Analysis of risk factors and construction of risk prediction model for batroxobin-related severe hypofibrinogenemia

CAI Le; ZHAO Yuqing; CUI Jiazhu; WEN Xiao; GUO Daihong; ZHU Man

doi:10.6039/j.issn.1001-0408.2026.04.09

您当前的位置：

首页 >

文章列表页 >

Analysis of risk factors and construction of risk prediction model for batroxobin-related severe hypofibrinogenemia

更新时间：2026-02-27

- Analysis of risk factors and construction of risk prediction model for batroxobin-related severe hypofibrinogenemia
- ZHONGGUO YAOFANG Vol. 37, Issue 4, Pages: 462-467(2026)
- 作者机构：
  
  1.解放军总医院医疗保障中心药剂科，北京　100853
  2.蚌埠医科大学药学院，安徽蚌埠　233030
  3.沈阳药科大学生命科学与生物制药学院，沈阳　110016
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.04.09
  CLC： R969.3
- Received：30 September 2025，
  
  Revised：2026-02-05，
  
  Accepted：05 February 2026，
  
  Published：28 February 2026
- 稿件说明：
移动端阅览
蔡乐,赵雨晴,崔佳珠,等.巴曲酶相关严重低纤维蛋白原血症的危险因素分析及风险预测模型构建[J].中国药房,2026,37(04):462-467.

CAI Le,ZHAO Yuqing,CUI Jiazhu,et al.Analysis of risk factors and construction of risk prediction model for batroxobin-related severe hypofibrinogenemia[J].ZHONGGUO YAOFANG,2026,37(04):462-467.
蔡乐,赵雨晴,崔佳珠,等.巴曲酶相关严重低纤维蛋白原血症的危险因素分析及风险预测模型构建[J].中国药房,2026,37(04):462-467. DOI： 10.6039/j.issn.1001-0408.2026.04.09.

CAI Le,ZHAO Yuqing,CUI Jiazhu,et al.Analysis of risk factors and construction of risk prediction model for batroxobin-related severe hypofibrinogenemia[J].ZHONGGUO YAOFANG,2026,37(04):462-467. DOI： 10.6039/j.issn.1001-0408.2026.04.09.

摘要

目的

探讨巴曲酶相关严重低纤维蛋白原血症（HFIB）的临床特征及危险因素，并构建其风险预测模型。

方法

回顾性收集2020年1月1日至2024年12月31日某三甲医院第一医学中心使用巴曲酶的住院患者资料，并根据发生HFIB的严重程度分为非严重HFIB组和严重HFIB组。采用单因素和多因素Logistic回归分析筛选巴曲酶相关严重HFIB的独立影响因素。采用R 4.5软件“rms”程序包绘制列线图；采用受试者工作特征曲线检验模型的预测性能；采用Bootstrap自助抽样法评估模型的校准度；采用Hosmer-Lemeshow检验评价模型的拟合优度。

结果

共纳入1 472例患者，其中1 445例发生HFIB，发生率为98.17%；895例为严重HFIB，发生率为60.80%。多因素Logistic回归分析结果显示，年龄增长、较高的首剂量/10 kg体重、使用维持剂量、合并使用糖皮质激素是巴曲酶相关严重HFIB的独立危险因素，较高的纤维蛋白原（FIB）基线值为其独立保护因素（

＜0.05）。模型的受试者工作特征曲线下面积为0.760[95%置信区间为（0.735，0.785）

]

；校准曲线的平均绝对误差为0.006；Hosmer-Lemeshow检验的

值为0.609。

结论

巴曲酶可快速、显著降低FIB，易引起严重HFIB；年龄增长、使用较高首剂量/10 kg体重、使用维持剂量以及合并使用糖皮质激素患者的巴曲酶相关严重HFIB的发生风险较高，而FIB基线值较高患者的巴曲酶相关严重HFIB的发生风险较低；基于上述因素建立的风险预测模型可用于预测巴曲酶相关严重HFIB的发生风险。

Abstract

OBJECTIVE

To investigate the clinical characteristics and risk factors for batroxobin-related severe hypofibrinogenemia （HFIB） and construct a risk prediction model.

