1例培门冬酶致急性胰腺炎病例的分析鉴别及文献复习

Analysis and identification of a case of pegaspargase-induced acute pancreatitis and literature review

目的 了解门冬酰胺酶相关胰腺炎(AAP)不良反应的临床特点,为临床安全用药提供参考。方法 针对我院1例急性淋巴细胞白血病患者使用培门冬酶后出现急性胰腺炎伴发糖尿病酮症酸中毒、肝损伤的严重不良反应病例进行分析鉴别。检索万方数据、中国知网、PubMed、Embase数据库中关于AAP的个案报道,将所有病例的人口学信息和药物使用、潜伏期、不良反应结局等信息进行汇总。结合本例患者信息,分析、讨论AAP的疾病特点及潜在危险因素。结果 经分析鉴别,判定本例患者出现AAP。在数据库中共检索到病例报道类文献47篇,共52例患者(包括本例患者)纳入分析,其中男性29例、女性23例,以未成年患者为主(65.4%)。左旋门冬酰胺酶是导致AAP的主要门冬酰胺酶制剂(80.8%),消化道症状为主要前驱症状(92.3%),可伴发其他门冬酰胺酶相关不良反应。AAP可发生在第1~33次给药之后,中位潜伏期为用药后14 d;成人患者AAP中位潜伏期较儿童明显缩短(11 d vs. 16 d,P=0.049),使用培门冬酶患者AAP中位潜伏期较左旋门冬酰胺酶有延长趋势(17 d vs. 12.5 d,P=0.490)。纳入分析的病例中,有8例患者因AAP死亡,其中1例与门冬酰胺酶制剂再暴露有关。结论 AAP是门冬酰胺酶制剂严重的、可致命的不良反应,临床医务人员应重视AAP的发生特点,如患者出现消化道症状等应考虑AAP发生的可能,做好患者教育和药学监护,以尽量降低AAP对患者造成的损害。

OBJECTIVE To investigate the clinical characteristics of adverse drug reactions of asparaginase-associated pancreatitis(AAP),so as to provide reference for clinical safe medication. METHODS Analysis and identification were performed on a severe adverse reaction case of acute pancreatitis complicated with diabetic ketoacidosis and liver injury in a patient with acute lymphoblastic leukemia in our hospital after using pegaspargase. Retrieved from Wanfang database,CNKI,PubMed and Embase database,case reports of AAP were collected and summarized in terms of patient demographics,drug use,incubation period and adverse reaction outcome. Combined with this case,the disease characteristics and potential risk factors of AAP were analyzed and discussed. RESULTS After analysis and identification,it was determined that AAP occurred in this patient. A total of 47 case reports were retrieved from the database,and a total of 52 patients(including this patient)were included in the analysis,including29 males and 23 females,mainly minors(65.4%). L-asparaginase was the main asparaginase preparation that causes AAP(80.8%).Gastrointestinal symptoms were the main prodromal symptoms(92.3%),which could be accompanied by other asparaginase related adverse reactions. AAP could occur after 1-33 times of administration, and the median latency was 14 days after administration;compared with children,median latency of AAP in adult patients was shortened significantly(11 d vs. 16 d,P=0.049);the median latency of AAP had longer tendency in patients treated with pegaspargase than that of L-asparaginase(17 d vs.12.5 d,P=0.490). Of the cases included in the analysis,8 patients died due to AAP,1 of which was related to re-exposure to asparaginase preparations. CONCLUSIONS Acute pancreatitis is a serious and potentially fatal adverse drug reaction of asparaginase preparations. Clinical medical staff should pay attention to the characteristics of AAP,consider the possibility of AAP when the patients have gastrointestinal symptoms and do a good job in patient education and pharmaceutical care to minimize the damage caused by AAP to patients.