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Presenting

Symposium Medicus- Batch roll nos. 120 to 140

MANAGEMENT OF

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Decrease in oxygen carrying capacity of blood

characterized by number of RBCs below 4million/cubic mm or content of haemoglobinless than 12gm/dL

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ANAEMIA

HAEMORRHAGIC DIETARY

DEFICIANCY

IRON DEFICIENCY MEGALOBLASTIC

APLASTIC HEMOLYTIC

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IRON PHYSIOLOGY

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CAUSES OF IRON DEFICIENCY

ANAEMIA

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LOW DIETARY INTAKE

IMPAIRED ABSORPTION

INCREASED REQUIREMENT

CHRONIC BLOOD LOSS

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SIGNS AND SYMPTOMS

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Signs and Symptoms

No symptoms if the anemia is mild.

Most of the time, symptoms are mild at first and

develop slowly. Symptoms may include:

Irritability Fatigue

Dyspnea during exercise

Headaches

Problems concentrating or thinking

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As the anemia gets

worse, symptoms may

include:Blue color to the whites

of the eyes

Brittle nails

Light-headedness

when one stands up

Pale skin color

Shortness of breathSore tongue

Symptoms of the

conditions that cause

iron deficiency anemiainclude:

Dark, tar-colored stools

or blood

Heavy menstrualbleeding (women)

Pain in the upper belly

(from ulcers)

Weight loss (in people

with cancer)

http://www.nlm.nih.gov/medlineplus/ency/article/003247.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003244.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003075.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003075.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003244.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003247.htm

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LABORATORY INVESTIGATIONS OF

ANAEMIA

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1.INITIAL INVESTIGATIONS

HEMATOLOGY PROFILE (Complete blood count) MCV,MCH,MCHC are decreased

MICROSCOPY

Blood picture reveals microcytosis, hypochromia,anisocytosis, poikilocytosis, pencil cells and target cells

Bone marrow findings show high cellularity, poorly

haemoglobinised normoblast and absence of stainable

iron

SERUM FERRITIN levels are decreased(normal levels-30 to

400ng/ml in males and 15 to 200 ng/ml in females)

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2.ADDITIONAL INVESTIGATIONS

SERUM IRON levels are decreased

(normal levels 65-176micrograms/dl in men,50-

170micrograms/dl in women,100-250micrograms/dl in

newborns and 50-120micrograms/dl in children)

TIBC (Total Iron Binding Capacity) is increased (normal-240 to

450micrograms/dl)

TRANSFERRIN SATURATION is decreased (normal-20 to 50%)

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NON PHARMACOLOGICAL

TREATMENT

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Dietary advice

To both anaemic and non-anaemic women.

Vitamin C significantly enhances iron absorption from

non-haem foods, the size of this effect increasing with

the quantity of vitamin C in the meal. Germination and fermentation of cereals and legumes

improve the bioavailability of non-haem iron by

reducing the content of phytate.

Tannins in tea and coffee inhibit iron absorption whenconsumed with a meal or shortly after.

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Oral iron therapy

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Oral iron therapy

Indication- women with mild to moderate deficiency withno absorption or compliance (or both) limiting factors

Ferrous iron salts are the preparation of choice. Oral dosein case anaemia due to iron deficiency should be 100-200mg of elemental iron daily. Doses not to be increasedto avoid saturation of absorption and dose related sideeffects.

Women should be counselled as to how to take oral ironsupplements correctly. This should be with a source ofvitamin C such as orange juice to maximise absorption.Consumption with meals may be necessary to avoid sideeffects. Other medications or antacids should not betaken at the same time.

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When side effects appear affecting compliance, titration of

dose to a level where side effects are acceptable or a trialof an alternative preparation may be necessary.Preparations with lower iron content should be tried.

Enteric coated or sustained release preparations should beavoided as the majority of the iron is carried past the

duodenum, limiting absorption. A repeat Hb at two weeks is required to assess response to

treatment.

The haemoglobin concentration should rise by

approximately 20 g/l over 3-4 weeks. Once the Hb is in the normal range, treatment should be

continued for a further 3 months and at least until 6 weekspostpartum to replenish iron stores.

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Parenteral Iron Therapy

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Parenteral Iron Therapy

Indications :

Deficiency is severe

Along with erythropoietin

Failure to tolerate oral iron

Failure to absorb oral iron

Non-compliance to oral therapy

Iron requirement = 4.4 x body weight (kg) x Hb deficit (g/dl)

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Parenteral Iron Therapy Preparations available for IM use:

Iron-dextran (Imferon): 1.5 ml vial, 50 mg of elemental

iron/ml

Iron-sorbitol-citric acid complex (Jectocos):1.5 ml vial,50 mg

of iron/ml

IM injection :

Common site : Gluteal region

Technique: Z track Dose: After an initial test dose of 25 mg,100 mg is

administered daily till calculated dose is attained.

