What is the next step in managing a patient with mild anemia (low hemoglobin (HGB) level of 13.6 g/dL), thrombocytopenia (low platelet (PLT) count of 90 K/uL), and elevated red cell distribution width (RDW) of 20.3%?

Management of Mild Anemia with Thrombocytopenia and Elevated RDW

The immediate next step is to obtain serum ferritin, transferrin saturation, and C-reactive protein to confirm iron deficiency, followed by comprehensive gastrointestinal evaluation with upper endoscopy (including small bowel biopsies) and colonoscopy to exclude malignancy and identify the source of blood loss. 1, 2

Understanding This Clinical Pattern

This constellation of findings—borderline low hemoglobin (13.6 g/dL), thrombocytopenia (90 K/uL), and markedly elevated RDW (20.3%)—requires systematic evaluation for multiple potential etiologies:

The Elevated RDW is the Critical Clue

• The RDW of 20.3% is significantly elevated and pathognomonic for iron deficiency when combined with low-normal MCV (89.3 fL) and low-normal MCH (28.6%). 1, 2
• High RDW reflects heterogeneous red cell populations with varying sizes as iron stores become progressively depleted, creating a distinctive signature that distinguishes iron deficiency from other causes. 1, 2
• The combination of borderline anemia with markedly elevated RDW indicates early-stage iron deficiency—normal hemoglobin does not exclude iron deficiency and may represent compensated iron depletion. 1

The Thrombocytopenia Requires Parallel Investigation

• Platelet count of 90 K/uL (grade 2 thrombocytopenia) mandates workup for autoimmune disease and exclusion of DIC or other causes of thrombocytopenia. 3
• The combination of mild anemia and thrombocytopenia raises concern for bone marrow pathology, consumptive processes, or immune-mediated cytopenias. 4

Immediate Diagnostic Workup

Confirm Iron Deficiency

• Serum ferritin is the single most powerful test and must be obtained immediately: 2
  • Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation 1, 2
  • Ferritin <100 μg/L may still indicate iron deficiency if concurrent inflammation is present 2
• Transferrin saturation <30% supports iron deficiency diagnosis. 1, 2
• C-reactive protein (CRP) is essential to interpret ferritin correctly, as inflammation elevates ferritin and can mask true iron deficiency. 1, 2

Evaluate the Thrombocytopenia

• Peripheral blood smear review (already completed per your report) to assess for schistocytes, platelet clumping, or morphologic abnormalities. 4, 5
• Coagulation studies (PT, aPTT, fibrinogen, D-dimer) to exclude DIC—the presence of consumptive coagulopathy with thrombocytopenia supports DIC, not TTP-HUS. 5
• Direct Coombs test to evaluate for hemolytic anemia if there are features suggesting hemolysis. 3

Mandatory Gastrointestinal Investigation

This is non-negotiable regardless of symptom presence or severity of anemia:

• Upper endoscopy with mandatory small bowel biopsies to exclude malignancy and detect celiac disease (present in 2-3% of iron deficiency anemia patients). 2
• Colonoscopy or CT colonography to exclude colonic cancer/polyps—dual pathology occurs in ~10% of patients, so lower GI evaluation is mandatory even if upper GI source is found. 1, 2
• All adult men and post-menopausal women with confirmed iron deficiency require complete gastrointestinal evaluation, as even mild anemia warrants investigation since severity does not correlate with likelihood of serious underlying disease. 1, 2

Treatment Approach

For Iron Deficiency

• Initiate oral iron supplementation immediately once iron deficiency is confirmed (ferritin <30 μg/L). 1, 2
• Continue iron for 3-6 months after hemoglobin normalizes to replete iron stores. 1, 2
• Address underlying causes including stopping NSAIDs and anticoagulants whenever possible. 2

For Thrombocytopenia

• At platelet count of 90 K/uL, patients are generally asymptomatic but should adhere to activity restrictions to avoid trauma-associated bleeding. 4
• Monitor closely while continuing evaluation—this grade 2 thrombocytopenia does not require immediate intervention unless bleeding occurs or invasive procedures are planned. 3
• If immune-mediated thrombocytopenia is confirmed and progressive, consider steroid intervention pending clinical condition. 3

Critical Pitfalls to Avoid

• Never assume normal or borderline hemoglobin excludes significant pathology—mild anemia or pre-anemic iron deficiency can indicate serious underlying disease including malignancy. 1
• Do not provide empiric iron therapy without confirming iron deficiency with ferritin testing, as this can cause harm in thalassemia patients and delays proper diagnosis. 1
• Do not transfuse platelets empirically—platelet transfusions are generally contraindicated if the underlying disorder is TTP or immune thrombocytopenia, as transfusion may fuel thrombosis and worsen clinical outcomes. 5
• Do not delay GI evaluation waiting for anemia to worsen—the combination of elevated RDW with borderline anemia mandates immediate investigation for GI blood loss and malignancy. 1, 2

Special Considerations for Combined Cytopenias

• If multiple cell lines are affected or pancytopenia develops, evaluation for pure red cell aplasia, autoantibodies, aplastic anemia, and myelodysplasia must be considered. 3
• If unexplained anemia and thrombocytopenia do not respond to initial management, consider bone marrow biopsy to exclude primary marrow pathology. 3