Table1_Heparin-induced thrombocytopenia associated with low-molecular-weight heparin: clinical feature analysis of cases and pharmacovigilance assessment of the FAERS database.docx

Background: Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are commonly used anticoagulants for the management of arterial and venous thromboses. However, it is crucial to be aware that LMWH can, in rare cases, lead to a dangerous complication known as heparin-induced thrombocytopenia (HIT). The objective of this study was to evaluate the pharmacovigilance and clinical features of HIT associated with LMWH, as well as identify treatment strategies and risk factors to facilitate prompt management.Methods: We extracted adverse event report data from the FDA Adverse Event Reporting System (FAERS) database for pharmacovigilance assessment. Case reports on LMWH-induced thrombocytopenia dated up to 20 March 2023 were collected for retrospective analysis.Results: Significantly elevated reporting rates of HIT were shown in adverse event (AE) data of LMWHs in the FAERS database, while tinzaparin had a higher proportional reporting ratio (PRR) and reporting odds ratio (ROR) than other LMWHs, indicating a greater likelihood of HIT. Case report analysis indicated that a total of 43 patients showed evidence of LMWH-induced thrombocytopenia with a median onset time of 8 days. Almost half of the events were caused by enoxaparin. LMWHs were mainly prescribed for the treatment of embolism and thromboprophylaxis of joint operation. Patients with a history of diabetes or surgery appeared to be more susceptible to HIT. Clinical symptoms were mostly presented as thrombus, skin lesion, and dyspnea. Almost 90% of the patients experienced a platelet reduction of more than 50% and had a Warkentin 4T score of more than 6, indicating a high likelihood of HIT. In all patients, LMWHs that were determined to be the cause were promptly withdrawn. Following the discontinuation of LMWHs, almost all patients were given alternative anticoagulants and eventually achieved recovery.Conclusion: LMWH-induced thrombocytopenia is rare but serious, with increased risk in patients with diabetes or a surgical history. Prompt recognition and management are crucial for the safe use of LMWHs.

背景：未经分离的肝素（UFH）和低分子量肝素（LMWH）是治疗动脉和静脉血栓形成的常用抗凝药物。然而，有必要注意到，在罕见情况下，LMWH可能导致一种称为肝素诱导的血小板减少症（HIT）的严重并发症。本研究旨在评估与LMWH相关的HIT的药监学特征及临床特征，并确定治疗方案和风险因素，以促进及时管理。方法：我们从美国食品药品监督管理局（FDA）的不良事件报告系统（FAERS）数据库中提取了不良事件报告数据，以进行药监学评估。收集了截至2023年3月20日的LMWH诱导的血小板减少症的案例报告，用于回顾性分析。结果：在FAERS数据库中LMWHs的不良事件（AE）数据中显示出HIT的报告率显著升高，与其它LMWHs相比，替奈肝素具有更高的比例报告比（PRR）和报告几率比（ROR），表明HIT的发生可能性更大。案例分析表明，共有43名患者表现出LMWH诱导的血小板减少症的证据，中位发病时间为8天。近一半的事件由依诺肝素引起。LMWHs主要用于治疗栓塞和关节手术的血栓预防。有糖尿病或手术史的患者似乎更容易受到HIT的影响。临床症状主要表现为血栓、皮肤病变和呼吸困难。近90%的患者血小板减少超过50%，且Warkentin 4T评分超过6，表明HIT的可能性很高。在所有患者中，确定LMWHs为病因后，均及时停用。在停用LMWHs后，几乎所有患者都接受了替代抗凝剂治疗，并最终康复。结论：LMWH诱导的血小板减少症虽属罕见，但病情严重，糖尿病或手术史的患者风险增加。及时识别和管理对于LMWHs的安全使用至关重要。