METHODS

A retrospective analysis was conducted on inpatients treated with batroxobin in the First Medical Center of a tertiary hospital from January 1， 2020， to December 31， 2024. Patients were categorized into non-severe HFIB group and severe HFIB group based on the severity of HFIB. Univariate and multivariate Logistic regression analyses were performed to identify the independent influencing factors for batroxobin-related severe HFIB. A nomogram was developed using the “rms” package in R 4.5 software. The predictive performance of the model was evaluated using the receiver operating characteristic curve. Calibration was assessed via the Bootstrap resampling method， and goodness-of-fit was evaluated with the Hosmer-Lemeshow test.

RESULTS

A total of 1 472 patients were included in this study. Of these， 1 445 developed HFIB， yi

elding an incidence of 98.17%. Furthermore， 895 were classified as severe HFIB， accounting for 60.80% of the cohort. Multivariate Logistic regression analysis showed that increased age， high initial dose per 10 kg body weight， use of maintenance dose， and concomitant glucocorticoid use were independent risk factors for batroxobin-related severe HFIB， while high baseline fibrinogen （FIB） level was identified as a protective factor. The model demonstrated an area under the curve of 0.760 （95% CI： 0.735-0.785）. The mean absolute error of the calibration curve was 0.006. The

value of the Hosmer-Lemeshow test was 0.609.

CONCLUSIONS

Batroxobin can rapidly and significantly reduce FIB levels and carries a risk of inducing severe HFIB. Patients with advanced age， high initial dose per 10 kg body weight， use of maintenance dose and concomitant glucocorticoid use had a higher risk of batroxobin-related severe HFIB， while high baseline FIB level had a lower risk of batroxobin-related severe HFIB. The risk prediction model developed based on these factors can be used to predict the likelihood of batroxobin-related severe HFIB.

关键词

Keywords

references

NATHWANI R ， PROUMEN A ， BLAINE K P . Etiology and management of hypofibrinogenemia in trauma [J ] . Curr Opin Anaesthesiol ， 2023 ， 36 （ 3 ）： 382 - 387 .

WEN X ， CAI L ， GAO A ， et al . Pharmacovigilance analysis of drug-induced hypofibrinogenemia using the FDA Adverse Event Reporting System [J ] . Int J Clin Pharm ， 2025 ， 47 （ 3 ）： 755 - 766 .

高奥，蔡乐，朱曼，等 . 药源性低纤维蛋白原血症自发报告分析及数据挖掘 [J ] . 临床药物治疗杂志， 2024 ， 22 （ 12 ）： 22 - 27 .

郑昕昕，王静，朱怀军，等 . 药源性低纤维蛋白原血症危险因素和可能机制的研究进展 [J ] . 中南药学， 2022 ， 20 （ 6 ）： 1366 - 1372 .

JIANG L Z ， ZUO W Q . Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss greater than but not less than 100 dB HL [J ] . J Laryngol Otol ， 2024 ， 138 （ 3 ）： 270 - 275 .

钟志耕，李又佳，黄燕，等 . 巴曲酶治疗脑梗死血浆纤维蛋白原动态变化：一项前瞻性随机对照研究 [J ] . 实用医学杂志， 2012 ， 28 （ 11 ）： 1793 - 1795 .

World Health Organization Uppsala Monitoring Centre . The use of the WHO-UMC system for standardised case causality assessment [EB/OL ] .[ 2026-02-01 ] . https：//www.who.int/docs/default-source/medicines/pharmacovigilance/whocausality-assessment.pdf https://www.who.int/docs/default-source/medicines/pharmacovigilance/whocausality-assessment.pdf .

郭海丽，郭代红，朱曼，等 . 左氧氟沙星致心律失常的发生特点和危险因素分析 [J ] . 药物流行病学杂志， 2024 ， 33 （ 1 ）： 37 - 44 .

National Cancer Institute . Common Terminology Criteria for Adverse Events（CTCAE）v5.0 [EB/OL ] . [ 2026-02-01 ] . https：//dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v5-8x11.pdf https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v5-8x11.pdf .

莫银竹，程贤雄，宋沧桑，等 . 耐碳青霉烯类肺炎克雷伯菌感染风险预测模型的构建及验证 [J ] . 中国药房， 2025 ， 36 （ 14 ）： 1786 - 1791 .

SADATSAFAVI M ， SAHA-CHAUDHURI P ， PETKAU J . Model-based ROC curve：examining the effect of case mix and model calibration on the ROC plot [J ] . Med Decis Making ， 2022 ， 42 （ 4 ）： 487 - 499 .

