Bosco Michael, Kish Troy
James J. Peters VA Medical Center, Bronx, NY, USA.
Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA.
J Pharm Technol. 2019 Feb;35(1):36-40. doi: 10.1177/8755122518803363. Epub 2018 Sep 28.
To report a case of heparin-induced hepatotoxicity in a patient without prior liver dysfunction who received prophylactic doses of unfractionated heparin (UFH). A 70-year-old man with no prior liver dysfunction was admitted to the hospital for presyncope, secondary to dehydration, and new-onset congestive heart failure. Prophylactic UFH was initiated for deep vein thrombosis prophylaxis. Within 2 days, he developed increases in aspartate aminotransferase and alanine aminotransferase. By day 4, aspartate aminotransferase and alanine aminotransferase were greater than 5 and 9 times the upper limit of normal, respectively. Alkaline phosphatase and bilirubin were markedly elevated as well. UFH was discontinued on day 4, and liver enzymes subsequently normalized. Hepatotoxicity, defined as increases in transaminases greater than 3 times the upper limit of normal, is relatively rare-estimated to occur in only 5% of those receiving therapy with UFH. Concurrent elevations in bilirubin have rarely been reported. Enzymes typically begin to rise after 4 to 5 days of UFH use and return to normal within 2 weeks of discontinuation. Previously published case reports of heparin-induced hepatotoxicity have occurred with therapeutic doses of either UFH or low-molecular-weight heparins. Heparin-induced hepatotoxicity may occur more rapidly than previously described, and even with the use of prophylactic doses of UFH. Given their widespread use, it is important for clinicians to consider heparins in their differential as a potential cause of hepatotoxicity especially in patients without underlying hepatic disease.
报告一例在接受普通肝素(UFH)预防剂量治疗且既往无肝功能障碍的患者中发生肝素诱导的肝毒性的病例。一名70岁男性,既往无肝功能障碍,因晕厥前状态(继发于脱水)及新发充血性心力衰竭入院。开始使用UFH进行深静脉血栓形成的预防。在2天内,他的天冬氨酸转氨酶和丙氨酸转氨酶升高。到第4天,天冬氨酸转氨酶和丙氨酸转氨酶分别高于正常上限的5倍和9倍。碱性磷酸酶和胆红素也显著升高。在第4天停用UFH,随后肝酶恢复正常。肝毒性定义为转氨酶升高超过正常上限的3倍,相对罕见,估计仅在接受UFH治疗的患者中5%会发生。同时出现胆红素升高的情况很少有报道。酶通常在使用UFH 4至5天后开始升高,并在停药后2周内恢复正常。先前发表的肝素诱导肝毒性的病例报告发生在UFH或低分子量肝素的治疗剂量使用时。肝素诱导的肝毒性可能比先前描述的发生得更快,甚至在使用UFH预防剂量时也会发生。鉴于肝素的广泛使用,临床医生在鉴别诊断时将肝素视为肝毒性的潜在原因很重要,尤其是在无潜在肝脏疾病的患者中。