What additional labs are needed for a patient with microcytic anemia and thrombocytosis?

Additional Laboratory Testing for Microcytic Anemia with Thrombocytosis

Order serum ferritin immediately as the first-line test, followed by iron studies (serum iron, TIBC, transferrin saturation) to confirm iron deficiency anemia, which is the most likely diagnosis given the microcytic indices. 1, 2

Initial Essential Tests

• Serum ferritin is the most specific test for iron deficiency, with levels <30 μg/L indicating iron deficiency and levels <15 μg/L indicating absent iron stores 1, 2
• A ferritin cut-off of 45 μg/L provides optimal sensitivity and specificity in clinical practice 1
• Complete iron panel including serum iron, total iron-binding capacity (TIBC), and transferrin saturation should be obtained if ferritin is not clearly low 3, 4
• Transferrin saturation <30% supports iron deficiency and is more sensitive than hemoglobin alone 1

Secondary Diagnostic Tests

• Peripheral blood smear to evaluate red cell morphology, confirm microcytosis, and assess for hypochromia 4, 5
• Reticulocyte count to assess bone marrow response—an appropriate response suggests hemolysis or blood loss, while a low count suggests production defect 5
• Red cell distribution width (RDW): An elevated RDW >14.0% with low MCV strongly suggests iron deficiency, while RDW ≤14.0% with low MCV suggests thalassemia trait 1, 2

Thrombocytosis Evaluation

• The elevated platelet count (435) is likely reactive thrombocytosis secondary to iron deficiency, which commonly causes platelet elevation 3
• If thrombocytosis persists after iron repletion, consider inflammatory markers (CRP, ESR) to evaluate for chronic inflammatory conditions 3

Additional Testing Based on Initial Results

If Iron Deficiency is Confirmed (Low Ferritin, Low Iron, High TIBC):

• Investigate the source of iron loss: In adults, iron deficiency is presumed to be from blood loss until proven otherwise 3, 2, 4
• Consider celiac serology (tissue transglutaminase antibodies) to screen for malabsorption 1
• Evaluate for gastrointestinal blood loss with fecal occult blood testing and consider GI referral for endoscopy, especially in men and post-menopausal women 3, 2

If Iron Studies are Normal or Equivocal:

• Hemoglobin electrophoresis should be ordered if microcytosis persists with normal iron studies, appropriate ethnic background, or MCV disproportionately low relative to degree of anemia 1, 2
• Elevated hemoglobin A2 levels suggest beta-thalassemia trait 4
• Consider lead level if there is occupational or environmental exposure history 4, 6

If Anemia of Chronic Disease is Suspected:

• Anemia of chronic disease typically shows low iron, low TIBC, and normal or elevated ferritin 2, 4
• Inflammatory markers (CRP, ESR) help confirm chronic inflammatory state 2

Critical Pitfalls to Avoid

• Do not assume dietary deficiency alone without investigating for blood loss—gastrointestinal malignancy must be excluded in adults with iron deficiency 3, 2
• Ferritin can be falsely elevated in the presence of inflammation, malignancy, or liver disease; if ferritin is 100-500 μg/L with suspected iron deficiency, add transferrin saturation to the workup 3, 1
• Do not overlook combined deficiencies: Check vitamin B12 and folate if RDW is elevated, as combined deficiencies can mask microcytosis 3
• Thalassemia trait is often missed: If MCV is severely low (<70) relative to mild anemia, or if iron studies are normal, hemoglobin electrophoresis is mandatory 1, 2

Rare Genetic Disorders (Consider Only if Standard Workup is Negative)

• If extreme microcytosis (MCV <70), family history of refractory anemia, or failure to respond to adequate iron therapy, consider genetic testing for disorders of iron metabolism (TMPRSS6/IRIDA, SLC11A2, ALAS2) 3, 1
• These conditions are exceedingly rare and should only be pursued after excluding common causes 3