1. IRON DEFICIENCY ANEMIA
Dr. Kunhikannan
Dept. of Gen. Medicine
Kannur Medical College

2. Absorption of Iron
Iron absorbed from upper SI in the form of Ferrous Iron
Iron gets attached to an intracellular iron carrier in mucosal cells of intestine where it is oxidised to ferric state
Intracellular iron carrier delivers a variable portion of absorbed iron to plasma which is carried away to various parts of the body in combination with iron carrier protein, transferrin

3. Absorption of Iron
Remainder iron is stored as mucosal ferritin in which iron is not absorbed but is lost from body after 3-4 days
Absorption of iron is controlled by amount of iron stores
When iron stores are reduced absorption is enhanced & vice versa

4. Iron deficiency anemia
It is the condition in which there is anemia and clear evidence of iron deficiency
It is the most common cause of anemia

5. Causes of iron deficiency
Increased demand of iron.
Increased iron loss.
Decreased iron intake / absorption.

6. Increased demand for iron
Rapid growth in infancy / adolescence.
Pregnancy
Erythropoietin therapy
Increased iron loss
c/c blood loss
Menses
a/c blood loss
Blood donation
Phlebctomy as treatment for polycythemia vera

7. Decreased iron intake or absorption
Malabsorption
Sprue
c/c disease
Mal absorption from surgery
Post gastrectomy
a/c or c/c inflammation

8. Clinical features General symptoms
Fatigue, lassitude, dyspnoea, palpitation.
Dizziness, headache, syncope, tinnitus, vertigo
Irritability, sleep disturbances.
Lack of concentration.
Throbbing in head and ears.
Parasthesia in fingers and toes.
Anorexia, indigestion, nausea.
Anemia, intermittent claudication, transient cerebral ischemia.
Amenorrhoea.
Symptoms of cardiac failure.

9. Signs
Pallor of skin palms and oral mucosa, nail beds and palpebral conjunctiva.
Tachycardia.
Wide pulse pressure.
Edema.
Cervical venous hum.
Ejection systolic murmur best heard in pulmonary area.
Cardiac dilatation.
Signs of cardiac failure.

10. Clinical presentation of iron deficiency anemia.
Pregnancy, adolescence, periods of rapid growth and an intermittent h/o blood loss of any kind should alert to possible iron deficiency.
Appearance of iron deficiency in an adult male means GI blood loss until proved otherwise.

11. Characteristics of iron deficiency
Angular stomatitis.
Glossitis.
Brittle finger nails.
Platynychia.
Koilonychia.
Pica
Carving for strange items-coal, earth, tomatoes, greens, starch and ice
PLUMMER VINSON SYNDROME
PATTERSON-KELLY SYNDROME
Sideropenic dysphagias
Occurs in long standing iron deficiency

12. Iron deficiency-features
Iron deficiency anemia.
Glossitis.
Koilonychia.
Postcricoid web
dysphagia
Intermittent & more for solids than liquids
Demonstrated endoscopically / barium meal.
Dilatation required in case of severe obstruction
Increased risk of Sq cell Ca of pharynx and esophagus.
Treatment is with iron.
For early diagnosis, upper GI endoscopy , every yr

13. Investigations To confirm iron deficiency anemia Hemoglobin - reduced.
MCV – reduced (microcytosis, <80fl )
Peripheral smear study
Microcytosis, hypochromia.
Elliptical cells and poikilocytes in severe cases.
Reticulocyte count
normal
elevated- blood loss with enough iron stores or on iron therapy.
Red Cell Indices
Normal Hb
Males: gm/dL
Females: gm/dL

14. Investigations MCV is volume of RBC Normocytic: 90+-8 fl
Microcytic: <80 fl
Macrocytic: >100 fl
MCH. It is amount of Hb in 1 RBC.
Normal: pg
MCHC. It is the average concentration of Hb in 1 RBC
Normal: gm/dL
Hypochromia: <31g/dL
Hyperchromia: >31 g/dL
Serum iron and Total Iron Binding Capacity (TIBC)
Serum iron – circulating iron bound to transferrin
TIBC - indirect measure of circulating transferrin
In normal adults, total amount of iron that serum transferrin can bind is 300 μg/dL. But actual amount of iron bound to transferrin is 100 μg/dL. So the percentage saturation

