From the Guidelines
For a 45-year-old female with macrocytosis and borderline low platelets on peripheral smear but normal B12 and folate levels, I recommend first obtaining a comprehensive alcohol use history and liver function tests, as alcohol is a common cause of both macrocytosis and mild thrombocytopenia even with normal B12/folate 1. This approach is based on the most recent and highest quality study available, which highlights the importance of considering alcohol use and liver function in the evaluation of macrocytosis 1.
Key Considerations
- Order thyroid function tests (TSH, free T4) as hypothyroidism can cause macrocytosis 1
- Check reticulocyte count to assess for hemolysis or blood loss 1
- Consider testing for hemolytic anemia with LDH, haptoglobin, and direct Coombs test 1
- Medication review is essential as certain drugs (anticonvulsants, methotrexate, hydroxyurea) can cause these findings 1
Further Evaluation
If these initial investigations are unrevealing, bone marrow examination may be warranted to rule out early myelodysplastic syndrome, particularly given the combination of macrocytosis and thrombocytopenia 1. The peripheral smear should be carefully reviewed for dysplastic changes in red cells, white cells, and platelets. This approach is systematic, addressing common reversible causes before proceeding to more invasive testing for hematologic disorders. Given the lack of strong evidence from the other studies 1 that directly addresses the specific question of macrocytosis and thrombocytopenia with normal B12 and folate levels, the recommendation is based on the most relevant and recent study 1.
From the Research
Approach to Macrocytosis and Thrombocytopenia
The approach to a 45-year-old female with macrocytosis and thrombocytopenia involves considering various potential causes.
- The patient's normal vitamin B12 and folate levels help to rule out megaloblastic hematopoiesis as a primary cause of macrocytosis, which is consistent with the findings of 2.
- The presence of thrombocytopenia, in addition to macrocytosis, suggests the possibility of liver disease, as both conditions can be associated with liver dysfunction, as discussed in 3 and 4.
- The study by 5 highlights the value of macrocytosis as a diagnostic indicator of alcoholism, particularly in patients with liver disease.
- Given the patient's borderline low platelets, it is essential to consider the potential for liver disease, as thrombocytopenia can be a consequence of splenic sequestration or impaired platelet production, as described in 3.
Potential Causes and Evaluation
Potential causes of macrocytosis and thrombocytopenia in this patient include:
- Alcohol-related liver disease, as suggested by 5 and 4
- Other forms of liver disease, such as metabolic dysfunction-associated steatotic liver disease (MASLD), as discussed in 6
- Drug-induced liver injury or other extrahepatic causes, as mentioned in 6
- Further evaluation may involve assessing liver function tests, hepatitis B and C serologies, and other laboratory tests to determine the underlying cause of the patient's macrocytosis and thrombocytopenia, as recommended in 6.