妇科手术后静脉血栓栓塞的独立危险因素及术后D-二聚体预测价值研究^*

Independent Risk Factors for Venous Thromboembolism After Gynecological Surgery and the Predictive Value of Postoperative D-Dimer

摘要

目的 探讨妇科手术后静脉血栓栓塞（venous thromboembolism, VTE）的独立危险因素，评估术后D-二聚体（D-dimer）对VTE的预测价值，为制定个体化抗凝策略提供依据。方法 收集2020年3月-2022年3月于四川大学华西上锦南府医院接受妇科手术的307例女性患者的围术期资料，纳入标准为Caprini评分≥3分且未接受VTE预防。收集资料包括年龄、体质指数（body mass index, BMI）、绝经状态、合并症（高血压等）、术前及术后凝血指标（凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原、D-二聚体等）、手术入路、麻醉时间、手术时间、美国麻醉医师协会（American Society of Anesthesiologists, ASA）分级，以及术后VTE发生情况（经影像学确诊）。根据术后是否发生VTE进行分组，单因素分析比较组间差异，二元logistic回归筛选独立危险因素，绘制受试者工作特征（receiver operating characteristic, ROC）曲线，计算曲线下面积（area under the curve, AUC）、灵敏度、特异度及约登指数，评估D-二聚体的诊断效能。结果 307例患者中，42例术后发生VTE，发生率为13.68%（42/307），其中深静脉血栓（deep vein thrombosis, DVT）30例（9.77%，30/307），肺栓塞（pulmonary embolism, PE）12例（3.91%，12/307）。多因素logistic回归分析显示，术后VTE的独立危险因素包括：年龄（OR=1.122/岁，95% CI：1.070~1.176）、BMI升高（OR=1.180，95% CI：1.031~1.351）、绝经状态（OR=13.753，95% CI：3.692~51.229）、高血压（OR=3.951，95% CI：1.837~8.498）、手术时间延长（OR=1.047/min，95% CI：1.013~1.082）、麻醉时间延长（OR=1.007/min，95% CI：1.002~1.011）、ASA分级升高（OR=8.122，95% CI：2.973~22.184）及术后D-二聚体升高（OR=1.177/mg/L，95% CI：1.029~1.346）。VTE组Caprini评分高于非VTE组（4.57±1.21 vs. 3.64±1.11，P<0.001），但多因素分析中Caprini评分无统计学意义（P=0.877）。术后D-二聚体为1.50 mg/L时，诊断VTE的灵敏度为54.76%，特异度为73.58%；术前后D-二聚体差值为2.50 mg/L时的灵敏度为26.19%，特异度为94.72%。结论 年龄增加、BMI升高、绝经状态、高血压、手术时间延长、麻醉时间延长及ASA分级升高是妇科术后VTE的独立危险因素。术后D-二聚体≥1.50 mg/L及术前后D-二聚体差值≥2.50 mg/L可作为VTE筛查与预警的实用指标，建议纳入术后常规监测。Caprini评分在该人群中预测价值有限，需整合上述因素构建面向妇科手术患者的专属风险评估模型。

