IRON DEFICIENCY ANEMIA

   


                               

IRON DEFICIENCYANEMIA

Table ofcontents

IRON METABOLISM

Iron storage

Site of iron storage

Sites of Iron distribution

Iron requirement of the body

Dietary sources of iron

Iron absorption

  CAUSES OF IRON DEFICIENCY

  CLINICAL FEATURES  OF IRON  DEFICIENCY ANEMIA

Initially/later

SIGNS AND SYMPTOMS

DIFFERENTIAL DIAGNOSIS 

INVESTIGATIONS 

TREATMENT

Treatment of the cause

Treatment of anemia

Iron replacement therapy

  Oral

  Parenteral route

 Blood transfusion

IRON DEFICIENCYANEMIA

DEFINITION

Iron deficiency anemia is defined as reduction in one or more of the RBC measurements- Hemoglobin concentration or

Hematocrit or

RBC count

Most accurately measured by obtaining a RBC mass via isotopic dilution methods. Iron deficiency anemia is a condition in which there is confirmed evidence of

Iron deficiency in bone marrow study.(Gold standard investigation)

Iron metabolism:

 Body Iron storage

Iron is an essential trace element

The human body requires iron for oxygen transport

Iron  must be in ferrous state for activity

Ferric iron cannot transport electron or O2

Iron is essential part of many enzyles

Iron is bound to other molecules

60% of iron is stored as hemoglobin needed to carry oxygen

4%in myoglobin

30% in liver,spleen,bonemarrow

Amount of iron in body is carefully controlled

Iron is stored in 2 forms.

1.Ferritin 2.hemosiderin

Site of iron storage

Liver, spleen, bonemarrow

Ferritin is found in blood,cells tissue fluids

Hemosiderin is found in macrophages

Detected by staining bone marrow with Prussian blue

  lmg.letmeget.net/blog/anemia-iron-

Where  all iron is distributed?

Apart from hemoglobin

Serum iron,tissue iron and myoglobin(O2 reserve in muscles) Tissue ,iron is present in cytochromes and peroxidases (Enzymes of cellular respiration)

How is iron transported in the body?

Iron is bound with a beta globulin named trasferrin and transported.(Serum iron) Normal serum iron level is 120microgram per deciliter(range50-170µgms)

Serum iron is circuating iron  bound to transferrin

Since so much iron is contained in hemoglobin ,

primary clinical manifestation of iron deficiency is anemia

Classification according to distribution

Hemoglobin

Tissue iron

Serum iron(transport iron) Storage iron

Myoglobin iron

Labile pool

Out of iron of average daily diet (40mg) 5-10% only is absorbed(1-2 mg)

What are the iron requirements of the body?

Adult men and post menopausal women—1mg per day. For growing children—1.5 to 2mg per day

For menstruating women 2.5 to 3.5 mg per day In 3rd trimester of pregnancy---4to 5mg per day Dietary Sources of iron

Meat, egg yolk green vegetables,fruits,figs,lentils Factors increasing iron absorption VitaminC,Erythropoitin,anemia perse,inorganic iron Factors reducing iron absorption Tetracyclines,phytates,phosphates

Where is iron absorbed?

In duodenum and proximal jejunum In what form is it absorbed? Ferrous form

Iron transport across the mucosal cell is an “active” process

How and how much iron is excreted normally?

Very little iron is excreted normally;that results from exfoliation of into gut lumen at the end of their life.

What is its significance?

If parenteral iron is given in excess of requirement the unwanted iron is deposited in different parts of the body resulting in acquired hemochromatosis.

Causes Of iron deficiency

!. Excess demand: Menstruation Pregnancy Growing child

2. Excess  Loss

hemorrhage

Menorrhagia,post partum bleed Bleeding esophageal varices Peptic ulcer

Gastritis Ca.stomach Ca.colon Ulcerative colitis Piles

Hook worm infestation

Aspirin ingestion

3. Lack of iron in diet and

4.Mal absorption

Post gastrectomy,

Celiac disease

Hook worm infestation

CLINICAL FEATURES OF IRON  DEFICIENCY ANEMIA

Initially –Non specific symptoms

Later stages- Changes in epithelial tissues

Also  Iron deficiency anemia can be mild or severe,temporary  or chronic.

Symptoms:

Palor,weakness, fatiguability,breathlessness,giddiness,palpitation,angina

Signs:

•   Palor of conjunctiva and mucous membrane

•   Koilonychia,Brittle and concave fingernails

•   glossitis,(atrophy of tongue papillae with bald tongue)angular stomatis,

•   CVS-systolic murmur at the base/venous hum

•   Dysphagia-this condition is called Plummer-Vinsons syndrome

Web of mucus and inflammatory cells at the opening of esophagus

•   Alopecia

•   Bluish sclera

•   Pica

•   Intestinal malabsorption

•   Spleen ‘may’ be enlarged.Liver may be enlarged

•   Organ dysfunction

Congestive cardiac failure in severe cases

Neurological and intellectual functions-irritability,behavioural changes

Some of these changes may not be readily reversible with Fe therapy

•   Reduced immune response

•   Pelvic and Rectal exam-to check internal bleeding

INVESTIGATIONS

1.  Complete hemogram

2.  Total count, differential count

Usually normal,but hyper segmented polymorph scan occur.

