anaemia presentation mnh

8/2/2019 Anaemia Presentation MNH

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Anaemia defined as a decrease in circulating RBC mass; theusual criteria being

Hb


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1 :Deficiency of nutrients(Iron, Folic acid,

Vitamin B12, Pyridoxine and Vitamin C)necessary for haemopoeisis.

2: Depression of bone marrow:

This is caused by toxins eg drugs used inchemotherapy,radiation therapy, diseases of the

bone marrow of unknown origin( eg idiopathic

aplastic anaemia,leukaemia) reduced production

or responsiveness to erythropoietin ( chronicrenal failure, rheumatoid arthritis, acquired

immunodeficiency disease).


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` Direct injury to the blood vessels.

` Acute blood loss most commonly occurs in the

gastrointestinal (GI)tract(gastritis due to alcohol or

NSAIDS,diverticulosis,or peptic or gastric ulcerdisease)and may be accompanied by epigastric

symptoms, nausea and vomiting or diarrhea.

` Worm infestation(hookworm infestation)


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This has many causes including

haemoglobinopathies such as sickle cell anaemia,

adverse reactions to drugs and inappropriate

immune reactions.


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` A systemic approach to anemiais best at

narrowing down the diagnosis and guiding the

diagnostic workup.


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` The history and physical exam play key roles in

approaching anemia.` Patient may be asymptomatic,but at the Hb

level30%) but pt may have

symptoms of fatigue,malaise,dizzness,syncope or

angina.


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Common signs & symptoms of anemia

` Pallor

` Tachycardia

` Hypotention

` Dizzness

` Tinnitus

` Headache

` Loss of concentration

` Fatigue

` Weakness

` Atrophic gastritis

` Angular cheilosis` Koilonychias(spoon nails)

` Brittle nails

` Reduced exercise toletance

` Dyspnoea on exertion

` Heart failure in more severe anemia


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IRON:

Total body content in a 70kg man is 4gm.Sixty five% of which circulates in blood as haemoglobin.

About half the remainder is stored in the

liver,spleen and bone marrow as ferritin and

haemosiderin.


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The iron in these molecules is

available for fresh haemoglobinsynthesis.

The rest which is not available for

haemoglobin synthesis is present inmyoglobin, cytochrome and various

enzymes.


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Pharmacokinetics:

Daily iron requirement in men is15mg, in growing children and

menstruating women is 15mg.

In pregnancy it is two to ten times thisamount.


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Iron in meat is present as haem

which is absorbable, and about 20-40% of haem iron is available for

absorption.

Non haem iron in food is mainly inferric state and this needs to be

converted to ferrous iron for

absorption.


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Ascorbic acid stimulates iron

absorption partly by forming solubleiron ascorbate chelates and partly

reducing ferric iron to the more

soluble ferrous form.Tetracycline forms an insoluble iron

chelate resulting in impaired uptake

of both substances.


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Iron stores:

Iron is stored in two forms thesoluble ferritin and insoluble

haemosiderin.

The precursor of ferritin is apoferritin.Apoferritn takes up ferrous iron,

oxidises it and deposits the ferric iron

in its core. In this form it constitutes ferritin.


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Excretion:

Small amounts of iron leave the bodythrough desquamation (peeling off )

of the mucosal cells containing

ferritin.Even smaller amounts leave in the

bile, sweat and urine.

A total of about 1mg is lost daily.


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Preparations:

Several salts are available for oral use. Ferroussulphate the main one but also Ferroussulphate, ferrous gluconate and Ferrous fumerate.

Parenteral preparations: Iron dextran for i.m. & i.v.Iron sorbitol for i.m. only.

These are used in malabsorption syndromes andin patients who have undergone surgicalprocedures or those who have inflammatoryconditions involving the gastrointestinal tract.


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Clinical uses:

To treat iron deficiency anaemia which can be

caused by:-

Chronic blood loss (menorrhagia,hookworm or

colon cancer).

Increased demand (pregnancy and early infancy).

Inadequate dietary intake.

Inadequate absorption (following gastrectomy).


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Unwanted effects:

Nausea abdominal cramps and diarrhoea.Acute toxicity:

Severe necrotising gastritis,withvomiting,haemorrhage followed by circulatorycollapse.

Chronic iron toxicity:

Iron overload is caused by chronic haemolyticanaemia(eg thalassaemia,repeated bloodtransfusions.


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Treatment:

This involves use of chelators eg

desferrioxamine which forms a

complex with ferric iron.

The complex is excreted in urine.

Deferipone is a new orally absorbed

iron chelator for thalassaemia where

desferrioxamine is contraindicated.


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Folic acid and Vitamin B12:

These are necessary for DNA

synthesis and cell proliferation.

Their actions are inter dependent.

Deficiency of either vit.B12 or Folicacid results in Megaloblastic

anaemia.