Abstract

Objective To investigate the independent risk factors for venous thromboembolism (VTE) after gynecological surgery, evaluate the predictive performance of postoperative D-dimer levels for VTE, and inform the development of individualized anticoagulation strategies. Methods Perioperative data were collected from 307 female patients who underwent gynecological surgeries at West China Shangjin Nanfu Hospital, Sichuan University between March 2020 and March 2022. The inclusion criteria were a Caprini score ≥ 3 and the absence of any VTE prophylaxis. The data collected included age, body mass index (BMI), menopause, comorbidities (e.g., hypertension), preoperative and postoperative coagulation parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, etc.), the surgical approach, anesthesia duration, surgery duration, American Society of Anesthesiologists (ASA) physical status classification, and postoperative VTE occurrence confirmed by imaging examinations. Patients were divided into VTE and non-VTE groups according to postoperative imaging findings. Univariate analysis was performed to compare differences between groups. Binary logistic regression was performed to identify independent risk factors. The receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC), sensitivity, specificity, and Youden index were calculated to evaluate the predictive performance of D-dimer levels. Results Among the 307 patients, 42 (13.68%) developed postoperative VTE, including 30 cases (9.77%) of deep vein thrombosis (DVT) and 12 cases (3.91%) of pulmonary embolism (PE). Multivariable logistic regression analysis showed that independent risk factors for postoperative VTE included age (odds ratio [OR] = 1.122 per year, 95% CI: 1.070-1.176), increased BMI (OR = 1.180, 95% CI: 1.031-1.351), menopause (OR = 13.753, 95% CI: 3.692-51.229), hypertension (OR = 3.951, 95% CI: 1.837-8.498), prolonged surgery duration (OR = 1.047 per minute, 95% CI: 1.013-1.082), prolonged anesthesia duration (OR = 1.007 per minute, 95% CI: 1.002-1.011), higher ASA classification (OR = 8.122, 95% CI: 2.973-22.184), and elevated postoperative D-dimer levels (OR = 1.177 per mg/L, 95% CI: 1.029-1.346). Although the Caprini score was significantly higher in the VTE group than that in the non-VTE group (4.57 ± 1.21 vs. 3.64 ± 1.11,P < 0.001), binary logistic regression analysis revealed no statistically significant association ( P = 0.877). A postoperative D-dimer level = 1.50 mg/L was the optimal threshold for diagnosing VTE, yielding a sensitivity of 54.76%, specificity of 73.58%. A preoperative-to-postoperative D-dimer change = 2.50 mg/L showed a sensitivity of 26.19%, specificity of 94.72%. Conclusion Increased age, higher BMI, menopause, hypertension, prolonged surgery duration and anesthesia duration, and higher ASA classification are independent risk factors for VTE after gynecological surgery. A postoperative D-dimer level ≥ 1.50 mg/L and a preoperative-to-postoperative D-dimer change ≥ 2.50 mg/L may serve as practical indicators for VTE screening and early risk identification and should be incorporated into routine postoperative monitoring. The Caprini score demonstrated limited predictive value for VTE risk in this gynecological patient cohort. Therefore, a risk assessment model tailored to patients undergoing gynecological surgery should be developed by incorporating these risk factors.

关键词

妇科手术 / 静脉血栓栓塞 / 危险因素 / D-二聚体 / Caprini评分 / 预测模型

Key words

Gynecological surgery / Venous thromboembolism / Risk factors / D-dimer / Caprini score / Predictive model

参考文献

[1] Lurie J M, Png C Y M, Subramaniam S, et al. Virchow's triad in "silent" deep vein thrombosis[J]. J Vasc Surg Venous Lymphat Disord, 2019, 7(5): 640. DOI: 10.1016/j.jvsv.2019.02.011.

[2] Chong W, Bui A H, Menhaji K. Incidence and risk factors for venous thromboembolism events after different routes of pelvic organ prolapse repairs[J/OL]. Am J Obstet Gynecol, 2020, 223(2): 268.e1. https://www.ajog.org/article/S0002-9378(20)30546-9/abstract. DOI: 10.1016/j.ajog.2020.05.020.

[3] Zhang Z, Lei J, Shao X, et al. Trends in hospitalization and in-hospital mortality from VTE, 2007 to 2016, in China[J]. Chest, 2019, 155(2): 342. DOI: 10.1016/j.chest.2018.10.040.

[4] Zhai Z, Kan Q, Li W, et al. VTE risk profiles and prophylaxis in medical and surgical inpatients: the Identification of Chinese Hospitalized Patients' Risk Profile for Venous Thromboembolism (DissolVE-2): a cross-sectional study[J]. Chest, 2019, 155(1): 114. DOI: 10.1016/j.chest.2018.09.020.

[5] Heit J A, Silverstein M D, Mohr D N, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study[J]. Arch Intern Med, 1999, 159(5): 445. DOI: 10.1001/archinte.159.5.445.

