Moderate Anemia with Normal Iron but Elevated Platelet Count: Iron-Deficiency Anemia with Reactive Thrombocytosis
Your laboratory pattern—hemoglobin 9.2 g/dL, hematocrit 29.4%, RBC 3.12 million/µL, normal serum iron, and elevated platelet count—most likely represents iron-deficiency anemia with reactive thrombocytosis, where "normal" serum iron is misleading because serum iron alone is an unreliable marker that fluctuates widely and does not reflect true iron stores. 1, 2
Why Serum Iron Alone Is Insufficient
Serum iron shows considerable day-to-day variability and cannot distinguish iron deficiency from other causes of anemia; you must measure serum ferritin and transferrin saturation to confirm or exclude iron deficiency. 1
Many individuals with normal serum iron levels have depleted iron stores (low ferritin) and are iron deficient; relying on serum iron alone misses a substantial proportion of iron-deficiency cases. 2
The most specific test for iron deficiency is serum ferritin, with levels <15 µg/L indicating absent iron stores and <30 µg/L indicating low body iron stores; a cut-off of 45 µg/L provides optimal sensitivity and specificity in practice. 1
Transferrin saturation <16–20% confirms iron deficiency even when serum iron appears normal, because it reflects the percentage of transferrin binding sites occupied by iron rather than the absolute serum iron concentration. 1, 3
Reactive Thrombocytosis in Iron Deficiency
Elevated platelet counts occur in approximately 13–15% of adults with iron-deficiency anemia and represent a reactive phenomenon that resolves with iron replacement. 4, 5
Iron-depleted individuals have higher platelet counts than those with adequate iron stores (mean difference approximately 18,000–20,000/µL), and oral iron replacement decreases platelet counts by an average of 20,000/µL within weeks. 5
Thrombocytosis in iron deficiency is typically moderate (400–700 × 10³/µL), but extreme elevations exceeding 1,000 × 10³/µL can occur in severe cases. 6, 4
The mechanism linking iron deficiency to thrombocytosis remains unclear; elevated erythropoietin levels correlate with high platelet counts, suggesting cross-reactivity between erythropoietin and thrombopoietin receptors, though other thrombopoietic cytokines do not change during treatment. 7
Required Diagnostic Workup
Immediate Laboratory Tests
Order serum ferritin, transferrin saturation (calculated as serum iron ÷ total iron-binding capacity × 100), and C-reactive protein together as the first-line panel to confirm iron deficiency and exclude inflammatory states that falsely elevate ferritin. 1, 3
Measure absolute reticulocyte count to assess bone marrow response; a low or inappropriately normal reticulocyte count in the setting of anemia indicates inadequate erythropoiesis consistent with iron deficiency. 8, 3
Obtain a peripheral blood smear to evaluate red-cell morphology for microcytosis and hypochromia, which are the hallmarks of iron-deficient erythropoiesis. 8, 1
Interpretation Thresholds
Ferritin <30 µg/L confirms iron deficiency in the absence of inflammation; when C-reactive protein is elevated, ferritin up to 100 µg/L may still be compatible with iron deficiency, and transferrin saturation <20% becomes the primary diagnostic criterion. 1, 3
An elevated red-cell distribution width (RDW >14%) together with microcytosis strongly supports iron deficiency over thalassemia trait, which typically shows RDW ≤14% because red cells are uniformly small. 1, 3
Investigation of the Underlying Cause
Once iron deficiency is confirmed, a systematic search for the source of iron loss is mandatory rather than treating with iron supplementation alone; in adults, gastrointestinal blood loss is the most common etiology and must be excluded. 1
Adult males with hemoglobin <110 g/L and non-menstruating women with hemoglobin <100 g/L should receive fast-track bidirectional endoscopy (upper endoscopy with duodenal biopsies plus colonoscopy) to evaluate for malignancy, angiodysplasia, peptic ulcer disease, and celiac disease. 1
In premenopausal women, heavy menstrual bleeding is the leading cause of iron deficiency, but gastrointestinal evaluation remains necessary if menstrual losses do not fully account for the severity of anemia or if iron deficiency persists despite treatment. 1
Upper endoscopy with duodenal biopsies screens for celiac disease (prevalence 2–3% in iron-deficiency cases), gastric cancer, and NSAID-induced gastropathy; colonoscopy detects colonic carcinoma, adenomatous polyps, and angiodysplasia. 1
Treatment and Monitoring
Begin oral iron supplementation with ferrous sulfate 325 mg once to three times daily immediately while the diagnostic workup proceeds; a rise in hemoglobin ≥10 g/L within 2 weeks confirms iron-deficiency anemia even when initial iron studies are equivocal. 1, 3
If hemoglobin does not increase by ≥2 g/dL within 4 weeks, reassess adherence, evaluate for ongoing occult bleeding or malabsorption, and consider switching to intravenous iron (iron sucrose or ferric carboxymaltose). 1
Continue iron supplementation for at least 3 months after hemoglobin normalization to replenish iron stores; monitor serum ferritin and aim for a target >50 µg/L to prevent recurrence. 1
Platelet counts will normalize spontaneously as iron stores are repleted; no specific antiplatelet therapy is required for reactive thrombocytosis in iron deficiency. 5, 7
Common Pitfalls to Avoid
Do not rely on serum iron alone to exclude iron deficiency; ferritin and transferrin saturation are essential to diagnose iron deficiency accurately. 1, 2
Do not attribute elevated platelet counts to a primary hematologic disorder (e.g., essential thrombocythemia) without first confirming or excluding iron deficiency, because reactive thrombocytosis resolves with iron replacement. 6, 4
Do not assume that normal hemoglobin and hematocrit exclude iron depletion; individuals with borderline-normal red-cell indices can have severely depleted iron stores and will progress to overt anemia if not treated. 2
Do not overlook combined nutrient deficiencies; iron deficiency can coexist with vitamin B12 or folate deficiency, a situation suggested by an elevated RDW, and both should be assessed. 1, 3
Do not delay gastrointestinal investigation in adults with confirmed iron deficiency, even when dietary insufficiency or menstrual bleeding appears explanatory, because occult malignancy must be excluded. 1