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Iron-dextran Iron-sorbitol-citric acid

High molecular weight Low molecular weight

Can be given i.m or i.v Can be given only i.m.

Not bound to transferrin Tends to saturate transferrin

Given i.m. 10-30% is locally bound Not locally bound

Not excreted About 30% excreted in urine

Given i.m. absorbed via lymphatics Absorbed directly into circulation

Taken up by macrophages Directly available

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Parenteral Iron Therapy

Preparations available for IV use:

High molecular weight iron dextran (Imferon):

1-2 ml vial,50 mg iron/ml

Low molecular weight iron dextran (Cosmofer):

2 ml vial,50 mg iron/ml

Iron saccharate: 5 ml vial,20 mg of iron/ml

Ferric gluconate: 5 ml vial,12.5 mg iron/ml

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Parenteral Iron Therapy

IV injection:

After an initial dose of 0.5 ml given over a a period of 5-10

mins, 2 ml can be injected over 10 mins every day.

Alternatively the total calculated dose is diluted in 500 ml of

glucose/saline solution & infused slowly over 6-8 hours.

Ferric gluconate or iron saccharose may be used in repeated

boluses in the dose of 100-200 mg of elemental iron.

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Management in

pregnancy

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Full blood count taken at the booking appointment and at 28 weeks.

Prophylaxis starting in 2nd trimester for all pregnant women with 30

mg oral elemental iron daily.

Hb < 11g/dl up until 2 months or

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IRON TOXICITY

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ADVERSE EFFECT OF ORAL IRON THERAPY

BLACKENING OF TEETH AND FAECES DUE TOFORMATION OF

IRON SULPHIDE

SEVERE VOMITING

ABDOMINAL PAIN

HEMATEMESIS

DIARRHOEA

CARDIOVASCULAR COLLAPSE AND SHOCK

SOME MAY DEVELOP JAUNDICE,HYPOGLYCEMIAAND CONVULSIONS

SYMPTOMS BECOME EVIDENT AFTER 6HRS OF

CONSUMPTIONDOSES OF 1gm OR MORE OF FERROUS SULPHATE ARE

CONSIDERED TOXIC IN CHILDREN

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ADVERSE REACTION TO IM PREPARATION

LOCAL PAIN

PERMANENT SKIN DISCOLOURATIONREGIONAL LYMPHADENOPATHY

MYALGIA

ATHRALGIA

TACHYCARDIAFLUSHING

CIRCULATORY COLLAPSE

HAEMOLYSIS

SYSTEMIC TOXICITY MAY DEVELOP WITHIN

10MINS OF INJECTION

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ADVERSE EFFECT OF I.V IRON THERAPY

SYSTEMIC REACTIONS SIMILAR TO IM iron

SEVERE CHEST PAINRESPIRATORY DISTRESS

CIRCULATORY COLLAPSE

EXTRAVASATION INTO SUBCUTANEOUS TISSUE CAN

CAUSE ABSCESS FORMATION

ANAPHYLACTOID REACTIONCAN OCCUR WITHIN FIRST

FEW MINUTES OF ADMINISTRATION. THEREFORE TEST

DOSE MUST BE GIVEN PRIOR TO STARTING THE

TREATMENT

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Toxic dosage

The amount of iron ingested may give a clue to

potential toxicity. The therapeutic dose for irondeficiency anemia is 36 mg/kg/day. Toxic effects begin

to occur at doses above 1020 mg/kg of elemental iron

IRON POISONING MAY BE-

1]ACUTE IRON POISONING

2]CHRONIC IRON OVERLOAD

ADVERSE EFFECTS OF EXCESSIVE IRON

SUPPLEMENTS

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CAUSES-

ACCIDENTAL CONSUMPTION BY

CHILDREN

INTENTIONAL INGESTION BY ADULTS

SYMPTOMS BECOME EVIDENT AFTER

6HRS OF CONSUMPTION

DOSES OF 1gm OR MORE OF FERROUS

SULPHATE ARE CONSIDERED TOXIC IN

CHILDREN

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CHRONIC IRON OVERLOAD

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Iron is an extremely corrosive substance to the. It acts on the and canmanifest with nausea, vomiting, abdominal pain,hematemesis, and diarrhea; patients may becomehypovolemic because of significant fluid and bloodloss

Severe overdose causes

, which can result in .METABOLIC ACIDOSIS

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TREATMENT OF IRON POISONING

MILK AND EGG YOLK MIXTURE-TO BIND IRON

Gastric lavage with water containing desferroxamine or if not available then

with calcium disodium edetate

DESFERRIOXAMINE 1-2gm IM IS ADMINISTERED

DOC for iron intoxication.

