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PRACTICE: Michael Galloway and Malcolm Hamilton Macrocytosis: pitfalls in testing and summary of guidance BMJ 2007; 335: 884-886 [Full text]

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do not forget the association of cobalamin deficiency and microcytic hypochromic anaemia

oscar,m jolobe   (27 October 2007)

homocystein and methylmalonic testing in vitamin B12 deficiency

Thein H Oo   (27 October 2007)

do not forget the association of cobalamin deficiency and microcytic hypochromic anaemia 27 October 2007
oscar,m jolobe, retired geriatrician manchester medical society, c/o john rylands university library, oxford road, manchester M13 9PP Send response to journal: Re: do not forget the association of cobalamin deficiency and microcytic hypochromic anaemia	Given the fact that the review of macrocytosis dealt mainly with pitfalls in the diagnosis of vitamin B-12(cobalamin) deficiency(1), this would be an opportune occasion to draw attention to the diagnostic trap of failing to consider the diagnosis of cobalamin deficiency when, instead of the expected macrocytosis, the haematological profile were characterised by microcytosis, due to co-existing iron deficiency(2). This is an almost counter-intuitive outcome, attributable to the fact that the commonest underlying cause of cobalamin deficiency in temperate climates, namely, auto-immune gastritis(3), has iron deficiency as its commonest manifestation(2). Out of 160 subjects with auto-immune gastritis, the haematological profile was characterised by microcytosis(mean corpuscular volume < 80 fl), normocytosis( mean conpuscular volume 80-100 fl), macrocytosis(mean corpuscular volume > 100 fl), in 51.9%, 30%, and 18.2%, respectively(2). As many as 38(ie 46%) of the 83 iron-deficient patients with microcytosis proved to have co-existing cobalamin deficiency(2). Histological validation of atrophic gastritis(by endoscopic biopsy during the course of investigation for the underlying cause of iron deficiency) should enhance the pre-test probability of co-existing cobalamin deficiency, the latter sometimes being characterised by serum vitamin B-12 levels as low as < 10 ng/L(4). Accordingly, the endoscopic "work-up" of iron deficient patients who prove not to have an upper gastrointestinal source of chronic blood loss should include, not only a duodenal biopsy(to check for coeliac disease)(5), but also a gastric biopsy, which, in the event of histological validation of atrophic gastritis, should be followed by evaluation of serum vitamin B-12 levels. References (1) Galloway M., Hamilton M Macrocytosis: pitfalls in testing and summary advice British Medical Journal 2007:335:884-6 (2)Hershko C., Ronson A., Souroujon M., et al Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion Blood 2006:107:1673-9 (3)Babior MB., Bunn HF Megaloblastic anemias. In Harrison's Principles of Internal Medicine 1998, 14th Edition Chapter 108 pages 653-658. Editors Fauci AS., Braunwald E., Isselbacher KJ., Wilson JD., Martin JB., Kasper DL., Hauser SL.,Longo DL. McGraw-Hill Health Professions Division, New York, St Louis, San Francisco. (4) Jolobe OMP Subnormal vitamin B12 concentration(letter) Journal of the American Geriatrics Society 1997:45:1158-9 (5) Jolobe OMP Iron deficiency anaemia(letter) Gut 1994:35:140 Competing interests: None declared
homocystein and methylmalonic testing in vitamin B12 deficiency 27 October 2007
Thein H Oo, Attending (Consultant) Physician, Hematology & Assistant Professor of Medicine Caritas St Elizabeth's Medical Center/ Tufts University School of Medicine, Boston, MA 02135, USA Send response to journal: Re: homocystein and methylmalonic testing in vitamin B12 deficiency	I was reading this article with interest. Congratulations to Drs Galloway and Hamilton for this great article. In this article, the authors describe the limited value of metabolite tests ( homocystein and methylmalonic acid ). These metabolite testings have particular value if performed on carefully collected samples (e.g. 10 -12 hours fasting, without renal insufficiency etc) in a subset of patient population. In general, serum vitamin B12 levels can be interpreted, as follows: (1) > 300 pg/mL - normal result; cobalamin deficiency is unlikely (i.e. 1-5%) (2) 200 - 300 pg/mL - borderline result; cobalamin deficiency possible (3) < 200 pg/mL - low, consistent with cobalamin deficiency (specificity 95-100%) Patients with low-normal or even normal serum B12 levels may be truly cobalamin deficient and therefore measurement of serum homocystein and methylmalonic acid is helpful in clarifying the diagnosis when serum cobalamin or folate concentrations are equivocal. However, metabolite testings should be reserved for those patients in whom a high degree of suspicion of cobalamin deficiency is present, especially with borderline serum cobalamin levels, in patients with unexplained neurologic symptoms, when it is essential to discover potentially reversible causes of neuropathy or dementia. References 1. Antony AC: Megaloblastic anemias. In: Hematology: Basic principles and practice, 4th ed, Hoffman R, Benz EJ, Shattil SJ, et al (Eds), Churchill Livingstone, New York 2005. p 519 2. Lindenbaum J, Savage DG, Stabler SP, Allen RH: Diagnosis of cobalamin deficiency, methylmalonic acid, and total homocystein concentrations. Am J Hematol 1990;34(2): 99-107 3.Matchar DB, McCrory DC, Millington DS, Feussner JR. Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency. Am J Med Sci 1994;308(5): 276-83 Competing interests: None declared