“Iron - Avoiding deficiency” Bronwyn Williams Haematologist – HSSA / RCH. Iron -. Points for Discussion. Iron metabolism and its regulation Prevalence and causes of iron deficiency Diagnostic workup /differential diagnosis Treatment of IDA.
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Haematologist – HSSA / RCH
Points for Discussion
Iron metabolism and its regulation
Prevalence and causes of iron deficiency
Diagnostic workup /differential diagnosis
Treatment of IDA
Haem iron compounds
cytochrome a,b,c (oxidative energy)
cytochrome P450 (drug metabolism)
catalase, peroxidase (ROS protection)
Non-haem iron compounds
NAD dehydrogenase (mitochondrial respiration)
xanthine oxidase (nucleotide catabolism)
ribonucleotide reductase (nucleotide synthesis)
Fairbanks VF, Beutler E. Ironmetabolism. In: Beutler E, et al. editors. Williams Hematology, 6th ed. New York: McGraw-Hill; 2001. p.295-.304.
ROS = reactive oxygen species.
Abnormal mental and motor development in infancy
Impaired work capacity / fatigue
Increased risk of premature delivery
Increased maternal and infant mortality in severe anaemia
Stoltzfus RJ. J Nutr. 2001;131(2 Suppl 2):697S-700S.
Tf = transferrin; TfR = transferrin receptor.
Tf = transferrin; TfR = transferrin receptor.
Low Fe stores
Ajioka RS, Prchal J. The Hematologist. 2008;5:(5)1.
Andrews NC. Blood. 2008;112(2):219-30 .
The population of Earth is estimated to be 6,993,000,000 ( US Census Bureau) – hence IDA may affect over 2 billion people worldwide
DeMaeyer E, Adiels-Tegman M. World Health Stat Q. 1985;38:302-16.
Typically low to normal RCCThe Blood in IDA
Hoffbrand AV, et al., editors. Essential haematology.5th ed. Malden, MA; Oxford: Blackwell, 2006.
Depleted iron stores
Iron deficiency (normal Hb)
Iron deficiency anaemia
CHr = haemoglobin content of reticulocytes; Hb = haemoglobin; Hypo = hypochromic erythrocytes; ZPP = zinc protoporphyrin.
Modified after Brugnara C. Clin Chem. 2002;48:981-2.
Hb 93, MCV 61
RDW 20 ( 11 – 15)
Tests depend on why
? diet ? bleeding ?? malabsorption
Case 2 – mahali
Hb 100, MCV 67
RDW 14.6 ( 11 – 15)
iron deficiency unlikely
Additional testing with haemoglobin studiesIron deficiency or thal trait? - A common conundrum
Hb, MCV, Tf saturation, serum ferritin +/- sTfR
Detailed medical +/-
gynaecological history +/-
Proceed to treatment
GI = gastrointestinal.
IgA level and endomysial and TTG antibodies
H. pylori infection
Occult bleeding, competition for iron, interferes with acid production ( iron conversion)
serology and urease breath test
Worth thinking about especially in certain ethnic groups ( see next slide)
Occult / overt bleeding
Eg GOR / oesphagitis; Meckels; telengiectasia / angiodysplasia; portal HT; Inflammatory bowel disease
Human Hb, calprotectin, endoscopy
Iron transport defect
Iron absorption challenge; genetic testing**
Autoimmune atrophic gastritis
Rare in children, association with H Pylori infection
gastrin, parietal cell antibodies, anti-IF
TTG = tissue transglutaminase;anti-IF = anti-intrinsic factor.
Logan RP, Walker MM. BMJ. 2001;323:920-2.
Oral medications: tablets
ferrous sulphate, gluconate or citrate containing ~ 50 mg elemental iron / tablet +/- vitamin C/ folate
Oral medications: syrup
ferrous sulphate – liquid 6mg elemental iron / ml
Parenteral preparations - IV
Venofer: iron saccharose 100 mg/5ml ampoule
Maximum dose 1 ampoule
Ferinject: iron carboxymaltose 100 mg/ 2ml or 500mg / 10ml vials ( dilute 100mg / 50ml N Saline)
Various dosing protocols – Formula; <35kg -15mg/kg, >35kg – 500mg; 15mg/kg up to 1000mg maximum
NOTE: Maximum weekly dose 1000mg
Muñoz M, et al. J Clin Pathol. 2011;64:287-96.
Response rate to parenteral and oral iron is similar
Difference between formulations mainly cost not quality
Choice based on age / acceptance by patient
Mostly trial oral replacement would precede IV iron
Compliance important to consider
Consider degree of symptoms / tolerance to decide dose/ frequency and agent
Duration of treatment should be very long
At least 4 months for adequate repletion with standard oral dosing
Response to iron is the ultimate test for IDA
Hershko C, Skikne B. Semin Hematol. 2009;46:339-50.
Iron = 0.17mg/5gm
10% absorption ~ 0.015mg/5gm
Iron = 6.5mg/5gm
(spinach 0.9mg / cup fresh)
if 5% absorption ~ 0.33mg / 5gm
+ Vitamin C ( and B12)
Few studies (rats / humans) - improves iron status /non toxic - ? doseFood for thought?