Approximately 8 mg of iron is bound by 100 mg of

deferoxamine.

Readily chelates iron from ferritin and hemosiderin but nottransferrin

Most effective when administered continuously by infusion

Iv infusion 10-15mg/kg/hr to a maximum of of 80mg/kg in

24hr

Early replacement of body fluids and electrolytes using

isotonic saline,correction of metabolic acidosis and

hypotension by using ringer lactate and vasopressor

diazepam

DESFERRIOXAMINE

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VITAMIN B12

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HISTORY

Addison described anaemia not responding to Fe as

PERNICIOUS ANAEMIA (PERNICIOUS for INCURABLE

and DEADLY) and also its relation to atrophy of gastric

mucosa.

Minot and Murphy-included liver in diet of such

patients-received Nobel prize.

Castles hypothesis-an extrinsic factor(in diet)

combines with intrinsic factor(produced by stomach)-gives rise to haemopoietic principle.

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Vitamin B12

Water soluble,thermostable,red crystals.

Synthesized in nature only by microorganisms; plants

and animals get from them.

DIETARY SOURCES-Liver,egg yolk,kidney,cheese. *ONLY vegetable source-LEGUMES(pulses).

*Vit. B12- synthesized by colonic microflora but not

available for absorption in man.

COMMERCIAL SOURCE- Strep. Griseus.

Daily req.-1 -3 micro gm. In pregnancy and lactation-3-

5 micro gm.

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Active coenzyme forms-deoxyadenosylcobalamin(DAB12) and Methylcobalamin(methyl B12).

1.

Conversion of homocysteine to methionine.2. Purine and pyrimidine synthesis.

3. Propionic acid metabolism.

4. Synthesis of phospholipid and myelin.

5. Essential for cell growth and multiplication.

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Methionine S-adenosyl methionate

Malonic acid Succinic acid

DAB12

DAB12

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UTILISATION 0F VIT.B12

TRANSPORTED-In combination with transcobalamin II.

Congenital absence or abnormal proteins(like TCI and

TCIII)-interfere with delivery of vit.B12 to tissues.

Not degraded in body. Excreted in bile.Significant Enterohepatic circulation

takes place.

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CAUSES OF DEFICIENCY

1. Addisonian pernicious anaemia- Auto Immune

disorder

2. Gastric mucosal damage

3. Malabsorption4. Blind loop syndrome

5. Nutritional deficiency

6. Increase in demand in pregnancy and infancy

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MANIFESTATIONS OF DEFICIENCY

1. MEGALOBLASTIC ANAEMIA- First manifestation-with

hypersegmented neutrophil,giant platelets.

2. Glossitis and G.I. disturbances: damage to epithelial

structures.3. Neurological:

a) Subacute Combined Degeneration of Spinal Cord

b) Peripheral neuritis

c) Mental changes

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PREPARATIONS DOSE ANDADMINISTRATION

1. CYANACOBALAMIN.

2. HYDROXOCOBALAMIN.

3. METHYLCOBALAMIN.

4. METHYL B12- Required for integrity of myelin.Dose

1.5mg/day.5. When deficiency due to decrease in Intrinsic factor-i.m.

or s.c. but not i.v.

6. Initially- 30-100 micro gm/ day for 10 days,then 100 micro

gm weekly then monthly.7. Neuro complications 500-1000micro gm/ day.

8. Prophylactic-3-10 micro gm/day.

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USES OF VIT. B12

1. TREATMENT of VIT. B12 DEFICIENCY.

2. PROPHYLAXIS of VIT. B12 DEFICIENCY.

3. Neuropathies and psychiatric disorders.

4. Tobacco amblyopiaADVERSE EFFECTS-

a) Large doses are also safe.

b) Allergic reactions due to injection.

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FOLIC ACID DEFICIENCY ANAEMIA

FOLIC ACID : PTERIDINE + PABA + GLUTAMATE

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DIETARY SOURCES :

yeast, liver, kidney, green

leafy vegetables ( spinach ),

egg, meat, milk

DAILY REQUIREMENT : 150-200 microgram in children

400 microgram in adults

600 microgram or greater in pregnancy

500 microgram in lactation

Hepatic stores of folate contain 15-20 mg of folate, which is very less and can be

easily exhausted within 3-4 months of stopping oral folate administration

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NORMAL SERUM FOLATE LEVELS : 2.7-17 ng/ml

UTILISATION : Present in foods as polyglutamates of n5 methyl THFA

Absorbed in upper part of jejunum after convertingpolyglutamate residues to monoglutamate residues

Absorbed in this form by active and passive transportprocesses and demethylated in the cells to THFA by vitb12