15. Investigations
In normal adults, total amount of iron that serum transferrin can bind is 300 μg/dL. But actual amount of iron bound to transferrin is 100 μg/dL. So the percentage saturation is 33%
Serum iron can vary from 10-40%
Its levels are influenced by recent iron medications
Serum iron shows diurnal variations. Highest value in morning and lowest in evening

16. Investigations Normal range for serum iron is 50-150 ug/dL
TIBC normal range ug/dL
Transferrin saturation which is normally 25-50% is obtained by formula
Serum iron x 100
TIBC
Iron deficiency states are associated with saturation levels below 18%

17. SERUM FERRITIN
Iron is stored complexed to protein as ferritin or hemosiderin
Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferrittin accumulates within the cells of RE system, protein aggregates are formed as hemosiderin
Iron in hemosiderin can be extracted for release by RE cells
Serum ferritin levels is the convenient lab test to estimate the iron stores as serum ferritin levels correlates with total body iron stores under steady state condn.
CONTD.

18. SERUM FERRITIN
Normal values for ferritin varies according to age & gender.
Adult males have serum ferritin values of 100 ug/L while adult female average 30 ug/L
As iron stores are depleted, serum ferritin falls to <15 ug/L. such levels diagnostic of absent body iron stores
It is unaffected by recent iron intake
It is the first abnormal lab test in iron deficiency

19. 7. EVALUATION OF BONE MARROW IRON STORES
Serum ferritin has largely supplanted bone marrow aspirates for determination of storage iron
Serum ferritin levels is a better indicator of iron overload than marrow iron stain
20-40% sideroblasts have visible ferritin granules in their cytoplasm, represents iron in excess of that needed for hemoglobin synthesis
In states in which release if iron from storage sites is blocked, RE iron will be detectable and there will be few or no sideroblasts

20. 8. RED CELL PROTOPORPHYRIN LEVELS
When heme synthesis is impaired, protoporphyrin accumulate within RBCs
Normal value <30ug/dL of RBCs
In iron deficiency, value I excess of 100ug/dL is seen

21. MOST COMMON CAUSE OF INCREASED RBC PROTOPORPHYRIN
Absolute or relative iron deficiency
Lead poisoning

22. 9. Serum Levels of Transferrin Receptor Protein (TRP)
Erythroid cells have highest number of TRP
TRP is released by cells into circulation
Serum levels of TRP reflect the total erythroid marrow mass
TRP is elevated in absolute iron deficiency
Normal value: 4-9 ug/L
Number of receptors increases with depletion of iron & vice versa
Concentration of serum transferrin receptor correlates with rate of erythropoeisis
In iron deficiency serum transferrin receptor increases due to increased erythropoeisis whereas in anemia of chronic disease, serum transferrin receptor decreases due to decreased erythropoeisis

23. Microcytic Hypochromic Anemia Pathogenic Classification:
Disorders of iron metabolism
Iron deficiency anemia
Anemia of Chronic disorders
Disorders of Globin synthesis
Alpha & Beta thalassemias
Hemoglobin E Syndrome
Hemoglobin C Syndrome
Sideroblastic anemia

24. Iron deficiency anemia
LABORATORY FEATURES IN MICROCYTIC HYPOCHROMIC ANEMIA
Iron deficiency anemia
Serum iron low
Serum Ferritin low
TIBC High
Percentage Saturation – low
Bone marrow
Sideroblast – Low
Iron stores – Low
Beta thalassemia Trait
Serum Iron N or High
Serum Ferritin N or High
TIBC Normal
Percentage saturation
Sideroblast Normal
Iron stores High

25. E. Sideroblastic anemia -Serum Iron – high -Serum Ferritin - High
LABORATORY FEATURES IN MICROCYTIC HYPOCHROMIC ANEMIA
Anemia of Chronic Disease
Serum iron –High
Serum Ferritin – High
Percentage Saturation – Normal or High
TIBC – Low
Bone marrow
Iron stores increased
E. Sideroblastic anemia
-Serum Iron – high
-Serum Ferritin - High
-Percentage saturation - high

26. To determine the cause of Iron Deficiency following investigations may be done mainly to check for chronic blood loss from GIT
Stool (Occult blood & Hook worm)
Zigmoidoscopy
Colonoscopy
Upper GI endoscopy
Barium meal
Barium enema
Urine for Schistosomias
Investigation for malabsorption

