Raru Yonas, Abouzid Mahmoud, Parsons Julia, Zeid Fuad
Internal Medicine Resident, Marshall University School of Medicine, Huntington, WV, USA.
Pulmonary and Critical Care Medicine, Marshall University School of Medicine, Huntington, WV, USA.
Respir Med Case Rep. 2018 Dec 23;26:142-145. doi: 10.1016/j.rmcr.2018.12.011. eCollection 2019.
Rasburicase is a recombinant urate-oxidase enzyme and is a very important medication for tumor lysis syndrome. Methemoglobinemia and hemolysis are known side effects of rasburicase that result from oxidative stress caused by hydrogen peroxide, a byproduct generated during the breakdown of uric acid to allantoin. Patients with G6PD deficiency have a decreased tolerance to oxidative stress and are therefore at a greater risk of hemolysis and methemoglobinemia with rasburicase. Our patient is a 56-year-old Caucasian male with a recent diagnosis of grade 2-3a non-Hodgkin's lymphoma who presented to our emergency department with shortness of breath and dark discoloration of urine. Patient was discharged 36 hours ago from our hospital after he was given a first course of R-CHOP regimen and a dose of rasburicase. On further evaluation, patient was found to have severe anemia with hemolytic picture, hyperkalemia and acute kidney injury. He also had a discrepancy of the transcutaneous saturation (75%) and the saturation in an arterial blood gas value (99%). His methemoglobin level was found to be 11.9%. We were aware that methylene blue is a contraindication in patients with G6PD deficiency but considering patient being Caucasian and low risk for it and his deteriorating respiratory condition, it was decided to offer the treatment and patient received 1 dose of methylene blue which failed to improve his methemoglobinemia. He was also given vitamin C and 8 units of packed red blood cell throughout his stay in the hospital. Patient's hospital course was complicated by ARDS needed to be on mechanical ventilation support for 4 days and acute renal failure secondary to pigment nephropathy and acute tubular necrosis which required a hemodialysis support. Even if rasburicase induced methemoglobinemia and hemolysis are not very common complications, clinicians who prescribe and follow patients should detect this serious complication early and manage it accordingly. Our case can be used as a reminder that patients should be followed closely and given the right instructions on discharge to treat these complications which are associated with severe consequences. It is also vital to assume a diagnosis of G6PD deficiency until proven otherwise in a patient who presents with rasburicase induced hemolysis and avoid administration of methylene blue even if the patient is from a low risk ethnicity for G6PD as in our patient.
拉布立酶是一种重组尿酸氧化酶，是治疗肿瘤溶解综合征的一种非常重要的药物。高铁血红蛋白血症和溶血是拉布立酶已知的副作用，这是由尿酸分解为尿囊素过程中产生的副产物过氧化氢引起的氧化应激导致的。葡萄糖-6-磷酸脱氢酶（G6PD）缺乏的患者对氧化应激的耐受性降低，因此使用拉布立酶时发生溶血和高铁血红蛋白血症的风险更高。我们的患者是一名56岁的白种男性，最近被诊断为2-3a级非霍奇金淋巴瘤，因呼吸急促和尿液颜色变深前来我院急诊科就诊。患者在接受第一个疗程的R-CHOP方案和一剂拉布立酶治疗后，于36小时前从我院出院。进一步评估发现，患者有严重贫血伴溶血表现、高钾血症和急性肾损伤。他还存在经皮血氧饱和度（75%）与动脉血气值中的饱和度（99%）不一致的情况。其高铁血红蛋白水平为11.9%。我们知道亚甲蓝是G6PD缺乏患者的禁忌药物，但考虑到患者为白种人且发生G6PD缺乏的风险较低，以及其呼吸状况不断恶化，决定给予治疗，患者接受了1剂亚甲蓝，但未能改善其高铁血红蛋白血症。在住院期间，他还接受了维生素C和8单位的浓缩红细胞。患者的住院过程因急性呼吸窘迫综合征（ARDS）而复杂化，需要机械通气支持4天，以及因色素肾病和急性肾小管坏死继发急性肾衰竭，需要血液透析支持。即使拉布立酶引起的高铁血红蛋白血症和溶血并非非常常见的并发症，开具处方并跟踪患者的临床医生也应尽早发现这种严重并发症并进行相应处理。我们的病例可以作为一个提醒，即应密切跟踪患者，并在出院时给予正确的指导，以治疗这些会带来严重后果的并发症。对于出现拉布立酶诱导溶血的患者，在未证实其并非G6PD缺乏之前，假定其为G6PD缺乏并避免使用亚甲蓝也至关重要，即使患者来自G6PD缺乏低风险种族，就像我们的患者一样。
