What does a high RDW (Red Cell Distribution Width) of 14.8 indicate?

High RDW of 14.8: Clinical Significance and Recommended Actions

An RDW of 14.8% is mildly elevated and indicates heterogeneous red blood cell populations, most commonly suggesting iron deficiency anemia, though it may also reflect chronic inflammation, nutritional deficiencies, or underlying systemic disease. 1, 2

Understanding Your RDW Value

• Your RDW of 14.8% exceeds the normal upper limit of 14.0%, indicating anisocytosis (variation in red blood cell size) 1, 2
• This elevation reflects the presence of both older normal-sized cells and newer abnormally-sized cells circulating simultaneously 1
• The degree of elevation is mild but clinically significant and warrants further investigation 2

Most Likely Causes to Investigate

Iron Deficiency Anemia (Primary Consideration)

• Iron deficiency is the most common cause of elevated RDW >14.0%, particularly when combined with low MCV (microcytosis) 3, 1
• The combination of low MCV + high RDW strongly indicates iron deficiency rather than thalassemia trait (which typically shows low MCV + normal RDW) 2
• Even with normal MCV, elevated RDW may indicate early or combined iron deficiency with other nutritional deficiencies 3, 2

Chronic Inflammation and Systemic Disease

• Inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease, and chronic infections can elevate RDW through oxidative stress and erythrocyte membrane damage 3, 1
• COVID-19 and other viral illnesses cause substantial RDW increases due to reduced red cell deformability and complement deposition 3, 2
• Malignancies, particularly lung cancer and lymphomas, are associated with elevated RDW through increased eryptosis (programmed red cell death) 2, 4

Essential Diagnostic Workup

Order these tests immediately to determine the underlying cause: 1, 2

1. Serum ferritin (most powerful test for iron deficiency):

   • <30 μg/L confirms iron deficiency in absence of inflammation 3, 2
   • <100 μg/L suggests iron deficiency when inflammation is present 3, 2

   • 100 μg/L makes iron deficiency unlikely 3

2. Complete blood count with MCV:

   • Low MCV + high RDW = iron deficiency anemia 1, 2
   • Normal MCV + high RDW = early iron deficiency, vitamin B12/folate deficiency, or hemolysis 2
   • Low MCV + normal RDW = thalassemia trait 2

3. Transferrin saturation:

   • <20% supports iron deficiency diagnosis 2
   • <30% may help confirm diagnosis when ferritin is equivocal 3

4. C-reactive protein (CRP):

   • Elevated CRP indicates inflammation, which can falsely elevate ferritin 2
   • Helps distinguish iron deficiency from anemia of chronic disease 2

5. Reticulocyte count:

   • Assesses bone marrow response and helps differentiate causes 2

Investigation for Source of Iron Deficiency

If iron deficiency is confirmed, investigate the underlying cause: 3

In Adult Men and Post-Menopausal Women:

• Gastrointestinal blood loss is the most common cause and requires investigation to exclude malignancy 3
• Upper endoscopy with small bowel biopsy (to exclude celiac disease) 3
• Colonoscopy or alternative lower GI imaging to exclude colorectal cancer, polyps, or angiodysplasia 3
• Document NSAID use and discontinue if possible, as this is a common cause of occult GI bleeding 3

In Pre-Menopausal Women:

• Menstrual blood loss is the most common cause 3
• Still investigate for GI sources if menstrual losses seem inadequate to explain severity 3

Additional Considerations:

• Dietary history to identify iron-deficient diets, though borderline deficient diets alone should not preclude full GI investigation 3
• Previous gastric surgery or malabsorption syndromes (celiac disease most common) 3

Treatment Approach

If iron deficiency is confirmed: 1, 2

• Initiate oral iron supplementation: ferrous sulfate 325 mg daily (or equivalent elemental iron 65 mg daily) 1
• Recheck complete blood count in 4-6 weeks to confirm reticulocyte response and declining RDW 1
• A therapeutic response to three weeks of oral iron helps confirm true iron deficiency 3

If inflammation or chronic disease is identified: 2

• Address the underlying inflammatory disorder as primary treatment 2
• Iron supplementation may still be needed if concurrent iron deficiency is documented 2

Prognostic Implications

Elevated RDW carries prognostic significance beyond anemia diagnosis: 5

• High RDW is an independent risk factor for mortality in cardiovascular disease, with RDW >14% associated with increased 5-year mortality in myocardial infarction patients 6
• In cancer patients, elevated RDW predicts worse outcomes, including lower complete response rates and shorter overall survival 7, 4
• RDW reflects underlying metabolic derangements including oxidative stress, inflammation, poor nutritional status, and impaired erythropoiesis 5

Critical Pitfalls to Avoid

• Do not assume dietary insufficiency alone explains iron deficiency without completing GI investigation, as asymptomatic GI malignancies commonly present with iron deficiency anemia 3
• Do not rely on RDW alone to distinguish thalassemia from iron deficiency, as nearly half of thalassemia cases may have elevated RDW 8
• Do not ignore mild anemia or assume it is less significant than severe anemia, as mild anemia may be equally indicative of serious underlying disease 3
• If ferritin is between 12-100 μg/L, consider concurrent inflammation or malignancy that may falsely elevate ferritin despite true iron deficiency 3
• If neutropenia or other cytopenias coexist with elevated RDW, pursue autoimmune or infectious workup even after addressing iron deficiency 1