Amegakaryocytic thrombocytopenia is a rare complication of systemic lupus erythematosus (SLE). Consequently, evidence for its treatment is limited to case reports.1–3 Here we report successful use of azathioprine in this setting.

A 48-year-old woman presented with polyarthralgia involving bilateral small and large joints, low-grade fever, and easy fatigability of eight years duration. She had Raynaud phenomenon but no skin rashes, oral ulcers, sicca symptoms or photosensitivity. The examination was unremarkable except for minor pedal edema.

For last two months, her creatinine had been elevated (3.3mg/dL). She had bland sub-nephrotic proteinuria and bilateral shrunken kidneys on sonography. She had been having intermittent thrombocytopenia in the past. Platelet count was 80,000/mm3 at her first presentation. She had never been worked up for lupus before, given the mild and intermittent nature of her arthralgia, and non-specific symptoms. Anti-nuclear antibody was positive by immunofluorescence in a speckled pattern. Anti-double-stranded DNA antibody was more than 300IU/mL, complement levels were normal and Direct Coombs test was negative. She was initiated on 0.25mg/kg prednisone and hydroxychloroquine with a diagnosis of systemic lupus erythematosus. She came back a week later with high-grade fever. This time she had thrombocytopenia of (10,000/mm3) and lymphopenia (300/mm3). The diagnostic possibilities considered were lupus disease activity, Macrophage Activation Syndrome (MAS) and viral fever. Serology for Dengue and Epstein–Barr virus were negative, as was polymerase chain reaction for Cytomegalovirus. Hemoglobin of 11.6g/dL, normal aspartate transaminase (16IU/L), alanine transaminase (21IU/L), and coagulation parameters made MAS unlikely. A bone marrow biopsy revealed reduced megakaryocytes with preserved erythroid and myeloid precursors, and plasma cell infiltrate in the interstitium. It ruled out myelophthisis from infiltrative disorders such as myelofibrosis, infections and neoplasia. She was not on any drug that could cause thrombocytopenia, nor had any evidence of exposure to toxins. Thus, with a background of lupus, she was diagnosed as having immune-mediated amegakaryocytic thrombocytopenia. Initially, she was administered intravenous methylprednisolone at a dose of 1g daily for three days and then, intravenous immunoglobulin at a dose of 1g/kg daily for two days. The platelet count rose to 80,000/mm3 over the next seven days, but the rise was ill sustained, necessitating the addition of another immunosuppressant. The literature on therapeutic options in this setting is limited to occasional reports of Cyclosporine, Rituximab, and Eltrombopag. Due to the presence of end-stage renal disease as well as cost considerations, azathioprine (AZA) was considered. The dose was gradually escalated from 25mg/day to 125mg/day. Platelet counts stabilized at >100,00/mm3 by two months. The patient has done well over 3 years after initiating AZA, without further thrombocytopenia or new organ involvement related to lupus.

It has been long believed that bone marrow aplasia in lupus is an exception rather than the rule.4 Recent series have described aplasia in 10–50% of biopsies from lupus patients, suggesting it may be more common than previously thought.5,6 In amegakaryocytic thrombocytopenia, the pathogenesis is believed to be immune-mediated. Antibodies to the thrombopoietin receptor (c-Mpl) can block signaling on megakaryocytes, thereby halting maturation of platelets in the bone marrow.7,8 T-cells in lupus have inhibitory effects on Colony forming unit-Monocyte (CFU-M).9 Change in T helper to suppressor cell ratio was one of the earliest cited reasons for impaired megakaryopoiesis.4 The infiltration of plasma cells in the bone marrow in our patient is surrogate for immune-mediated pathogenesis, though we haven’t substantiated this by the antibody or in vitro T cell assays.

Since there is evidence of a role of both cell-mediated and humoral factors in the pathogenesis of this entity in lupus, azathioprine may be a good choice when other therapies fail or cannot be used. In our knowledge, literature on the use of AZA in this setting is limited to a single case report.10 With successful treatment in our patient, we suggest that azathioprine should be added to the armamentarium to treat this rare entity.