Combined cobalamin and iron deficiency anemia: a diagnostic approach using a model based on age and homocysteine assessment

Abstract

Macrocytosis, the hallmark of cobalamin/folate deficiency anemia, is frequently absent. Clinicians have to be aware of coexisting conditions that can mask the macrocytosis expression of megaloblastic anemia, especially iron deficiency. The objective of this work was to investigate the degree of overlap between iron deficiency anemia (IDA) and cobalamin deficiency and to develop a predictive model for differentiating IDA from combined deficiency. A prospective case and control study was carried out to investigate vitamin B₁₂ and folate status in iron deficiency anemia. A total of 658 patients were recruited, 41 of whom (6.2 %) were excluded. The remaining 617 subjects consisted of 130 controls and 487 with IDA. Low vitamin B₁₂ (LB12) was considered when serum vitamin B₁₂ was ≤200 pmol/L. High serum homocysteine (Hcy) was defined by Hcy >17 μM/L. A multivariate analysis (including a logistic regression) was performed to develop a diagnostic model. Low vitamin B₁₂ levels were found in 17.8 % of IDA subjects. Ten out of 11 subjects (91 %) with IDA and serum vitamin B₁₂ (B12) ≤100 pmol/L showed vitamin B₁₂ deficiency. Moreover, vitamin B₁₂ deficiency was demonstrated in 48 % of cases with IDA and B12 between 101 and 150 pmol/L and in 40 % with IDA and B12 between 151 and 200 pmol/, respectively. As a result of multivariate logistic analysis, neutrophil counts and age predicted subjects with vitamin B₁₂ ≤200 and Hcy >17 μmol/L, $y=1/1+{e^{{-\left( {-5.45 + 0.057\,\mathrm{age} - 0.187\ \mathrm{neutrophils}} \right)}}}$. Using the age of 60 as a cutoff, sensitivity was 91 % (39 out of the 43 patients with vitamin B₁₂ deficiency and IDA were identified). In summary, low vitamin B₁₂ was found in 18 % of patients with IDA. Vitamin B₁₂ deficiency was demonstrated in many patients with LB12 and IDA. Age over 60 years was used to separate patients with combined deficiency (sensitivity 91 %). Therefore, for a diagnostic purpose, serum vitamin B₁₂ should be evaluated in IDA patients over 60 years. This diagnostic model needs to be validated in a different population.