History

Fact Explanation
Shortness of breath Iron deficiency is the most common form of malnutrition in the world where there is insufficient iron to support normal red cell production. Adult human body contains an average of 3.5 g where majority of them are in the form of haemoglobin (2.1 g) and rest is in the myoglobin, cytochromes with very small amount in the plasma bound to transferrin. [3] Anaemia cause low oxygenation of the blood, Hypoxia can be sensed by the carotid chemoreceptors and it will increase the depth of respiration. If the patient has heart failure anemia can worsen the symptoms.
Lethargy, fatigue Due to the anaemia, the patient feels very tired during exercise. [4] This is because, iron is an essential component for the creation of hemoglobin, that carries oxygen in the blood, and for the activation of many enzymes associated with the production of energy. If there is deficiency of iron body lacks sufficient oxygen and energy where person feels fatigue and lethargy.
Pica The ingestion of substances that are inappropriate for consumption. Eg:- kaolin, it has a negatively charged surface which can exchange and adsorb cations in the duodenum, where iron absorption occurs. [1]
Poor dietary habits If the diet does not contain enough iron, specially if the person is a strict vegetarian deficiency will occur. An average diet provides 10–20 mg per day of the iron requirement. Heme (mainly in red meat) have better iron absorption than nonheme (white meat, vegetables, and cereals). Daily iron requirement will be around 1-2 mg/ day. [3] Phytate and tannin containing food are known to cause reduce iron absorption. Phytates are prominent in wheat and some other cereals, while tannins are prevalent in (non-herbal) teas. Therefore these foods has to be avoided simultaneously with iron rich food.
Peptic ulcer disease and oesophageal varices from cirrhosis Cause upper gastrointestinal bleeding. [3]
Celiac disease, crohn disease Dietary iron is absorbed in the duodenum of the small intestine and any pathology in this area can cause poor absorption. [3]
Menorrhaga Excess iron loss can occur due to menorrhagia. [3] Usual blood loss per cycle is around 80 ml. Heavy and prolonged long menstrual periods cause excess blood loss.
Pregnancy or breastfeeding Body needs more iron than normal in these situations. Pregnant mothers need extra iron for the fetal development, placental development and loss due to the delivery. Total requirement for iron is around 1360 mg and there is saved 360 mg due to the absence of menstruation. Maternal anemia during pregnancy affects the neurodevelopment in the fetus as neurogenesis, development, and myelination dependent on iron. [2]
Cancer in the esophagus, stomach, small bowel, or colon Cancers causes chronic gastrointestinal blood loss. [7]
Use of aspirin, ibuprofen for a long time These drugs can cause gastrointestinal bleeding. [6]
Obstetric complications Maternal anemia increases the risk of low birth weight, premature birth [3] or fetal growth restriction. [2] Anaemia also increase the risk if postpartum haemorrhage.
Asymptomatic Patients with iron deficiency are not always symptomatic, they can be detected on incidental check ups by full blood count. [5]
References
  1. VON GARNIER C, STüNITZ H, DECKER M, BATTEGAY E, ZELLER A. Pica and refractory iron deficiency anaemia: a case report J Med Case Reports [online] :324 [viewed 27 July 2014] Available from: doi:10.1186/1752-1947-2-324
  2. BAROOTI E, REZAZADEHKERMANI M, SADEGHIRAD B, MOTAGHIPISHEH S, TAYERI S, ARABI M, SALAHI S, HAGHDOOST AA. Prevalence of Iron Deficiency Anemia among Iranian Pregnant Women; a Systematic Review and Meta-analysis J Reprod Infertil [online] 2010, 11(1):17-24 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719272
  3. SANTIAGO P. Ferrous versus Ferric Oral Iron Formulations for the Treatment of Iron Deficiency: A Clinical Overview ScientificWorldJournal [online] :846824 [viewed 27 July 2014] Available from: doi:10.1100/2012/846824
  4. COATS AJ. Anaemia and heart failure Heart [online] 2004 Sep, 90(9):977-979 [viewed 18 September 2014] Available from: doi:10.1136/hrt.2003.012997
  5. MCGILLIVRAY G, SKULL SA, DAVIE G, KOFOED SE, FRYDENBERG A, RICE J, COOKE R, CARAPETIS JR. High prevalence of asymptomatic vitamin D and iron deficiency in East African immigrant children and adolescents living in a temperate climate Arch Dis Child [online] 2007 Dec, 92(12):1088-1093 [viewed 18 September 2014] Available from: doi:10.1136/adc.2006.112813
  6. BLACK DA, FRASER CM. Iron deficiency anaemia and aspirin use in old age. Br J Gen Pract [online] 1999 Sep, 49(446):729-730 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1313502
  7. BAYRAKTAR UD, BAYRAKTAR S. Treatment of iron deficiency anemia associated with gastrointestinal tract diseases World J Gastroenterol [online] 2010 Jun 14, 16(22):2720-2725 [viewed 18 September 2014] Available from: doi:10.3748/wjg.v16.i22.2720

