What is the best approach to manage anemia in a patient with rheumatoid arthritis (RA), thrombocytosis, and an elevated platelet count?

Management of Anemia in Rheumatoid Arthritis with Thrombocytosis

The primary approach is to optimize RA disease control while simultaneously investigating and treating the specific type of anemia, recognizing that the elevated platelet count (530) and anemia likely reflect active inflammatory disease requiring aggressive disease-modifying therapy. 1

Understanding the Clinical Picture

The combination of anemia and thrombocytosis in RA is characteristic of active inflammatory disease. Thrombocytosis accompanies more severe cases of rheumatoid disease and correlates inversely with hemoglobin levels, reflecting compensatory platelet production associated with active intravascular coagulation and inflammation. 2 This presentation suggests anemia of chronic disease (ACD), though iron deficiency must be excluded as it commonly coexists. 3, 4

Diagnostic Algorithm

Step 1: Determine the Type of Anemia

Measure serum ferritin, mean corpuscular volume (MCV), and transferrin saturation to distinguish between anemia of chronic disease and iron deficiency without requiring bone marrow biopsy in most cases. 1, 4

• If ferritin <100 μg/L: Iron deficiency is likely, even though inflammatory conditions can elevate ferritin up to 100 μg/L 1
• If ferritin >100 μg/L with low transferrin saturation (<30%): Suggests ACD 4
• If MCV is low with ferritin 15-100 μg/L: Use a 3-step algorithm: ferritin <50 μg/L indicates iron deficiency; ferritin >100 μg/L suggests ACD; intermediate values (50-100 μg/L) require transferrin saturation assessment 4

Step 2: Additional Diagnostic Tests

• Check C-reactive protein to assess inflammatory activity 1
• Measure reticulocyte count and obtain peripheral blood smear 1
• Calculate soluble transferrin receptor (sTfR)/log ferritin ratio if available: ratio <1 indicates ACD, ratio >2 suggests iron deficiency 3

Step 3: Investigate for Blood Loss

Screen for gastrointestinal blood loss and coeliac disease, particularly if iron deficiency is confirmed, as these are common causes even in RA patients. 5, 1 This is critical because assuming anemia is purely disease-related without excluding occult bleeding can miss treatable pathology. 5

Treatment Strategy

Primary Intervention: Optimize RA Disease Control

The cornerstone of treating anemia in RA is achieving optimal control of systemic disease activity with disease-modifying antirheumatic drugs (DMARDs) and/or biologics. 1, 6 The thrombocytosis will typically resolve as inflammation is controlled. 2

• IL-6 is the key driver of both anemia and thrombocytosis through hepcidin upregulation, making IL-6 antagonists (tocilizumab) particularly effective for this presentation 3, 7
• Second-line agents and corticosteroids have historically been used to control the underlying disease 6

Iron Supplementation

For confirmed iron deficiency, initiate oral ferrous sulfate 200 mg twice daily and continue for 3 months after anemia correction to replenish stores. 5, 1

However, intravenous iron is preferred in RA patients with active inflammation because it overcomes hepcidin-induced absorption blockade that limits oral iron efficacy. 1, 3 Options include:

• Iron sucrose (Venofer) 200 mg over 10 minutes 5
• Ferric carboxymaltose (Ferinject) up to 1000 mg over 15 minutes 5
• Iron dextran (Cosmofer) up to 20 mg/kg over 6 hours (higher anaphylaxis risk 0.6-0.7%) 5

Erythropoiesis-Stimulating Agents

Consider erythropoietin only after optimizing RA treatment and if there is insufficient response to intravenous iron, with a target hemoglobin not exceeding 12 g/dL. 1 This is reserved for refractory cases, as controlling inflammation is more effective. 6

Blood Transfusion

Reserve transfusions for hemoglobin <7 g/dL, or >7 g/dL if the patient is symptomatic or has cardiovascular risk factors. 1 Follow transfusions with intravenous iron supplementation to address underlying deficiency. 1

Monitoring

Recheck hemoglobin after initiating treatment to assess response. 1 If hemoglobin cannot be restored or maintained with iron therapy, investigate for occult blood loss or small bowel disease. 1 Screen for Helicobacter pylori in patients with recurrent iron deficiency and normal endoscopic findings, and eradicate if present. 5, 1

Critical Pitfalls to Avoid

• Do not assume anemia is purely disease-related without excluding iron deficiency—47% of anemic RA patients have true iron deficiency 4
• Do not rely on ferritin alone in inflammatory states—it can be falsely elevated up to 100 μg/L 1
• Do not use oral iron as first-line in active inflammation—hepcidin blocks absorption, making intravenous iron more effective 1, 3
• Do not overlook gastrointestinal pathology, particularly if using NSAIDs or methotrexate, which can cause occult bleeding 5, 8
• Monitor for methotrexate-induced bone marrow suppression with monthly complete blood counts, as this can worsen anemia and thrombocytopenia 8