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The deficiency of these two vitamins

affects tissues with a rapid cellturnover particullary bone marrow.

Vitamin B12 deficiency also causes

important disorders of nerves(peripheral neuropathy, dementia as

well as subacute combined

degeneration of the spinal cord).


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Folic acid deficiency:

This occurs in dietary deficiency,during

pregnancy,increased demand as it occurs inchronic haemolysis (haemoglobinopathies).

Vitamin B12 deficiency:

Occurs in decreased absorption caused by a lack

of intrinsic factor ( in patients with pernicious

anaemia, resection of diseased ileum eg Crohns

disease ).


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Folic acid:

Sources: Liver,green vegetables.

Daily requirements: 200mcg.

Actions: Dihydrofolate (FH2) and tetrahydrofolate

(FH4) act as carriers and donors of methylgroups

(1 carbon transfers )in a number of metabolic

pathways.

FH4 is essential for DNA synthesis as a cofactor in

the synthesis of purines and pyrimidines.


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Folates are important for the

conversion of deoxyuridylatemonophosphate to deoxythymidylate

monophosphate- the rate limiting in

mammalian DNA synthesis andcatalysed by thymidylate synthetase.


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Pharmacokinetics:

Folate in food is in the form ofpolyglutamate.

It is converted to monoglutamate for

absorption and reconverted topolyglutamate the more active form in

the tissues.

Folate is absorbed in the ileum.


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Methyl-FH4 is the form in which folateis usually carried in blood and which

enters the cell. It is functionally inactive until it is

demethylated in a vitamin B12

dependent reaction.Methyl- FH4 is a poor substrate for

polyglutamate formation.

Adverse effects: There is a theoreticalrisk of precipitating neuropathy in anundiagnosed anaemia.


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Vitamin B12 ( Hydroxocobalamin )

Source: Meat,liver,eggs and diaryproducts.

All cobalamins must be converted to

methylcobalamin (methyl vit.B12 ) or 5-deoxydenosylcobalamin for activity.

Daily requirement of vit B12 is 2 3

mcg.


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Pharmacokinetics:

Absorption requires an intrisic factor. The stomach secretes large amounts

of intrisic factor.

The vitamin is stored in the liver(4mg).

Def. symptoms will occur only 2- 4

years after total gastrectomy.


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Actions:

1 Conversion of methyl- FH4 to FH4.

2 Isomerisation of methylmalonyl-CoA to succinylCoA.

Conversion of methyl-FH4 to FH4:

The reaction involves both conversion of 5-methyltetrahydrofolate (methyl-FH4) to FH4 andhomocysteine to methionine, and the enzymewhich accomplishes this is homocysteine-

methionine methyl-transferase; the reactionrequires B12 as a cofactor and 5-methyltetrahydrofolate as a methyl donor.


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It is thought that the 5-mehtyltetrahydrofolate

donates the methyl group to B12, the cofactor.

The methyl group is then transferred to

homocysteine to form methionine.

This vitamin B12 dependent reaction thus has a

significant role in the generation of tetrahydrofolate

from methyltetrahydrofolate.


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Vitamin B12 deficiency results in the

trapping of the inactive

methyltetrahydrofolate form and the

consequent depletion of all intracellular

folate polyglutamate coenzymes (which

are necessary for early stages of DNAsynthesis) since methyltetrahydrofolate

is not converted to the polyglutamate

form which is the active form of thecoenzyme.


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The preferred substrate for

polyglutamate synthesis isformyltetrahydrofolate, and the

conversion of tetrahydrofolate to

formyltetrahydrofolate requires aformate donor such as methionine.


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Isomerization of methylmalonyl-CoA to succinyl-CoA

Propionate is converted to succinate.

Through this pathway cholesterol, odd chain fatty

acids, some aminoacids and thymine may be usedfor energy production via the tricarboxylic acid

cycle,or for gluconeogenesis.

Vitamin B12 in the form of deoxyadenosyl cobalamin

(ado-B12) is a cofactor in the reaction. In vitamin B12 def. states the reaction cannot occur

and methylmalonylCoA accumulates.

This distorts fatty fatty acid in neural tissue and may

be the basis of neuropathy which occurs in vit. B12deficency.


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Haematopoietic growth factors:

1.Erythropoietin: Produced in juxtatubular cells inthe kidney and also in macrophages.

Action:Erythropoietin stimulates committed erythroid

progenitor cells to proliferate and generateerythrocytes.

Two forms of recombinant human erythropoietin Epoetin alpha and Epoetin beta are available.

These are clinically indistinguishable and arereferred to as Epoetin.


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Pharmacokinetics:

Epoietin can be given i.v., s.c. or i.p.,

the response is greater after s.c.injection and fastest after i.v. injection.

Clinical uses of epoetin:

Anaemia of chronic renal failure.Anaemia during chemotherapy for

cancer.

