Transient appearance of GPI-deficient population in a patient with azathioprine-associated bone marrow aplasia

Abstract

Dear Editor, Blood cells with glycosylphosphatidylinositol (GPI) deficiency are occasionally seen in bone marrow failure syndromes such as aplastic anemia [1–5]; they tend to persist for long time and may or may not be associated with clinical or laboratory evidence of hemolysis or other manifestations of paroxysmal nocturnal hemoglobinuria (PNH). We describe the first case of transient appearance of GPIdeficient population in a patient during azathioprineinduced marrow aplasia. The size of GPI-deficient population was large (67 %), but disappeared upon the marrow regeneration following discontinuation of the drug. An 8-year-old boy with active Crohn’s disease presented with fever and neutropenia. There was no discoloration of urine and there were no signs of clinically relevant intravascular hemolysis. His presentation followed a 3-month exposure to increasing doses of azathioprine from 12.5 to 50 mg/day with monitoring of blood counts, transaminase levels, and serum 6-thioguanine nucleotide metabolite (TGN) level. Laboratory investigations showed (Table 1) a total leukocyte count of 0.8×10/L, neutrophils of 0.43×10/L, hemoglobin of 88 g/L, platelet count of 131×10/L, and reticulocyte count of 3×10/L. The blood film did not show any blasts or features of dysplasia, megaloblastic state, or hemolysis. Serum LDH, cobalamin, and RBC folate levels were normal. Blood, urine, and stool cultures and serologic tests for hepatitis A, B, C, HIV, CMV, Parvovirus B19, and EBVwere negative. A repeat TGN level on azathioprine 50 mg daily was 327 pmole/8×10. Red blood cell level of 6-methyl mercaptopurine ribonucleotide metabolite was 807 pmole/8×10 RBC. A bone marrow aspirate and biopsy showed aplasia with cellularity of 5 %. Sugar water test was positive. Flow cytometric testing of blood for PNH at admission and a week later showed partial absence of CD55, 59, and fluorescent aerolysin (FLAER) on granulocytes, and of CD59 on RBCs. The size of the GPI-deficient clone was 67% by FLAER analysis of neutrophils (Fig. 1). The child was rehydrated and given antimicrobials and steroids. Azathioprine was discontinued. His clinical condition and blood counts recovered within 3 weeks. Repeat flow cytometric testing for PNH at 6 months showed complete disappearance of the GPIdeficient population. The patient was subsequently managed for Crohn’s disease with methotrexate, followed by infliximab and then adalimumab. He eventually underwent subtotal colectomy and end ileostomy and has remained well since then. Transient bone marrow aplasia caused by azathioprine exposure in patients with 6-thiopurine methyl transferase deficiency has been reported [6]; our patient showed partial deficiency of 6A. Z. Al Riyami : B. I. Dalal (*) Division of Laboratory Hematology, Vancouver General Hospital, Suite JPPN 1557, 910, 10th Avenue West, Vancouver BC V5Z 4E3, Canada e-mail: bakul.dalal@vch.ca