Is it reasonable to monitor a patient with mild, stable macrocytosis (large cell size) without anemia for 3 years after ruling out Vitamin B12 (cobalamin) deficiency, folate deficiency, alcohol use, thyroid disease, monoclonal gammopathy, and liver disease?

From the Guidelines

It is reasonable to monitor a patient with mild, stable macrocytosis without anemia for 3 years after ruling out common causes, with annual complete blood counts (CBCs) to track the macrocytosis and ensure it remains stable. For such patients, if the MCV (mean corpuscular volume) has been consistently elevated but stable (typically 100-110 fL) without progression to anemia, and comprehensive workup has excluded vitamin B12 deficiency, folate deficiency, alcohol use, thyroid disease, monoclonal gammopathy, and liver disease, then the condition likely represents a benign variant 1. During follow-up visits, it's essential to reassess for any new symptoms, medication changes, or lifestyle factors that could affect red blood cell size. The approach of monitoring patients with smoldering multiple myeloma, as outlined in the study by 1, also supports the idea of regular follow-up, although the specific condition of macrocytosis without anemia may not require as frequent monitoring. If the macrocytosis remains stable without development of anemia or other cytopenias over this 3-year period, the frequency of monitoring could potentially be reduced. The rationale for this approach is that truly benign macrocytosis tends to remain stable over time, while pathologic causes typically show progression in cell size abnormalities or development of anemia or other blood count abnormalities.

Key points to consider in the monitoring process include:

• Annual CBCs to track the macrocytosis
• Reassessment for new symptoms, medication changes, or lifestyle factors that could affect red blood cell size
• Comprehensive workup to exclude common causes of macrocytosis
• Consideration of the patient's overall health status and risk factors for progression to more severe conditions.

By following this approach, clinicians can balance the need for monitoring with the risk of over-testing and over-treatment, ultimately prioritizing the patient's morbidity, mortality, and quality of life.

From the Research

Monitoring Patients with Mild, Stable Macrocytosis

• Patients with mild, stable macrocytosis without anemia may still require close follow-up, as the condition can be a precursor to underlying bone marrow disorders 2.
• A study of 9779 patients with macrocytosis found that 11.6% developed a primary bone marrow disorder, and 16.3% developed worsening cytopenias, over a median follow-up of 4 years 2.
• The probability of a bone marrow biopsy establishing a diagnosis of a primary disorder was lower in patients with macrocytosis without anemia (33.3%) compared to those with anemia (75%) 2.

Evaluation and Follow-up

• The evaluation of macrocytosis should include a careful history and physical examination, complete hematologic profile, reticulocyte count, and peripheral blood smear 3, 4.
• Follow-up with blood cell counting every 6 months is suggested, with bone marrow biopsy considered when cytopenias are present 2.
• Macrocytosis can be caused by various factors, including vitamin B12 and folate deficiencies, alcoholism, liver disease, and primary bone marrow dysplasias 3, 4, 5.

Duration of Monitoring

• While there is no specific guideline on the duration of monitoring, a study with a median follow-up of 4 years suggests that prolonged follow-up may be necessary to detect underlying conditions 2.
• Monitoring for 3 years may be reasonable, considering the median time to first cytopenia was 18 months, and the mean time to diagnosis of bone marrow disorder was 31.6 months in one study 2.