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METABOLIC FUNCTIONS : active form : THFA

1. Conversion of homocysteine to methionine

2. Conversion of d ump to d TMP

3. Conversion of serine to glycine4. Purine synthesis which requires formyl and methenyl THFA histidine

metabolism for mediating formimino group transfer

FOLIC ACID DEFICIENCY IS SEEN IN :

Chronic alcoholic patients Liver disease

Pregnant women Hemolytic anaemia

Malabsorbtion syndrome Renal dialysis patients

Drugs likemethotrexate, trimethoprim, pyrimethamine, phenytoin

PREPARATIONS AND DOSE ti f 2 d

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PREPARATIONS AND DOSE : preparations of 2 compoundsavailable:

FOLIC ACID : FOLVITE , FOLITAB 5mg TABS

FOLINIC ACID : CALCIUMLEUCOVORIN, FASTOVORIN, RECOVORIN

PARENTERAL ADM IS RARELY NECESSARY AS ORAL FOLIC ACID ID=S WELLABSORBED EVEN IN PATIENTS WITH MALABSORBTION SYNDROMES

DOSE OF 1mg ORAL FOLIC ACID DAILY IS SUFFICIENT TO REVERSEMEGALOBLASTIC ANAEMIA, RESTORE NORMAL SERUM FOLATE LEVELSAND REPLENISH THE FOLATE STORES

THERAPY SHOULD BE CONTINUED TILL UNDERLYING CAUSE OFDEFICIENCY IS REMOVED OR CORRECTED

SHOTGUN ANTI ANAEMIA PREPARATIONS

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USES :

MEGALOBLASTICANAEMIAS DUE TO NUTRITIONAL FOLATE DEFICIENCY,

PERNICIOUS ANAEMIA, PREGNANCY, LACTATION, HEMOLYTIC ANAEMIA,MALABSORBTION SYNDROME, PROLONGED ANTIEPILEPTIC THERAPY

WITH PHENYTOIN

FOLATE ADM WILL REVERSE HEMATOLOGICAL CHANGES OF FOLATE AND

VIT B12 DEFICIENCY ANAEMIA, BUT NUEROLOGICAL DEFICIT OF VIT B12DEF ANAEMIA CANNOT BE REVERSED WITH FOLATE ADM

THE USA FDA HAD INTRODUCED GRAINS RICH IN FOLIC RICH

SUPPLEMENTATION TO ALL ITS CITIZENS TO REDUCE FOLATE DEFICIENCY.

INCIDENCES OF NTDS REDUCED BY 30% BUT THIS WAS FINALLY STOPPEDAS IT WAS THOUGHT IT WOULD MASK VIT B12 DEFICIENCY

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PROPHYLAXIS : 1mg/day IN PREGNANCY TO REDUCE NTDs

METHOTREXATETOXICITY : FOLINIC ACID IS USED AS

TREATMENT AS IT DOES NOT REQUIRE DHFRase TOCONVERT TO ACTIVE FORM

CITROVORUM FACTOR RESCUE

ADVERSE EFFECTS : ORAL FOLIC ACID IS ENTIRELY NONTOXIC, SENSITIVITY REACTIONS MAY OCCUR ONPARENTERAL ADM

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ERYTHROPOIETIN

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Sialoglycoprotein hormome (MW 34000) produced byperitubular cells of the Kidney.

Anaemia and hypoxia sensed by Kidney cells

Kidney cells

Rapid secretion of EPO

Acts on erythroid marrow

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ACTIONS

1. Stimulates proliferation of colony forming cells of the

erythroid series.

2. Induces haemoglobin formation and erythroid blast

maturation.

3. Releases reticulocytes in circulation

EPO binds to specific receptors that alters phosphorylation

of intracellular proteins and activates transcription factors to regulate

Gene expression.

Erythropoiesis is directly proportion to dose and has no effect on

Lifespan of RBC

USES

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US S

1. Anaemia of chronic renal failure due to low EPO

25-100 U/Kg s.c. or i.v. 3 times a week (600 U/kg max)

Raises Haematocrit and HBReduces need for transfusion

Improves quality of life

Start with low dose and titre upwards; Haematocrit between

30-36%, Hb 10-12g/dl

2. Anaemia in AIDs patients treated with zidovudine

3. Cancer chemotherapy induced anaemia

4. Preoperative increased blood production for autologous

transfusion during surgery

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ADVERSE EFFECTS

EPO is nonimmunogenic

Sudden increase in Haematocrit, blood viscosity and

peripheral vascular resistance

Increased clot formation in the A-V shunts

Hypertensive episodes

Seizures

Flu like symptoms lasting 2-4 hrs in some patients

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THANK YOU