Hemochromatosis and Secondary Polycythemia
No, hemochromatosis does not cause secondary polycythemia—in fact, patients with hemochromatosis characteristically have elevated hemoglobin and hematocrit levels due to increased iron availability for erythropoiesis, which represents a distinct physiological mechanism from true secondary polycythemia. 1, 2
Understanding the Hematologic Profile in Hemochromatosis
Elevated Red Blood Cell Parameters Are Expected
Patients with hemochromatosis typically demonstrate increased hemoglobin levels, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) related to increased iron availability for erythropoiesis. 3
In a retrospective cohort of 213 hemochromatosis patients, the mean hemoglobin was 15.0 g/dL, with 27.6% meeting criteria for polycythemia, while only 10.8% had anemia despite multiple comorbidities that typically cause anemia in the general population. 1
Median hemoglobin and hematocrit values in C282Y homozygotes were 15.5 g/dL and 44.9% respectively, with similar or higher values in other HFE mutation patterns. 2
Mechanism: Iron Availability, Not Hypoxia
The elevated red blood cell parameters in hemochromatosis result from increased iron uptake by erythroid precursors in bone marrow due to increased availability of both transferrin-bound and non-transferrin-bound iron (NTBI), not from hypoxia-driven erythropoietin production. 2
This distinguishes hemochromatosis from true secondary polycythemia, which is defined as a physiological increase in red blood cell mass in response to hypoxemia or pathological erythropoietin production. 3
True secondary polycythemia causes include hypoxic processes (chronic lung disease, cardiac shunts, high altitude, sleep apnea), hemoglobinopathies with high oxygen affinity, and erythropoietin-producing tumors (renal cell carcinoma, hepatocellular carcinoma, cerebellar hemangioblastoma). 4
Critical Clinical Distinction
Anemia in Hemochromatosis Should Prompt Investigation
Anemia is NOT a characteristic feature of hemochromatosis—finding anemia in a patient with hemochromatosis should prompt thorough investigation for other unrelated causes. 3
In the cohort study, concurrent malignancy and chronic renal insufficiency were significantly associated with anemia (p < 0.001), but serum ferritin levels were not associated with anemia or polycythemia on multivariate analysis. 1
Patients with hemochromatosis maintained normal or elevated hemoglobin despite conditions typically associated with anemia (gastrointestinal bleeding, end-stage renal disease), suggesting a protective effect of iron overload. 2
Clinical Pitfall to Avoid
Do not confuse the elevated hemoglobin/hematocrit commonly seen in hemochromatosis with true secondary polycythemia requiring different management. 4 The elevated red cell parameters in hemochromatosis are a consequence of iron excess and resolve with phlebotomy therapy, whereas secondary polycythemia requires addressing the underlying hypoxic or erythropoietin-driven process. 3
In the study cohort, 67.1% of hemochromatosis patients received phlebotomy, and elevated hemoglobin levels persisted despite absence of established reasons for secondary polycythemia (only 21.7% were tobacco users and 8.6% had pulmonary diagnoses). 2