Examination

Fact Explanation
Pallor Due to the anaemia. [1]
Koilonychia Spoon shaped nails are a characteristic finding. [4]
Glossitis Is a non specific finding that also seen in Folate and vitamin B12 deficiency. [5]
Impaired development mile stones Impaired neurocognitive function affects the development, in the areas of gross motor, fine motor, vision, social-emotional behavior [3] and cognition etc. [2]
Inteligence score Lower IQ, is found in children who had iron deficiency during the critical periods of life. Iron if deficient can cause maldevelopment of neurocognitive function. [2]
Murmers Flow murmurs can be detected in anaemic patients. [6]
Tachycardia, peripheral oedema, elevated jugular venous pressure, hepatomegallt, bibasal fine crepitations Features of congestive heart failure are seen in severe disease especially in patients with a history of cardiac lesions. [6]
Dyspnea Due to the anaemia. As there is low haemoglobin in the blood leading to hypoxia, that can trigger carotid chemoreceptors result in rapid breaths. Worsening of heart failure can also be a cause for dyspnoea. [6]
References
  1. VON GARNIER C, STüNITZ H, DECKER M, BATTEGAY E, ZELLER A. Pica and refractory iron deficiency anaemia: a case report J Med Case Reports [online] :324 [viewed 27 July 2014] Available from: doi:10.1186/1752-1947-2-324
  2. RADLOWSKI EC, JOHNSON RW. Perinatal iron deficiency and neurocognitive development Front Hum Neurosci [online] :585 [viewed 27 July 2014] Available from: doi:10.3389/fnhum.2013.00585
  3. BEARD JL. Why Iron Deficiency Is Important in Infant Development J Nutr [online] 2008 Dec, 138(12):2534-2536 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415871
  4. KUMAR V, AGGARWAL S, SHARMA A, SHARMA V. Nailing the Diagnosis: Koilonychia Perm J [online] 2012, 16(3):65 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442766
  5. DAWSON AA, OGSTON D, FULLERTON HW. Evaluation of Diagnostic Significance of Certain Symptoms and Physical Signs in Anaemic Patients Br Med J [online] 1969 Aug 23, 3(5668):436-439 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1984179
  6. COATS AJ. Anaemia and heart failure Heart [online] 2004 Sep, 90(9):977-979 [viewed 18 September 2014] Available from: doi:10.1136/hrt.2003.012997

Differential Diagnoses

Fact Explanation
Thalassemia Ineffective erythropoiesis, due to excess production of free alpha (α) globin chains is the major abnormality in thalassemia. [1] Thalassemia patients have anemia that requires chronic blood transfusions and chelation therapies to prevent iron overload. Beta-thalassemia intermedia, is relatively a mild disease that does not require chronic blood transfusions. On examination they will have thalassemic facies maxillary hyperplasia, splenomegaly etc. These patients will also have the microcytic hypochromic anaemia as in iron deficiency. [3] Red cell distribution width is normal in thalassemia unlike in iron deficiency where it is high.
Sideroblastic anemias Sideroblastic anaemia will have hypochromic microcytic anemia as in iron deficiency and, elevated serum iron, decreased unsaturated iron-binding capacity. There is low Fe incorporation into erythrocytes, but normal erythrocyte survival is seen. Bone marrow will show erythroblastic hyperplasia of marrow with increased iron, and marked increase in marrow sideroblasts particularly ringed sideroblasts. [2] Sideroblastic anemia differs from the iron deficiency anaemia as they will have almost complete saturation of the serum transferrin, when compared to iron deficiency.
Lead poisoning Lead poisoning will have characteristic signs and symptoms of lead poisoning such as abdominal pain, confusion, headache, anemia, irritability, and in severe cases seizures, coma, and death. [4]
References
  1. RECHAVI G, RIVELLA S. Regulation of Iron Absorption in Hemoglobinopathies Curr Mol Med [online] 2008 Nov, 8(7):646-662 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722362
  2. PRASAD AS, TRANCHIDA L, KONNO ET, BERMAN L, ALBERT S, SING CF, BREWER GJ. Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a negro family J Clin Invest [online] 1968 Jun, 47(6):1415-1424 [viewed 27 July 2014] Available from: doi:10.1172/JCI105833
  3. SCRIVER CR, BARDANIS M, CARTIER L, CLOW CL, LANCASTER GA, OSTROWSKY JT. Beta-thalassemia disease prevention: genetic medicine applied. Am J Hum Genet [online] 1984 Sep, 36(5):1024-1038 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684522
  4. GORDON JN, TAYLOR A, BENNETT PN. Lead poisoning: case studies Br J Clin Pharmacol [online] 2002 May, 53(5):451-458 [viewed 18 September 2014] Available from: doi:10.1046/j.1365-2125.2002.01580.x

