骨科患者达肝素钠双场景真实世界研究与药学监护策略分析

doi:10.12092/j.issn.1009-2501.2026.07.007

摘要/Abstract

摘要：

目的: 基于“预防-治疗”双场景分析框架，系统分析骨科患者达肝素钠应用中“预防出血可控、治疗剂量失守”的非对称性风险格局，为骨科患者的精细化抗凝管理提供参考视角。方法: 回顾性纳入某三甲医院骨科2023年9月至2025年3月使用达肝素钠的200例住院患者，分为预防组（n=185）与治疗组（n=15）。预防组采用多因素Logistic回归分析出血事件的独立危险因素，并通过分层分析、倾向性评分匹配（propensity score matching，PSM）验证“指征混杂”假设；治疗组因骨科小样本数据特征，采用Fisher确切概率法、Firth惩罚似然回归、贝叶斯回归分析等多种方法进行探索性分析。结果: 预防组出血事件发生率22.70%，Caprini评分≥5分是出血事件的独立危险因素（OR=8.06，95%CI：1.79～36.20，P=0.007）；给药时机不合理为出血事件的保护因素（OR=0.14，95%CI：0.05～0.46，P=0.001），分层分析与PSM验证结果提示，该关联可能源于“指征混杂”。治疗组患者剂量不足率93.33%，治疗失败率21.43%，观察到所有治疗失败的患者均属于剂量不足组，但受限于样本量，其关联强度未能确证。结论: 骨科达肝素钠应用呈现预防场景出血风险集中、治疗场景剂量执行偏差显著的双场景特征，Caprini评分≥5分是预防场景下出血风险的关键预警指标，治疗场景中基于体质量分层剂量的执行不足或为治疗失败的潜在诱因。本研究构建的分阶式药学监护体系，可为达肝素钠在骨科的临床应用和优化提供实践参考。

关键词: 达肝素钠, 骨科, 出血事件, 治疗失败, 真实世界研究

Abstract:

AIM: To analyze the asymmetric risk pattern of "controllable bleeding in prophylaxis versus suboptimal dosing in treatment" during dalteparin sodium use in orthopedic patients using a dual-scenario framework, providing insights for refined anticoagulation management. METHODS: This retrospective study included 200 inpatients receiving dalteparin sodium in an orthopedic department (September 2023 to March 2025). Patients were categorized into prophylaxis (n=185) and treatment (n=15) groups. Multivariate logistic regression identified bleeding risk factors in the prophylaxis group, with stratified analysis and propensity score matching (PSM) assessing potential confounding by indication. For the small treatment group, exploratory analyses (Fisher's exact test, Firth regression, Bayesian methods) were employed. RESULTS: In the prophylaxis group, bleeding events occurred in 22.70% of patients. A Caprini score ≥5 was an independent risk factor (OR=8.06, 95%CI: 1.79–36.20, P=0.007), while inappropriate dosing timing was associated with reduced bleeding risk (OR=0.14, 95%CI: 0.05–0.46, P=0.001). Stratified analysis and PSM suggested confounding by indication. In the treatment group, subtherapeutic dosing was observed in 93.33% of patients, with a 21.43% treatment failure rate. All failures occurred in the subtherapeutic dosing subgroup, though sample size limitations precluded definitive conclusions. CONCLUSION: Dalteparin sodium use in orthopedics shows a dual-scenario pattern: concentrated bleeding risk in prophylaxis and prevalent dosing deviations in treatment. A Caprini score ≥5 serves as a key bleeding risk indicator in prophylaxis. Failure to implement weight-stratified dosing may contribute to therapeutic failure. The proposed tiered pharmaceutical care framework offers practical guidance for optimizing dalteparin sodium use in orthopedic practice.

Key words: dalteparin sodium, orthopedics, bleeding events, treatment failure, real-world study

中图分类号:

R969.3

刘炎, 邱季, 吴国翠, 李瑞麟, 陈义昭. 骨科患者达肝素钠双场景真实世界研究与药学监护策略分析[J]. 中国临床药理学与治疗学, 2026, 31(7): 913-920.

Yan LIU, Ji QIU, Guocui WU, Ruilin LI, Yizhao CHEN. Dual-scenario real-world study and pharmaceutical care strategy analysis of dalteparin sodium in orthopedic patients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(7): 913-920.

图/表 6

参考文献 21

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Variable	Bleeding group (n=42)	Non-bleeding group (n=143)	OR (95%CI)	P
Inappropriate administration timing	4(9.52)	72(50.35)	0.10 (0.04-0.31)	<0.001
Caprini score ≥5	40(95.24)	87(60.84)	12.87 (2.99-55.39)	<0.001
Anemia	7(16.67)	6(4.20)	4.57 (1.44-14.45)	0.011*
Age ≥65 years	25(59.52)	56(39.16)	2.28 (1.13-4.61)	0.019
Male sex	15(35.71)	66(46.15)	1.54 (0.76-3.14)	0.23
Initial hemoglobin <115 g/L	6(14.29)	31(21.68)	0.60 (0.23-1.56)	0.30
Concomitant systemic NSAID use	40(95.24)	139(97.20)	0.58 (0.10-3.26)	0.62*
eGFR<60 mL/min	1(2.38)	11(7.69)	0.92 (0.25-3.48)	1.00*

Variable	Bleeding group (n=42)	Non-bleeding group (n=143)	OR (95%CI)	P
Inappropriate administration timing	4(9.52)	72(50.35)	0.10 (0.04-0.31)	<0.001
Caprini score ≥5	40(95.24)	87(60.84)	12.87 (2.99-55.39)	<0.001
Anemia	7(16.67)	6(4.20)	4.57 (1.44-14.45)	0.011*
Age ≥65 years	25(59.52)	56(39.16)	2.28 (1.13-4.61)	0.019
Male sex	15(35.71)	66(46.15)	1.54 (0.76-3.14)	0.23
Initial hemoglobin <115 g/L	6(14.29)	31(21.68)	0.60 (0.23-1.56)	0.30
Concomitant systemic NSAID use	40(95.24)	139(97.20)	0.58 (0.10-3.26)	0.62*
eGFR<60 mL/min	1(2.38)	11(7.69)	0.92 (0.25-3.48)	1.00*

Variable	β	SE	OR(95%CI)	P	VIF
Caprini score ≥5	2.09	0.77	8.06(1.79-36.20)	0.007	1.062
Inappropriate administration timing	?1.90	0.57	0.14(0.05-0.46)	0.001	1.062
Constant	?2.73	0.76	—	<0.001	—

Variable	β	SE	OR(95%CI)	P	VIF
Caprini score ≥5	2.09	0.77	8.06(1.79-36.20)	0.007	1.062
Inappropriate administration timing	?1.90	0.57	0.14(0.05-0.46)	0.001	1.062
Constant	?2.73	0.76	—	<0.001	—

Subgroup	Variable	β	SE	OR(95%CI)	P
Caprini score ≥5 (n=127,40 bleeding events)	Inappropriate administration timing	?1.890	0.594	0.151 (0.047-0.484)	0.001
	Anemia	0.717	0.642	2.047 (0.581-7.212)	0.265
	Age≥65 years	0.623	0.421	1.864 (0.816-4.257)	0.139
	Concomitant systemic NSAID use	?1.790	1.342	0.167 (0.012-2.317)	0.182