Pentamidine-Induced Hemolytic Anemia in an AIDS Patient
Pentamidine-Induced Hemolytic Anemia in an AIDS Patient
复制标题
艾滋病患者喷他脒诱发的溶血性贫血
DOI：
10.1345/aph.18253
复制
发表时间：
1999
影响因子：
--
通讯作者：
A. Iwamoto
中科院分区：
文献类型：
--
作者：
H. Taguchi;T. Takahashi;Y. Wada;T. Nakamura;A. Iwamoto
致编辑：卡氏肺孢子虫肺炎（PCP）是艾滋病患者最常见的机会性肺部感染。注射用喷他脒经常被用作PCP的治疗选择。1迄今为止，已报告的静脉注射喷他脒的主要不良反应为肾脏和胰腺毒性。我们报告一例溶血性贫血引起的肠外喷他脒的病人谁随后发展血红蛋白尿。病例报告。一名55岁的日本男子因结核性胸膜炎和颈部淋巴结炎入院。他是艾滋病毒血清阳性，有同性恋活动的风险因素。采用逆转录-聚合酶链反应（Amplicor检测试剂盒），CD 4+细胞计数为98 × 103/mm 3，血浆HIV-1 RNA浓度为820 000拷贝/mL（下限400拷贝/mL）。给予异烟肼、利福平、吡嗪酰胺、乙胺丁醇四联抗结核治疗8周。然后，三种抗逆转录病毒药物，齐多夫定，拉米夫定，奈非那韦，开始与异烟肼和乙胺丁醇。开始使用甲氧苄啶/磺胺甲恶唑（TMP/SMX）作为PCP的一级预防;发生过敏性皮肤反应伴发热，因此停用TMP/SMX，并开始使用喷他脒4 mg/kg/mo iv。患者在3个月后出现PCP，开始使用喷他脒3 mg/kg/d iv和皮质类固醇，同时停用抗逆转录病毒药物。PCP改善，每日喷他脒治疗3周后，患者转为静脉注射喷他脒4 mg/kg，每2周一次，作为PCP的二级预防;继续使用异烟肼和乙胺丁醇。二级预防（喷他脒总剂量3740 mg）首次给药后2天出现发热和躯干红斑。除预防性喷他脒外，停用所有药物。三天后，突然出现贫血（血红蛋白<7 g/dL）和嗜酸性粒细胞增多症（>500/mm 3）以及发热和皮疹。实验室检查结果显示乳酸脱氢酶升高（>2000 IU/L）、触珠蛋白降低（11.2 mg/dL;正常55-324 mg/dL）和血小板减少症（<105/mm 3）。直接Coombs试验阳性，无葡萄糖-6-磷酸脱氢酶缺陷，聚合酶链反应未检出人细小病毒B19和人疱疹病毒6型DNA。为了确定胃肠外喷他脒是否引起这些不良反应，我们在获得知情同意后，以10 mg（第1天）和50 mg（第2天）的低剂量静脉注射喷他脒进行再激发。我们得出结论，这些条件是由喷他脒引起的，因为血红蛋白尿和眼黄疸在药物再激发的第二天给予喷他脒50 mg后出现发热和新发皮疹。这些症状在我们停用喷他脒几天后得到改善。停用喷他脒后14天，直接Coombs试验也变为阴性。讨论药物性溶血性贫血分为免疫性和非免疫性两类，葡萄糖-6磷酸脱氢酶缺乏引起的溶血就是非免疫性的一个例子。继发于药物的免疫溶血性贫血有两种不同的作用机制。药物诱导的疾病几乎与温抗体免疫溶血性贫血相同，或者它们可以与红细胞的表面糖蛋白结合，并产生针对红细胞-药物复合物的抗体。在后者中，除非将药物加入孵育混合物中，否则间接Coombs试验不呈阳性。2我们发现，即使将喷他脒加入反应混合物中，该患者的抗体在间接Coombs试验中也未检出。HIV检测呈阳性的患者往往会出现药物过敏。艾滋病与多种血液学异常有关。3 TMP/SMX和氨苯砜4已被列为HIV感染患者药物诱导的溶血性贫血的病原体。最近有报道称，在接受蛋白酶抑制剂茚地那韦治疗的艾滋病患者中发生了致命的急性溶血。5据我们所知，这是首次报道静脉注射喷他脒引起的溶血性贫血。我们认为，当艾滋病患者发生突发性贫血时，喷他脒应被认为是导致溶血的致病药物之一。
TO THE EDITOR: Pneumocystis carinii pneumonia (PCP) is the most frequent opportunistic pulmonary infection occurring in patients with AIDS. Parenteral pentamidine has frequently been used as a treatment option for PCP.1 Major adverse effects of intravenously administered pentamidine reported thus far are renal and pancreatic toxicities. We report a case of hemolytic anemia induced by parenteral pentamidine in a patient who subsequently developed hemoglobinuria. Case Report. A 55-year-old Japanese man was admitted to the hospital with tuberculous pleuritis and cervical lymphadenitis. He was HIV-seropositive, with a risk factor of homosexual activity. CD4+ cell count was 98 × 103/mm3, and plasma HIV-1 RNA concentration was 820 000 copies/mL (lower limit 400 copies/mL) using reverse transcription-polymerase chain reaction (Amplicor examination kit). He was given antituberculosis therapy of the four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol for eight weeks. Then three antiretroviral agents, zidovudine, lamivudine, and nelfinavir, were started with isoniazid and ethambutol. Trimethoprim/sulfamethoxazole (TMP/SMX) was started for primary prophylaxis of PCP; allergic skin reactions with fever developed, so TMP/SMX was discontinued and pentamidine 4 mg/kg/mo iv was initiated. He developed PCP three months later and pentamidine 3 mg/kg/d iv with corticosteroids was started, while the