What are the causes of high Mean Corpuscular Volume (MCV) and low Mean Corpuscular Hemoglobin (MCH)?

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From the Guidelines

High Mean Corpuscular Volume (MCV) with low Mean Corpuscular Hemoglobin (MCH) is typically caused by early B12 or folate deficiency, alcohol abuse, certain medications, myelodysplastic syndromes, liver disease, reticulocytosis, or hypothyroidism. This combination indicates macrocytic red blood cells (large cells) that contain less hemoglobin than expected. The most common causes include early B12 or folate deficiency, where the cells have begun to enlarge but hemoglobin synthesis is impaired 1.

Causes of High MCV and Low MCH

  • Early B12 or folate deficiency: where the cells have begun to enlarge but hemoglobin synthesis is impaired 1
  • Alcohol abuse: through direct toxic effects on red blood cell production 1
  • Certain medications: like anticonvulsants, chemotherapy agents, and antiretrovirals may disrupt normal erythropoiesis, leading to this combination 1
  • Myelodysplastic syndromes: can present with this pattern due to ineffective hematopoiesis 1
  • Liver disease: affects both cell membrane composition and hemoglobin synthesis 1
  • Reticulocytosis: (increased immature red cells) during recovery from hemolysis or blood loss can temporarily show this pattern as young cells are larger but haven't completed hemoglobin synthesis 1
  • Hypothyroidism: occasionally presents with this combination due to altered erythropoiesis 1

Diagnostic Workup

Diagnostic workup should include:

  • Complete blood count with peripheral smear
  • Vitamin B12 and folate levels
  • Liver function tests
  • Thyroid studies
  • Medication review

Treatment

Treatment targets the underlying cause rather than the laboratory abnormality itself. According to the most recent and highest quality study 1, the best approach is to identify and treat the underlying condition.

Note: The evidence from 1, 1, and 1 supports the causes and diagnostic workup, but the most recent and highest quality study 1 provides the most comprehensive guidance on the diagnosis and management of high MCV and low MCH.

From the Research

Causes of High MCV and Low MCH

  • High Mean Corpuscular Volume (MCV) is often associated with macrocytic anemia, which can be caused by various factors including megaloblastic and nonmegaloblastic anemias 2, 3, 4.
  • Megaloblastic anemia is typically caused by deficiency or impaired utilization of vitamin B12 and/or folate, while nonmegaloblastic macrocytic anemia can be caused by diseases such as myelodysplastic syndrome, liver dysfunction, alcoholism, hypothyroidism, and certain drugs 2, 3, 4.
  • Low Mean Corpuscular Hemoglobin (MCH) can occur in various types of anemia, including iron deficiency anemia, thalassemia, and anemia of chronic disease 5, 6.
  • The combination of high MCV and low MCH can be seen in cases of macrocytic anemia with concurrent iron deficiency or other conditions that affect hemoglobin synthesis 2, 3, 4.
  • A careful evaluation of the patient's medical history, physical examination, and laboratory tests, including blood smear, reticulocyte count, vitamin B12 and folate levels, and thyroid and liver function tests, is necessary to determine the underlying cause of high MCV and low MCH 2, 3, 4.

Possible Underlying Conditions

  • Vitamin B12 or folate deficiency 2, 3, 4, 6
  • Alcoholism 2, 3, 4
  • Liver disease 2, 3, 4
  • Hypothyroidism 2, 3, 4
  • Myelodysplastic syndrome 3, 4, 5
  • Iron deficiency anemia 5, 6
  • Thalassemia 5, 6
  • Anemia of chronic disease 5, 6

Diagnostic Approach

  • Careful medical history and physical examination 2, 3, 4
  • Laboratory tests, including blood smear, reticulocyte count, vitamin B12 and folate levels, and thyroid and liver function tests 2, 3, 4
  • Bone marrow biopsy and cytogenetic analysis may be necessary in some cases 3, 4, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Macrocytic anemia.

American family physician, 1996

Research

Diagnosis and treatment of macrocytic anemias in adults.

Journal of general and family medicine, 2017

Research

Unexplained macrocytosis.

Southern medical journal, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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