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12  Haematology  299

             Causes of Vitamin B 12  Deficiency
             •  Decreased intake: Nutritional deficiency (vegans, breastfed infants of vegan mothers)
             •  Impaired absorption:
               •  Gastric causes: Pernicious anaemia, destruction of gastric mucosa or gastric bypass surgery
               •  Intestinal causes: Malabsorption due to enteritis, celiac disease or tropical sprue,
                 competition for vitamin B 12  in fish tapeworm (Diphyllobothriumlatum) infestation or
                 blind loop syndrome (bacterial overgrowth in diverticulae of bowel)
               •  Drug-induced malabsorption: Implicated drugs include PAS, colchicine, neomycin,
                 ethanol and KCL
               •  Chronic pancreatic disease: Lack of pancreatic proteases and inability to degrade
                 R proteins, which compete with IF
               •  Zollinger–Ellison syndrome: Impaired absorption due to low pH of intestinal con-
                 tents reaching ileum
               •  Haemodialysis: Cause unknown

             Causes of Folate Deficiency
             •  Inadequate intake: Young persons on junk food diets, elderly and terminally ill people
             •  Inappropriate cooking methods: Polyglutamates are sensitive to heat; boiling, steam-
               ing or frying the food destroys folate content
             •  Excess utilization: Pregnancy, haemolysis and tumours
             •  Alcoholism: Reduces serum folate levels are attributed to inadequate diet, excessive
               urinary loss and interference with the enterohepatic circulation of folate by alcohol.
             •  Impaired absorption
               •  Celiac disease and tropical sprue
               •  Drugs  that  block  dihydrofolate  reductase  (methotrexate  and  trimethoprim),  block
                 conversion of polyglutamates to monoglutamates (phenytoin), decrease absorption
                 and  increase  metabolism  (anticonvulsants)  and  decrease  absorption  and  increase
                 urinary excretion (oral contraceptives)
             •  Complication of haematological illness: Increased demand due to rapid proliferation of
               haematopoietic cells in haemolytic anaemia, PNH, myelofibrosis, sideroblastic anaemia,
               leukaemia and multiple myeloma.
             Causes of Nonmegaloblastic Macrocytic Anaemia
             •  Haemolytic  and  posthaemorrhagic  anaemia:  Result  in  accelerated  erythropoiesis,
               which leads to increased reticulocyte count, premature release of the bone marrow re-
               ticulocytes and shortened time between all cell divisions/skipping of cell division, all of
               which cause macrocytosis.
             •  Thin  macrocytosis:  Thin  macrocytes  typically  have  increased  surface  area  to
               volume ratio. Increased surface area is attributed to excessive lipid content which
               in turn may be seen in:
                                                 g
                                                                  h
                                                                                    h
               •  Hepatic disease (obstructive jaundice):   Bile salt excretion n  Bile salt in plasma n
                 Free cholesterol due to decreased esterification n Increased uptake of cholesterol by
                 RBCs n Increased membrane surface area
               •  Postsplenectomy state: During maturation of reticulocytes in spleen, there is loss of
                 lipids; in the absence of spleen, there is decreased loss and excessive accumulation of
                 lipids in the RBC membrane resulting in increased surface area.
             •  Myelodysplastic syndrome (MDS), eg
               •  Aplastic anaemia
               •  5q-refractory anaemia syndrome
               •  Acquired sideroblastic anaemia
               •  Hereditary dyserythropoietic anaemia
             •  Miscellaneous
               •  Alcoholism
               •  Hypothyroidism
               •  Myelophthisic anaemia
             Clinical Features of Vitamin B 12  Deficiency
             •  General signs and symptoms of anaemia: Weight loss, angular cheilosis, dermatitis,
               osteomalacia, pallor, icterus (lemon tint), low-grade fever (in severe anaemia), mucocu-
               taneous bleeding (with thrombocytopenia)
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