antiretroviral drugs were stopped. The PCP improved and after three weeks of daily pentamidine therapy the patient was switched to intravenous pentamidine 4 mg/kg every two weeks as secondary prophylaxis of PCP; isoniazid and ethambutol were continued. Fever and trunkal erythema developed two days after the first administration of secondary prophylaxis (total doses of pentamidine 3740 mg). All drugs except prophylactic pentamidine were stopped. Three days later, sudden anemia (hemoglobin <7 g/dL) and eosinophilia (>500/mm3) together with fever and skin eruptions developed. Laboratory findings indicated increased lactate dehydrogenase (>2000 IU/L), decreased haptoglobin (11.2 mg/dL; normal 55–324 mg/dL), and thrombocytopenia (<105/mm3). Direct Coombs’ test was positive, and no deficiency of glucose-6-phosphate dehydrogenase was found. The DNA of human parvovirus B19 and human herpesvirus 6 was not detected in his serum by polymerase chain reaction. To determine whether parenteral pentamidine caused these adverse effects, we rechallenged with intravenous pentamidine at low doses of 10 mg (day 1) and 50 mg (day 2), after receiving informed consent. We concluded that these conditions were induced by pentamidine because hemoglobinuria and ocular icterus developed with fever and new skin eruptions after pentamidine 50 mg was administered on the second day of drug rechallenge. These manifestations improved several days later after we discontinued the pentamidine. Direct Coombs’ test also became negative 14 days after parenteral pentamidine was stopped. Discussion. Drug-induced hemolytic anemia is classified as immune and nonimmune; an example of nonimmune is hemolysis in glucose-6phosphate dehydrogenase deficiency. Immunohemolytic anemia secondary to drugs is distinguished by two kinds of mechanisms of action. Drugs induce a disorder almost identical to warm-antibody immune hemolytic anemia, or they can become associated with surface glycoprotein of red blood cells and produce the formation of an antibody directed against the red blood cells–drug complex. In the latter, indirect Coombs’ test is not positive unless the drug is added to the incubation mixture.2 We found that the antibody of this patient was not detected in the indirect Coombs’ test even when pentamidine was added to the reaction mixture. Patients who test positive for HIV tend to develop drug allergies. AIDS is related to a variety of hematologic abnormalities.3 TMP/SMX and dapsone4 have been listed as causative agents for drug-induced hemolytic anemia in HIV-infected patients. It has recently been described that fatal acute hemolysis occurred in a patient with AIDS treated with a protease inhibitor, indinavir.5 To our knowledge, this is the first report of hemolytic anemia induced by intravenous pentamidine. We believe that pentamidine should be considered as one of the causative drugs leading to hemolysis when patients with AIDS develop sudden anemia.
影响因子：
158.5
作者：
WARRELL, RP;FRANKEL, SR;DMITROVSKY, E
通讯作者：
DMITROVSKY, E