[6] Cohoon K P, Leibson C L, Ransom J E, et al. Costs of venous thromboembolism associated with hospitalization for medical illness[J/OL]. Am J Manag Care, 2015, 21(4): e255. https://pmc.ncbi.nlm.nih.gov/articles/PMC4586032/.

[7] Heit J A. Epidemiology of venous thromboembolism[J]. Nat Rev Cardiol, 2015, 12(8): 464. DOI: 10.1038/nrcardio.2015.83.

[8] Geerts W H, Pineo G F, Heit J A, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy[J]. Chest, 2004, 126(S3): 338S. DOI: 10.1378/chest.126.3_suppl.338S.

[9] Cronin M, Dengler N, Krauss E S, et al. Completion of the Updated Caprini Risk Assessment Model (2013 Version)[J/OL]. Clin Appl Thromb Hemost, 2019, 25: 1076029619838052. https://pmc.ncbi.nlm.nih.gov/articles/PMC6714938/. DOI: 10.1177/1076029619838052.

[10] Stroud W, Whitworth J M, Miklic M, et al. Validation of a venous thromboembolism risk assessment model in gynecologic oncology[J]. Gynecol Oncol, 2014, 134(1): 160. DOI: 10.1016/j.ygyno.2014.04.051.

[11] Karasu A, Šrámek A, Rosendaal F R, et al. Aging of the venous valves as a new risk factor for venous thrombosis in the elderly: the BATAVIA study[J]. J Thromb Haemost, 2018, 16(1): 96. DOI: 10.1111/jth.13880.

[12] Hu Z, Xu J, Shen R, et al. Combination of biological aging and genetic susceptibility helps identifying at-risk population of venous thromboembolism: a prospective cohort study of 394,041 participants[J]. Am J Hematol, 2025, 100(4): 575. DOI: 10.1002/ajh.27605.

[13] 中国老年医学学会周围血管疾病管理分会. 老年人静脉血栓栓塞症防治中国专家共识[J]. 中国普外基础与临床杂志, 2023, 30(10): 1173. DOI: 10.7507/1007-9424.202308048.

[14] Peripheral Vascular Disease Management Branch of Chinese Geriatric Society. Chinese expert consensus on prevention and treatment of venous thromboembolism in the elderly[J]. Chin J Bases Clin Gen Surg, 2023, 30(10): 1173. DOI: 10.7507/1007-9424.202308048.

[15] Xu Y, Jia Y, Zhang Q, et al. Incidence and risk factors for postoperative venous thromboembolism in patients with ovarian cancer: systematic review and meta-analysis[J]. Gynecol Oncol, 2021, 160(2): 610. DOI: 10.1016/j.ygyno.2020.11.010.

[16] Shiota M, Kotani Y, Umemoto M, et al. Risk factors for deep-vein thrombosis and pulmonary thromboembolism in benign ovarian tumor[J]. Tohoku J Exp Med, 2011, 225(1): 1. DOI: 10.1620/tjem.225.1.

[17] Yang T, Tian S, Wang Y, et al. Evaluation of risk factors for venous thromboembolism in patients who underwent gynecological surgery and validation of a fast-rating assessment table[J]. Med Sci Monit, 2019, 25: 8814. DOI: 10.12659/MSM.920198.

[18] Tasaka N, Minaguchi T, Hosokawa Y, et al. Prevalence of venous thromboembolism at pretreatment screening and associated risk factors in 2086 patients with gynecological cancer[J]. J Obstet Gynaecol Res, 2020, 46(5): 765. DOI: 10.1111/jog.14233.

[19] Montoya T I, Leclaire E L, Oakley S H, et al. Venous thromboembolism in women undergoing pelvic reconstructive surgery with mechanical prophylaxis alone[J]. Int Urogynecol J, 2014, 25(7): 921. DOI: 10.1007/s00192-013-2315-4.

[20] Vilahur G, Ben-Aicha S, Badimon L. New insights into the role of adipose tissue in thrombosis[J]. Cardiovasc Res, 2017, 113(9): 1046. DOI: 10.1093/cvr/cvx086.

