Management of Iron Overload with Functional Iron Deficiency
This 49-year-old Filipino woman has iron overload (total iron 361 µg/dL, transferrin saturation 80%) with paradoxically low ferritin (22 ng/mL), requiring immediate investigation for hemochromatosis or other iron-loading disorders before any iron supplementation is considered.
Immediate Diagnostic Workup Required
Stop all iron supplementation immediately – the transferrin saturation of 80% indicates severe iron overload that can cause organ damage (liver, heart, pancreas). 1
Order genetic testing for hereditary hemochromatosis (HFE gene mutations C282Y and H63D) – this is the most common cause of elevated iron saturation in adults. 1
Measure serum iron studies in fasting state to confirm the elevated iron saturation, as non-fasting samples can be falsely elevated. 1
Check liver function tests and consider liver imaging – iron overload causes hepatic iron deposition leading to cirrhosis and hepatocellular carcinoma. 2
Screen for secondary causes of iron overload: chronic hemolytic anemia (thalassemia is common in Filipino populations), repeated blood transfusions, excessive dietary iron intake, or chronic liver disease. 2
Why This Patient Should NOT Receive Iron Therapy
Transferrin saturation >45% defines iron overload – this patient's 80% saturation indicates the body's iron transport system is completely saturated, and additional iron will deposit in organs. 1
The low ferritin (22 ng/mL) is misleading – ferritin can be falsely low in the presence of inflammation or may reflect a mixed picture where iron is maldistributed (loaded in tissues but depleted in storage sites). 1
Normal hemoglobin (15 g/dL) and hematocrit (45%) confirm no anemia – there is no indication for iron supplementation based on red blood cell parameters. 1
Potential Explanations for This Pattern
Hereditary hemochromatosis with early presentation – Filipino ancestry has lower prevalence than Northern European, but it must be excluded. 1
Thalassemia trait – common in Filipino populations, causes ineffective erythropoiesis with increased iron absorption despite adequate iron stores. 2
Chronic liver disease – impairs hepcidin production, leading to unregulated iron absorption. 1
Dysmetabolic iron overload syndrome – associated with metabolic syndrome, causes elevated transferrin saturation with normal-to-low ferritin. 1
Management Algorithm
Step 1: Confirm iron overload with repeat fasting iron studies (serum iron, TIBC, transferrin saturation, ferritin). 1
Step 2: Order HFE genetic testing for C282Y and H63D mutations. 1
Step 3: If genetic testing is negative, evaluate for secondary causes:
- Complete blood count with red cell indices to assess for thalassemia (low MCV, elevated RBC count). 2
- Hemoglobin electrophoresis if thalassemia suspected. 2
- Liver ultrasound or MRI to assess hepatic iron content. 2
Step 4: If hereditary hemochromatosis confirmed (homozygous C282Y or compound heterozygous C282Y/H63D):
- Initiate therapeutic phlebotomy to reduce iron stores. 2
- Target ferritin <50 ng/mL and transferrin saturation <50%. 2
- Perform phlebotomy weekly (500 mL) until targets achieved, then maintenance every 2-4 months. 2
Step 5: If secondary iron overload identified, treat underlying condition and consider phlebotomy if transferrin saturation remains >50%. 2
Critical Pitfalls to Avoid
Do not prescribe oral or intravenous iron – this will worsen organ damage from iron deposition. 1
Do not attribute the low ferritin to iron deficiency – in the presence of 80% transferrin saturation, the ferritin does not reflect true iron stores. 1
Do not delay genetic testing – early diagnosis and treatment of hemochromatosis prevents cirrhosis, diabetes, and cardiomyopathy. 2
Do not overlook thalassemia screening – Filipino ancestry carries significant risk, and thalassemia patients should never receive iron supplementation. 2
Do not use ferritin alone to guide therapy – transferrin saturation is the primary screening test for iron overload. 1