of 0.929 (95% CI: 0.899, 0.959), with a sensitivity of 82.8% (95% CI: 0.751, 0.905) and a specificity of 88.7% (95% CI: 0.839, 0.935). The combined detection of TM, TAT, PIC, t-PAIC, D-D, and FDP yielded an AUC of 0.944 (95% CI: 0.919, 0.970), with a sensitivity of 87.1% (95% CI: 0.803, 0.939) and a specificity of 89.9% (95% CI: 0.853, 0.944). Compared with the non-death group, the death group had a higher age (P < 0.05), higher TM levels (P < 0.05), and lower PIC levels (P < 0.05). Multivariable stepwise logistic regression analysis indicated that increased age [O^R=1.042 (95% CI: 1.017, 1.068) ] and elevated TM levels [O^R=1.022 (95% CI: 1.001, 1.044) ] were independent risk factors for the prognosis of DIC patients (P < 0.05).Conclusion The thrombotic markers TAT, TM, PIC, and t-PAIC are of great significance for the accurate diagnosis, bleeding risk assessment, and prediction of adverse outcomes in patients with DIC.