Case report Agranulocytosis secondary to propylthiouracil

A 36-year-old Caucasian female presented with sore throat, malaise and fever for 5 days. She was febrile and physical examination was remarkable for moderate pharyngeal erythema and mild tonsil hypertrophy. A complete blood count (CBC) showed a white blood cell (WBC) count of 810/ml [87% lymphocytes, 8% variant lymphocytes, 5% monocytes and an absolute neutrophil count (ANC) of zero], hemoglobin (Hgb) of 9.8 gm/dl, and a platelet count of 124 000/ml. A comprehensive metabolic panel, rapid strep screen, urine analysis and chest X-ray were unremarkable. She was admitted and empirically started on ceftriaxone and levofloxacin. The patient had no known drug allergies and a family history was significant for Graves’ disease (mother and three maternal aunts), and Factor V Leiden deficiency (father and sister). A review of the recent past medical history revealed an emergent cesarean section 4 weeks ago at 32 weeks of gestation secondary to abruptio placentae. Post-operatively the patient developed a pulmonary embolus followed by respiratory distress, tachycardia and thyrotoxicosis. During that hospitalization a CBC was unremarkable, TSH 0.005 ulU/ml, T4 16 ng/dl and T3 31.2 pg/dl, consistent with thyrotoxicosis. The patient was treated with high dose propylthiouracil, corticosteroids, beta-blockers and enoxaparin. The patient was discharged home 2 weeks later on propylthiouracil 150mg daily along with propranolol, warfarin and prednisone. At 1 week follow-up visit T4 was 1.92 ng/dl, T3 was within normal range and an unremarkable CBC with a WBC count of 6240/ml. During the current admission propylthiouracil was empirically stopped. An extensive work up for agranulocytosis was unremarkable including vitamin B12, folic acid, serology for viral infections (hepatitis, HIV, CMV, EBV, parvovirus), lupus antigen and pan-cultures. A peripheral smear showed leukopenia with absent granulocytic lineages (Figure 1A), and bone marrow aspirate revealed maturation arrest in granulocytic lineages at the myelocyte/metamyelocyte stage (Figure 1B). Marked hypocellularity (10%) with panhypoplasia most pronounced in the granulocyte series was noticed on bone marrow biopsy (Figure 1C). Flow cytometry showed 4% myeloblasts, multiple immature cells and very few normal maturing myeloid cells. Once infection and malignancy were ruled out, propylthiouracil was thought to be the culprit as a diagnosis of exclusion. The patient was treated with lithium (to block thyroid hormone release) and granulocyte colony stimulating factor (G-CSF). The patient improved and discharged home after 5 days with a WBC count of 8520/ml.