From the Guidelines
Yes, someone can have baseline mild macrocytosis as a normal variant, as long as common causes such as vitamin B12 or folate deficiency, alcohol use, medications, liver disease, hypothyroidism, and nutritional deficiencies are ruled out. Macrocytosis refers to enlarged red blood cells (MCV >100 fL), and while it often indicates underlying conditions, certain individuals maintain slightly elevated MCV values without any pathology. This benign macrocytosis can be constitutional or familial, representing their normal physiological state. When evaluating mild macrocytosis (typically MCV between 100-110 fL), clinicians should first rule out common causes including alcohol use, medications (anticonvulsants, methotrexate), liver disease, hypothyroidism, and nutritional deficiencies, as suggested by 1. If these investigations are negative and the patient has no symptoms, stable blood counts, and no other hematologic abnormalities, the macrocytosis may be considered a normal variant. Regular monitoring is still recommended, typically with annual complete blood counts, to ensure stability, as indicated by 2. The biological basis for this normal variant likely involves genetic factors that influence red blood cell development and membrane characteristics without causing disease. Key points to consider in the evaluation of mild macrocytosis include:
- Ruling out common causes of macrocytosis
- Evaluating the patient's symptoms and medical history
- Conducting regular monitoring with complete blood counts
- Considering genetic factors that may influence red blood cell development. In the absence of any underlying conditions, mild macrocytosis can be considered a normal variant, and the patient can be monitored regularly to ensure that the condition does not progress or indicate any underlying pathology, as supported by 1.
From the Research
Baseline Mild Macrocytosis
- Macrocytosis is generally defined as a mean corpuscular volume (MCV) greater than 100 fL 3
- The most common etiologies of macrocytosis are alcoholism, vitamin B12 and folate deficiencies, and medications 3
- However, some studies suggest that macrocytosis can also be a benign familial condition, unrelated to any underlying disease 4
- A study found that in some cases, macrocytosis could not be explained by any known cause, suggesting that it may be a normal variant in some individuals 5
Normal Variants of Macrocytosis
- A case study identified a family with benign familial macrocytosis, characterized by persistent macrocytosis without evidence of disease 4
- The study suggested that macrocytosis in these individuals was likely related to a genetic defect 4
- Another study found that 41 cases of macrocytosis could not be explained by any known cause, suggesting that macrocytosis may be a normal variant in some individuals 5
Evaluation of Macrocytosis
- Evaluation of macrocytosis typically involves a complete blood count, peripheral blood smear, vitamin B12 and folate levels, and other tests to rule out underlying causes 3, 6, 7, 5
- A thorough medical history and physical examination are also essential in determining the underlying cause of macrocytosis 3, 5
- In some cases, macrocytosis may be the first clue to an underlying pathology, even in the absence of anemia 5