What does it mean if a patient has low red and white blood cell counts along with high MCV (Mean Corpuscular Volume) and MCH (Mean Corpuscular Hemoglobin) values?

Evaluation of Low RBC, Low WBC with High MCV and MCH

The combination of low red blood cells, low white blood cells, with high MCV and MCH most strongly suggests vitamin B12 or folate deficiency causing megaloblastic anemia with pancytopenia. 1, 2

Diagnostic Approach

When evaluating these abnormal blood parameters, a systematic approach is essential:

1. Morphologic Classification Based on MCV

• High MCV (>100 fL) with high MCH indicates macrocytic anemia 1
• This is most commonly megaloblastic, suggesting:
  • Vitamin B12 deficiency
  • Folate deficiency
  • Less commonly: alcoholism, myelodysplastic syndrome (MDS), or medication effects 1

2. Additional Laboratory Assessment

• Complete blood count with peripheral smear - Look for:

  • Macro-ovalocytes
  • Hypersegmented neutrophils
  • Red cell fragmentation 3

• Red cell distribution width (RDW):

  • Markedly elevated RDW strongly suggests megaloblastic anemia
  • RDW is significantly higher in megaloblastic anemia (mean 87.7 fL) compared to other causes of macrocytosis like aplastic anemia (mean 71.4 fL) 4

• Reticulocyte count:

  • Low or normal reticulocyte count suggests impaired production (typical of megaloblastic anemia)
  • High reticulocyte count would suggest hemolysis or blood loss 1, 2

• Vitamin levels:

  • Serum B12 level
  • Serum folate level
  • RBC folate level (more reliable than serum) 5

3. Differential Diagnosis for Low RBC, Low WBC with High MCV/MCH

1. Megaloblastic anemia (most likely) 1, 5:

   • B12 deficiency (65% of megaloblastic anemia cases) 5
   • Folate deficiency (6% of cases) 5
   • Combined B12 and folate deficiency (12% of cases) 5

2. Aplastic anemia - can present with pancytopenia and macrocytosis, but typically has lower RDW 4

3. Myelodysplastic syndrome - consider in older patients 1

4. Medication-induced - drugs like hydroxyurea, diphenytoin, or chemotherapeutic agents 1

5. Alcohol-related macrocytosis - common cause of non-megaloblastic macrocytosis 2

6. Liver disease - can cause macrocytosis without megaloblastic features 2

7. Hypothyroidism - can present with macrocytosis 2

Important Clinical Considerations

Pitfalls to Avoid

1. Don't dismiss vitamin deficiency with normal MCV:

   • Severe B12 deficiency can present with normal MCV in some cases due to concurrent iron deficiency or thalassemia trait 3
   • Blood smear review is crucial when pancytopenia is present, even with normal MCV 3

2. Don't overlook mixed deficiencies:

   • Iron deficiency can mask macrocytosis in B12/folate deficiency 1, 5
   • Check ferritin, iron, TIBC if mixed picture is suspected 6

3. Beware of pre-analytical factors affecting results:

   • EDTA-induced agglutination can cause falsely low WBC counts
   • Lipids, cryoglobulins can affect RBC indices 7

Clinical Correlation

• Patients with megaloblastic anemia commonly present with:
  • Fatigue, anorexia, gastritis
  • Low-grade fever
  • Shortness of breath, palpitations
  • Mild jaundice (due to ineffective erythropoiesis)
  • Glossitis and hyperpigmentation in severe cases 5

Management Approach

1. Confirm the specific deficiency:

   • Vitamin B12 level
   • Serum and RBC folate levels
   • Additional tests based on suspected etiology (e.g., intrinsic factor antibodies, methylmalonic acid)

2. Treat the underlying deficiency:

   • For B12 deficiency: parenteral B12 replacement initially, followed by oral supplements
   • For folate deficiency: oral folate supplementation
   • Continue treatment for 3 months after normalization of hemoglobin 6

3. Investigate underlying cause:

   • Dietary history (vegetarian/vegan diet)
   • Medication review (acid suppressants, metformin)
   • GI evaluation for malabsorption (celiac disease, pernicious anemia)
   • Alcohol use assessment 6, 5

4. Monitor response to therapy:

   • Reticulocyte count should increase within 3-5 days of starting appropriate therapy
   • Hemoglobin should begin to rise within 1-2 weeks
   • Monitor CBC weekly until stable, then every 2-4 weeks 6

The combination of low RBC, low WBC with high MCV and MCH represents a serious hematologic abnormality requiring prompt evaluation and treatment to prevent neurologic and other complications, particularly if vitamin B12 deficiency is the underlying cause.