Define haematinics. Describe iron metabolism, iron preparations, vitamin B12 and folic acid with their uses.

Definition and Iron Metabolism

Dietary iron is largely ferric (Fe3+) and must be reduced to ferrous (Fe2+) to be absorbed — helped by gastric acid and by ascorbic acid → Absorbed in the duodenum and upper jejunum through the DMT1 transporter → Within the enterocyte it is either stored as ferritin (and lost when the cell is shed) or exported → Export to plasma is through ferroportin → hepcidin, made by the liver, blocks ferroportin — it is the master regulator, rising in inflammation and iron excess → In plasma iron is carried on transferrin to the marrow and stored as ferritin and haemosiderin → There is NO physiological mechanism for excreting iron — balance is controlled entirely at absorption

Iron Preparations

• The usual therapeutic dose is 100 to 200 mg of elemental iron daily; prescriptions must specify elemental content, since salts differ several-fold
• Alternate-day dosing may be better absorbed than daily dosing, since a dose raises hepcidin for about 24 hours and blunts absorption of the next one

Factors Affecting Absorption, and Adverse Effects

• Enhanced by — ascorbic acid (vitamin C), gastric acid, meat and fish (haem iron), an empty stomach, and iron deficiency itself
• Reduced by — phytates (cereals, pulses), tannins in tea and coffee, calcium and milk, antacids, proton pump inhibitors, tetracyclines and fluoroquinolones (mutual chelation), and food generally
• Oral adverse effects — nausea, epigastric pain, metallic taste, constipation or diarrhoea, and black stools (harmless, but it masks melaena and confuses faecal occult blood testing). Tolerated better if taken with food, though absorption falls
• Parenteral adverse effects — injection site pain and staining, fever, arthralgia, hypophosphataemia (ferric carboxymaltose), and rarely anaphylaxis
• Parenteral iron is not faster at raising haemoglobin than oral iron in a patient who absorbs and takes it — it replaces stores more completely, which is a different advantage

Vitamin B12 and Folic Acid

Response to Treatment and Uses

• Expected response to iron — a sense of wellbeing within days; reticulocytosis peaking at 5 to 10 days; haemoglobin rising about 1 g/dL every 2 weeks. Treatment continues for 3 to 6 months after the haemoglobin normalises to replenish stores
• Failure to respond — consider non-adherence (much the commonest), continuing blood loss, wrong diagnosis (thalassaemia trait, anaemia of chronic disease), malabsorption, or coexisting B12 or folate deficiency
• Folic acid 5 mg periconceptionally prevents neural tube defects, and is given to all women planning pregnancy and at higher dose with antiepileptics or a previous affected child
• Folic acid is given routinely with methotrexate to reduce toxicity, and in chronic haemolysis where demand is high
• Hydroxocobalamin is also the antidote in cyanide poisoning, binding cyanide to form cyanocobalamin

Classification of Anaemia BY Cause and its Treatment

• Prescribing iron for every anaemia is a common and harmful error — in thalassaemia trait and anaemia of chronic disease the stores are normal or raised, and adding iron achieves nothing while risking overload

Applied Aspects

• Iron deficiency anaemia is extremely common in India, particularly in women and children, from a phytate-rich low-meat diet, hookworm, malaria and repeated pregnancy; the Anaemia Mukt Bharat programme supplies iron and folic acid to at-risk groups
• Iron deficiency is a sign, not a diagnosis — in an adult man or a postmenopausal woman it requires investigation of the gastrointestinal tract for occult malignancy
• Advise taking iron with vitamin C or citrus, and away from tea, milk and antacids; drinking tea with meals is a genuine and common contributor in India
• Acute iron poisoning is a paediatric emergency — tablets look like sweets. It causes corrosive gastrointestinal injury and haematemesis, then an apparent recovery, then shock, metabolic acidosis and hepatic necrosis. Treated with desferrioxamine, and prevented by child-resistant containers
• Chronic iron overload from repeated transfusion in thalassaemia is treated with deferoxamine (parenteral), or oral deferasirox and deferiprone — the oral agents transformed adherence and survival in thalassaemia, which is common in parts of India
• Screen for B12 deficiency in long-term metformin users and in vegans, both of which are common in India; a macrocytosis or a neuropathy should prompt measurement rather than assumption
• Check the reticulocyte count at 5 to 10 days to confirm a response before assuming treatment failure; it rises well before the haemoglobin does
• Continue iron for 3 to 6 months after the haemoglobin normalises, or the stores remain empty and the anaemia returns within months
• Erythropoietin is the treatment for renal anaemia, not iron alone — though iron must be replete first or the erythropoietin cannot work
• Give folic acid in chronic haemolysis — thalassaemia, sickle cell disease and hereditary spherocytosis all consume folate rapidly through increased erythropoiesis
• Combined deficiency is common in malnutrition and malabsorption, and treating only one leaves the anaemia partly uncorrected and the diagnosis apparently wrong
• Blood transfusion is not a treatment for nutritional anaemia except in life-threatening decompensation; it carries real risks and does nothing about the cause