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                   472 Chapter 12: Haematology and clinical immunology


                     blocking antibodies (bind to intrinsic factor and pre-  deficiency is associated with neural tube defects in
                     vents binding to B 12 )orbinding antibodies (bind to  the fetus.
                     the IF:B 12 complex preventing absorption).     Antifolate drugs include methotrexate, trimetho-
                   Atrophic gastritis is present with plasma cell and lym-  prim, anticonvulsants and alcohol.
                   phoid infiltration affecting the fundus and body of the
                   stomach. There is achlorydia and absent secretion of in-
                                                                Clinical features
                   trinsic factor.
                                                                Symptoms and signs of anaemia (see page 467). Patients
                                                                may also complain of a sore mouth and tongue (glossi-
                   Clinical features
                                                                tis).
                   Theonsetofperniciousanaemiaisusuallyinsidiouswith
                   worseningsymptomsofanaemia(seepage467).Patients
                                                                Investigations
                   may also have neurological complications of vitamin B 12
                                                                Redcell folate level are low. In many cases the cause is
                   deficiency (see page 471).
                                                                not obvious and further investigations may have to be
                                                                undertaken including barium follow through or upper
                   Investigations
                                                                gastrointestinal endoscopy and biopsy.
                   Full blood count will demonstrate a macrocytic anaemia
                   (raised MCV). Vitamin B 12 is low. The Schilling test is
                   used to differentiate the causes of vitamin B 12 deficiency  Management
                   (see Table 12.4).                            The underlying cause should be identified and treated
                                                                where possible. Prior to treatment with oral folic acid
                   Management                                   supplements, concurrent vitamin B 12 deficiency must be
                   Parenteral vitamin B 12 replacement is required for life.  identified and treated to avoid the neurological compli-
                   Clinical improvement can be seen in 48 hours and a  cations of B 12 deficiency. Prophylaxis is advised in preg-
                   reticulocytosis can be demonstrated 2–3 days after com-  nancy, haemolytic anaemias, premature babies, dialysis
                   mencing therapy.                             patients and those taking methotrexate.


                   Folate deficiency                             Haemolytic anaemia
                   Definition
                                                                Definition
                   Deficiency of folate causes a megaloblastic anaemia due
                                                                Haemolytic anaemia is defined as an anaemia resulting
                   to abnormal DNA synthesis.
                                                                from increased breakdown of red cells and shortened red
                                                                blood cell life span (normal 120 days).
                   Aetiology/pathophysiology
                   Folic acid is the precursor to the folates, which are in-
                   volved in the synthesis of DNA (see Fig. 12.4). Causes of  Aetiology
                                                                The causes of haemolytic anaemia are shown in Table
                   folic acid deficiency:
                                                                12.5.
                     Low intake is most common in elderly, people living

                     in poor social conditions and chronic alcoholics. Folic
                     acid is found in fresh vegetables and meat, but may  Pathophysiology
                     be destoyed by overcooking.                Shortening of the life span of red cells does not always
                     Malapsorption occurs due to small bowel disease (es-  cause anaemia. If the increased loss can be compen-

                     pecially if affecting the jejunum) such as coeliac dis-  sated for by an up-regulation of the bone marrow (which
                     ease.                                      can increase output between six and eight times) then a
                     Increased requirements occur in haemolytic con-  compensated haemolytic state will arise. In addition to

                     ditions, myeloproliferative disorders, other rapidly  bone marrow up-regulation, reticulocytes (red cell pre-
                     growing tumours and severe inflammatory disease.  cursors) may be released prematurely. Haemolysis can
                     In pregnancy there are increased requirements and  be divided into two categories:
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