Management of Iron Deficiency with Thrombocytosis
Treat the iron deficiency with oral iron supplementation (ferrous sulfate 200 mg twice daily) and investigate for underlying gastrointestinal pathology, as the elevated platelets are a reactive phenomenon that will resolve with iron repletion. 1
Understanding the Relationship
The thrombocytosis you're seeing is reactive thrombocytosis secondary to iron deficiency, not a primary hematologic disorder. 2, 3 This is a well-recognized phenomenon where:
- Iron-depleted patients have significantly higher platelet counts compared to those with normal iron stores (mean difference approximately 18-24 × 10³/µL higher) 3
- Extreme thrombocytosis (>1000 × 10³/µL) can occur with severe iron deficiency, though most cases show mild-to-moderate elevation 2
- Platelet counts decrease by an average of 20,000/µL following iron replacement therapy 3
Immediate Management Priorities
1. Confirm Iron Deficiency
- Serum ferritin is the most powerful diagnostic test for iron deficiency 1
- Ferritin <12-15 µg/dL confirms iron deficiency 1
- Red cell indices (microcytosis, hypochromia) provide sensitive indication in the absence of chronic disease 1
- Screen for coeliac disease in all patients 1
2. Investigate the Underlying Cause
For men and postmenopausal women: Upper and lower GI investigations should be performed to exclude malignancy unless there is obvious non-GI blood loss 1
The investigation algorithm includes:
- Upper GI endoscopy with small bowel biopsies (to screen for coeliac disease, which occurs in 2-3% of IDA patients) 1
- Colonoscopy or CT colography for lower GI evaluation 1
- Both investigations are necessary even if one reveals a benign lesion, as dual pathology occurs in 10-15% of patients 1
For premenopausal women: Screen for coeliac disease; reserve upper/lower GI investigations for those >45 years, those with GI symptoms, or those not responding to iron therapy 1
3. Initiate Iron Replacement
All patients require iron supplementation to correct anemia and replenish stores: 1
- First-line: Ferrous sulfate 200 mg twice daily (lower doses may be better tolerated and equally effective) 1
- Continue for 3 months after correction to replenish stores 1
- Alternative oral preparations (ferrous fumarate, ferrous gluconate) if intolerance occurs 1
Parenteral iron options when oral iron fails or is not tolerated: 1
- Iron sucrose (Venofer): 200 mg over 10 minutes
- Ferric carboxymaltose (Ferinject): up to 1000 mg over 15 minutes
- Iron dextran (Cosmofer): can give total dose but carries higher anaphylaxis risk (0.6-0.7%)
The Thrombocytosis Component
Do NOT treat the elevated platelets directly - they are reactive and will normalize with iron repletion. 3, 4 However, be aware that:
- Iron deficiency with thrombocytosis may carry increased thromboembolic risk in both arterial and venous systems 4
- Only 4.4% of iron-deficient patients develop true thrombocytosis (>400 × 10³/µL) 3
- Rarely, severe iron deficiency can paradoxically cause thrombocytopenia rather than thrombocytosis 5
Common Pitfalls to Avoid
- Don't assume dietary deficiency alone - even with positive dietary history, full GI investigation is required in men and postmenopausal women 1
- Don't stop at finding one lesion - dual pathology is common; complete both upper and lower GI evaluation 1
- Don't accept benign upper GI findings (esophagitis, gastric erosions) as the sole cause without investigating the colon 1
- Don't initiate cytoreductive therapy for the thrombocytosis before ruling out reactive causes 2
- Don't forget to check for H. pylori if IDA persists after negative endoscopy, as eradication may reverse anemia 1
Monitoring Response
- Hemoglobin should rise by 2 g/dL after 3-4 weeks of oral iron 1
- Monitor hemoglobin and red cell indices every 3 months for one year, then annually 1
- Platelet counts will normalize as iron stores are repleted 3
- Failure to respond suggests non-compliance, continued blood loss, malabsorption, or misdiagnosis 1