Xu Huanying, Xu Ningning, Wang Yingju, Zou Haoxi, Wu Suzhen
Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, Guangdong, China.
TCM Gynecology Department, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China.
Front Pharmacol. 2024 Aug 12;15:1442002. doi: 10.3389/fphar.2024.1442002. eCollection 2024.
Low molecular weight heparin (LMWH) is extensively utilized as an anticoagulant for the prevention and management of various thrombotic conditions. However, despite the widespread use of LMWH in clinical indications, its adverse events (AEs) have not received substantial attention, and there is a lack of systematic and comprehensive AE studies. This study aims to evaluate AE signals associated with LMWH in the overall population and in pregnancy women from the FDA Adverse Event Reporting System database.
We used the Standardized MedDRA Query to identify pregnancy-related AE reports. Disproportionality analyses were employed to identify LMWH-related AE by calculating the reporting odds ratios (ROR), proportional reporting ratios (PRR), bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM).
For the overall population, the significantly reported adverse signals in SOCs were pregnancy, puerperium, and perinatal conditions, vascular disorders, blood and lymphatic system disorders, and product issues. The five strongest AEs signal of LMWH-related were anti factor X antibody positive (n = 6, ROR 506.70, PRR 506.65, IC 8.31, EBGM 317.03), heparin-induced thrombocytopenia test positive (n = 19, ROR 263.10, PRR 263.02, IC 7.65, EBGM 200.79), anti factor X activity increased (n = 10, ROR 255.93, PRR 255.89, IC 7.62, EBGM 196.61), heparin-induced thrombocytopenia test (n = 14, ROR 231.85, PRR 231.80, IC 7.51, EBGM 182.09), and spontaneous heparin-induced thrombocytopenia syndrome (n = 3, ROR 230.31, PRR 230.30, IC 7.50, EBGM 181.16). For pregnancy women, the five strongest AEs signals of LMWH-related included sternal fracture (n = 3, ROR 243.44, PRR 243.35, IC 6.61, EBGM 97.94), syringe issue (n = 12, ROR 97.49, PRR 97.34, IC 5.94, EBGM 61.21), bleeding time prolonged (n = 3, ROR 97.38, PRR 97.34, IC 5.94, EBGM 61.21), spinal compression fracture (n = 10, ROR 90.24, PRR 90.13, IC 5.87, EBGM 58.30), and injection site haematoma (n = 19, ROR 79.23, PRR 79.04, IC 5.74, EBGM 53.47). Additionally, unexpected AEs associated with LMWH in pregnancy women were observed, including premature baby death, placental necrosis, abortion, antiphospholipid syndrome, systolic dysfunction, compartment syndrome, body height decreased, rubella antibody positive, and ultrasound doppler abnormal.
This study identified unexpected AE signals of LMWH-relate in pregnancy women. Our study could provide valuable evidence for the clinical practice of LMWH, especially for identifying AEs and ensuring safe usage in pregnancy women.
低分子量肝素（LMWH）被广泛用作抗凝剂，用于预防和治疗各种血栓形成病症。然而，尽管LMWH在临床适应症中广泛使用，但其不良事件（AE）尚未得到充分关注，并且缺乏系统和全面的AE研究。本研究旨在评估来自美国食品药品监督管理局不良事件报告系统数据库的总体人群和孕妇中与LMWH相关的AE信号。
我们使用标准化医学术语词典查询来识别与妊娠相关的AE报告。采用不成比例分析，通过计算报告比值比（ROR）、比例报告比值（PRR）、贝叶斯置信传播神经网络（BCPNN）和经验贝叶斯几何均值（EBGM）来识别与LMWH相关的AE。
对于总体人群，在系统器官分类（SOCs）中显著报告的不良信号是妊娠、产褥期和围产期情况、血管疾病、血液和淋巴系统疾病以及产品问题。与LMWH相关的五个最强AE信号是抗X因子抗体阳性（n = 6，ROR 506.70，PRR 506.65，IC 8.31，EBGM 317.03）、肝素诱导的血小板减少症检测阳性（n = 19，ROR 263.10，PRR 263.02，IC 7.65，EBGM 200.79）、抗X因子活性增加（n = 10，ROR 255.93，PRR 255.89，IC 7.62，EBGM 196.61）、肝素诱导的血小板减少症检测（n = 14，ROR 231.85，PRR 231.80，IC 7.51，EBGM 182.09）以及自发性肝素诱导的血小板减少症综合征（n = 3，ROR 230.31，PRR 230.30，IC 7.50，EBGM 181.16）。对于孕妇，与LMWH相关的五个最强AE信号包括胸骨骨折（n = 3，ROR 243.44，PRR 243.35，IC 6.61，EBGM 97.94）、注射器问题（n = 12，ROR 97.49，PRR 97.34，IC 5.94，EBGM 61.21）、出血时间延长（n = 3，ROR 97.38，PRR 97.34，IC 5.94，EBGM 61.21）、脊柱压缩性骨折（n = 10，ROR 90.24，PRR 90.13，IC 5.87，EBGM 58.30）以及注射部位血肿（n = 19，ROR 79.23，PRR 79.04，IC 5.74，EBGM 53.47）。此外，还观察到孕妇中与LMWH相关的意外AE，包括早产婴儿死亡、胎盘坏死、流产、抗磷脂综合征、收缩功能障碍、骨筋膜室综合征、身高降低、风疹抗体阳性以及超声多普勒异常。
本研究确定了孕妇中与LMWH相关的意外AE信号。我们的研究可为LMWH的临床实践提供有价值的证据，特别是用于识别AE并确保孕妇安全使用。
