Iron deficiency 

1. Decreased intake
   1. Lack of iron in diet
      1. infants, teenagers, elderly, poor, vegetarians.
   2. ↓ absorption
      1. Diseases of the small intestine
         1. chronic diarrhoea
         2. gluten intolerance
         3. Crohn’s disease
         4. Gastric surgery/Gastrerctomy
      2. Intake of iron absorption inhibitors
         1. phytate (nuts, bran products)
         2. polyphenols (tea, coffee, cocoa
         3.  calcium (milk products)
         4. other factors (e.g. soy protein)
         5. Medicaitons: Non-steroidal anti-inflammatory drugs, proton pump inhibitors, glucocorticoids
2. Increased Iron Loss
   1. GI bleed
      • Hookworm
      • Schistosomiasis
      • Hermorrhoids
      • Peptic ulcer
      • Gastritis
      • Diverticulosis
      • IBD
      • AV malformation
      • Varices
      • Meckel’s diverticulum
      • Recet trauma/surgery
   2. Gynecological
      • Excessive menstruation
      • Gyne/Bladder Neoplasm
   3. Renal
      • CRF and hemodialyis
   4. Other: Chronic Disease, TB, Blood donation, Epistaxis
3. Increased need 
   • Pregnancy, lactation
   • Rapid childhood growth.

At risk groups:

Women	Infants	Elderly	Athletes	Vegetarians
↑requirement (pregnancy, breast feed) ↑loss Fe (menstrual bleed, blood donation) Teenagers (menstrual loss, poor diet,growth)	↑requirement Fe	Poor dietGI disease	Poor diet GI bleed, urine & sweat loss	Low Fe diet

N.B. Dietary inadequacy alone is rarely a cause.

History

• Colonic symptoms
  • Change in bowel habit
  • Rectal bleeding malaena, haematochezia
  • Steatorrhoea
  • Haematemesis
  • Pain
  • Diarrhoea
  • Gastric or oesophageal pathology- reflux, vomiting, pain, dysphagia, dyspepsia

• Consititutional symptoms– weight loss, fatigue, lethargy, SOB
• Drug Hx– NSAIDs, aspirini
• Diet– vegans, alcoholics, elderly
• Surgical history– gastrectomy
• FHx of GIT malignancy
• PICA

Examination

• Signs of chronic iron deficiency anaemia- angular stomatitis, glossitis and koilonychia (spooning), thinning and flattening of nails
• Palpable abdo massess, tenderness, irregular hepatomegaly
• Mouth ulcers>>> coeliac disease or IBD
• Signs of chronic liver disease or portal hypertension
• Careful exam of hands, face and mucous membranes of nose and mouth HHT
• Rectal exam for mass and faecal occult blood (a negative result does not preclude a thorough GIT exam)

Investigations

• Iron studies
• Colonoscopy + biopsies ± therapeutic procedures
• Endoscopy ( if the patient has a benign PU, a colon cancer still needs to be excluded) + small bowel biopsies (even if no symptoms of malabsorptiuon)

If still no findings consider other radiological evidence-

• Angiography
• Technetium labelled RBC scanning

30% patients, no cause can be found

Should be continually monitored both clinically and with regular Hb levels

If anaemia persists despite Iron supplement- repeat investigation

Hypochromicmicrocytic		Normochromic normocytic		Normochromic macrocytic
MCV	<80	MCV	80-100	MCV	>100
MCH	LOW	MCH	NORMAL	MCH	HIGH
Fe def anaemia Thalassaemia Chronic disease Sideroblastosis (enzyme defect involving porphorin ring of Hgb)		↑ retics	↓ retics	megalobalstic	Non megaloblastic
		Blood Loss Trauma Operation Haemolysis	Chronic Disease Renal Dysfunction Thyroid Disease Myelodysplasia Myeloma (CA Of Plasma Cells) Leukaemia CA	Vit B12 defFolate def	Myelodysplastic syndromes Alcohol Liver disease Hypothyroid Drugs Pregnancy reticulocytosis

Interpreting iron profile results 

	Anaemia of chronic disease	Iron deficiency without anaemia	Severe iron deficiency with anaemia
Serum iron	↓	↓	↓
Transferrin or TIBC	↓ or low normal	↑ or high normal	↑
Transferrin saturation (%)	↓	↓	↓
Ferritin	↑ or high normal	↓	↓
Blood film	Normal	Normal	Hypochromia + microcytosisLow MCV, Hb, SSx Pallor, Pica, epithelial changes

Iron Studies – low serum Fe, serum ferritin, transferrin saturation; high TIBC

1. Serum iron and iron-binding capacity 
   1. measures the extent to which iron-binding sites in the serum can be saturated 
   2. The serum iron falls and the total iron-binding capacity (TIBC) rises in iron deficiency compared with normal. transferrin saturation % = serum iron/TIBC = Iron deficiency if < 19%
   3. Anemia of chronic disease:
      1. the body holds iron out of the serum but also produces less transferrin (presumably as part of a response to keep iron away from pathogens that require it for their metabolism)
      2. In this case, serum iron is low but the TIBC (that is, the transferrin) is low. 
      3. So the percent transferrin saturation is normal.

