Microcytic Hypochromic Anemia with High RDW: Diagnosis and Management
The combination of low RBC count, low MCHC (hypochromic), and high RDW is pathognomonic for iron deficiency anemia (IDA) and mandates immediate serum ferritin testing followed by comprehensive gastrointestinal evaluation in adult men and post-menopausal women to exclude malignancy. 1
Diagnostic Significance of High RDW
- High RDW (>14-16.9%) is the critical distinguishing feature that differentiates iron deficiency anemia from thalassemia trait, which typically presents with normal or only slightly elevated RDW despite microcytosis 1, 2
- The elevated RDW reflects heterogeneous red cell populations as iron stores become progressively depleted, creating a distinctive signature for IDA 1
- Low MCV combined with elevated RDW is pathognomonic for iron deficiency anemia 1
Essential Laboratory Confirmation
Serum ferritin is the single most powerful test and must be obtained immediately to confirm iron deficiency: 1
- Ferritin <12 μg/dL is diagnostic of iron deficiency 1
- Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation 3, 1
- Ferritin <100 μg/L may still indicate iron deficiency if concurrent inflammation, malignancy, or hepatic disease is present 3, 1
- Transferrin saturation <30% supports iron deficiency 1, 4
- C-reactive protein (CRP) should be measured to interpret ferritin correctly in the context of inflammation 3, 1
Mandatory Gastrointestinal Investigation
All adult men and post-menopausal women with confirmed iron deficiency require complete gastrointestinal evaluation, regardless of symptom presence or severity of anemia: 1
- Upper endoscopy with mandatory small bowel biopsies to exclude malignancy and detect coeliac disease (present in 2-3% of IDA patients) 1
- Colonoscopy or CT colonography to exclude colonic cancer/polyps 1
- Common GI sources include NSAID use, colonic cancer/polyps, gastric cancer, angiodysplasia, coeliac disease, Crohn's disease, and ulcerative colitis 1
- Even mild anemia warrants investigation in adult men and post-menopausal women, as severity does not correlate with likelihood of serious underlying disease 1, 4
Treatment Protocol
Oral iron supplementation should be initiated immediately once iron deficiency is confirmed (ferritin <30 μg/L): 1
- Continue treatment for 3-6 months after hemoglobin normalizes to replete iron stores 1
- The vast majority of patients respond effectively to inexpensive and usually well-tolerated oral iron preparations 5
- In rare circumstances of malabsorption, losses exceeding maximal oral replacement, or true intolerance, parenteral iron dextran is effective 5
- Address the underlying cause of iron deficiency, including stopping NSAIDs and anticoagulants whenever possible, and addressing any identified GI pathology 1
Critical Differential Diagnosis Considerations
While high RDW strongly indicates IDA, exclude these alternative causes of microcytic anemia: 3
- Thalassemia trait: Presents with low MCV but normal or only slightly elevated RDW, confirmed with hemoglobin electrophoresis 1, 2
- Anemia of chronic disease: May present with normal or low MCV and normal MCH, but typically has normal or low RDW 3
- Combined deficiencies (iron plus folate or B12): May present with elevated RDW even when MCV appears normal 1, 4
- Rare genetic disorders of iron metabolism (IRIDA, sideroblastic anemia, congenital erythropoietic porphyria) should be considered if family history suggests autosomal recessive inheritance or if patient fails to respond to oral iron 3
Common Pitfalls to Avoid
- Do not assume thalassemia based on ethnicity alone when high RDW is present—high RDW makes thalassemia unlikely 1, 2
- Do not delay gastrointestinal investigation in adult men and post-menopausal women, even with mild anemia 1, 4
- Do not stop investigation after initiating iron supplementation—identifying the source of blood loss is mandatory 1
- Consider that ferritin is an acute phase reactant and may be falsely elevated in the presence of inflammation, requiring interpretation with CRP 3, 1