疑似 Diclofenac 誘發的溶血性貧血 馬偕紀念醫院淡水分院藥劑科藥師溫學琴 汪曉嵐 吳美慧 賴慧如 摘要 oxaliplatin α-methyldopa diclofenac Diclofenac diclofenac diclofenac (warmreactive autoantibodies) diclofenac 壹 前言 貳 案例報告 33 2010 3 2 diclofenac potassium (25 mg/tab) 1# TID Hb 10.6 g/dl Ht 30.5 % 2012 8 7-9 14-22 mefanemic acid (500 mg/tab) 1# QID 8 31 9 2 GOT 80 IU/L BUN/Cr 18/0.7 mg/dl Hb/Ht 8.8 g/dl/25.1% ( ) 8 diclofenac strocain (oxethazaine 5 mg, polymigel 244 mg) 1# Q6H B C 9 4 GOT 104 IU/L BUN/Cr 32/1.4 mg/dl Hb/Ht 5.4 g/ dl/15.7 % Hb/Ht 20 Hb 10.1 mg/dl Ht 29.3 % 9 4 6 10 13 9 24 96 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.3 Sep. 30 2013
Diclofenac NSAID-diclofenac 表一患者藥歷 / cefoxitin (1 g) 2 vial Q8H metronidazole (250 mg) 1# TID Ergonovine (0.2 mg) 1# QID mefenamic acid (500 mg) 1# QID magnesium oxide (250 mg) 2# TID iron sucrose complex (100 mg) 2 vial QD folic acid (5 mg) 1# QD Sennoside (20 mg) 1# QHS Cefuroxime (250 mg) 2# BID diclofenac potassium (25 mg) 1# QID PRN strocain 1# QID PRN Ertapenem (1 g) 1 vial QD Famotidine (20 mg) 1# BID acetaminophen (500 mg) 1# Q6H PRN 8/7-9 8/15 8/16 8/17 8/18-21 8/22-29 9/2-9/8 ER 9/2-4 3 9/2-4 3 1# stat 1V stat 9/3 9/4 9/5-6 2V stat 表二檢驗數據記錄 / 8/06 9/02 9/04 9/06 9/10 9/13 9/24 GOT (15-41 IU/L) 80 104 56 51 46 9/04 GPT (14-40 IU/L) 24 22 25 31 Bilirubin D. (0.1-0.5 mg/dl) 0.3 0.2 Bilirubin T. (0.3-1.2 mg/dl) 1.0 0.7 1.2 Alk-Phosphatase (38-126 IU/L) 90 13 LDH (98-192 IU/L) 1120 BUN (8-20 mg/dl) 18 32 12 13 Creatinine (0.4-1.2 mg/dl) 0.7 1.4 1.1 1.0 0.9 CRP (< 0.8 mg/dl) 3.19 WBC (4-10 10 3 ul) 10.6 4.50 3.30 3.70 4.30 6.10 Band (0-6%) 0.0 0.0 0.0 1.0 0.0 68.9 Neut. (55-75%) 77 59.0 58.0 51.0 48.0 Eosinophil (0-5%) 0.0 0.0 1.0 1.0 1.0 1.1 Basophil (0-1%) 0.0 0.0 0.0 0.0 0.0 0.9 Monocyte (0-10%) 3.0 19.0 15.0 11.0 16.0 6.4 Lymphocyte (20-40%) 20.0 22.0 26.0 33.0 35.0 22.7 Platelet (140-450 10 3 ul) 208 134 149 213 172 RBC (3.90-5.00 10 6 ul) 3.83 1.57 1.62 1.81 2.79 Hb (11-16) (13-18 g/dl) 10.2 8.8 5.4 5.6 6.7 7.3 10.1 Anti-IgG: negative Anti-C3d: positive 1+ 9/06 Stool OB ( ): Negative RBC Morphology Spherocytosis & Anisocytosis 9/07 urine hemosiderin negative 9/08 Heptoglobin < 10 mg/dl (30-178 mg/dl) 29 3 Sep. 30 2013 藥學雜誌第 116 冊 97
/ 8/06 9/02 9/04 9/06 9/10 9/13 9/24 Ht (40-54%) 31.1 25.1 15.7 16.7 19.4 21.6 29.3 MCV (80-98 fl) 81.3 99.8 102.0 107.2 105.1 MCHC (32.0-36.0 g/dl) 35.0 Reticulocyte (5-15/1000 RBC) 123 37.5 Serum iron (50-175 ug/dl) 110 TIBC (255-400 ug/dl) 232 參 藥物誘發免疫溶血的分類與機轉 3 一 第一類藥物誘發自體抗體 (autoantibodies;aab) Rh Rh (direct antiglobulin test or direct coombs' test) anti-igg anti-c3 1 (idiopathic form) 2 α methyldopa L-dopa procainamide mefanemic acid 3 3-4 ( ) 1 二 第二類藥物成為抗原的一部分參與抗原抗體反應 ( 一 )Penicillin 型 ( n o n - complement-activating drug-dependent antibodies; ddab) IgG IgG 3 penicillin penicillin ( > 2 /day) 3 anti-igg anti-c3 (indirect antiglobulin test or indirect coombs' test) penicillin IgG penicillin 3 2 ( 二 ) 免疫複合型 (complementactivating drug-dependent antibodies) (immunogenic conjugated) 3 98 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.3 Sep. 30 2013
