低分子肝素诱发肝损伤：个案报道并文献统计分析

Low Molecular Weight Heparin as Cause of Liver Injury: Case Report and Literature Review

关键词:  低分子肝素  肝损伤  不良反应

Key words:  low molecular weight heparin  liver injury  adverse reactions

摘要:

目的 探讨低分子肝素诱发的肝脏系统不良反应。方法 报告1例低分子肝素致患者肝损伤的不良反应，检索国内外相关文献，汇总后进行文献统计分析。结果 共检索到相关文献15篇，提取病例23例。其中男性12例，女性11例，患者年龄为26~75岁(平均年龄54岁)。原发病主要为肺栓塞和深静脉血栓(肺栓塞多于深静脉血栓)。诱发的肝脏系统不良反应主要有肝细胞损伤型(7例)、混合型(7例)、胆汁淤积型(1例)、未知(9例)。从开始接受低分子肝素治疗到诱发肝脏系统不良反应的时间为1~33 d (平均6 d)。出现不良反应后10例停药，11例停药并予对症治疗，2例无任何处理。不良反应结果中除1例患者结果未知以外，其余22例患者停用低分子肝素后，肝功能均好转，有11例患者康复，1例患者康复时间未知，其余10例患者的平均康复时间为66.5 d。结论 低分子肝素相关的肝损伤是不常见和可逆的，康复时间长，建议关注低分子肝素对肝脏的不良反应，在使用低分子肝素期间定期监测肝功能相关指标，以便及时发现、诊断和治疗药物性肝损伤，保障患者用药安全。

Abstract:

OBJECTIVE To explore the adverse reactions of liver system induced by low molecular weight heparin(LMWH). METHODS One case of liver injury induced by LMWH was reported. Relevant literatures at home and abroad were retrieved and analyzed statistically. RESULTS A total of 15 related reports were retrieved and 23 cases were identified in the study. There were 12 males and 11 females patients with the age ranged from 26 to 75 years(mean age 54 years). The primary diseases were pulmonary embolism and deep vein thrombosis (pulmonary embolism was more than deep vein thrombosis). The adverse reactions induced by the liver system were mainly hepatocellular injury type(n=7), mixed pattern of injury(n=7), cholestatic injury(n=1) and unknown(n=9). The average duration from an initiation of LMWH treatment to an induction of adverse reactions of liver dysfunction was 1 to 33 d(mean 6 d). LMWH was then discontinued for 10 cases, 11 cases were stopped and given symptomatic treatment, and 2 patients did not receive any treatment. Among the adverse reaction results, except for one patient whose outcome was unknown, the liver function of the remaining 22 patients improved after the discontinuation of LMWH, 11 patients were recovered, and the recovery time of one patient was unknown. The average recovery time of the remaining 10 patients was 66.5 d. CONCLUSION LMWH related liver injury is not common and reversible, and the recovery time of liver injury is long. While prescribing LMWH, clinicians and pharmacists should pay close attention to adverse reactions of liver and regularly monitor the changes of liver function parameters, in order to timely detection, diagnosis and treatment of drug-induced liver injury, to ensure the safety of patients with medication.