Investigations - for Diagnosis

Fact Explanation
Full blood count Low haemoglobin is there due to the anaemia. Hemoglobin level <13 g/dL in men and <12 g/dL in nonpregnant women is the definition for the anaemia. [1] Red cell count and pack cell volume may also be reduced. Red cell indices such as mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and mean corpuscular volume are reduced as this is a microcytic hypochromic anaemia. [1,2]
Blood picture Hypochromic microcytic blood picture [3] is seen. Red cells are smaller than the normal. Occasional target cells and poikilocytes are seen.
Reticulocyte count Reticulocytes are increased due to ineffective erythropoiesis. [1]
Serum ferritin Ferritin is an marker of iron stores, In iron deficiency anaemia this is decreased due to the depleted stores. Levels are also elevated in patients with coexisting inflammation. [1]
Soluble transferring receptor (sTfR) levels This reflects the tissue iron deficiency, Transferrin saturation level is increased in the presence of iron deficiency anaemia. [3]
Serum hepcidin level Hepcidin is encoded as an 84-amino acid prepropeptide. Hepcidin production is induced by inflammation and iron overload and is reduced in patients with iron deficiency, hypoxia, anemia, and increased erythropoietic activity. Immunochemical and mass spectrometric assays are used to measure the levels of hepcidin in serum, plasma, and urine. [1]
References
  1. Good Clinical Practice Recommendations for Iron Deficiency Anemia in Pregnancy (IDA) in Pregnancy in India J Obstet Gynaecol India [online] 2011 Oct, 61(5):569-571 [viewed 28 July 2014] Available from: doi:10.1007/s13224-011-0097-5
  2. NEERU S, NAIR NS, RAI L. Iron Sucrose Versus Oral Iron Therapy in Pregnancy Anemia Indian J Community Med [online] 2012, 37(4):214-218 [viewed 28 July 2014] Available from: doi:10.4103/0970-0218.103467
  3. OUSTAMANOLAKIS P, KOUTROUBAKIS IE, MESSARITAKIS I, NINIRAKI M, KOUROUMALIS EA. Soluble transferrin receptor-ferritin index in the evaluation of anemia in inflammatory bowel disease: a case-control study Ann Gastroenterol [online] 2011, 24(2):108-114 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959302

Investigations - Fitness for Management

Fact Explanation
Haemoglobin level Anaemic patient will have low haemoglobin level. Management will differ according to the level of haemoglobin. If the haemoglobin level below 100 g/L, parenteral iron may be needed. [1] Specially in conditions like pregnancy, severe anemia with maternal Hb levels less than 6 g/dl needs blood transfusion as it is known to cause abnormal fetal oxygenation and further complications. [2]
References
  1. GOZZARD D. When is high-dose intravenous iron repletion needed? Assessing new treatment options Drug Des Devel Ther [online] :51-60 [viewed 28 July 2014] Available from: doi:10.2147/DDDT.S15817
  2. Good Clinical Practice Recommendations for Iron Deficiency Anemia in Pregnancy (IDA) in Pregnancy in India J Obstet Gynaecol India [online] 2011 Oct, 61(5):569-571 [viewed 28 July 2014] Available from: doi:10.1007/s13224-011-0097-5

Investigations - Followup

Fact Explanation
Full blood count Haemoglobin level increases with the treatment, it takes at least 1 month to come to the normal level with normalizing the red cell indices. Target is to correct the hemoglobin levels within 4 weeks (or achieving an increase of >2 g/dL) and replenishing iron stores (transferrin saturation >30%). [1]
References
  1. GOLDBERG ND. Iron deficiency anemia in patients with inflammatory bowel disease Clin Exp Gastroenterol [online] :61-70 [viewed 28 July 2014] Available from: doi:10.2147/CEG.S43493