Diclofenac 1 anti-igg anti-c3 1 6 (continous or intermittent therapy) 4 Diclofenac diclofenac diclofenac IgG ( ) IgM Diclofenac ( ) 5 Diclofenac-induce hemolysis 5 (indirect bilirubin) (hemoglobinemia) (hemoglobinuria) (reticulocyte) (haptoglobin) (spherocytes) (nucleated red blood cells) 肆 案例討論 (anisocytosis) (spherocytosis) (LDH) 9 4 anti-igg negative anti C3d postive Diclofenac diclofenac 2 9 7 hemosiderin negative diclofenac 9 13 Naranjo score 4 ( ) diclofenac (25 mg/tab) 表三 Diclofenac 藥物不良反應評估單 (Naranjo score) 1 +1 0 0 +1 2 +2-1 0 +2 3 +1 0 0 +1 4 +2-1 0 0 5 ( ) -1 +2 0-1 6-1 +2 0 0 7 +1 0 0 0 8 +1 0 0 0 9 +1 0 0 0 10 +1 0 0 +1 9 ( ) 5-8 1-4 0 ( ) 4 5. 1 29 3 Sep. 30 2013 藥學雜誌第 116 冊 99
伍 結論 Diclofenac IgG (indirect bilirubin) 5 參考資料 : 1. Wendell F Rosse, Stanley L Schrier: Pathogenesis of autoimmune hemolytic anemia: Warm agglutinins and drugs. UpToDate online. Available at http://www.uptodate. com (cited: 22/11/2012). 2. Abdulgabar Salama Drug-induced immune hemolytic anemia Expert Opin Drug Saf. 2009 Jan; 8(1): 73-9. 3. Samuel I. Raoaoirt /, 2002. 4. J. S. Jürgensen, A. Seltsam, A. Jörres: Fatal acute diclofenac-induced immune hemolytic anemia Ann Hematol (2001) 80: 440-442. 5. Norbert Ahrens, Ramona Genth, Holger Kiesewetter, et al: Misdiagnosis in patients with diclofenac-induced hemolysis: New cases and a concise review. Am J Hematol. 2006 Feb; 81(2): 128-31. Suspected Diclofenac-Induced Hemolytic Anemia Hsueh-Chin Wen, Hsiao-Lan Wang, Mei-Hui Wu, Hui-Ru Lai Department of Pharmacy, Mackay Mermorial Hospital Tamsui Branch Abstract Drug-induced immune hemolytic anemia is a rare but a serious adverse reaction. Antibiotics, nonsteroidal anti-inflammatory drug, oxaliplatin, alpha-methyldopa etc are the drugs that most frequently cause immune hemolytic anemia. The case of a 33-year-old woman who developed Hb/Ht dropping sharply after treated with diclofenac (25 mg) prn used for fever. Diclofenac was discontinued and the patient was treated with ferrous and folic acid. She was discharged in good prognosis. Diclofenac induced immune hemolytic anemia in severe case may cause acute renal failure, disseminated intravascular coagulation, shock and even be fatal. Diclofenac is a widely used nonsteroidal anti-inflammatory drug. Nevertheless, it cause hemolytic syndrome very similar to autoimmune hemolytic anemia of warm type. In this review, the pathogenic mechanisms and types of drug induced immune hemolytic anemia for reminding the medical staff to be careful to the adverse drug reactions. 100 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.3 Sep. 30 2013