Should iron replacement be initiated in a patient with iron deficiency (ID), high ferritin levels, extreme fatigue, and leukocytosis?

From the Guidelines

Iron replacement should not be initiated in a patient with iron deficiency, high ferritin levels, extreme fatigue, and leukocytosis without further investigation, as this clinical picture presents a paradox that requires resolution before treatment. High ferritin levels typically indicate adequate or excess iron stores, which contradicts the diagnosis of iron deficiency. The combination of high ferritin, extreme fatigue, and leukocytosis suggests an inflammatory condition, infection, or possibly a hematologic disorder that needs to be identified first. Ferritin is an acute phase reactant that increases during inflammation, potentially masking underlying iron deficiency 1.

Before initiating iron therapy, additional testing should be performed, including:

• Complete blood count with differential
• Comprehensive metabolic panel
• C-reactive protein or ESR to assess inflammation
• Possibly transferrin saturation and total iron binding capacity to better evaluate iron status Once the underlying cause is identified and true iron deficiency is confirmed despite elevated ferritin, appropriate iron replacement can be considered, typically starting with oral ferrous sulfate 325 mg daily or alternative iron formulations if oral therapy is not tolerated. It's also important to note that in cases of inflammatory anemia, IV iron administration may be necessary, and recent data suggest that ferric carboxymaltose may be a suitable option 1.

In patients with inflammation, a serum ferritin up to 100 mg/L may still be consistent with iron deficiency 1, and measurement of transferrin saturation may be helpful in evaluating iron status. The decision to supplement iron in patients without anaemia is more controversial and will depend on the patients' history, symptoms, and individual preferences. Iron supplementation in the presence of normal or even high ferritin values is, however, not recommended and is potentially harmful 1.

Overall, a thorough evaluation of the patient's condition is necessary to determine the best course of treatment, and iron replacement should only be initiated after careful consideration of the potential benefits and risks. The most recent and highest quality study 1 suggests that iron deficiency should be treated when it is associated with anemia and/or low ferritin levels, and that IV iron administration may be necessary in certain cases.

From the FDA Drug Label

16 HOW SUPPLIED Ferrous Sulfate Tablets are available as follows: Each tablet contains 324mg of ferrous sulfate, equivalent to 65mg of elemental iron, providing 362% of the U.S. recommended daily intake (RDI) of iron for adults and children 4 and older. Available in bottles of 100 tablets (NDC 72789-322-01)

The FDA drug label does not answer the question.

From the Research

Iron Replacement Considerations

• The patient's high ferritin level (481) may indicate an acute phase reaction or an underlying condition, rather than iron overload 2.
• Iron deficiency is typically diagnosed by low serum ferritin (<30 ng/mL) in individuals without inflammatory conditions 3, 4, 5.
• However, in this case, the patient's ferritin level is elevated, which may be due to an acute phase reaction or an underlying condition, rather than iron deficiency 2.
• The patient's symptoms, such as extreme fatigue, may be related to iron deficiency, despite the high ferritin level 3, 4, 5.
• Leukocytosis (WBC 15) may indicate an underlying infection or inflammatory condition, which could be contributing to the elevated ferritin level 2.

Diagnostic Considerations

• Further testing, such as transferrin saturation or bone marrow iron content, may be necessary to determine the patient's iron status 3, 6.
• The patient's medical history, physical examination, and laboratory results should be carefully evaluated to determine the underlying cause of the elevated ferritin level and leukocytosis 2.

Treatment Considerations

• Iron replacement therapy may be considered if the patient is found to have iron deficiency, despite the high ferritin level 3, 4, 5.
• However, the patient's elevated ferritin level and leukocytosis should be carefully monitored, as they may indicate an underlying condition that requires alternative treatment 2.
• The patient's response to iron replacement therapy should be closely monitored, and adjustments to the treatment plan should be made as necessary 3, 4, 5.