Microsoft word - problems with the diagnosis of vitamin b12 deficienc1.doc

Problems with the diagnosis of Vitamin B12 deficiency Vitamin B12 deficiency is a major problem. There is no consensus on how to diagnose the deficiency; the various tests are not perfect. The problem is increasingly common, particularly mild sub-clinical deficiency in the elderly. The classical Pernicious Anaemia presentation of macrocytic anaemia, paraesthesia, abnormal gait and glossitis, is rare. Most patients have subtle clinical features or only laboratory abnormalities, making the diagnosis of true tissue deficiency difficult. It is important to keep Vitamin B12 deficiency high on the differential list as irreversible neuro-psychiatric defects can occur without appropriate replacement therapy. A significant minority of patients will have no anaemia or macrocytosis but only present with neurological or psychiatric features. SUSPECT B12 DEFICIENCY IN: Unexplained anaemia (usually macrocytic, but not always) Unexplained neurological or psychiatric features (eg reduced proprioception and paraesthesia) [even in absence of anaemia or macrocytosis] GI manifestations (sore tongue, anorexia, diarrhoea); gut surgery, IBD The elderly [quite common, subtle deficiency] Prolonged PPI, H2 blocker or metformin therapy Diet - vegan Intrinsic Factor (IF) deficiency = Pernicious Anaemia Ileal disease; gastric disease; parasites; pancreatic disease Food-B12 malabsortion (? reduced salivary haptocorrin) Achlorhydria – impairs extraction of B12 from food Drugs: PPI, H2 antagonists or biguanides may impair B12 absorption Lab Tests used to diagnose vitamin B12 deficiency The challenge is to find a reliable test for true vitamin B12 deficiency. To date no single test is without flaws. Test False –ve if HC high (CML) Borderline levels in Folate deficiency = Intrinsic Factor (IF) from gastric Parietal Cells Distal ileum epitheal cell
Tissue / Cell
of free B12 (<1%) Schema for diagnosing Vitamin B12 Deficiency Determining the cause of vitamin B12 Deficiency Clinical History – any features of autoimmune disorders (thyroid, vitiligo, etc) associated with PA; gastric or ileal surgery; malabsorption Intrinsic Factor Abs: present in around 50% of PA and very specific [parietal cell Ab common in around 90% of PA but not specific] Schillings Test: Obsolete; not available [beef source of IF therefore potential for vJCD] The serum folate level will be high but red cell folate equivocal in B12 deficiency Macrocytosis (high MCV often >120); oval macrocytes; red cell stippling; Hypersegmented neutrophils (early); pancytopenia High LDH; High bili [ineffective erythropoiesis and degree of haemolysis] Hypercellular marrow; megaloblastic; giant metamyelocytes Sub-Acute Combined Degeneration (SACD) of the spinal cord. Leads to posterior and lateral column defect and peripheral sensory neuropathy. Paraesthesia in hands & feet; early loss of vibration and joint position sense; progressive spastic & ataxic weakness ± superimposed peripheral neuropathy leads to loss of reflexes. Differential Diagnosis Megalobastic Anaemia: B12 and/or folate deficiency Abnormal B12/folate metabolism: congential enzyme deficiency, TCII defic, N2O, DHF reductase inhibitors (Methotrexate, sulphas), chemotherapy (Thioguianine, Mercaptopurine, azathioprine, 5-flurouracil) DNA synthesis defects: orotic aciduria, drugs (cytarabine, hydroxyurea), sideroblastic anaemia, erythroleukaemia, Leish-Nyhan Macrocytic: alcohol, liver disease, myxoedema, reticulocytosis, cytotoxics, aplastic anaemia, pregnancy, MDS, myeloma Therapy Vitamin B12 1000mcg im weekly for 4 weeks; then 3 monthly for life Oral therapy is adequate for vegans with no pathology Replacing B12 will lead to a huge increase in haemopoiesis and can lead to rapid depletion of folate and iron stores; this can then limit the expected recovery of Hb. Both iron and folate may be needed. Note Giving Folate to a B12 deficient person without B12 can lead to an irreversible exacerbation in neurological features.


Step therapy criteria

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The Transition of Appalachia and the Transformation of Prosperity in the United States I. Overview Nearly two centuries ago, English economist David Ricardo put forth the “Theory of Comparative Advantage” to guide trade policy between nations. The theory posited that nations should specialize in the production of a small number of goods which they could manufacture efficiently,

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