What is the diagnostic workup for anemia with elevated Mean Corpuscular Hemoglobin (MCH)?

Diagnostic Workup for Anemia with Elevated MCH

The diagnostic workup for anemia with elevated Mean Corpuscular Hemoglobin (MCH) should focus on identifying vitamin B12 or folate deficiency as the most likely causes, while also ruling out other potential etiologies such as liver disease, alcohol abuse, or medication effects. 1

Initial Laboratory Assessment

• Complete blood count (CBC) with red cell indices is essential to confirm anemia and characterize the elevated MCH, which typically corresponds with macrocytosis (elevated MCV) 2
• Reticulocyte count should be obtained to assess bone marrow response - a low or normal count suggests impaired erythropoiesis while an elevated count suggests hemolysis or blood loss 2, 1
• Peripheral blood smear to evaluate red cell morphology - look for macrocytes, hypersegmented neutrophils (suggestive of megaloblastic anemia) 3, 4
• Serum ferritin, transferrin saturation, and iron studies to rule out concomitant iron deficiency, as mixed deficiencies can occur 2
• C-reactive protein (CRP) to assess for underlying inflammation that may affect interpretation of iron studies 2

Specific Tests for Elevated MCH

• Vitamin B12 and folate levels - deficiencies are the most common causes of macrocytic anemia with elevated MCH 1, 5
• Liver function tests - liver disease can cause macrocytosis and elevated MCH 3, 4
• Thyroid function tests - hypothyroidism can contribute to macrocytic anemia 5
• Lactate dehydrogenase (LDH), haptoglobin, and bilirubin if hemolysis is suspected 2, 1
• Medication review - certain drugs like methotrexate, trimethoprim, triamterene, and anticonvulsants can cause macrocytosis and elevated MCH 5
• Alcohol use assessment - chronic alcohol consumption is a common cause of macrocytosis and can deplete folate stores 5

Advanced Testing When Initial Workup Is Inconclusive

• Methylmalonic acid and homocysteine levels if B12 deficiency is suspected despite normal B12 levels 1, 4
• Bone marrow examination may be necessary in cases where the diagnosis remains unclear after initial testing, particularly to rule out myelodysplastic syndromes or other primary bone marrow disorders 2, 3
• Consider hemoglobin electrophoresis to rule out hemoglobinopathies, especially in patients with appropriate ethnic background 2

Interpretation and Diagnostic Algorithm

1. If elevated MCH is accompanied by elevated MCV (>100 fL), focus on causes of macrocytic anemia:

   • Check B12 and folate levels first 1
   • Assess liver function and alcohol use 5
   • Review medications that may cause macrocytosis 5

2. If elevated MCH occurs with normal MCV (80-100 fL):

   • Consider mixed deficiency states (e.g., combined iron and B12/folate deficiency) 2
   • Evaluate red cell distribution width (RDW) - high RDW suggests coexisting deficiencies 2

3. If elevated MCH occurs with hemolysis:

   • Check LDH, haptoglobin, and bilirubin 1
   • Consider autoimmune hemolytic anemia or other causes of hemolysis 4

Common Pitfalls and Caveats

• An elevated MCH without macrocytosis may occur in hemoglobinopathies or in cases of laboratory error - confirm with repeat testing 2
• Normal B12 levels do not always rule out B12 deficiency - consider methylmalonic acid and homocysteine levels in suspected cases 4
• Patients on certain medications (especially thiopurines like azathioprine) may have macrocytosis without true vitamin deficiency 2
• Mixed nutritional deficiencies can mask typical findings - for example, concurrent iron deficiency can normalize MCV in a patient with B12 deficiency while MCH remains elevated 2
• Reticulocytosis can cause elevated MCH without underlying vitamin deficiency - this represents a normal response to bleeding or hemolysis 1

By systematically following this diagnostic approach, the underlying cause of anemia with elevated MCH can be identified and appropriate treatment initiated to address both the anemia and its root cause.