低分子量肝素(LMWH)被广泛用作预防和管理各种血栓形成病症的抗凝剂。然而,尽管LMWH在临床适应症中广泛使用,其不良事件(AE)尚未得到实质性关注,缺乏系统全面的AE研究。本研究旨在从FDA不良事件报告系统数据库中评估总体人群和妊娠妇女中与LMWH相关的AE信号。
■我们使用标准化MedDRA查询来识别妊娠相关的不良事件报告。通过计算报告优势比(ROR),采用不成比例分析来识别LMWH相关的AE,比例报告比率(PRR),贝叶斯置信传播神经网络(BCPNN),和经验贝叶斯几何平均值(EBGM)。
■对于总人口,SOCs中显著报告的不良信号是怀孕,产褥期,和围产期条件,血管疾病,血液和淋巴系统疾病,和产品问题。LMWH相关的五个最强AE信号是抗X因子抗体阳性(n=6,ROR506.70,PRR506.65,IC8.31,EBGM317.03),肝素诱导的血小板减少试验阳性(n=19,ROR263.10,PRR263.02,IC7.65,EBGM200.79),抗X因子活性增加(n=10,ROR255.93,PRR255.89,IC7.62,EBGM196.61),肝素诱导的血小板减少试验(n=14,ROR231.85,PRR231.80,IC7.51,EBGM182.09),和自发性肝素诱导的血小板减少综合征(n=3,ROR230.31,PRR230.30,IC7.50,EBGM181.16)。对于孕妇来说,与LMWH相关的五个最强AE信号包括胸骨骨折(n=3,ROR243.44,PRR243.35,IC6.61,EBGM97.94),注射器问题(n=12,ROR97.49,PRR97.34,IC5.94,EBGM61.21),出血时间延长(n=3,ROR97.38,PRR97.34,IC5.94,EBGM61.21),脊柱压缩性骨折(n=10,ROR90.24,PRR90.13,IC5.87,EBGM58.30),注射部位血肿(n=19,ROR79.23,PRR79.04,IC5.74,EBGM53.47)。此外,观察到孕妇中与LMWH相关的意外AE,包括婴儿过早死亡,胎盘坏死,流产,抗磷脂综合征,收缩功能障碍,筋膜室综合征,身高下降,风疹抗体阳性,超声多普勒异常。
■这项研究确定了妊娠妇女中LMWH相关的意外AE信号。本研究可为LMWH的临床实践提供有价值的证据,特别是用于识别AE并确保孕妇的安全使用。
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.