27. DIFF. DIAGNOSIS OF MICROCYTIC HYPOCHROMIC ANEMIA
Iron def. anemia
Thalassemia
Chronic inflammatory disease with inadequate iron supply to erythroid marrow
Myelodysplastic Syndrome

28. Impaired hemoglobin synthesis with mitochondrial dysfunction
DIFF. DIAGNOSIS OF MICROCYTIC HYPOCHROMIC ANEMIA
Thalassemia
Serum iron level normal or increased
Transferrin saturation normal or increased
Chronic Inflammatory Disease
Anemia is normocytic & normochromic
Ferritin level normal or increased
TIBC below normal
MyeloDysplastic Syndromes
Impaired hemoglobin synthesis with mitochondrial dysfunction
Iron values reveal normal stores & more than adequate supply to bone marrow

29. MANAGEMENT OF IRON DEFICIENCY ANEMIA

30. Appropriate approach is determined by the severity & cause
Elderly patients with severe iron deficiency anemia & cardiovascular instability require RED CELL TRANSFUSION
Younger persons who have compensated for the anemia can be treated more conservatively with iron replacement
For majority, oral iron therapy will suffice
Specific diagnostic tests & appropriate therapy take priority inpatients with unusual blood loss or malabsorption

31. ONCE IRON DEFICIENCY ANEMIA IS DIAGNOSED & ITS CAUE IS MADE, THERE ARE 3 MAJOR APPROACHES

32. 1. RED CELL TRANSFUSION
Reserved for those with anemia, cardiovascular instability, continued and excessive blood loss & those who require immediate intervetion
Transfusion corrects anemia acutely & transfused red cells provide a source of iron for reutilization

33. 2. ORAL IRON THERAPY
Adequate in asymptomatic patients with established anemia iron deficiency anemia
Common used iron salts:
Ferrous sulphate (30% elemental iron tabs.)
Ferrous gluconate (12% elemental iron tabs.)
Ferrous fumarate (33% elemental iron tabs.)
DOSE
1 tab. 2 to 3 times a day
Ideally, in empty stomach since food inhibit absorption

34. COMPLICATIONS OF ORAL IRON THERAPY
gastrointestinal distress
most prominent
seen in 15-20% of patients
abdominal pain, nausea, vomiting or constipation – lead to non compliance
major impediment
can be relieved by
taking iron with food or
changing to controlled release preparations or
using liquid preparations

35. RESPONSE TO ORAL IRON THERAPY
Typically RBC count begin to increase within 4 to 7 days of therapy
Peak at 1.5 weeks

36. FAILURE OF ORAL IRON THERAPY
May be due to
Not taking the tablets
Continuing blood loss
Ingestion of certain drugs which reduce iron absorption (antacids, H2 receptor blockers, proton pump inhibitors, tetracyclins)
Severe malabsorption
Wrong diagnosis

37. PARENTERAL IRON THERAPY INDICATIONS
Gastro intestinal intolerance to oral iron
Severe malabsorption
When rate of iron loss exceeds rate at which iron can be absorbed
to correct anemia associated with rheumatoid arthritis, late pregnancy & following major operations
Anemia associated with chronic renal failure (along with erythropoietin)
In patients with regular hemodialysis

38. PARENTERAL IRON THERAPY
Used in 2 ways
To administer the total dose of iron required to correct the hemoglobin deficit and provide patient with atleast 500 mg of iron stores
Give repeated small doses over a protracted period (common in dialysis centers to augment the response to erythropoietin therapy) Amount of iron reqd. calculated by the formla – body wt. (kg) X 2.3 X (15 pts. Hemoglobin g/dL or 1000 mg (for stores)

39. PARENTERAL IRON THERAPY
Anaphylaxis
is a concern with i.v. iron dextran (Imferon)
not a concern with newer preparations like i.v. sodium ferric gluconate & iron sucrose

40. TOXICITY
Arthralgias
Skin rash
Fever

41. If a large dose of iron dextran is to be given (>100 mg)
Dilute with 5% Dextrose in water or 0.9% NaCl solution
Infuse it over min.
A test dose (25 mg) can be given, but a slow infusion of a largeer dose will give same kind of early warning
If chest pain, wheezing, hypotension occur, stop infusion immediately
Iron Dextran (Imferon) can also be given deep i.m.ly, but is ideal for i.v. use. It is the most commonly used preparation