Prevention of anaemia that occurs inpremature infants.


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To increase the yield of autolgous

blood before donation.Anaemia of AIDS (which is

exacerbated by Zidovudine

treatment).Anaemia of chronic inflammatory

conditions such as rheumatoid

arthritis(investigational).


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Unwanted effects:

Transient influenza-like symptoms. Hypertension is common and can

cause encephalopathy and headache,

disorientation and sometimesconvulsions also occur.

Iron deficiency can be induced as

more iron is required for enhancederythropoiesis.


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Blood viscosity increases as the

haematocrit of the blood rises andincreasing the risk of thrombosis

especially during dialysis.

2 Colony stimulating factors:These stimulate the formation of

maturing colonies of leucocytes in

semi solid medium in vitro.


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Colony stimulating factors not only stimulate

particular committed progenitor cells to proliferate,

but also cause irriversible differentiation. (a) Granulocyte colony stimulating factor(G-CSF)

eg Filgrastim, Lenograstim.

(b) Granulocyte-macrophage colony stimulating

factor (GM-CSF) eg Molgrasmostim is available foruse clinically.


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Actions.

GM-CSF stimulates the development

of progenitors of neutrophils,monocytes, eosinophils and (undersome circumstances) megakaryocytesand erythrocytes.

It also enhances the functional activityand survival of the mature cells.

GM-CSF may increase the production

of other cytokines.


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G-CSF acts only on the neutrophil line

increasing the proliferation and

maturation of neutrophils.

It also stimulates their release from

bone marrow storage pools and

enhancing their function.


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Pharmacokinetics:

GM-CSF and G-CSF are given s.c. ori.v. and both are well tolerated butbone pain occurs in 10-20% of pts.

GM-CSF frequently produces fever,skin rashes, muscle pain and lethargy.There may be pain and reddening at

the site of injection.


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G-CSF has produced mild dysuria(rare) and

reversible abnormalities in liver function tests.

Vasculitis has been reported with long term use.With i.v. infusion a syndrome of flushing,

hypotension, tachycardia, breathlessness, nausea

and vomiting and arterial oxygen desaturation has

occurred but can be reversed by oxygen and i.v.fluid administrtion.


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Clinical uses of the colony-stimulating factors:

CSFs are used in specialist centres.

1. To reduce the severity and duration of

neutropenia induced by cytotoxic drgs during:-

-conventional anticancer chemotherapy

-intensive courses of chemotherapy that

damage haemopoietic tissue, necessitating

autologous bone marrow rescue

-following bone marrow transplant


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2. To stimulate release into the

circulation of progenitor cells, whichcan then be harvested and infused

with, or instead of bone marrow cells

after high-dose, intensivechemotherapy.

3. To expand the number of harvested

progenitor cells ex vivo before re-infusing them.


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4. For persistent neutropenia in

advanced HIV infection.5. They may have a role in treatment

of aplastic anaemia.


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THE MOST USEFULL INDICES ARE

1.MCV-mean volume of the red cells & normal range 80-96fl

` Microcytic ifMCV96fL

` Normocytic 80-96fL

2.RDW -is reflection of availability in the size of RBC and

with the proportional to the standard deviation of the

MCV.

` An elevated RDWindicate increased variability of RBC

size.3.MCH-describe the concetration of Hb in each cell.

` Elevation level indicate_spherocytes or

hemoglobinopathy.


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4.RETICULOCYTECOUNT-measures the % of

immature RBC in the blood and reflect the bonemarrow(BM)response to anemia.(i.e.bone marrow

response to anemia is to increase production of

RBC there fore the R is increased).

` Normal R is ~1%` In anemia or blood loss BM should increse

production ofRBC in proportion to loss of

RBC,there fore 1% R count in anemia is

inappropiate.


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5. RETICULOCYTE INDEX(RI)

Calculated as R% actual Hct/normal Hct,and is

important in determining if patients BM isresponding appropiately to the level of anemia.

` Normal 1.0-2.0

` RI2 with anemia-indicate hemolysis or loss of

RBCs-laeding to inreased compeensatory

production ofR(hypoproliferative anemia)

6.PERIPHERAL SMEAR-Necessary part of innitial

hematologic evaluation.shape,size,presence of

inclusions,orientation of cells to each other.


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1.A BM BIOPSY

` Indicated in case of normocytic anemias with low

R without identifiable cause or anemia associated

with other cytopenias.` The biopsy may confirm myelophthisic process(i.e.

presence of tear drop or fragmented

cells,normoblasts,or immature WBCs on

peripheral blood smear) in setting of pancytopenia


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1.Mng of anemias with derceased RBC production.` Microcytic anemia

` Thalassemia

` Myelodysplastic syndrome

` Sideroblastic anemia` Macrocytic/megaloblastic anemia

` Anemia with chronic renal insuficiency

` Anemia of chronic disease

` Anemia in cancer patients

` Anemia associated with HIV infection

` Aplastic anemia


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2.Anemia associated with incresed RBC destruction

The anemia associated with increased

erythropoiesis(elevated reticulocyte count).caused

by bleeding(much more common) orHemolysis,and my exceed the capacity of bone

marrow to correct Hb.

