What abnormalities would you see on a Complete Blood Count (CBC) with hemochromatosis?

CBC Findings in Hemochromatosis

The CBC is typically normal in hemochromatosis—this is a key diagnostic feature that distinguishes it from other iron disorders. 1

Expected CBC Pattern

In uncomplicated hemochromatosis, you will see:

• Normal hemoglobin and hematocrit - Most patients maintain normal red blood cell parameters despite massive iron overload 2
• Normal MCV (mean corpuscular volume) - Red cells are normocytic, not microcytic 3
• Normal white blood cell count 1
• Normal platelet count (unless cirrhosis develops) 1

This normal CBC occurs even when patients have accumulated 10-20 grams of excess parenchymal iron. 1

Why the CBC Stays Normal

The fundamental pathophysiology explains this paradox: hemochromatosis causes parenchymal iron overload (liver, heart, pancreas, joints) rather than reticuloendothelial system overload. 4, 5 Iron deposits preferentially in hepatic storage sites during early and intermediate stages of disease, with bone marrow hemosiderin remaining sparse even as liver iron accumulates massively. 5

Polycythemia: An Uncommon Finding

Approximately 28% of hemochromatosis patients develop polycythemia (elevated hemoglobin/hematocrit above normal range), though this is not the typical presentation. 2 Female patients are relatively protected against polycythemia compared to males. 2 The mean hemoglobin in hemochromatosis populations is approximately 15.0 g/dL. 2

Anemia: A Red Flag for Complications

Anemia occurs in only 10-11% of hemochromatosis patients and signals either:

Iatrogenic Iron Deficiency from Overtreatment

• Develops from excessive therapeutic phlebotomy - the most common cause of anemia in treated hemochromatosis 3
• Presents with hypochromia, microcytosis, transferrin saturation <15%, and ferritin <10 ng/mL 3
• Hemoglobin levels may paradoxically remain higher than expected for the degree of iron deficiency (compared to non-hemochromatosis patients) 3
• Prevention requires monitoring hemoglobin before each phlebotomy session and checking ferritin monthly during induction phase 1, 3

Advanced Cirrhosis with Portal Hypertension

• Splenomegaly causes sequestration and mild pancytopenia 1
• Platelet count <200,000 combined with ferritin >1,000 μg/L predicts cirrhosis in 80% of C282Y homozygotes 6
• Thrombocytopenia becomes a critical marker for advanced fibrosis 1

Concurrent Malignancy or Renal Disease

• Malignancy and chronic renal insufficiency are significantly associated with anemia in hemochromatosis patients (p<0.001) 2
• These represent independent causes of anemia, not direct effects of iron overload 2

Variceal Bleeding

• Acute or chronic blood loss from esophageal varices in cirrhotic patients 3

Critical Clinical Pitfall

Never diagnose hemochromatosis based on CBC findings alone. The diagnosis requires:

• Elevated transferrin saturation ≥45% (primary screening test) 1
• Elevated serum ferritin (reflects hepatic iron content) 1
• HFE genetic testing for C282Y and H63D mutations 1, 6

The CBC serves primarily to monitor for treatment complications (iatrogenic iron deficiency) and identify advanced liver disease (thrombocytopenia), not to diagnose the condition. 1, 3

Monitoring During Phlebotomy Therapy

Check hemoglobin at every phlebotomy session: 1

• If hemoglobin <12 g/dL: decrease phlebotomy frequency 1
• If hemoglobin <11 g/dL: discontinue phlebotomy and reassess 1
• Target ferritin 50-100 μg/L during maintenance, not lower, to avoid iatrogenic iron deficiency 1, 3