Investigations - Screening/Staging

Fact Explanation
Neurocognitive tests Perinatal iron deficiency will cause abnormalities of neurocognitive function. Trail Making test, Intra-Extra-dimensional Shift, Spatial Working Memory, Rapid Visual Information Processing, Pattern Recognition Memory, and Spatial Recognition Memory are important in detecting the impairment in neurocognitive function. [2]
Upper endoscopy [1] If there is a history or suspicion of upper GI blood loss (peptic ulcer disease, varices) upper and iron deficiency associated with symptoms such as dyspepsia, dysphagia, loss of appetite and loss of weight, upper GI endoscopy needs to be done. [1]
Colonoscopy [1] Is done specially in the presense of bleeding per rectum inorder to check any lesions causing the problem. There can be benign and malignant polyps, lumps and ulcers in the colon. [1]
Fecal occult blood test [1] To diagnose any microscopic lower gastrointestinal blood loss. [1]
References
  1. BAROOTI E, REZAZADEHKERMANI M, SADEGHIRAD B, MOTAGHIPISHEH S, TAYERI S, ARABI M, SALAHI S, HAGHDOOST AA. Prevalence of Iron Deficiency Anemia among Iranian Pregnant Women; a Systematic Review and Meta-analysis J Reprod Infertil [online] 2010, 11(1):17-24 [viewed 27 July 2014] Available from:
  2. RADLOWSKI EC, JOHNSON RW. Perinatal iron deficiency and neurocognitive development Front Hum Neurosci [online] :585 [viewed 27 July 2014] Available from: doi:10.3389/fnhum.2013.00585

Management - General Measures

Fact Explanation
Treatment of the underlying condition The precipitating factors for the iron deficiency like menorrhagia, peptic ulcer disease, oesophageal varices, lower gastrointestinal neoplasms etc need specific management. [3]
Prevention of iron deficiency in high risk people People with increased demand for iron such as pregnant mothers [2] , breast feeding mothers and adolescents need supplementation to avoid the deficiency. School medical programmes can provide iron tablets for the adolescents, Pregnant mothers should receive iron supplements starting from the first trimester up to 6 months postpartum Because it has been studied that fetal brain growth continues the first 2 years after birth due to dendritic growth, synaptogenesis, and glial cell proliferation. [1] On the other hand if the mother is deficient of iron during the pregnancy, newborn infants will also develop low serum ferritin.
Worm treatment Worm infestations (eg:- hookworm) can cause chronic lower intestinal blood loss. [4]
Avoid inhibitors for iron absorption Certain foods rich in tannates (e.g. tea), phytates (e.g., bran, cereal) are negative factors for iron absorption. Antacids, proton pump inhibitors [6] , histamine H2 blockers increase the gastric pH that reduce the absorption and should be avoided if possible. Tetracycline shoud be taken 3 hours apart from the iron. [5]
References
  1. RADLOWSKI EC, JOHNSON RW. Perinatal iron deficiency and neurocognitive development Front Hum Neurosci [online] :585 [viewed 27 July 2014] Available from: doi:10.3389/fnhum.2013.00585
  2. BAROOTI E, REZAZADEHKERMANI M, SADEGHIRAD B, MOTAGHIPISHEH S, TAYERI S, ARABI M, SALAHI S, HAGHDOOST AA. Prevalence of Iron Deficiency Anemia among Iranian Pregnant Women; a Systematic Review and Meta-analysis J Reprod Infertil [online] 2010, 11(1):17-24 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719272
  3. BAYRAKTAR UD, BAYRAKTAR S. Treatment of iron deficiency anemia associated with gastrointestinal tract diseases World J Gastroenterol [online] 2010 Jun 14, 16(22):2720-2725 [viewed 18 September 2014] Available from: doi:10.3748/wjg.v16.i22.2720
  4. SMITH JL, BROOKER S. Impact of hookworm infection and deworming on anaemia in non-pregnant populations: a systematic review Trop Med Int Health [online] 2010 Jul, 15(7):776-795 [viewed 18 September 2014] Available from: doi:10.1111/j.1365-3156.2010.02542.x
  5. NEUVONEN PJ, PENTIKäINEN PJ, GOTHONI G. Inhibition of iron absorption by tetracycline. Br J Clin Pharmacol [online] 1975 Feb, 2(1):94-96 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1402485
  6. ITO T, JENSEN RT. Association of Long-term Proton Pump Inhibitor Therapy with Bone Fractures and effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium Curr Gastroenterol Rep [online] 2010 Dec, 12(6):448-457 [viewed 18 September 2014] Available from: doi:10.1007/s11894-010-0141-0

