Some patients present with macrocytosis with MCV up to 110–112 fL independent of vitamin B12 and folate. Causes are as follows:
• Chronic alcohol abuse
• Myelodysplastic syndromes
• Hypothyroidism
• Chronic lung disease with hypoxia
• Heavy smokers
• Chronic liver diseases
• Chronic hemolytic anemia
• Therapy with antiepileptic drugs
• Myeloma (some cases)
• Hypoplastic anemia
In some physiological conditions, such as infants and women with physiological pregnancies, macrocytosis could be observed.
The laboratory diagnosis of megaloblastic anemia is based on the following findings:
• Normochromic macrocytic anemia (MCV >102 fL; ranging from 100 to 160 fL). Macrocytosis may not be as evident if iron deficiency anemia, thalassemic trait, or intercurrent infections coexist. It is possible that even in the presence of vitamin B12 deficiency, the hematocrit value may be normal; hemoglobin and erythrocyte count are both significantly reduced, and MCH is increased with normal MCHC. It should be kept in mind that MCHC represents the ratio of the mean mass of hemoglobin contained in each erythrocyte to the mean mass of the erythrocyte itself. This ratio tends to be rather conservative in many hematologic disorders, ranging between 32% and 35%. As mentioned above, the most well-known condition in which MCHC increases is hereditary spherocytosis. In this condition, MCHC is higher because the erythrocyte membrane mass decreases and erythrocytes accumulate excess H2O due to altered extrusion mechanisms.
• Low reticulocyte count, unless a hemolytic component is present.
• Possible decrease of leukocytes and platelets.
• Hypersegmented neutrophils; a plurilobed nucleus with 5–6 lobes is always indicative of megaloblastic anemia.
Other data that may be altered are those related to possible ineffective bone marrow erythropoiesis and hemolysis, in particular:
• Indirect bilirubin: increased
• Sideremia: increased
• Ferritin: increased
• LDH: increased
• Haptoglobin: decreased or absent.
Erythrocytes show variations in shape (macro-ovalocytes) and volume. They contain within them basophilic inclusions and nuclear remnants (Cabot rings and Howell–Jolly bodies).
The bone marrow aspirate is rich in megaloblasts and hyperplastic cells, with a decreased ratio of myeloid and erythroid series. Obvious alterations are present in the precursors of all cell lines, but the erythroid line is especially affected. Widespread basophilia of the precursors gives the megaloblasts a blue May-Grünwald-Giemsa (blue marrow) coloration. The nuclear chromatin is scattered and appears poorly stained, with fenestrated aspects typical of megaloblastic anemia. The presence of ringed sideroblasts in the marrow, as well as hypersideremia and hyperferritinemia, indicates decreased iron utilization.