王源，杨向红 . 有创机械通气患者发生急性肾损伤的危险因素分析及列线图风险预测模型构建 [J ] . 浙江医学， 2023 ， 45 （ 17 ）： 1836 - 1841 .

LAN D ， JIAO B L ， SONG S Y ， et al . Effects of batroxobin on the antithrombotic system in patients with cerebral venous thrombosis：clues to mechanisms [J ] . CNS Neurosci Ther ， 2024 ， 30 （ 8 ）： e14861 .

黄一宁 . 尿激酶和巴曲酶治疗早期急性脑梗死的疗效和安全性研究 [J ] . 中华老年心脑血管病杂志， 2006 ， 8 （ 2 ）： 104 - 107 .

文笑，蔡乐，高奥，等 . 药源性低纤维蛋白原血症临床特征及危险因素的文献分析 [J ] . 中国药房， 2025 ， 36 （ 13 ）： 1648 - 1654 .

SUGAI K ， IMAMURA Y ， UECHI S ， et al . Metabolic fate of batroxobin in human [J ] . Yakugaku Zasshi ， 1986 ， 106 （ 4 ）： 335 - 342 .

LENG B ， SHEN C W ， GAO T T ， et al . Incidence，characteristics and risk factors of hypofibrinogenemia associated with tigecycline：a multicenter retrospective study in China [J ] . Front Pharmacol ， 2022 ， 13 ： 943674 .

ZOU F ， WU M T ， WANG Y Y . Risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding [J ] . World J Gastrointest Surg ， 2024 ， 16 （ 11 ）： 3437 - 3444 .

CAI L ， WEN X ， QIU Z H ， et al . Characteristics，risk factors and a risk prediction model of tocilizumab-induced hypofibrinogenemia：a retrospective real-world study of inpatients [J ] . BMC Pharmacol Toxicol ， 2025 ， 26 （ 1 ）： 5 .

WANG B ， ZHANG W ， ZHANG J ， et al . Efficacy and fibrinogen correlations of defibrinogen therapy in idiopathic sudden sensorineural hearing loss [J ] . Sci Rep ， 2025 ， 15 （ 1 ）： 4311 .

SUGAI K ， IMAMURA Y ， MIHASHI S ， et al . Plasma levels and urinary excretion of batroxobin and its defibrinogenating effects in various animal species [J ] . J Toxicol Sci ， 1986 ， 11 （ 2 ）： 135 - 143 .

张冀琳，汪艳 . 巴曲酶联合地塞米松治疗突发性耳聋患者疗效及对凝血指标的影响 [J ] . 血栓与止血学， 2022 ， 28 （ 3 ）： 970 - 971 .

屈慧文，吴丹丹，金建平 . 巴曲酶联合甲泼尼龙对突发性耳聋患者血液流变学及听力的影响 [J ] . 中国医学创新， 2024 ， 21 （ 21 ）： 61 - 65 .

WOODS A ， BRULL D J ， HUMPHRIES S E ， et al . Genetics of inflammation and risk of coronary artery disease：the central role of interleukin-6 [J ] . Eur Heart J ， 2000 ， 21 （ 19 ）： 1574 - 1583 .

中华耳鼻咽喉头颈外科杂志编辑委员会，中华医学会耳鼻咽喉头颈外科学分会 . 突发性聋诊断和治疗指南：2015 [J ] . 中华耳鼻咽喉头颈外科杂志， 2015 ， 50 （ 6 ）： 443 - 447 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Study on the risk factors and predictive model for acute kidney injury during tacrolimus treatment for pediatric steroid-resistant nephrotic syndrome

巴曲酶治疗老年突发性耳聋的临床观察

某“三甲”教学医院耐碳青霉烯类鲍曼不动杆菌感染的危险因素分析

重症颅脑损伤患者气管切开术后继发肺部真菌感染的危险因素分析

静脉滴注万古霉素致中国人群急性肾损伤危险因素的系统评价

Related Author

ZHAO Lei

HAN Zhaohuan

ZHU Lei

LIU Yuqing

FU Liping

BIE Guoliang

DONG Yalin

XIE Jiao

Related Institution

Dept. of Pharmacy， Xuzhou Children’s Hospital

Dept. of Critical Care Medicine， Xuzhou Children’s Hospital

Dept. of Pharmacy， the Affiliated Hospital of Xuzhou Medical University

Department of Gynecology,The First Affiliated Hospital of Nanyang Medical College

⁰