目的

探索围产期肺栓塞（pulmonary embolism，PE）患者使用那曲肝素（nadroparin calcium，NC）引起嗜酸性粒细胞（eosinophil，Eos）增多不良反应的临床特点，为临床用药安全提供参考依据。

方法

选择2020 年1 月至2023 年1 月我院收治的肺栓塞的围产期患者在使用那曲肝素治疗过程中出现嗜酸粒细胞增多的病例，提取患者基本信息，包括年龄、体重、基础疾病、诊断肺栓塞时机、那曲肝素用法用量、合并用药、嗜酸粒细胞计数基线值、嗜酸粒细胞增多发生时间、嗜酸粒细胞计数峰值、是否伴随皮肤症状、嗜酸粒细胞计数恢复至正常值时间及不良反应转归。

结果

共有8 例围产期肺栓塞患者在使用那曲肝素过程中出现嗜酸粒细胞增多的不良反应。 患者年龄介于27～34 岁之间，在确诊肺栓塞后予那曲肝素规范化治疗，无其他合并用药。 监测到嗜酸粒细胞增多发生时间最早为用药后的12 d，该患者嗜酸粒细胞计数基础值（0.26×10⁹/L）较其他患者稍高；嗜酸粒细胞增多发生时间最迟为用药后的70 d，该患者不良反应最轻微，其嗜酸粒细胞计数峰值为0.55×10⁹/L。 1 例患者达到嗜酸粒细胞重度增多临床诊断，其嗜酸粒细胞计数峰值为5.31×10⁹/L。 3 例患者伴随皮肤症状，停药后症状消失。 7 例患者在出现嗜酸粒细胞增多后予减量/停药/抗凝方案的调整，停药后2～114 d 嗜酸粒细胞计数恢复至正常水平，未予其他干预措施，其中减量处理的患者监测其嗜酸粒细胞计数持续增多，后予停药处理后好转。 1 例患者在出现嗜酸粒细胞增多后未调整治疗方案，其嗜酸粒细胞持续升高，后失去随访资料。

结论

围产期肺栓塞患者使用那曲肝素致嗜酸粒细胞增多发生时间一般在用药后的10 周内，部分患者伴随皮肤症状如皮肤瘙痒等，停药后可恢复。 临床在使用那曲肝素治疗围产期肺栓塞患者时，应密切关注嗜酸粒细胞计数变化，以便及时发现并妥善处理这一不良反应，保障患者的用药安全和治疗效果。

Objective

To explore the clinical characteristics of nadroparin-induced eosinophilia in perinatal women with pulmonary embolism and provide a reference for clinical drug safety.

Methods

Cases of perinatal patients diagnosed with pulmonary embolism who developed eosinophilia during treatment with nadroparin between 2020-2023 were collected.Basic patient information was extracted，including age，body weight，underlying disease，pulmonary embolism diagnosis timing，nadroparin dosage，comorbidities，baseline eosinophil count，time to onset of eosinophilia，peak eosinophil count，presence of skin symptoms，time for eosinophil count to return to normal level，and regression of adverse effects.

Results

A total of 8 perinatal women with pulmonary embolism experienced eosinophilia during the administration of nadroparin.The patients were aged 27 to 34 years and all were treated with nadroparin after diagnosis of pulmonary embolism without other concomitant medications.Eosinophilia was detected as early as 12 days post-dose，with a slightly higher basal eosinophil count （0.26×10⁹/L） than the other patients.Eosinophilia was detected as late as 70 days postdose，and this patient had the mildest adverse effect with a peak eosinophil count of 0.55×10⁹/L）.One patient reached the clinical diagnosis of severe eosinophilia with a peak eosinophil count of 5.31×10⁹/L.Three patients had accompanying skin symptoms，which disappeared after discontinuation of the drug.Seven patients had their dosage reduced，discontinued the drug，or changed their anticoagulation regimen after the eosinophil count increased.The eosinophil count returned to normal levels 2-114 days after drug withdrawal without other intervention measures.Among them，the eosinophil count of patients treated with reduced dosage continued to increase and then improved after drug withdrawal.Another patient did not adjust the treatment plan，and her eosinophils continued to rise，subsequent follow-up data were lost.

Conclusion

Nadroparin-induced eosinophilia in perinatal women with pulmonary embolism occurs within 10 weeks，and some patients may experience skin symptoms such as itchiness，which generally recover after drug discontinuation.When using nadroparin to treat perinatal patients with pulmonary embolism，clinicians should closely monitor eosinophil count changes to promptly detect and appropriately manage this adverse reaction.