What causes low MCV (Mean Corpuscular Volume), MCH (Mean Corpuscular Hemoglobin), MCHC (Mean Corpuscular Hemoglobin Concentration), high RDW (Red Cell Distribution Width), and slight traces of microcytosis and macrocytosis?

Mixed Microcytic and Macrocytic Anemia with High RDW

Your laboratory pattern of low MCV, MCH, MCHC with high RDW and traces of both microcytosis and macrocytosis indicates a mixed nutritional deficiency—most commonly iron deficiency coexisting with vitamin B12 or folate deficiency, where the opposing effects on red cell size neutralize each other to produce a falsely near-normal or low MCV. 1

Understanding the Laboratory Pattern

The key to interpreting your results is recognizing that microcytosis and macrocytosis can coexist simultaneously, causing the two abnormalities to neutralize each other and result in a paradoxically low or normal MCV 1. In this situation:

• High RDW (red cell distribution width) is the critical clue, as it indicates a wide size range of red cells and serves as a sensitive indicator of mixed deficiencies 1
• Low MCH is more sensitive than MCV for detecting iron deficiency and may reveal iron deficiency even when macrocytosis masks the expected microcytosis 2
• Low MCHC further supports iron deficiency (hypochromia) despite the presence of macrocytic cells 2

Most Likely Causes

Primary Diagnosis: Combined Iron and Vitamin Deficiency

Iron deficiency is the most common cause of microcytic anemia 3, 4, while macrocytosis typically indicates vitamin B12 or folate deficiency 1. When both occur together:

• The microcytic cells from iron deficiency mix with macrocytic cells from vitamin deficiency 1
• RDW becomes elevated (>14%) due to the wide variation in cell sizes 1, 5
• MCH and MCHC remain low because iron deficiency affects hemoglobin content regardless of cell size 2, 6

Additional Considerations

Medication-induced macrocytosis can occur with thiopurines (azathioprine, 6-mercaptopurine), particularly in inflammatory bowel disease patients, which may coexist with iron deficiency 2. This is especially relevant if you have:

• Crohn's disease or ulcerative colitis 1, 2
• Chronic inflammatory conditions causing both blood loss and impaired iron absorption 1

Reticulocytosis from recent hemorrhage or hemolysis can elevate MCV while iron deficiency from blood loss causes microcytosis 2. However, this would typically show elevated reticulocyte count 1.

Required Diagnostic Workup

Minimum Essential Tests

You need the following tests immediately to confirm the diagnosis 1:

• Serum ferritin (if <30 μg/L confirms iron deficiency; if 30-100 μg/L with inflammation, still suggests iron deficiency) 1, 2
• Transferrin saturation (low in iron deficiency) 1
• Vitamin B12 level (low indicates B12 deficiency) 1
• Folate level (low indicates folate deficiency) 1
• Reticulocyte count (low/normal suggests deficiency; elevated suggests hemolysis or hemorrhage) 1, 2
• CRP (to assess for inflammation that may affect ferritin interpretation) 1

Extended Workup If Initial Tests Are Inconclusive

If vitamin levels are normal but macrocytosis persists 2:

• Methylmalonic acid (specific for B12 deficiency with better sensitivity than serum B12) 2
• Homocysteine (elevated in tissue deficiency of B12 or folate despite normal serum levels) 2
• Haptoglobin, LDH, and bilirubin (if hemolysis suspected) 1, 2
• Peripheral blood smear to evaluate red cell morphology and look for schistocytes 2

Clinical Algorithm for Management

Step 1: Confirm Iron Deficiency

• If ferritin <30 μg/L or transferrin saturation <20%: Iron deficiency confirmed 1, 6
• If ferritin 30-100 μg/L with elevated CRP: Functional iron deficiency in inflammation 1, 2

Step 2: Confirm Vitamin Deficiency

• If B12 <200 pg/mL or folate <4 ng/mL: Vitamin deficiency confirmed 1
• If borderline levels with high RDW: Check methylmalonic acid and homocysteine 2

Step 3: Identify Underlying Cause

• Review medications for thiopurines, methotrexate, or other myelosuppressive agents 2
• Assess for gastrointestinal blood loss (most common cause of iron deficiency in adults) 3
• Evaluate for malabsorption if inflammatory bowel disease, celiac disease, or gastric surgery history 1, 2
• Check for dietary insufficiency or increased demands (pregnancy, menstruation) 3

Step 4: Treatment Approach

For confirmed iron deficiency 3:

• Oral iron supplementation (ferrous sulfate 325 mg daily) is first-line for most patients
• Intravenous iron if malabsorption, intolerance, or losses exceeding oral replacement capacity
• Must replete iron stores, not just correct anemia

For confirmed vitamin deficiency 1:

• B12 replacement (oral or intramuscular depending on cause)
• Folate supplementation if deficient
• Address underlying malabsorption if present

Monitor response 2:

• Repeat CBC in 4-8 weeks to verify MCV normalization and RDW improvement
• Reticulocyte count should increase within 1-2 weeks of appropriate treatment
• Continue monitoring even after correction, as deficiencies may recur

Critical Pitfalls to Avoid

• Do not assume normal MCV excludes iron deficiency when macrocytosis is present—the high RDW and low MCH/MCHC are your diagnostic clues 1, 2
• Do not rely on ferritin alone in inflammatory conditions—levels up to 100 μg/L may still indicate iron deficiency when inflammation is present 1, 2
• Do not stop at treating one deficiency—both iron and vitamin deficiencies must be addressed simultaneously in mixed patterns 1, 6
• Do not neglect follow-up—unexplained persistent abnormalities require hematology consultation to exclude bone marrow disorders 2

When to Consult Hematology

Seek hematology consultation if 1, 2:

• Cause remains unclear after complete workup
• No response to appropriate replacement therapy after 8-12 weeks
• Other concerning cytopenias are present
• Progressive worsening despite treatment
• Bone marrow evaluation is needed to exclude primary marrow disorders