Development of a Thrombin-antithrombin Complex Detection Kit and Study in Venous Thromboembolism Complicated by Cervical Cancer

Abstract

Background 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. Methods 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. Results 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 R2 = 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.