2. Serum ferritin 
   1. reflects the amount of stored iron.
   2. Ferritin is a water-soluble complex of iron and protein.
   3. More easily mobilized than haemosiderin for Hb formation. 
   4. It is present in small amounts in plasma.
   5. iron deficiency: a low serum ferritin confirms the diagnosis.
      1. However, ferritin is an acute-phase reactant, and levels increase in the presence of inflammatory or malignant diseases. 
      2. In these cases, measurement of serum iron/TIBC

3. Serum soluble transferrin receptors 
   1. Transferes iron to cells
   2. The number of transferrin receptors increases in iron deficiency. 
   3. can help to distinguish between iron deficiency and anaemia of chronic disease

Australian Prescriber – VOLUME 39 : NUMBER 6 : DECEMBER 2016

Treatment

• Diet

• Heme iron
  • Liver
  • Red meat
  • Seafood
  • Poultry
• Non-heme iron
  • (veganism. In general
  • Poorly absorbed, however co-ingestion of an antioxidant such as vitamin C (e.g. a glass of orange juice) may improve absorption.
    • Beans
    • Dark green leafy vegetables
    • Dried fruit, raisins and apricots
    • Iron-fortified bread, cereal, pasta
• Oral Fe
  • ferrous sulfate at a dose of 325–650 mg daily
    • equivalent to 105–210 mg elemental iron 
  • Ferrous fumarate and gluconate salts are equally effective in practice.
  • Vitamin C enhances iron absorption
  • Patients should be advised to take oral iron supplementation on an empty stomach as phosphates, phytates and tannates in food bind iron and impair absorption. 
  • Patients should also be advised to take iron either two hours before or four hours after the ingestion of antacids.
  • Adverse effects
    •  Constipation
    • Dysgeusia
    • nausea 

1. Oral iron preparations

Brand name	Formulation	Elemental iron content
Ferro-gradumet	Ferrous sulfate 325 mg Controlled-release tablets	105 mg
Ferrograd C	Ferrous sulfate 325 mg Vitamin C 500 mg Controlled-release tablets	105 mg
FGF	Ferrous sulfate 250 mg Folic acid 300 microgram Controlled-release tablets	80 mg
Fefol	Ferrous sulfate 270 mg Folic acid 300 microgram Controlled-release capsules	87 mg
Ferro-F-tab	Ferrous fumarate 310 mg Folic acid 350 microgramNon-controlled-release tablets	100 mg
Ferro-tab	Ferrous fumarate 200 mg	65.7 mg
Ferro-liquid	Ferrous sulfate 30 mg/mL	6 mg/mL

Reasons for failure to respond to oral iron therapy

• Inadequate iron intake – Non-adherence, insufficient iron content in supplement
• Inadequate iron absorption
  • Concomitant consumption of inhibitors of iron absorption (e.g. tea, calcium)
  • Coexisting inflammation with iron sequestration
  • Intestinal mucosal disorders (e.g. coeliac disease)
  • Helicobacter pylori infection
  • Impaired gastric acid secretion (use of proton pump inhibitors)
• Ongoing blood losses
  • Occult blood loss
• Coexisting condition interfering with bone marrow response
  • Concomitant vitamin B12 or folate deficiency, primary bone marrow disease

IV Fe

• Intravenous infusion results in a rapid replenishment of iron stores with peak ferritin concentrations at 7–9 days after infusion.
• haemoglobin should rise within 2–3 weeks in the majority of patients. 

Ganzoni formula

Total iron dose (mg iron) = Body weight (kg) x (Target – Actual haemoglobin) (g/L) x 0.24 + Iron for iron stores (mg iron)**

* Haemoglobin must be in g/L

** Iron stores

<35 kg body weight = 15 mg/kg body weight

>35 kg body weight = 500 mg

Example: 80 kg female with a haemoglobin of 80 g/L

needs a dose of 80 x (150–80) x 0.24 + 500 = 1844 mg iron

• Ferric carboxymaltose
  •  is the preferred formulation in ambulatory settings, such as Hospital in the Home
  • can deliver up to 1 g of iron in 15 minutes
  • One limitation is ferric carboxymaltose can only be infused in doses up to 1 g per week. It therefore cannot always provide the amount of iron required according to the Ganzoni formula 
  • Two infusions at least one week apart may be needed
• Iron polymaltose
  • for inpatients as a larger dose of iron can be infused in a single sitting. 
  • logistical limitations such as preparation time (the case illustrating the Ganzoni formula would require 19 ampoules) and the lengthy duration of administration of up to 5 hours that requires frequent observations. 

Adverse effects of intravenous iron preparations

1. Immediate adverse effects
   1. Headache
   2. Nausea
   3. Vomiting
   4. Dysgeusia
   5. Arthralgia
   6. Myalgia
2. Anaphylactoid
   1. Wheezing
   2. Flushing
   3. Dyspnoea
   4. Dizziness
3. Infusion site reactions
   1. Localised pain
   2. Discolouration of skin
4. Delayed adverse effects (1–2 days post infusion)
   1. Mild fever
   2. Headache
   3. Arthralgia
   4. Myalgia
5. Hypophosphatemia