Sulfasalazine

Valery Teplitsky, Irit Virag, Aaron Halabe, 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 :he 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.[2-4] 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]

[1] Petz LD, Branch DR. Drug-induced immune hemolytic anemia. In: Chaplin H, ed. Methods in hematology: immune hemolytic anemia. New York: Churchill Livingstone, 1985:47-94.

[2] Mechanick JI. Coomb's positive hemolytic anemia following sulfasalazine therapy in ulcerative colitis. Mt Sinai J Med 1985;52:667-70.

[3] Bell DW, Urban E, Sears DA, Walder AI, Ostrower VS. Ulcerative colitis complicated by autoimmune hemolytic anemia. South Med J 1981;74:359-61.

[4] Balint JA, Hammack WJ, Patton TB. Association of ulcerative colitis and red blood cells coated with autoimmune antibody. Am J Dig Dis 1963;8:537-44.

[5] Giannadaki E, Potamianos S, Roussomoustakaki M, Kyriakou D, Fragkiadakis N, Manousos ON. Autoimmune hemolytic anemia and positive Coomb's test associated with ulcerative colitis. Am J Gastroenterol 1997;92:1872-4.

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