How to manage leukocytosis (elevated white blood cell count) in a patient with iron deficiency anemia?

Management of Leukocytosis in Iron Deficiency Anemia

In patients with iron deficiency anemia who present with leukocytosis, iron supplementation should be the primary treatment as it will correct both the anemia and the associated leukocytosis. 1

Understanding Leukocytosis in Iron Deficiency

Iron deficiency can occasionally present with not only anemia but also with abnormal white blood cell counts. While leukocytosis is not a typical feature of iron deficiency anemia, there are documented cases where:

• Reactive leukocytosis can occur as a secondary phenomenon to iron deficiency 2
• Chronic unexplained leukopenia (low white blood cell count) may resolve with iron supplementation 1
• Extreme thrombocytosis (elevated platelets) can accompany leukocytosis in severe iron deficiency 2

Diagnostic Approach

When encountering leukocytosis in a patient with iron deficiency anemia:

1. Confirm iron deficiency diagnosis:

   • Check serum ferritin (most powerful test for iron deficiency) 3
   • Ferritin <15 μg/L is diagnostic of iron deficiency 3
   • In patients with inflammation, higher thresholds may apply (ferritin up to 100 μg/L) 4
   • Assess transferrin saturation (TSAT <20% suggests iron deficiency) 4

2. Evaluate the leukocytosis:

   • Rule out common causes of leukocytosis:
     • Infections or inflammatory processes
     • Physical or emotional stress
     • Medications (corticosteroids, lithium, beta agonists) 5
   • Check for concerning features that suggest primary bone marrow disorders:
     • WBC count >100,000/mm³ (medical emergency)
     • Concurrent abnormalities in RBC or platelet counts
     • Weight loss, bleeding, bruising
     • Hepatosplenomegaly or lymphadenopathy 5

Treatment Algorithm

1. Initiate iron supplementation:

   • Oral iron is first-line therapy: ferrous sulfate 200 mg three times daily 3
   • Alternative preparations include ferrous gluconate or ferrous fumarate if better tolerated 3
   • Continue iron supplementation for three months after correction of anemia to replenish iron stores 3

2. Consider parenteral iron if:

   • Intolerance to at least two oral preparations
   • Non-compliance with oral therapy
   • Need for rapid iron repletion 3, 4

3. Monitor response:

   • Hemoglobin should rise by 2 g/dL after 3-4 weeks 3
   • Check ferritin and transferrin saturation after 2-4 weeks of therapy 4
   • Monitor WBC count to confirm resolution of leukocytosis
   • Target ferritin level of at least 100 ng/mL 4

4. Address underlying cause of iron deficiency:

   • For men and postmenopausal women: investigate GI tract (upper and lower endoscopy) 3
   • Screen all patients for celiac disease 3
   • For premenopausal women: evaluate for menorrhagia and other gynecological causes 3

Special Considerations

• If leukocytosis persists despite iron repletion, consider:

  • Concurrent infection or inflammation
  • Medication-induced leukocytosis
  • Primary hematologic disorder requiring hematology consultation

• If extreme leukocytosis (>100,000/mm³):

  • Consider urgent hematology consultation
  • This represents a medical emergency due to risk of brain infarction and hemorrhage 5

• Follow-up monitoring:

  • Once normal, monitor hemoglobin and red cell indices at 3-month intervals for one year, then after another year 3
  • Additional iron should be given if hemoglobin or MCV falls below normal 3

Pitfalls to Avoid

• Failing to investigate the underlying cause of iron deficiency
• Misinterpreting ferritin levels in the presence of inflammation
• Inadequate duration of iron supplementation
• Attributing leukocytosis solely to other causes without recognizing the potential relationship with iron deficiency
• Failing to monitor both hemoglobin and white blood cell counts during treatment

By following this approach, both the iron deficiency anemia and associated leukocytosis should resolve with appropriate iron supplementation while ensuring any underlying causes are properly identified and addressed.