Anemia with High Platelet Count and Low Iron
The most likely diagnosis is iron deficiency anemia (IDA) with reactive thrombocytosis, and you should immediately initiate iron supplementation while investigating the underlying cause of iron deficiency. 1
Diagnostic Approach
Initial Laboratory Evaluation
The minimum workup must include 1:
- Complete blood count with MCV and RDW
- Reticulocyte count
- Serum ferritin
- Transferrin saturation (TfS)
- CRP or ESR (critical for interpreting ferritin)
Interpreting Iron Studies
Without inflammation (normal CRP/ESR):
- Iron deficiency is confirmed if ferritin <30 μg/L or TfS <16% 1
With inflammation present (elevated CRP/ESR):
- Ferritin <100 μg/L still indicates iron deficiency 1
- Ferritin 30-100 μg/L with TfS <20% suggests combined iron deficiency and anemia of chronic disease 1
- Ferritin >100 μg/L with TfS <20% indicates anemia of chronic disease alone 1
Understanding the Thrombocytosis
Reactive thrombocytosis from iron deficiency is common but can be extreme:
- Platelet counts typically range 450-700 × 10³/μL, but can exceed 1,000 × 10³/μL 2, 3
- The highest reported case reached 1,953 × 10³/μL in severe iron deficiency 3
- Serum iron and transferrin saturation correlate inversely with platelet count - the more severe the iron deficiency, the higher the platelets 4
- Platelet counts normalize with iron repletion 2, 3, 4
Critical distinction: While extreme thrombocytosis (>1,000 × 10³/μL) raises concern for myeloproliferative neoplasm (especially essential thrombocythemia), reactive thrombocytosis from iron deficiency can reach these levels 2, 3
Investigating the Underlying Cause
Essential Evaluations
Gastrointestinal blood loss (most common):
- Stool guaiac testing for occult blood 1
- Consider endoscopy if indicated by symptoms or positive testing
- Celiac disease screening - can present without typical GI symptoms but cause severe iron deficiency and extreme thrombocytosis 2
Menstrual blood loss (in premenopausal women):
- Detailed menstrual history
- Gynecologic evaluation if excessive bleeding
Malabsorption syndromes:
- History of bariatric surgery (particularly important - can cause severe iron malabsorption) 3
- Celiac disease (small bowel biopsy if suspected) 2
- Inflammatory bowel disease 1
Chronic kidney disease:
- Serum creatinine and estimated GFR 1
Management Strategy
Iron Supplementation
Intravenous iron should be considered first-line treatment in patients with:
- Active inflammatory bowel disease 1
- Severe anemia (hemoglobin <8 g/dL) 1
- Intolerance to oral iron
- Need for rapid correction
Goal of treatment:
- Normalize hemoglobin levels and iron stores 1
- Expect hemoglobin increase of at least 2 g/dL within 4 weeks 1
- Monitor platelet count - should decrease as iron stores replete 2, 3, 4
Monitoring Response
Reassess at 4 weeks:
- Complete blood count (hemoglobin and platelet count)
- Reticulocyte count
- Iron studies (ferritin, transferrin saturation)
If inadequate response, consider:
- Non-compliance or inadequate dosing
- Ongoing blood loss
- Coexisting anemia of chronic disease 1
- Alternative diagnoses (vitamin B12/folate deficiency, bone marrow disorder) 1
Important Caveats
Thromboembolic risk: Iron deficiency with thrombocytosis may increase thromboembolic risk in both arterial and venous systems 5. While not universally established, consider this in patients with additional risk factors.
Don't assume myeloproliferative disease: Even with platelet counts >1,000 × 10³/μL, reactive thrombocytosis from iron deficiency remains possible 2, 3. However, if platelets remain elevated after iron repletion, bone marrow evaluation for essential thrombocythemia or other myeloproliferative neoplasm becomes necessary 1.
Inflammatory conditions complicate diagnosis: In inflammatory bowel disease, chronic kidney disease, or malignancy, ferritin can be falsely elevated despite true iron deficiency 1. Use the inflammation-adjusted ferritin threshold of <100 μg/L in these contexts 1.