[21] Lee Y J, Kwon S B, An J M, et al. Increased protein oxidation and decreased expression of nuclear factor E2-related factor 2 protein in skin tissue of patients with diabetes[J]. Clin Exp Dermatol, 2015, 40(2): 192. DOI: 10.1111/ced.12487.

[22] Chen L, Zhu Y, Yang X, et al. Leptin aggravates thoracic aortic dissection through impairment of energy metabolism in Nrip2(+) smooth muscle cells[J/OL]. Adv Sci (Weinh), 2025, 12(38): e02027. https://doi.org/10.1002/advs.202502027.

[23] Rocha A T, De Vasconcellos A G, Da Luz Neto E R, et al. Risk of venous thromboembolism and efficacy of thromboprophylaxis in hospitalized obese medical patients and in obese patients undergoing bariatric surgery[J]. Obes Surg, 2006, 16(12): 1645. DOI: 10.1381/096089206779319383.

[24] Hotoleanu C. Association between obesity and venous thromboembolism[J]. Med Pharm Rep, 2020, 93(2): 162. DOI: 10.15386/mpr-1372.

[25] Chen H, Lei X, Yang Z, et al. Effects of combined metformin and semaglutide therapy on body weight, metabolic parameters, and reproductive outcomes in overweight/obese women with polycystic ovary syndrome: a prospective, randomized, controlled, open-label clinical trial[J/OL]. Reprod Biol Endocrinol, 2025, 23(1): 108. https://doi.org/10.1186/s12958-025-01447-3.

[26] Korolova D, Suranyi A, Pavlenko A, et al. Obesity is a thrombotic risk factor in pregnant women[J/OL]. J Clin Med, 2025, 14(15): 5310. https://doi.org/10.3390/jcm14155310.

[27] Bucciarelli P, Mannucci P M. The hemostatic system through aging and menopause[J]. Climacteric, 2009, 12(S1): 47. DOI: 10.1080/13697130903006365.

[28] Menazza S, Murphy E. The expanding complexity of estrogen receptor signaling in the cardiovascular system[J]. Circ Res, 2016, 118(6): 994. DOI: 10.1161/CIRCRESAHA.115.305376.

[29] Caulin-Glaser T, García-Cardeña G, Sarrel P, et al. 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca²⁺ mobilization[J]. Circ Res, 1997, 81(5): 885. DOI: 10.1161/01.RES.81.5.885.

[30] Sowers M R, Matthews K A, Jannausch M, et al. Hemostatic factors and estrogen during the menopausal transition[J]. J Clin Endocrinol Metab, 2005, 90(11): 5942. DOI: 10.1210/jc.2005-0591.

[31] Marcarini W D, Marques V B, Teixeira A C, et al. The role of aldosterone on the endothelial dysfunction induced by female hormone deficiency[J/OL]. Mol Cell Endocrinol, 2025, 605: 112571. https://www.sciencedirect.com/science/article/abs/pii/S0303720725001224?via%3Dihub. DOI: 10.1016/j.mce.2025.112571.

[32] Lewis G K, Spaulding A C, Brennan E, et al. Caprini assessment utilization and impact on patient safety in gynecologic surgery[J]. Arch Gynecol Obstet, 2023, 308(3): 901. DOI: 10.1007/s00404-023-07038-0.

[33] Agnelli G, Bolis G, Capussotti L, et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project[J]. Ann Surg, 2006, 243(1): 89. DOI: 10.1097/01.sla.0000193959.44677.48.

[34] Pham N K, Jalloul R J, Chen H Y, et al. Venous thromboembolism after abdominal and minimally invasive large specimen hysterectomy[J]. J Minim Invasive Gynecol, 2023, 30(11): 884. DOI: 10.1016/j.jmig.2023.06.017.

[35] Moulder J K, Moore K J, Strassle P D, et al. Effect of length of surgery on the incidence of venous thromboembolism after benign hysterectomy[J/OL]. Am J Obstet Gynecol, 2021, 224(4): 364.e1. https://www.ajog.org/article/S0002-9378(20)31179-0/abstract. DOI: 10.1016/j.ajog.2020.10.007.