Management - Specific Treatments

Fact Explanation
Dietary advice Fish, chicken , meats (liver is the highest source), dried lentils, peas, and beans, soybeans and whole-grain are the food that are rich in iron. Adding lime juice which is rich in vitamin C, for the green leaves may enhance the absorption of iron. Advice should be given to avoid inhibitors of iron absorption simultaneouly with the iron rich food. eg:- tanin in the tea, phytates [3]
Oral iron therapy Standard treatment in majority of the institutions is oral iron, with blood transfusion reserved for severe or emergency cases. [4] Oral iron is available as ferrous sulphate, ferrous gluconate and ferrous fumarate. [4] Iron supplementation to correct anaemia which takes atleast 1-3 months and replenish body stores needs further 3-6 months. The hemoglobin improvement goal is 20 g/L in four weeks. [5] Oral iron will have certain disadvantages such as side effects (constipation, nausea, vomiting and darkening of the stools) leading to poor compliance and poor absorption. Laxatives, stool softeners, and adequate hydration can reduce this constipating effect.
Parenteral iron therapy Iron dextran [4] is the first parenteral therapy introduced for the iron deficiency treatment and iron sucrose was later introduced. Parentaral therapy is more safer in pregnancy as it corrects anemia at short duration and replenishes iron stores better than oral iron. Intravenous and intramuscular routes are used for for parenteral iron. Intramuscular route causes pain, staining at injection site and arthralgia whish are not seen with intravenous route. The rise in haemoglobin is no quicker than with oral preparations. Delayed reactions including myalgia, headache and arthralgias and anaphylactic reactions are the side effects of parenteral therapy. Fe–sucrose is given as either a bolus over 5–10 min or short infusion less than 30 mi in 0.9 % normal saline. [3] Indications would be hemoglobin level below 100 g/L , oral therapy failure, severe intestinal disease activity and in an emergency situations where rapid correction is needed. [5] Sodium ferric gluconate is a safer form of parenteral with reduced incidence of anaphylaxis. The newer drugs such as ferric carboxymaltose and iron isomaltoside 1000 provide the opportunity to treat rapidly without a test dose which is more convenient to the clinician. [5]
Blood transfusion As the standard treatment in majority of iron deficiency anaemia is oral iron, and therefore blood transfusion is reserved for severe or emergency cases. Though rare, blood transfusion has certain disadvantages like, transmission of infections like HIV, CMV, hepatitis and anaphylaxis. [4] In pregnancy severe anemia with maternal Hb levels less than 6 g/dl is known to cause abnormal fetal oxygenation. Therefore maternal transfusion is indicated in postpartum anemia with signs of shock, severe acute blood loss following spontaneous delivery or cesarean section and severe anemia during pregnancy associated with maternal decompensation. [3]
References
  1. SANTIAGO P. Ferrous versus Ferric Oral Iron Formulations for the Treatment of Iron Deficiency: A Clinical Overview ScientificWorldJournal [online] :846824 [viewed 27 July 2014] Available from: doi:10.1100/2012/846824
  2. CHRISTY BA, SCANGOS GA. In vitro methylation of bovine papillomavirus alters its ability to transform mouse cells. Mol Cell Biol [online] 1986 Aug, 6(8):2910-2915 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC367859
  3. Good Clinical Practice Recommendations for Iron Deficiency Anemia in Pregnancy (IDA) in Pregnancy in India J Obstet Gynaecol India [online] 2011 Oct, 61(5):569-571 [viewed 28 July 2014] Available from: doi:10.1007/s13224-011-0097-5
  4. NEERU S, NAIR NS, RAI L. Iron Sucrose Versus Oral Iron Therapy in Pregnancy Anemia Indian J Community Med [online] 2012, 37(4):214-218 [viewed 28 July 2014] Available from: doi:10.4103/0970-0218.103467
  5. GOZZARD D. When is high-dose intravenous iron repletion needed? Assessing new treatment options Drug Des Devel Ther [online] :51-60 [viewed 28 July 2014] Available from: doi:10.2147/DDDT.S15817