What laboratory studies should be ordered for a patient with microcytic, hypochromic anemia (hemoglobin 8.9 g/dL, hematocrit 31 %, mean corpuscular volume 66 fL, mean corpuscular hemoglobin 18 pg, mean corpuscular hemoglobin concentration 28 g/dL, red cell distribution width 16 %) and a normal comprehensive metabolic panel?

Laboratory Workup for Microcytic Hypochromic Anemia

Order serum ferritin, transferrin saturation (TSAT), and C-reactive protein (CRP) immediately—these three tests will determine whether this is iron deficiency anemia versus other causes of microcytosis. 1, 2

Initial Essential Laboratory Tests

First-Line Iron Studies

• Serum ferritin is the single most specific test for iron deficiency, with <15 μg/L confirming absent iron stores and <30 μg/L indicating low body iron stores 1, 2
• A ferritin cut-off of 45 μg/L provides optimal sensitivity and specificity for iron deficiency in clinical practice 1, 2
• Transferrin saturation (TSAT) <16-20% confirms iron deficiency, especially when ferritin may be falsely elevated by inflammation 1, 2
• If ferritin is >100 μg/L, iron deficiency is almost certainly not present 3

Inflammatory Markers

• C-reactive protein (CRP) must be checked because ferritin is an acute phase reactant that can be falsely elevated in inflammation, infection, malignancy, or liver disease 2, 3
• In the presence of inflammation, ferritin levels up to 100 μg/L may still indicate iron deficiency 2

Secondary Diagnostic Tests Based on Initial Results

If Iron Studies Are Normal or Equivocal

• Hemoglobin electrophoresis should be ordered to exclude thalassemia, particularly since your MCV of 66 fL is disproportionately low relative to the degree of anemia 1, 2
• The combination of low MCV (66) with elevated RDW (16) strongly suggests iron deficiency over thalassemia, as thalassemia typically presents with RDW ≤14.0% 2, 4

If Thalassemia and Iron Deficiency Are Excluded

• Consider reticulocyte count to assess bone marrow response 2
• In rare cases with extreme microcytosis (MCV <70) or family history of refractory anemia, genetic testing for disorders like IRIDA (iron-refractory iron deficiency anemia) or sideroblastic anemia may be warranted 2, 4

Critical Interpretation Points

Ferritin Interpretation in Context

• Ferritin <15 μg/L has 99% specificity for iron deficiency 1
• Ferritin <45 μg/L has 92% specificity and should prompt consideration of GI investigation, especially with chronic inflammatory processes 1
• Ferritin >150 μg/L makes absolute iron deficiency unlikely even with inflammation 1

TSAT Interpretation

• TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease rather than iron deficiency 2
• TSAT <16% strongly supports iron deficiency diagnosis 2

Investigation of Underlying Cause

Once iron deficiency is confirmed, you must investigate the source of iron loss—do not simply treat with iron supplementation alone. 1, 2

Mandatory GI Evaluation

• Men with Hb <110 g/L (your patient has 89 g/L) warrant fast-track GI referral for upper endoscopy and colonoscopy 1, 2
• Investigation should be considered at any level of anemia with confirmed iron deficiency, as more severe degrees are more likely to have serious underlying GI pathology 1
• Upper endoscopy with duodenal biopsies to screen for celiac disease, which accounts for 2-3% of iron deficiency anemia cases 2
• Colonoscopy to exclude colonic cancer, polyps, and angiodysplasia 2

Common Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 2, 4
• Do not rely on ferritin alone in inflammatory states—add TSAT to accurately diagnose iron deficiency 2
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW 2, 4
• Do not order bone marrow examination initially—serum ferritin and TSAT obviate the need for bone marrow in most cases 5