[36] Catanzarite T, Saha S, Pilecki M A, et al. Longer operative time during benign laparoscopic and robotic hysterectomy is associated with increased 30-day perioperative complications[J]. J Minim Invasive Gynecol, 2015, 22(6): 1049. DOI: 10.1016/j.jmig.2015.05.022.

[37] Albayati M A, Grover S P, Saha P, et al. Postsurgical inflammation as a causative mechanism of venous thromboembolism[J]. Semin Thromb Hemost, 2015, 41(6): 615. DOI: 10.1055/s-0035-1556726.

[38] Hendrix J M, Garmon E H. American Society of Anesthesiologists Physical Status Classification System[M/OL]. StatPearls, 2025. https://www.ncbi.nlm.nih.gov/books/NBK441940/.

[39] Sedra S, Mallick R, Nayak A L, et al. Venous thromboembolism after blood transfusions in women undergoing hysterectomy for non-malignant indications: a retrospective cohort study[J]. J Obstet Gynaecol Can, 2021, 43(2): 167. DOI: 10.1016/j.jogc.2020.09.016.

[40] Swift B E, Maeda A, Bouchard-Fortier G. Low incidence of venous thromboembolism after gynecologic oncology surgery: who is at greatest risk?[J]. Gynecol Oncol, 2022, 164(2): 311. DOI: 10.1016/j.ygyno.2021.12.011.

[41] Voney G, Biro P, Roos M, et al. Interrelation of peri-operative morbidity and ASA class assignment in patients undergoing gynaecological surgery[J]. Eur J Obstet Gynecol Reprod Biol, 2007, 132(2): 220. DOI: 10.1016/j.ejogrb.2006.04.028.

[42] Escobar C M, Gomez-Viso A, Agrawal S, et al. Venous thromboembolism prophylaxis in vaginal surgery for pelvic organ prolapse: predictors of high risk in a low-risk population[J]. Neurourol Urodyn, 2021, 40(1): 176. DOI: 10.1002/nau.24529.

[43] Mrad M A, Al Qurashi A A, Shah Mardan Q N M, et al. Venous thromboembolism risk assessment models in plastic surgery: a systematic review and meta-analysis[J/OL]. Plast Reconstr Surg Glob Open, 2022, 10(12): e4683. https://doi.org/10.1097/GOX.0000000000004683.

[44] Oliver W M, Mackenzie S A, Lenart L, et al. Age, personal and family history are independently associated with venous thromboembolism following acute Achilles tendon rupture[J]. Injury, 2022, 53(2): 762. DOI: 10.1016/j.injury.2021.10.009.

[45] Kodama J, Seki N, Masahiro S, et al. D-dimer level as a risk factor for postoperative venous thromboembolism in Japanese women with gynecologic cancer[J]. Ann Oncol, 2010, 21(8): 1651. DOI: 10.1093/annonc/mdq012.

[46] Shi J, Ye J, Zhuang X, et al. Application value of Caprini risk assessment model and elevated tumor-specific D-dimer level in predicting postoperative venous thromboembolism for patients undergoing surgery of gynecologic malignancies[J]. J Obstet Gynaecol Res, 2019, 45(3): 657. DOI: 10.1111/jog.13832.

[47] 郎景和, 王辰, 瞿红, 等. 妇科手术后深静脉血栓形成及肺栓塞预防专家共识[J]. 中华妇产科杂志, 2017, 52(10): 649. DOI: 10.3760/cma.j.issn.0529-567x.2017.10.001.

[48] Lang J H, Wang C, Qu H, et al. Expert consensus on prevention of deep vein thrombosis and pulmonary embolism after gynecological surgery[J]. Chin J Obstet Gynecol, 2017, 52(10): 649. DOI: 10.3760/cma.j.issn.0529-567x.2017.10.001.

基金资助

*深地国家科技重大专项(2024ZD1000602)