3.  RBC count

4.  Reticulocyte count

5.  Hemoglobin level

6.  Packed cell volume

7.  RBC Morphology –evaluation of smear

Microcytic,hypochromic

May show-Anisocytosis(RBCs of different sizes)

May show-polychromasia(Blue tinge to RBG due to presence of immature RBCs)

8.  Reticulocyte count

Red cell indices

9.  MCHC reduced

10. MCHC is mean corpuscular hemoglobin

Normal MCHC is 315 to 335gms/L

11. MCV(mean corpuscular volume)(the volume of red blood cells) reduced

Normal MCV is about 90fL (range83 to 100fl)(Femto liter)

12. MCH is reduced

Normal range is 27-33pg

MCH is  hemoblobin content of average red cell

Short notes about  RBC indices-(MCV MCH, MCHC.)

MCV is mean cell volume-an estimate of volume of red blood cell

MCH is hemoglobin content of average red cell

MCHC is average hemoglobin concentration in a given volume of packed red cells.

.MCV is useful for determining the type of anemia

MCV- less than normal is - Microcytic anemia

MCV- within normal range is –Normocytic anemia

MCV-greater than normal is macrocytic anemia

Low MCV indicates –iron deficiency, chronic disease, pregnancy, thalassemia, Anemia due to blood cell destruction or bone marrow disorder

High MCV- anemia due to nutritional deficiency, bone marrow abnormalities, liver disease, alcoholism, due to certain drugs

MCH-Mean corpuscular hemoglobin

Hemoglobin amount per red blood cell

MCH is low when red cells are abnormally small.

MCH –high when RBCs are enlarged as in  B12 deficiencyfolic acid deficiency,

MCHC –Mean corpuscular hemoglobin concentration

Amount of hemoglobin relative to the size of cell per red blood cell.

MCHC-Hb/Hct

MCHC is low in iron deficiency, blood loss ,pregnancy, anemia of chronic diseases.

In summary in iron deficiency anemia FE,MCV.MCH,MCHC,Ferritin,trans ferrin saturation are all reduced But TIBC-total iron binding capacity is increased Criteria;HB<normal limits,MCV <76fl,ferritin<15mcg/dl

Investigations to measure body iron status

13. Serum iron value

Iron levels are highest in the morning; best to do the test in the morning

Normal value 120mcg/dl (range50-150mcg/dl)

(Normal value ranges may differ slightly from lab to lab,with regards RBC indices) In iron deficiency anemia serum iron may be reduced to 15-60mcg/dl

14. Total serum iron binding capacity(TIBC) TIBC  normal range-250 to 450 mcg/dl TIBC increase in iron deficiency anemia

15. Transferrin saturation

Serum iron/TIBC ×100

Normal 20-50%

16. Serum ferritin-levels correlate with body stores

Normal 50-300mcg/L

17. Hemosederin-assesed in bone marrow

18. Bone marrow Biopsy- in iron deficieny shows

Hyper cellularity, some erthroid hyperplasia polychromacia and

Micro normoblastic reaction,absence of stainable iron.

Evaluation should also include

19. Evaluation for celiac disease,H.pylori,atrophic gastritis

-which can cause refractory anemia

Investigations to find the cause of iron deficiency

1.Upper GI endoscopy

2.Fibroptic bronchoscopy,Xray chest

3.Barium studies

4,Colonoscopy

5. motion exam for occult blood,ova ,cysts

6.Urine exam for hematuria

Note

Make sure there is no GI bleed

If there is GI bleed consider malignancy

DIFFERENTIAL DIAGNOSIS  OF MICROCYTIC ANEMIA

1.  Anemia of chronic diseases

2.  Sideroblastic anemia

3.  Thalassemic trait

  

Table1.Differences between thalassemia trait and iron deficiency anemia

TEST FINDING Serum ferritin TIBC Iron/TIBC	BETA THAL TRAIT Normal Normal Normal	IRON DEFICIENCY decreased increased decreased
Hb A2 HbF MCV/RBC FEP RDW RBC morphology	Increased Increased <1 span="">3 Normal Normal Abnormal,basophilic stippling	decreased Normal >13 increased Higher Slightly abnormal

INVESTIGATIONAL APPROACH IN A CASE OF PROBABLE IRON DEFICIENCY ANEMIA

See the flow chart below

( from Asian journal of transfusion science)

