Complete Blood Count in Hereditary Hemochromatosis
The CBC is Typically Normal in Hemochromatosis
The complete blood count (CBC) in patients with hereditary hemochromatosis is characteristically normal, as hemochromatosis is defined by normal erythropoiesis despite iron overload. 1 This distinguishes it from iron-loading anemias and other secondary causes of iron overload.
Expected CBC Parameters
Hemoglobin and hematocrit remain within normal reference ranges because hereditary hemochromatosis does not disrupt red blood cell production. 1
Red blood cell indices (MCV, MCH, MCHC) are normal, unlike iron deficiency anemia (microcytic) or iron-loading anemias such as thalassemia. 2
White blood cell count and differential are typically unremarkable unless advanced cirrhosis has developed. 3
Platelet count is usually normal in early disease, but a platelet count <200 × 10⁹/L combined with ferritin >1000 μg/L and elevated liver enzymes predicts cirrhosis in approximately 80% of C282Y homozygotes. 2
When the CBC Becomes Abnormal: Advanced Disease
Thrombocytopenia (platelets <200 × 10⁹/L) is a critical marker of cirrhosis when combined with elevated ferritin and transaminases, and should trigger consideration for liver biopsy. 2
Pancytopenia may develop in end-stage cirrhosis due to hypersplenism and portal hypertension, representing late-stage complications. 3
Anemia in a patient with suspected hemochromatosis should prompt investigation for alternative diagnoses, including gastrointestinal bleeding from portal hypertension, concurrent iron deficiency, or other causes of secondary iron overload. 2
Critical Diagnostic Pitfall
If a patient presents with microcytic anemia and elevated iron studies, consider beta-thalassemia trait or other iron-loading anemias rather than classic HFE-related hemochromatosis. 2 Hemoglobin electrophoresis with HbA₂ quantification (>3.5% confirms beta-thalassemia trait) should be performed to distinguish these conditions. 2
The CBC's Role in Monitoring Treatment
Hemoglobin and hematocrit must be monitored during phlebotomy therapy to prevent iron avidity (overtreatment), which can mimic undertreatment with persistently elevated transferrin saturation. 4
A declining hemoglobin during phlebotomy indicates approaching iron depletion and should prompt measurement of ferritin to guide frequency adjustments. 2
Why the CBC Alone Cannot Diagnose Hemochromatosis
The diagnosis of hereditary hemochromatosis requires transferrin saturation ≥45% and elevated serum ferritin (>300 μg/L in men, >200 μg/L in women), followed by HFE genetic testing for C282Y and H63D mutations. 2, 5 The CBC provides no specific diagnostic information for hemochromatosis itself, serving primarily to exclude alternative diagnoses and monitor for complications.