In a 70-year-old woman with mild microcytic-to-normocytic anemia (Hb 11.8 g/dL, Hct 35 %, MCH 26.9 pg, MCHC 33.5 g/dL) and thrombocytosis (platelets 333 ×10³/µL, MPV 9.5 fL), what laboratory studies should be ordered and what is the most likely diagnosis?

Diagnostic Evaluation and Management of Microcytic Anemia with Thrombocytosis in a 70-Year-Old Woman

Most Likely Diagnosis

This patient has iron deficiency anemia (IDA) with reactive thrombocytosis secondary to chronic iron deficiency. The combination of microcytic anemia (MCH 26.9 pg, MCHC 33.5 g/dL, Hb 11.8 g/dL) with thrombocytosis (platelets 333 ×10³/µL) is characteristic of iron deficiency, as thrombocytosis typically peaks in the third week of iron-deficient states and serves as a reactive marker 1, 2.

Essential Laboratory Studies to Order Immediately

First-Line Iron Studies (Order Together)

• Serum ferritin – the single most powerful test for confirming iron deficiency, with <30 μg/L diagnostic in the absence of inflammation 2, 3
• Transferrin saturation (TSAT) – calculated as serum iron/TIBC × 100; <16-20% confirms iron-deficient erythropoiesis even when ferritin appears normal 1, 2
• Total iron-binding capacity (TIBC) – elevated in iron deficiency (typically >400 μg/dL) 3
• C-reactive protein (CRP) – essential because ferritin is an acute-phase reactant that can be falsely elevated by inflammation, infection, malignancy, or hepatic disease 2

Supportive Studies

• Complete blood count with red cell distribution width (RDW) – RDW >14% combined with low MCV strongly indicates iron deficiency rather than thalassemia trait 1, 2
• Reticulocyte count – should be low in iron deficiency, reflecting inadequate bone marrow response 1

Interpretation Thresholds

The diagnostic algorithm proceeds as follows:

• Ferritin <15 μg/L = 99% specific for iron deficiency; confirms diagnosis 2
• Ferritin <30 μg/L = diagnostic of iron deficiency in the absence of inflammation 2, 3
• Ferritin 30-100 μg/L with TSAT <16-20% = confirms iron deficiency despite borderline ferritin 2
• Ferritin >100 μg/L with TSAT <20% = suggests anemia of chronic disease rather than pure iron deficiency 2

Critical Next Step: Identify the Source of Blood Loss

In a 70-year-old woman with confirmed iron deficiency anemia, gastrointestinal malignancy must be excluded through urgent endoscopic evaluation. 2, 3

Mandatory Gastrointestinal Investigation

• Upper endoscopy with duodenal biopsies – identifies gastric cancer, peptic ulcer disease, NSAID gastropathy, angiodysplasia, and screens for celiac disease (present in 2-3% of IDA cases) 2
• Colonoscopy – detects colonic carcinoma, adenomatous polyps, and angiodysplasia, which are particularly high-yield in elderly patients 2

Do not attribute iron deficiency to dietary insufficiency alone in a 70-year-old without complete GI investigation, as asymptomatic gastrointestinal malignancy commonly presents this way. 2, 3

Additional Sources to Evaluate

• Menstrual history – although less likely at age 70, late perimenopausal bleeding or postmenopausal bleeding requires gynecologic evaluation 2
• Medication review – assess for antiplatelet agents (aspirin, clopidogrel) or NSAIDs that increase GI bleeding risk 2
• Dietary assessment – vegetarian/vegan diets increase risk, but this alone does not explain severe deficiency in elderly patients 2

Secondary Diagnostic Considerations

When to Order Hemoglobin Electrophoresis

Order hemoglobin electrophoresis only if iron studies are normal or borderline, or if MCV is disproportionately low relative to anemia severity. 2 In this case, the combination of low MCH (26.9 pg) with expected low ferritin makes thalassemia trait unlikely, as thalassemia typically presents with RDW ≤14% and normal iron stores 1, 2.

Excluding Anemia of Chronic Disease

If CRP is elevated and ferritin >100 μg/L with TSAT <20%, this pattern suggests anemia of chronic disease rather than pure iron deficiency 2. However, the thrombocytosis in this patient strongly favors iron deficiency over chronic disease 1.

Immediate Treatment While Awaiting Workup

Initiate oral iron supplementation immediately (ferrous sulfate 200 mg three times daily) while pursuing diagnostic evaluation. 2, 3 The reticulocyte count should rise within 3-5 days, and hemoglobin should increase ≥10 g/L within 2 weeks if responding appropriately 2, 3.

When to Switch to Intravenous Iron

Consider IV iron if 2, 3:

• Intolerance to oral iron despite trying alternative formulations (ferrous gluconate, ferrous fumarate)
• Inadequate hemoglobin response after 3-4 weeks of oral therapy
• Malabsorption confirmed (celiac disease, inflammatory bowel disease)
• Hemoglobin <10 g/dL with significant symptoms

Common Diagnostic Pitfalls to Avoid

• Do not rely on ferritin alone when inflammation is suspected – always add TSAT and CRP to the workup 2
• Do not delay GI investigation in elderly patients – age >70 years with IDA mandates urgent endoscopic evaluation regardless of symptom severity 2
• Do not overlook combined deficiencies – iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW 2
• Do not assume all microcytic anemia is iron deficiency – anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 2

Monitoring and Follow-Up

• Recheck CBC and iron parameters at 4-8 weeks after initiating treatment 3
• Continue oral iron for at least 3 months after hemoglobin correction to replenish iron stores 2
• If no response to oral iron after 3 weeks, consider bone marrow aspiration or therapeutic trial to confirm true iron deficiency 3