What is the cause of normochromic anemia with marked anisopoikilocytosis including acanthocytes, elliptocytes, and occasional schistocytes in an elderly woman with moderate anemia, thrombocytopenia, normal ferritin, normal serum iron, normal transferrin saturation, low total iron‑binding capacity and low unsaturated iron‑binding capacity, and normal C‑reactive protein and erythrocyte sedimentation rate?

Myelodysplastic Syndrome or Bone Marrow Infiltrative Process

This clinical presentation—normochromic anemia with marked anisopoikilocytosis (acanthocytes, elliptocytes, rare schistocytes), thrombocytopenia, normal inflammatory markers, and low TIBC/UIBC—strongly suggests a primary bone marrow disorder, most likely myelodysplastic syndrome (MDS) or an infiltrative marrow process such as myeloma, lymphoma, or metastatic malignancy. 1

Diagnostic Reasoning

The constellation of findings systematically excludes common causes of normocytic anemia:

• Anemia of chronic disease is ruled out by the normal CRP and ESR, since this condition requires active inflammation with elevated inflammatory markers 2, 3
• Absolute iron deficiency is excluded by the normal ferritin and normal serum iron 2
• Chronic kidney disease is unlikely given the absence of renal insufficiency markers, though GFR should still be measured 4
• Hemolysis is improbable because schistocytes are only "rare" rather than abundant, and the clinical picture lacks other hemolytic features 2

The low TIBC and UIBC with normal iron and ferritin is the critical diagnostic clue. This pattern indicates impaired hepatic transferrin synthesis, which occurs in three settings: severe liver disease, nephrotic syndrome, or bone marrow failure/infiltration 2, 1. Combined with thrombocytopenia (platelet count 120), this points to a multilineage bone marrow problem 1.

Peripheral Blood Smear Findings

The marked anisopoikilocytosis with specific morphologies provides additional diagnostic direction:

• Acanthocytes and elliptocytes suggest membrane abnormalities that can occur in MDS or liver disease 1
• Rare schistocytes indicate some degree of mechanical red cell fragmentation, which may occur with marrow fibrosis or microangiopathy 2
• The combination of cytopenias with dysplastic red cell morphology is characteristic of myelodysplastic syndrome 1

Immediate Diagnostic Workup

Essential Laboratory Tests

• Peripheral blood smear review by hematopathology to assess for dysplastic features, blasts, or abnormal white cells 1
• Reticulocyte count to confirm hypoproliferative anemia (expected to be low, reticulocyte index <1.0) 2
• Comprehensive metabolic panel including creatinine, GFR, liver function tests, calcium, and total protein 1
• Serum protein electrophoresis (SPEP) with immunofixation to screen for myeloma 1
• LDH, haptoglobin, indirect bilirubin to definitively exclude hemolysis 2
• Vitamin B12 and folate levels to rule out combined deficiency masking as normocytic anemia 2, 1

Bone Marrow Examination—Mandatory in This Case

Bone marrow aspiration and biopsy are indicated immediately because this patient has:

1. Unexplained bicytopenia (anemia + thrombocytopenia) 1
2. Marked dysplastic red cell morphology on peripheral smear 1
3. No identifiable cause after comprehensive noninvasive workup 1
4. Low transferrin synthesis suggesting marrow pathology 1

The bone marrow examination should include:

• Morphologic assessment for dysplasia, blast percentage, and cellularity 1
• Cytogenetics to detect clonal abnormalities characteristic of MDS 1
• Flow cytometry if lymphoproliferative disorder is suspected 1
• Iron staining to assess for ring sideroblasts (seen in some MDS subtypes) 2, 1

Differential Diagnosis Priority

Most Likely: Myelodysplastic Syndrome

• MDS typically presents in elderly patients with normocytic anemia, cytopenias, and dysplastic morphology 2, 1
• The low TIBC reflects ineffective erythropoiesis and altered iron metabolism in MDS 1
• Approximately 75% of MDS patients have anemia at diagnosis 1

Alternative: Bone Marrow Infiltration

• Multiple myeloma can present with normocytic anemia, low TIBC, and thrombocytopenia; SPEP and bone marrow biopsy will distinguish this 1
• Lymphoma or metastatic carcinoma infiltrating marrow can produce identical findings 1
• Myelofibrosis may show teardrop cells and leukoerythroblastic picture on smear 1

Less Likely but Consider

• Severe liver disease can cause low TIBC, but would show elevated liver enzymes and acanthocytes are more prominent 1
• Aplastic anemia presents with pancytopenia but typically lacks the marked anisopoikilocytosis 1

Management Approach

Before Bone Marrow Results

• Do not transfuse unless hemoglobin drops below 7-8 g/dL or the patient develops severe symptoms (chest pain, dyspnea at rest, hemodynamic instability) 2, 1
• Avoid empiric iron supplementation, as the iron studies do not support deficiency and inappropriate iron may worsen outcomes in MDS 2, 1
• Monitor complete blood count weekly until diagnosis is established 1

After MDS Diagnosis

• Low-risk MDS (hemoglobin ≤10 g/dL, serum erythropoietin ≤500 mU/mL): consider erythropoiesis-stimulating agents 1
• High-risk MDS (elevated blast count): hypomethylating agents (azacitidine or decitabine) are indicated 1
• Supportive care includes transfusion support and infection prophylaxis as needed 1

Critical Pitfalls to Avoid

• Do not assume anemia of chronic disease based solely on age and comorbidities when inflammatory markers are normal 2, 3
• Do not delay bone marrow examination in elderly patients with unexplained cytopenias and dysplastic morphology, as early MDS diagnosis affects prognosis 1
• Do not attribute thrombocytopenia to "age-related changes"—this always requires investigation 1
• Do not give iron empirically when the pattern suggests marrow pathology rather than deficiency 2, 1

The combination of bicytopenia, dysplastic red cell morphology, low transferrin synthesis, and absence of inflammation makes primary bone marrow pathology the diagnosis until proven otherwise, and bone marrow examination is the definitive next step 1.