An 85-year-old male is referred for chronic fatigue. He is on home oxygen for advanced COPD. A CBC three years ago was normal apart from mild macrocytic anemia (Hb 102 g/L, MCV 105 fL).
- What is the differential diagnosis for his macrocytosis?
- What investigation would you order next?
Click for answer:
Diagnosis: myelodysplastic syndrome (MDS)
CBC findings suggestive of diagnosis:
(1) Macrocytic anemia, (2) Leucoerythroblastic picture (i.e. early red and white cell precursors)
Q1: What is the differential diagnosis for his macrocytosis?
Mnemonic is FAT-RBC + drugs (see Box).
Q2: What investigation would you order next?
Vitamin B12, TSH, beta-HCG, and liver function testing.
Myelodysplastic syndrome is a hematologic disorder characterized by cytopenias, most commonly anemia. It results from accumulation of genetic defects in hematopoietic stem cells that leads to dyserythropoiesis and abnormal myeloid cell maturation. Risk factors include elderly age and prior chemotherapy or radiation exposure.
Macrocytic Anemia Differential
Fetus (pregnancy)
Alcohol
Thyroid (hypo)
Reticulocytosis
B12/folate deficiency
Cirrhosis/chronic liver disease
Drugs (methotrexate, sulfasalazine, etc.)
MDS can be stratified into low- and high-risk (beyond our scope). Low-risk is generally managed supportively with transfusions and growth factors. MDS carries a high risk of transformation to acute myeloid leukemia, so careful monitoring is warranted.
CBC Pearls
• Leucoerythroblastic is the presence of immature red/white cells in blood
• Subacute/chronic presentation is more suggestive of MDS
Leucoerythroblastic refers to the presence of immature leukocytes (myelocytes, metamyelocytes) and immature erythrocytes (nucleated RBC) in the peripheral blood. These cells should generally reside within the bone marrow and are considered abnormal on a CBC. In this case, pancytopenia with macrocytosis warrants a bone marrow biopsy to identify the cause.
A differential of macrocytic anemia can be remembered by the acronym FAT-RBC + drugs. It is important to test for these other causes of macrocytic anemia prior to confirming MDS. Therefore, Vitamin B12, TSH, beta-HCG, and liver function testing should be completed in all cases.