B12 and Folate

B12 deficiency

  • Causes
    • Pernicious Anaemia
    • Gastric – atrophic gastritis, gastrectomy
    • Intestinal – resection, malabsorption
    • Dietary
    • Medications – colchicine, PPIs/H2 receptor antagonists
  • Apparent deficiency
    • Metformin
    • Pregnancy
    • Oral contraceptives
    • HRT
  • Investigations
    • Consider intrinsic factor and parietal cell antibodies
    • Consider anti-TTG
  • Treatment
    • Patients with neurological symptoms
      • Do not delay treatment
      • Loading: 1000mcg hydroxycobalamin IM every second day until no further improvement
      • Maintenance: 1000mcg hydroxycobalamin IM every 2 months for life
    • Patients with no neurological symptoms
      • Loading: 1000mcg hydroxycobalamin IM Mon/Weds/Fri for two weeks
      • Maintenance:
      • Non dietary: 1000mcg hydroxycobalamin IM every three months for life
      • Dietary: 1000mcg hydroxycobalamin IM twice per year or 100mcg cyanocobalamin PO (if dietary deficiency is corrected, treatment can be stopped when levels normalised but ensure dietary advice given)
  • Refer B12 deficiency if
    • Haematology: Pregnancy, neurological symptoms, uncertain aetiology, persistent symptoms despite replacement
    • Gastroenterology: suspected malabsorption, pernicious anaemia with GI symptoms
    • Dietician: concerns regarding diet
  • Monitoring response to B12 replacement
    • FBC and reticulocytes 10 days following initiation of treatment – check folate if no improvement
    • FBC at 8 weeks to ensure normalisation of Hb

 

B12 raised

  • Causes
    • Excess intake
      • Oral or IM B12
    • Excess production of transcobalamins
      • liver disease
      • myeloproliferative disorders
      • neoplasms – particular liver
      • inflammation – SLE, RA
    • Defective clearance of transcobalamins
      • renal failure
      • anti TCB antibodies
    • Hepatic release of transcobalamins
      • liver disease – alcohol, hepatitis, cirrhosis
    • Other
      • Congenital deficiency in transcobalamins
      • Defect in TCB-B12 affinity
  • Investigations
  • Physical examination – lymphadenopathy
  • FBC, U+Es, LFTs inc GGT, ESR, CRP
  • CXR
  • USS abdomen + pelvis
  • NB: transcobalmins are involved with delivery of B12 to cells

 

Folate deficiency

  • Causes
    • Dietary – often secondary to alcohol
    • Malabsorption – Coeliac disease, tropical sprue, IBD, jejunal resection
    • Excess requirements – Physiological (pregnancy, infancy), Haemolysis (Sickle cell), Inflammation (TB, Crohn’s), Malignancy
    • Medications – Methotrexate, sulfasalazine, anticonvulsants, cholestyramine
    • Metabolic
    • Excess urinary excretion – CCF, chronic dialysis, acute liver damage
  • Treatment
    • Ensure B12 levels normal/replaced (to avoid subacute combined degeneration of the cord)
    • Dietary advice
    • Folic acid 5mg OD for four months (may require prolonged treatment if cause persists)
  • Monitoring response to folate replacement
    • FBC and reticulocytes 10 days after intiation of treatment
    • FBC at 8 weeks to ensure normalisation of Hb