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凝血酶 - 抗凝血酶复合物检测试剂盒的研制及在宫颈癌合并静脉血栓栓塞症中的研究

Development of a thrombin-antithrombin complex detection kit and study in venous thromboembolism complicated by cervical cancer.

作者信息

Qiu Yanru, Han Shuang, Ji Yu, Lu Zhixian, Huang Xuan

机构信息

Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, China.

Department of Pathology, Jiangnan University Hospital, Wuxi, Jiangsu, China.

出版信息

BMC Biotechnol. 2024 Dec 18;24(1):103. doi: 10.1186/s12896-024-00930-w.

DOI:10.1186/s12896-024-00930-w
PMID:39696289
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11653829/
Abstract

OBJECTIVE

Our study successfully developed an assay kit for thrombin-antithrombin complex (TAT) and demonstrated the predictive value of plasma TAT concentration in the development of venous thromboembolism (VTE) in patients with cervical cancer.

METHOD

A retrospective analysis was conducted on 177 patients with cervical cancer who received treatment at the Affiliated Hospital of Jiangnan University in Wuxi City from July 1, 2023 to October 1, 2023. This study provides a comprehensive analysis of cervical cancer patients and their VTE risk factors. The patients were divided into two groups: 27 cases with VTE (Thrombosis group) and 150 cases without VTE (Non-thrombotic group). Additionally, the patients were classified into four stages based on tumor stage: 42 cases of stage I, 45 cases of stage II, 62 cases of stage III, and 28 cases of stage IV. The control group consisted of 80 healthy patients undergoing medical check-ups. Thrombin-antithrombin complex (TAT), fibrinolytic enzyme-α2-fibrinolytic inhibitor complex (PIC), thrombomodulin (TM), and tissue-type plasminogen activator inhibitor 1 complex (t-PAIC) were detected using quantitative chemiluminescence immunoassay. The study assessed the variations in thrombotic marker levels among cervical cancer patients of different stages through a receiver operating characteristic (ROC) curve.

RESULT

The TAT reagent demonstrated a detection limit of 0.048 ng/mL, with a linear R value of 0.9997, indicating high accuracy and precision. The reagent's accelerated stability was also excellent, with deviations of less than 10%. Furthermore, the correlation coefficient of this method with Hyson Mecon was R = 0.9683. Notably, in patients with cervical cancer, TAT and PIC levels were found to be elevated compared to those of the healthy population. Cervical cancer patients who developed thrombosis had significantly elevated levels of TAT and fibrinogen degradation products (FDP) compared to those who did not. Furthermore, patients with stage III-IV cervical cancer exhibited higher levels of the six markers than those with stage I-II during staging. Notably, the combination of four or six markers significantly improved the sensitivity and specificity of the diagnosis, as demonstrated by the ROC curves.

CONCLUSION

Our developed TAT test kit has excellent performance and low cost, making it a clinically valuable tool for widespread use. Elevated TAT levels have significant predictive value for thrombosis occurrence in cervical cancer patients. The combination of t-PAIC, TM, TAT, PIC, D-dimer(D-D), and FDP markers is superior to using a single marker for diagnosing VTE in patients with malignant tumors. Screening cervical cancer patients for the six markers is essential to aid in active prophylaxis, determine optimal treatment timing, and implement nursing interventions to improve prognosis, reduce venous thrombosis incidence and mortality, and prolong survival time.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/bb92a2f3dd89/12896_2024_930_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/fabf7bf18786/12896_2024_930_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/d5049fe33f85/12896_2024_930_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/d8049bcb56f4/12896_2024_930_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/95db9a7f5993/12896_2024_930_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/bb92a2f3dd89/12896_2024_930_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/fabf7bf18786/12896_2024_930_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/d5049fe33f85/12896_2024_930_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/d8049bcb56f4/12896_2024_930_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/95db9a7f5993/12896_2024_930_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11653829/bb92a2f3dd89/12896_2024_930_Fig5_HTML.jpg
摘要

目的

我们的研究成功开发了一种凝血酶 - 抗凝血酶复合物(TAT)检测试剂盒,并证明了血浆TAT浓度在宫颈癌患者静脉血栓栓塞(VTE)发生中的预测价值。

方法

对2023年7月1日至2023年10月1日在无锡市江南大学附属医院接受治疗的177例宫颈癌患者进行回顾性分析。本研究对宫颈癌患者及其VTE危险因素进行了全面分析。患者分为两组:27例发生VTE的患者(血栓形成组)和150例未发生VTE的患者(非血栓形成组)。此外,根据肿瘤分期将患者分为四个阶段:I期42例,II期45例,III期62例,IV期28例。对照组由80名接受体检的健康患者组成。采用定量化学发光免疫分析法检测凝血酶 - 抗凝血酶复合物(TAT)、纤溶酶-α2-纤溶酶抑制剂复合物(PIC)、血栓调节蛋白(TM)和组织型纤溶酶原激活物抑制剂1复合物(t-PAIC)。该研究通过受试者操作特征(ROC)曲线评估了不同阶段宫颈癌患者血栓形成标志物水平的变化。

结果

TAT试剂的检测限为0.048 ng/mL,线性R值为0.9997,表明具有高准确性和精密度。该试剂的加速稳定性也很好,偏差小于10%。此外,该方法与希森美康的相关系数为R = 0.9683。值得注意的是,在宫颈癌患者中,发现TAT和PIC水平高于健康人群。发生血栓形成的宫颈癌患者的TAT和纤维蛋白原降解产物(FDP)水平明显高于未发生血栓形成的患者。此外,III - IV期宫颈癌患者在分期时这六种标志物的水平高于I - II期患者。值得注意的是,ROC曲线表明,四种或六种标志物的组合显著提高了诊断的敏感性和特异性。

结论

我们开发 的TAT检测试剂盒性能优异且成本低廉,是一种具有临床应用价值的广泛使用的工具。TAT水平升高对宫颈癌患者血栓形成的发生具有重要预测价值。t-PAIC、TM、TAT、PIC、D-二聚体(D-D)和FDP标志物的组合在诊断恶性肿瘤患者的VTE方面优于使用单一标志物。对宫颈癌患者进行这六种标志物的筛查对于积极预防、确定最佳治疗时机以及实施护理干预以改善预后、降低静脉血栓形成的发生率和死亡率以及延长生存时间至关重要。

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