Causes of MCH 36.1 pg
An MCH of 36.1 pg is elevated and most commonly indicates vitamin B12 or folate deficiency causing megaloblastic anemia, though chronic alcohol use, certain medications (particularly chemotherapy agents and anticonvulsants), liver disease, hypothyroidism, reticulocytosis, or hemochromatosis should also be considered. 1, 2
Primary Etiologies of Elevated MCH
Nutritional Deficiencies
- Vitamin B12 deficiency impairs DNA synthesis and produces megaloblastic anemia with large RBCs containing increased hemoglobin, representing the most common cause of elevated MCH 1, 2
- Folate deficiency causes megaloblastic anemia with macrocytic RBCs through similar mechanisms 1, 2
Toxic and Medication-Related Causes
- Chronic alcohol abuse is directly toxic to bone marrow and causes macrocytosis even without anemia, independent of nutritional deficiencies 1, 2
- Medications including chemotherapeutic agents, anticonvulsants (particularly phenytoin), methotrexate, hydroxyurea, and thiopurines commonly cause macrocytosis with elevated MCH 1, 2
- Antiretroviral drugs, specifically zidovudine and stavudine, can elevate MCH and MCV, though tenofovir does not have this effect 3
Metabolic and Systemic Conditions
- Liver disease affects red cell membrane composition, leading to macrocytosis and elevated MCH 1
- Hypothyroidism slows metabolism and affects erythropoiesis, resulting in elevated red cell indices 1
Hematologic Conditions
- Reticulocytosis produces increased immature RBCs that are larger and have higher MCH 1
- Hemochromatosis (particularly HFE C282Y homozygosity) is associated with elevated MCV and MCH, with mean MCH values of 33.9-70.7% sensitivity for detection in men 4, 5, 6
Systematic Diagnostic Approach
Initial Laboratory Assessment
- Check MCV first, as elevated MCH typically occurs alongside elevated MCV (>100 fL) in true macrocytosis 1, 2
- Obtain a complete blood count with peripheral smear to look for macrocytes, hypersegmented neutrophils (megaloblastic), or spherocytes 2
- Measure reticulocyte count to distinguish between production defects (low/normal count) versus hemolysis or blood loss (elevated count) 1, 2
Essential Laboratory Tests
- Serum vitamin B12 and folate levels should be measured simultaneously, as concurrent deficiencies can occur 1, 2
- Liver function tests to evaluate for hepatic disease 1
- Thyroid-stimulating hormone to screen for hypothyroidism 1
- Iron studies (serum ferritin and transferrin saturation) must be checked in all patients to exclude concurrent iron deficiency, which can mask macrocytosis and normalize the MCV 2
Targeted Additional Studies
- If reticulocyte count is elevated, evaluate for hemolysis with haptoglobin, lactate dehydrogenase, indirect bilirubin, and peripheral smear for schistocytes 1, 2
- Consider hemoglobin electrophoresis if iron studies are normal and thalassemia trait is suspected, particularly in patients with appropriate ethnic background 1
- Transferrin saturation and ferritin should be checked if hemochromatosis is suspected, especially in patients with elevated MCH and family history 4, 5
Critical Clinical Pitfalls
Mixed Deficiency States
- Concurrent iron deficiency with B12/folate deficiency can neutralize the MCV, yielding a normal MCV but elevated RDW; therefore, iron studies remain essential even when MCH is elevated 2
- In elderly patients or those with inflammatory bowel disease, simultaneous iron and vitamin B12 deficiencies can mask expected macrocytosis 1
Inflammatory Conditions
- Ferritin can be falsely elevated in the presence of inflammation, chronic disease, malignancy, or liver disease, requiring clinical context for interpretation 1
- C-reactive protein should be measured to interpret ferritin values, as ferritin rises as an acute-phase reactant during inflammation 1
Medication Review
- Systematically review all medications for agents known to cause macrocytosis, including anticonvulsants, methotrexate, hydroxyurea, and antiretroviral drugs 2, 3
Management Based on Etiology
Vitamin Deficiency Treatment
- B12 deficiency should be treated with B12 replacement, typically intramuscular initially for pernicious anemia, then oral maintenance 2
- Folate deficiency should be treated with oral folate supplementation, but always check B12 first to avoid masking B12 deficiency neurologic complications 2
Other Interventions
- Medication-induced macrocytosis should be managed by considering discontinuation or dose adjustment of offending agents if clinically feasible 2
- Alcohol cessation is essential for alcohol-related macrocytosis 1