What are the implications and treatment options for an adult patient with a high Red Cell Distribution Width (Rdw) value, potentially indicating iron deficiency anemia or other underlying conditions?

High RDW: Diagnostic Approach and Management

A high RDW (>14-16%) in an adult patient most strongly suggests iron deficiency anemia and mandates immediate serum ferritin testing, followed by comprehensive gastrointestinal evaluation in adult men and post-menopausal women to exclude malignancy. 1

Understanding High RDW

• High RDW reflects anisocytosis (heterogeneous red cell populations), which occurs as iron stores become progressively depleted, creating a distinctive signature of iron deficiency 1
• The combination of high RDW with low MCV is pathognomonic for iron deficiency anemia, strongly distinguishing it from thalassemia trait (which typically has normal or only slightly elevated RDW) 1, 2, 3
• High RDW can also indicate active erythropoiesis in hemoglobinopathies, hemolytic anemias, or combined nutritional deficiencies (iron plus folate or B12) 4, 1
• Elevated RDW beyond anemia has prognostic significance in cardiovascular disease, thromboembolism, chronic diseases, and mortality risk in the general population 5

Immediate Diagnostic Workup

Confirm Iron Deficiency

• Serum ferritin is the single most powerful test and must be obtained immediately 1
  • Ferritin <12 μg/L is diagnostic of iron deficiency regardless of inflammatory status 6
  • Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation 1, 6
  • Ferritin <100 μg/L may still indicate iron deficiency if concurrent inflammation, malignancy, or hepatic disease is present 1, 6

Additional Laboratory Tests

• Measure transferrin saturation (<30% supports iron deficiency) 1, 6
• Check C-reactive protein (CRP) to interpret ferritin correctly in the context of inflammation 1, 6
• Obtain reticulocyte count to assess bone marrow response 6
• Review complete blood count parameters: low MCH and low MCHC alongside high RDW further support iron deficiency 6

Population-Specific Investigation Algorithms

Adult Men and Post-Menopausal Women

Complete gastrointestinal evaluation is mandatory regardless of symptom presence or severity of anemia 1, 6:

• Upper endoscopy with mandatory small bowel biopsies to exclude malignancy and detect coeliac disease (present in 2-3% of IDA patients) 1, 6
• Colonoscopy or CT colonography to exclude colonic cancer/polyps 1
• Common GI sources to investigate: NSAID use, colorectal cancer/polyps, gastric cancer, angiodysplasia, coeliac disease, Crohn's disease, ulcerative colitis 1, 6
• Even mild anemia warrants investigation, as severity does not correlate with likelihood of serious underlying disease 1

Young Women (Premenopausal)

GI investigation is NOT routinely indicated unless specific risk factors are present 7:

• Screen all for coeliac disease (found in up to 4% of cases) 7
• Endoscopic investigation is appropriate if:
  • Age over 50 years 7
  • Non-menstruating (e.g., post-hysterectomy) 7
  • Red flag symptoms per NICE guidelines 7
  • Major genetic risk of GI pathology 7
  • Recurrent or persistent IDA disproportionate to menstrual losses 7

Young Men

Confirmed IDA warrants the same investigational algorithm as older people (complete upper and lower GI evaluation), as the yield of pathology is considerably higher than in women of the same age 7

Treatment Protocol

Iron Supplementation

• Initiate oral iron supplementation immediately once iron deficiency is confirmed (ferritin <30 μg/L) 1, 8
• Continue treatment for 3-6 months after hemoglobin normalizes to replete iron stores 1
• Response to three weeks of oral iron can confirm true iron deficiency if diagnostic uncertainty remains 6
• Consider intravenous iron for malabsorption, intolerance, or severe deficiency 7

Address Underlying Cause

• Stop NSAIDs and aspirin whenever possible 6
• Address any identified GI pathology through appropriate treatment 1
• Anticoagulant use should not deter investigation but may need adjustment based on findings 6

Critical Pitfalls to Avoid

• Do not assume thalassemia based on ethnicity alone: high RDW strongly argues against thalassemia trait and favors iron deficiency 6, 3
• Do not skip GI investigation in adult men and post-menopausal women: occult malignancy must be excluded 6
• Do not overlook combined deficiencies: iron deficiency can coexist with folate or B12 deficiency, which may normalize MCV but maintain elevated RDW 6
• Do not attribute IDA to dietary causes without investigation: GI blood loss is the most common cause in adult men and post-menopausal women 6
• Do not empirically treat with iron based solely on anemia without confirming iron deficiency: low RDW makes iron deficiency less likely 9

Special Considerations in Elderly Patients

• Iron deficiency is often multifactorial in the elderly, affecting >20% of those over 85 years 7
• Carefully weigh risks and benefits of invasive endoscopic investigation in those with major comorbidities and/or limited performance status 7