What is the diagnosis and treatment for a patient with elevated Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Red Cell Distribution Width (RDW)?

Elevated MCV, MCH, and RDW: Diagnostic Approach

The combination of elevated MCV, MCH, and RDW most strongly suggests vitamin B12 or folate deficiency, though this pattern can also indicate early iron deficiency coexisting with macrocytosis, myelodysplastic syndrome, or hemolysis. 1

Understanding This Pattern

The elevated RDW is the critical finding here—it indicates a wide variation in red blood cell sizes (anisocytosis), which helps distinguish between different causes of macrocytosis. 1

• High RDW with elevated MCV/MCH suggests either vitamin deficiency (B12 or folate) or a mixed deficiency state where both microcytic and macrocytic processes coexist, neutralizing each other's effect on MCV while still producing heterogeneous cell sizes. 1
• RDW is highly sensitive (62.5-75%) for detecting B12, folate, and iron deficiencies, though it lacks specificity for determining which deficiency is present. 2
• Approximately 31-35% of patients with pernicious anemia can have normal RDW despite B12 deficiency, so a normal RDW does not exclude this diagnosis. 3

Essential Diagnostic Workup

Minimum laboratory evaluation must include: 1

• Reticulocyte count (distinguishes deficiency states from hemolysis or bone marrow disorders)
• Serum ferritin and transferrin saturation (iron status)
• Vitamin B12 and folate levels (macrocytic deficiency evaluation)
• CRP (identifies inflammation that affects ferritin interpretation)
• Peripheral blood smear (evaluates for megaloblastic changes, though only 30% of vitamin deficiency cases show clear megaloblastic features) 4
• Haptoglobin and LDH if reticulocytes are elevated (to assess for hemolysis) 1

Algorithmic Interpretation

Step 1: Check Reticulocyte Count 1

If reticulocytes are LOW or NORMAL:

• Vitamin B12 deficiency (check B12 level, consider methylmalonic acid if borderline)
• Folate deficiency (check folate level)
• Myelodysplastic syndrome (especially if age >60, requires hematology referral)
• Combined iron and vitamin deficiency (the high RDW suggests this possibility)
• Medication effect (azathioprine, 6-mercaptopurine) 1
• Hypothyroidism or chronic liver disease 4

If reticulocytes are ELEVATED:

• Hemolytic anemia (check haptoglobin, LDH, direct antibody test)
• Recent bleeding with reticulocyte response
• Note: Elevated reticulocytes exclude deficiency states 1

Step 2: Assess Iron Status 1

• Ferritin <30 μg/L (without inflammation) confirms iron deficiency
• Ferritin <100 μg/L (with inflammation/elevated CRP) may still indicate iron deficiency
• Transferrin saturation <30% supports iron deficiency 1
• Combined iron and vitamin deficiency is uncommon but possible, particularly in malabsorption states 1

Step 3: Evaluate for Vitamin Deficiency 5, 4

For B12 deficiency:

• Serum B12 level is first-line test
• If B12 is low-normal (200-400 pg/mL) with high clinical suspicion, check methylmalonic acid
• Macrocytosis (MCV >105 fL) with elevated RDW strongly suggests B12 or folate deficiency 4
• MCV levels can differentiate diagnostic categories—higher MCV values more specific for vitamin deficiency 4

For folate deficiency:

• Serum or red cell folate level
• Often coexists with B12 deficiency or malabsorption 6

Treatment Based on Diagnosis

If Vitamin B12 Deficiency Confirmed: 5

Immediate treatment is critical to prevent irreversible neurologic damage:

• Cyanocobalamin 100 mcg IM daily for 6-7 days
• Then 100 mcg IM on alternate days for 7 doses
• Then 100 mcg IM every 3-4 days for 2-3 weeks
• Maintenance: 100 mcg IM monthly for life 5
• If folate deficiency coexists, administer folic acid concomitantly 5

If Folate Deficiency Confirmed:

• Oral folic acid supplementation
• Critical warning: Never give folic acid alone if B12 deficiency is not excluded—folic acid can correct the anemia but allows irreversible neurologic damage from B12 deficiency to progress 5

If Iron Deficiency Confirmed: 1

• Oral iron supplementation (or IV iron if malabsorption or intolerance)
• Investigate source of blood loss, particularly gastrointestinal in men and postmenopausal women
• Upper endoscopy with small bowel biopsy and colonoscopy to exclude malignancy 1

Critical Pitfalls to Avoid

• Never assume folic acid supplementation is adequate without excluding B12 deficiency—this can mask anemia while allowing spinal cord degeneration 5
• Do not delay B12 treatment if deficiency is suspected—neurologic damage becomes irreversible after 3 months 5
• High ferritin does not exclude iron deficiency in inflammatory states; ferritin up to 100 μg/L may still represent iron deficiency when inflammation is present 1
• Normal RDW does not exclude vitamin deficiency—31% of pernicious anemia patients have normal RDW 3
• Macrocytosis may be masked by coexisting iron deficiency, resulting in normal MCV but elevated RDW 1
• In patients with pernicious anemia, there is 3-fold increased risk of gastric carcinoma, requiring appropriate surveillance 5

When to Refer to Hematology

Immediate hematology consultation if: 1

• Cause remains unclear after complete workup
• Suspicion for myelodysplastic syndrome (age >60, cytopenias, dysplastic features on smear)
• Hemolytic anemia confirmed
• Pancytopenia present
• No response to appropriate vitamin or iron replacement after 2-3 weeks