Limited value of serum holo-transcobalamin II measurements in the differential diagnosis of macrocytosis

Aim-To study the value of serum holo-transcobalamin II (holo-TCII) measurements in the differential diagnosis of macrocytosis. Methods-Holo-TCH concentrations were measured in serum samples from 50 healthy non-vegetarian subjects and 30 patients with macrocytosis, using a technique based on the adsorption of holo-TCII with amorphous, precipitated silica. Deoxyuridine (dU) suppression tests were performed on the bone marrow cells of all the patients. Haematological diagnoses were made using standard criteria. Results-The causes of macrocytosis were cobalamin (Cbl) deficiency due to pernicious anaemia or following partial gastrectomy (10 patients), dietary folate deficiency with/without Cbl deficiency (four patients), chronic alcoholism (four patients), myelodysplastic syndrome (five patients), treatment with methotrexate or azathioprine (three patients), and congenital dyserythropoietic anaemia (CDA) (four patients). Undetectable or low holo-TCII concentrations were found in all patients with Cbl deficiency and in some or all patients from each of the other diagnostic categories. There was also no correlation between the dU suppressed value and the holo-TCII concentration: all 15 patients with high dU suppressed values and nine of 15 with normal dU suppressed values, including four patients with CDA, had low holo-TCII concentrations. Conclusions-Measurements of serum holo-TCII concentrations by the silica adsorption method are not of value in the differential diagnosis of macrocytosis. The finding of low serum holo-TCII concentrations in patients with macrocytosis due to causes other than Cbl deficiency may result not only from a state of negative Cbl balance but also from other factors, such as increased utilisation of holo-TCII as a consequence of erythroid hyperplasia.