Laboratory testing for cobalamin deficiency in megaloblastic anemia

Abstract

Cobalamin (vitamin B12) deficiency is a common cause of megaloblastic anemia in Western populations. Laboratory evaluation of megaloblastic anemia frequently includes the assessment of patient cobalamin and folate status. Current total serum cobalamin measurements are performed in the clinical laboratory with competitive binding luminescence assays, whose results may not always accurately reflect actual cobalamin stores. Surrogate markers of cobalamin deficiency such as methylmalonic acid and homocysteine have been utilized to improve diagnostic accuracy; however, the specificity of these tests by themselves is rather low. Measurement of the biologically active fraction of cobalamin, holotranscobalamin, has been proposed as a replacement for current total cobalamin assays. Although holotranscobalamin measurements appear to have slighter better sensitivity, the specificity of this assay remains to be determined. The relative merits and demerits of commonly available methods to assess cobalamin deficiency in patients with suspected megaloblastic anemia are discussed. Am. J. Hematol. 88:522–526, 2013. © 2013 Wiley Periodicals, Inc.

Anemias

“…Cerebellar changes can also lead to ataxia and cognitive deficits (eg, depression and dementia). 24 As cobalamin deficiency progresses it can also negatively affect hematopoiesis in all 3 cell lines in the bone marrow and eventually lead to pancytopenia.…”

“…The consequence is ineffective DNA production and development of megaloblastic anemia and neurodegenerative disease. 24 Cobalamin deficiency is common worldwide and more prevalent among the elderly. It is estimated that 10% to 20% of the elderly are cobalamin deficient, mainly because of malabsorption, but only 5% to 10% are symptomatic.…”

False-normal vitamin B12 results in a patient with pernicious anaemia

“…of patients with true vitamin B12 deficiency [7][8] and it represents a useful test as it is relatively widely available. However it should be noted that this is not specific for vitamin B12 deficiency as concentrations can also be increased in folate deficiency, pyridoxine deficiency, renal failure or with inborn errors of homocysteine metabolism.…”

A woman with macrocytic anaemia and confusion

“…Furthermore, the testing of vitamin B 12 involves the use of competitive binding luminescence assays and results may not always accurately reflect actual vitamin B 12 stores. 32 Consequently, a clear gold standard test is lacking. 10 Coexisting treatments and medical conditions that falsely lower serum B 12 values include use of the oral contraceptive pill, multiple myeloma, pregnancy, and folate deficiency.…”