Algorithm for investigation macrocytic anaemia

The patient has macrocytic anaemia.

Now perform a reticulocyte count. A reticulocyte count <1% indicates underproduction, while a finding of >2% is associated with hyperproliferation due to haemolysis or haemorrhage, which should prompt a haemolytic anaemia work-up. Additionally, if findings consistent with hyperproliferation are reported, a vitamin B12 level should be performed and folate levels (intrinsic factor if B12 deficiency) should be ordered.

Vitamin B12 values <100 pg/mL indicate deficiency; an RBC folate level (not serum folate due to lack of sensitivity) should be ordered for a B12 >400 pg/mL. However, low levels may also indicate folate deficiency.

Homocysteine and methylmalonic acid (MMA) should be measured in patients with a B12 level of 100 pg/mL to 400 pg/mL, as these are biochemical compounds important in cell metabolism pathways and use folate and vitamin B12 as cofactors - the measurement of serum B12 alone can miss upwards of 50% of cases. (1)

Note - consider referral in the following cases;
Suspected myelodysplastic syndrome (based on the blood film report)
MCV >100 fl with accompanying cytopenia (excluding B12/folate deficiency);
- Hb < 100 g/l
- Absolute neutrophil count 1.8 x 10⁹/l
- Platelets 100 x 10⁹/l
Persistent unexplained MCV >104 fl confirmed on repeated FBC over months.

Reference

1. Iltar U, Göçer M, Kurtoğlu E. False elevations of vitamin B12 levels due to assay errors in a patient with pernicious anemia. Blood Res. 2019 Jun;54(2):149-151.