From the Guidelines
Low MCV without anemia is typically caused by iron deficiency, thalassemia, or other genetic disorders of iron metabolism or heme synthesis, and should be evaluated with serum ferritin, iron studies, and hemoglobin electrophoresis. The most recent and highest quality study, published in 2021 in the journal Gut 1, highlights the importance of iron deficiency as a cause of microcytosis, even in the absence of anemia. According to this study, mean cell Hb (MCH) is a more reliable marker of iron deficiency than MCV, as it is less dependent on storage and the counting machine used.
Key Causes of Low MCV without Anemia
- Iron deficiency: characterized by low serum ferritin, low transferrin saturation, and low iron levels 1
- Thalassemia: a genetic disorder that can cause microcytosis, often with a normal or elevated serum ferritin level 1
- Chronic disease: can cause microcytosis due to inflammation and impaired iron utilization 1
- Lead poisoning: can cause microcytosis due to impaired heme synthesis 1
- Sideroblastic anemia: a rare genetic disorder that can cause microcytosis due to impaired heme synthesis 1
Evaluation and Management
- Initial workup should include serum ferritin, iron studies, and hemoglobin electrophoresis to rule out thalassemia trait 1
- For suspected iron deficiency, oral iron supplementation with ferrous sulfate 325 mg daily or ferrous gluconate 300 mg daily is recommended, taken on an empty stomach with vitamin C to enhance absorption 1
- Treatment should continue for 3-6 months to replenish iron stores, even after MCV normalizes 1
- Regular monitoring of complete blood counts and iron studies every 2-3 months during treatment is advisable to track improvement 1
From the Research
Causes of Low Mean Corpuscular Volume (MCV) without Anemia
- Iron deficiency is a common cause of low MCV, as stated in 2, 3, 4, 5, 6
- Hemoglobinopathy, such as thalassemia, can also cause low MCV, as mentioned in 3, 4, 5
- Sideroblastic anemia is another inherited cause of microcytic anemia, as noted in 4, 5
- Other hereditary disorders due to iron metabolism abnormalities, such as atransferrinemia, DMT1 deficiency, ferroportin disease, and iron-refractory iron deficiency anemia, can also lead to low MCV, as discussed in 5
- Chronic disease can also cause microcytosis, as stated in 6
Diagnostic Approaches
- Serum ferritin concentration is a suitable marker for assessing iron deficiency, with high sensitivity and specificity, as mentioned in 6
- Red cell distribution width (RDW) is a parameter with high sensitivity for iron deficiency, as noted in 6
- Evaluation of several red blood cell and iron parameters, including mean corpuscular hemoglobin, reticulocyte hemoglobin content, serum iron and serum ferritin levels, total iron-binding capacity, transferrin saturation, hemoglobin electrophoresis, and sometimes reticulocyte count, can help diagnose causes of microcytosis, as discussed in 5