TREATMENT   OF IRON DEFICIENCY ANEMIA

I.    Treating the cause

II.   Treatment of anemia

I.    Treatment of cause :

History and clinical exam is enough to exclude serious disease(Pregnancy,lactation,adolescence) History and examination-insufficient ino-ld men and postmenopausal women-in these find the cause and treat

TREATMENT OF ANEMIA Iron replacement therapy

Usually ORAL-Safest and first line treatment

Ferrous sulphate is drug of choice; safest and cheapest

Daily dose200 mg  of elemental iron  per day before meals

For eg-one 325 mg of Feso4 tab taken tds supplies 195 mg of elemental iron per day

Requires acid environment for absorption

Absorption enhanced  by Vit C, orange juice,fish inhibited by- tea,coffee,milk,cereals,tetracyclines

Heme iron is more absorbable than inorganic iron

200mg of feso4 contains 60 mg of elemental iron

Enteric coated tablets are not advised because they do not release the tablets at the site of absorption but further down.

How long to give?(duration of treatment)

Correction anemia takes 2-3 mths;

 Hb should rise by 2gms/dl after one month This is mark of successful iron supplementation .Confirm by blood test.

It is important to continue therapy for at least 3-6 months even after correction of anemia-

-This is to replenish the stores: assuming no further loss of blood /iron

If the patient does not tolerate FeSo4 ,

ferrous gluconate,(300mg daily) or ferrous fumerate  can be tried.

Or Ferric salt like ferric et ammonium citrate

Liquid preparation may be better tolerated if tablets are not. Ferrous gluconate contains- 28 -36 mg of elemental iron per tablet Ferrous  fumerate- contains 106mg of elemental iron per tablet Ferrous sulphate liquid contains 44mg of elemental iron per teaspoon

Side effects

Gastritis,heart burn,constipation

Most importantly causes dark coloured stools (not to be mistaken for melena)

Food rich in iron

Spinach,other green leafy vegetables

Iron fortified bread and cereals, peas,chicpeas,beans,soys beans

Dried fruits,prunes,raisins,apricots

Large amount of iron can be harmful.

Failure of oral therapy(intolerence like inflammatory bowel disese)

Incorrectdiagnosis,

(thalassemia)

Anemia of chronic disease,

Non compliance,

Not absorbedEnteric coated) Rapid iron loss

Parenteral  iron

Indications for:

1.Intolerance to oral iron

2. 3rd trimester of pregnancy with anemia  and patient unwilling to take oral iron.

3.Necessity of quick management-like CCF,CHD,late pregnancy

3. Intestinal malabsorption

4.Active blood loss,dialysis,cancer

Contra indications for parenteral iron

Allergy to  parenteral iron- can be immediate or delayed reaction

Rheumatoid arthritis

Precautions

Immediate or delayed anaphylactic reaction can occur with parenteral iron

Intravenous iron replacement

Only in hospital

Given as slow IV infusion after test dose

Intra muscular Can be given as outpatient after test dose

Indicated in asthma,allergic disorders if  very essential

Parenteral  iron preparations

2 iron preparations available

1.Sodium ferric gluconte (muchless allergic than Iron dextran)

2.Iron sucrose

(3rd.Iron dextran-Imferon withdrawn from market(allergy,anaphylaxis))

1and 2 are of less serious adverse effects

Indication of parenteral iron

When rapid increase in Hb is required as alternative to blood transfusion

(e.g.severe anemia in late pregnancy,peripartum anemia,peripoerative anemia)

 IV iron preparations available:

 Ferric gluconate(FG)

Iron sucrose(IS)(Venofer)

Ferric corboxy Maltose(FCM)-advantage-large and rapid replacement dose possible(15to60minutes)

Iron sucrose –upto3 times aweek-slow IV injection or short IV infusion

In first trimester of pregnancy parenteral iron is contra indicated.

Blood transfusion

Surest way of replacing blood.

Indications

.If Hb level is less than 7gm% or PCV is less than25%

If Congestive failure is present packed cells must be given.

Packed red cells eliminate plasma,white cells and platelets. Each packed red blood cells(PRBCs) contains 200 mg of iron Each packed red blood cells raises hb by 1gm per /dl

Foot Note:

1.Each Feso4 tablet contains 60mg of elemental iron

Hb raises by 1gm/dl/week with oral iron

100mg of iron is required IM to raise Hb level by 4% Before giving parenteral iron test dose must be given

.

IRON REQUIREMENT CALCULATION

The total iron deficit is calculated using the Ganzoni formula:

Total iron deficit =
Body weight [kg] x (Target Hb - Actual Hb) [g/dL] x 2.4 + 500mg ( to replenish the iron store if body weight

In practice, total doses above 1000 mg (1gram)of elemental iron is not necessary.

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