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Immune complex haemolytic anaemia associated with sulfasalazine

BMJ 2000; 320 doi: (Published 22 April 2000) Cite this as: BMJ 2000;320:1113
  1. Valery Teplitsky,
  2. Irit Virag,
  3. Aaron Halabe
  1. Department of Internal Medicine E, Hematological Institute, Wolfson Medical Center, Tel Aviv University, Israel

    A 79 year old woman was admitted because of a positive Coombs's test result for haemolytic anaemia (haemoglobin concentration 8.2 g/dl). She had been taking sulfasalazine for ulcerative colitis for five years.

    The patient's medical history included a cerebrovascular accident and atrial fibrillation, which were treated with digoxin, verapamil, aspirin, and oxazepam. On admission, aspirin, sulfasalazine, and oxazepam were discontinued, and two units of blood were given. After sulfasalazine was reintroduced, the patient showed evidence of haemolysis: her haemoglobin concentration had decreased by 2.5 g/dl, lactate dehydrogenase concentration had increased from 494 to 2620 U/l, and total bilirubin concentration had increased from 0.4 to 1.4 mg/dl. Sulfasalazine was discontinued, and all biochemical parameters returned to normal. Haematological studies were performed according to published methods.1

    The possibility of a drug dependent immune complex was assessed. Agglutination occurred when a mixture of sulfasalazine and the patient's serum was added to normal erythrocytes treated with the endopeptidase ficin. No reactivity was noted when control serum was used or when sulfasalazine was omitted. Preincubation of sulfasalazine with normal erythrocytes gave negative results on addition of the patient's serum, excluding the possibility of a penicillin-like reaction.

    Sulfasalazine causes Heinz body anaemia in patients with abnormal haemoglobin and haemolysis in patients deficient in glucose-6-phosphate dehydrogenase. Our patient had a normal concentration of glucose-6-phosphate dehydrogenase, and no Heinz bodies were seen on a blood smear. A few patients with ulcerative colitis treated with sulfasalazine and who have immune haemolytic anaemia have been described, but in none was sulfasalazine clearly implicated.24 The manufacturer (Pharmacia Upjohn) could provide no additional information about this side effect. Our report is important as 1.7% of patients with ulcerative colitis develop immune haemolytic anaemia even in the absence of treatment with sulfasalazine.5


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