Is Hematocrit Elevated in Hemochromatosis?
No, hematocrit is not typically elevated in hereditary hemochromatosis. In fact, hematologic parameters including hemoglobin, hematocrit, and complete blood counts remain normal in most patients with hemochromatosis until advanced cirrhosis develops, at which point pancytopenia may occur due to hypersplenism and portal hypertension 1.
Why Hematocrit Remains Normal Despite Iron Overload
The fundamental pathophysiology of hereditary hemochromatosis involves excessive iron absorption and deposition in parenchymal tissues (liver, heart, pancreas, endocrine organs), not increased red blood cell production 2, 3. The iron is sequestered in organs rather than being utilized for erythropoiesis, so there is no stimulus for increased red cell mass 2.
- Iron overload in hemochromatosis affects parenchymal cells of the liver, pancreas, heart, and endocrine organs—not the bone marrow or red blood cell production 4, 2.
- The disease results from inappropriately decreased hepcidin expression, which increases iron export from enterocytes and reticuloendothelial cells into circulation, where it deposits in vulnerable tissues rather than supporting erythropoiesis 3.
- White blood cell count, differential, and red cell indices remain normal in uncomplicated hemochromatosis 1.
When Hematologic Abnormalities Do Occur
Hematologic changes in hemochromatosis are late findings that signal end-stage disease:
- Pancytopenia develops only in advanced cirrhosis due to hypersplenism and portal hypertension 1.
- Platelet count < 200 × 10³/µL is a key predictor of cirrhosis when combined with ferritin > 1,000 µg/L and elevated aminotransferases, predicting cirrhosis in approximately 80% of C282Y homozygotes 5.
- These changes reflect hepatic decompensation, not the iron overload itself 1.
Critical Diagnostic Pitfall to Avoid
Do not expect polycythemia or elevated hematocrit in hemochromatosis. If a patient presents with both elevated hematocrit and elevated iron studies, consider alternative diagnoses:
- Polycythemia vera can cause secondary iron overload and should be evaluated with JAK2 mutation testing 6.
- The combination of elevated ferritin with elevated hematocrit suggests a myeloproliferative disorder rather than hereditary hemochromatosis 6.
Correct Diagnostic Approach
The diagnosis of hereditary hemochromatosis relies on iron parameters, not hematologic indices:
- Transferrin saturation ≥ 45% is the most sensitive early marker and primary screening threshold 5.
- Ferritin > 300 µg/L in men or > 200 µg/L in women (when combined with elevated transferrin saturation) triggers HFE genetic testing 5, 4.
- Complete blood count is normal in uncomplicated disease and only becomes abnormal with cirrhosis 1.
Bottom line: Hereditary hemochromatosis does not cause elevated hematocrit. Normal hematologic parameters are the rule until end-stage liver disease supervenes, at which point pancytopenia—not polycythemia—develops 1.