When the Marrow Runs Out of Iron: Severe Iron Deficiency Masquerading as Bone Marrow Failure

Introduction

Pancytopenia with severe anemia and impaired reticulocyte production typically raises concern for primary bone marrow failure or infiltration. Although iron deficiency is common, profound iron deficiency causing pancytopenia is rare. We present a patient whose severe pancytopenia mimicked marrow failure, with bone marrow examination revealing preserved hematopoiesis but completely absent storage iron.

Case Description

A 39-year-old woman with no known chronic medical conditions presented with acute chest pain and reported two years of fatigue and exertional dyspnea. She described longstanding severe menorrhagia, easy bruising, and prolonged bleeding after minor trauma. Initial studies revealed hemoglobin 3.3 g/dL, mean corpuscular volume 58 fL, white blood cell count 2.66 K/µL, platelet count 73 K/µL, absolute neutrophil count 0.74 K/µL, and absolute reticulocyte count 0.0163 M/µL. Peripheral smear demonstrated marked microcytosis, hypochromia, anisopoikilocytosis, teardrop cells, and rare reticulocytes, raising concern for marrow aplasia or infiltration. Cardiac evaluation was unrevealing. Extensive evaluation for infectious, autoimmune, hemolytic, nutritional, and clonal hematologic disorders was negative. Pelvic ultrasound demonstrated a leiomyomatous uterus with 4.2-cm fundal subserosal and 5.3-cm anterior lower-segment intramural/subserosal leiomyomas. Following four units of packed red blood cells, hemoglobin increased to approximately 9 g/dL, but thrombocytopenia persisted. Bone marrow biopsy demonstrated a markedly hypercellular marrow with erythroid hyperplasia, preserved granulocytic and megakaryocytic maturation, no fibrosis, and critically, absent storage iron. Flow cytometry showed no immunophenotypic abnormalities and cytogenetics demonstrated a normal 46,XX karyotype. Initial ferritin was 2.8 ng/mL. Subsequent iron studies showed iron 29 µg/dL, total iron-binding capacity 407 µg/dL, and iron saturation 7.1%. She received intravenous iron sucrose 200 mg daily for five days. Her leukocyte count, hemoglobin, platelet count, and mean corpuscular volume progressively improved, reaching 6.02 K/µL, 10.4 g/dL, 90 K/µL, and 76.9 fL, respectively.

Discussion

This case demonstrates that profound iron deficiency can produce pancytopenia despite a markedly hypercellular marrow. The absence of marrow storage iron provided a critical diagnostic clue: hematopoiesis was preserved, but iron availability was profoundly depleted. Together with severe microcytosis, ferritin of 2.8 ng/mL, chronic menstrual blood loss, and multilineage recovery following iron replacement, these findings supported severe iron deficiency rather than intrinsic marrow failure. Clinicians should recognize that pancytopenia does not necessarily indicate a hypocellular or infiltrated marrow and should carefully evaluate iron stores when marked microcytosis accompanies unexplained cytopenias.