What is the diagnosis and treatment plan for a patient with microcytic hypochromic anemia?

Diagnosis: Iron Overload, Not Iron Deficiency

This patient has iron overload with a transferrin saturation of 61% and serum iron of 183 μg/dL, which rules out iron deficiency anemia and instead suggests a genetic disorder of iron metabolism, most likely hereditary hemochromatosis or ferroportin disease. 1

Critical Laboratory Interpretation

• Transferrin saturation of 61% is markedly elevated (normal <45%), indicating iron overload rather than iron deficiency 2
• The serum iron of 183 μg/dL is elevated, further confirming excess iron availability 1
• MCH of 26.4 pg and MCHC of 31.2 g/dL indicate mild hypochromia, but this occurs in the context of high iron stores 1
• This pattern is pathognomonic for genetic iron metabolism disorders, not simple iron deficiency 1, 3

Differential Diagnosis Priority

Most Likely: Hereditary Hemochromatosis or Ferroportin Disease (Gain-of-Function)

• Elevated transferrin saturation >60% with high serum iron is the hallmark presentation 1
• The mild microcytosis with iron overload distinguishes this from typical hemochromatosis 1
• Ferroportin disease gain-of-function mutations present with this exact pattern: elevated iron saturation, normal to mildly low hemoglobin, and microcytosis 1

Alternative Consideration: Hypotransferrinemia

• Would present with low transferrin, fully saturated transferrin, high ferritin, and low serum iron 3
• The iron binding capacity of 300 μg/dL (normal range) makes this less likely 3

Ruled Out: Iron Deficiency Anemia

• Iron deficiency requires transferrin saturation <16-20%, not 61% 1, 2
• Serum iron would be low (<60 μg/dL), not 183 μg/dL 4, 5

Immediate Diagnostic Workup Required

• Serum ferritin level is essential - expect it to be elevated (>200-300 μg/L) in hereditary hemochromatosis 1
• Genetic testing for HFE mutations (C282Y, H63D) to confirm hereditary hemochromatosis 1
• Genetic testing for SLC40A1 mutations if HFE testing is negative, to identify ferroportin disease 1
• Liver function tests and consider liver MRI to assess for iron deposition and early organ damage 2, 3
• Reticulocyte count to assess bone marrow response 6

Treatment Plan

DO NOT Give Iron Supplementation

• Iron therapy in a patient with iron overload will cause severe organ damage including liver cirrhosis, diabetes, and cardiomyopathy 1, 6
• This is the most critical pitfall to avoid 2, 6

Initiate Therapeutic Phlebotomy

• Phlebotomy is first-line treatment for hereditary hemochromatosis and gain-of-function ferroportin disease 1
• Initial phlebotomy schedule: 500 mL weekly until ferritin <50 μg/L and transferrin saturation normalizes 1
• Monitor hemoglobin before each phlebotomy session 1
• Risk of developing anemia during phlebotomy is 14.8%, particularly in older patients and those with loss-of-function ferroportin mutations 1

If Loss-of-Function Ferroportin Disease is Confirmed

• Phlebotomy may cause profound anemia due to inability to mobilize iron from macrophages 1
• Consider iron chelation therapy instead of phlebotomy in this specific subtype 1

Monitoring Protocol

• Weekly CBC during initial phlebotomy phase to prevent excessive anemia 1, 6
• Ferritin and transferrin saturation every 2-4 weeks until target levels achieved 2, 6
• Once maintenance phase reached, monitor every 3-6 months 1
• Annual liver imaging and glucose screening for complications of iron overload 2, 3

Critical Pitfalls to Avoid

• Never assume microcytic anemia equals iron deficiency - always check transferrin saturation and serum iron 2, 4
• Never give iron supplementation without confirming true iron deficiency (ferritin <30 μg/L without inflammation, transferrin saturation <16-20%) 1, 2
• Do not overlook family screening once genetic diagnosis is confirmed, as this is an inherited condition 3
• Avoid excessive phlebotomy causing anemia - monitor hemoglobin closely and adjust frequency if hemoglobin drops below 11 g/dL 1