` Sicklecell disease

` G6PD Deficiency` Drug induced hemolytic anemia

` Miroangiopathic hemolytic anemia


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3. Approach to transfussion therapy

1.General principles

` Indication/containdication

` Manipulation of blood product` Procedure

2.Special consideration

3.Complications


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Indication/contraindicationRBC T is indicated to increase the oxygen-carrying capacity of

blood in anemic patients.

Transfusion threshold in general

-Hb 7-8g/dl with no cardiac risk

-Hb 10g/dl with Hx of coronary artery disease or risk of ischemia-all children with Hct12% or Hb 4g/dl

-less severely anemic children with Hct 13-18% and Hb 4-6g/dl

with ant of the following

*clinical detectable dehydration

*shoch*impared consciousness

*deep and laboured breathing

*Verry high malaria parasitemia>10% of RBC with parasite


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1 unit of RBCs increases Hb level by 1g/dl in the average

adult.

If cause of anemia iseasly treatable(e.g iron or folic acid

deficiency) and no CVSor cardiopulmonary compromise

is present,it is preferable to avoid transfusion.


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Pretransfusion` dispensed for a pt.Type and screen procedure

tests the recipients RBCs for the A,B & D(Rh)Ag

and also screen the recipients serum for

antibodies against other RBC Ag` Cross matching tests the Pts serum for antibodies

against Ag on the donors RBCs is performed

before specific unit of blood is dispensed for a pt.


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Manipulation of blood product

1.Leukoreduced

` Prevent formation of platelet alloantibodies.

2.Irradiation-eliminate immunological

component.used in pt with imminocompromisedBM or organ transplant recipient,pt receiving direct

donation from HLA matched donors or first

degree relatives

3.Washed RBCs .-rare indicated should beconsidered when in patient whom plasmaproteins

may cause serious reaction.(Ig-deficient pt or

other anaphylactic reaction)


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1.Long term RBC transfusion therapy

` For >20 unts of RBC-Iron chelation therapy

` To epand RBC antigen pannel to decrease the risk

of RBC alloimmunization and delayed hemolytic

transfusion reaction.2.Emergency RBC therapy used only in situation in

which massive blood loss has resulted in

cardiovascular compromise-

` But volume expansion with NS should attemptedinitially.

` If unmatched blood must be used,should be group

O/Rh ve that have been screened for reactive

antbody.


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2.Pt who are unwilling to receive RBC

transfussion(e.g Jehovas Witness)

` Epo is of benefit

`

Use of orl and parenterol Iron


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1.Transfusion-transmited infections

` HIV1/2,T-lymphotrophic virus type ,epatitis B&

C,Syphilis and West Nile Virus.

` CMV transmision from RBC and Platelets

transfusion is an important risk in

immunocompromised patients.

2.Hemolytic transfusion reaction

` Acute hemolytic reaction

*Mgm-urine output mintained or equal to 7.5


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1.Caused by either a primary or amnestic antibody

response to specific RBC antigen or donor RBC

.pt with IgA deficiency who receive IgA containing

blood productMGN similar as acute.

2.Nonhemolytic febrile transfusion(fevers & chils)

` Decrease incidence with leucoredused product

` The cause is release of cytokines from WBCs


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` Mng.

` Acetminophen and Prestorage leucoredused

blood products.

`

Pretretment with glucocorticoids and WBCs orvolume reduced platelets.


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` If volume overload is suspected esp in pts with

CHC and cardiovascular overload he IV diuretics

should be used.

` Transfusion related acute lung injury(TRALI)

occurs 4hrs after BT

Cause

Ant-human leucocyte antgen (HLA)or

antgranulocyte antibodyDespite clinical or radiologic findings suggesting

edema data indicate that diuretics have no role

and may be detrimental.


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` More common to immunocompromised

patientsdue to result of immunocompetent T

lymphocyte(I pts who share HLA haplotype with

HLA homozygous blood donors(esp close relative

or members of inbred pop)

` Mortality >80%

` Irrariation of blood broduct it prevent the disease


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Administration ofblood products >than the normal

blood volume of pt over 24hrs

` Hypothermia

`

Hypocalcemia(mgn calcium gluconate 10ml of10%)

` Hypercalaemia

` Hypokalaemia

` Bleeding complication


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` Oral iron therapy

*ferrous sulphate

*ferrous gluconate

*ferrous fumarate

*vit C` Parenterol iron therary

*iron dextran

*sodium ferric gluconate(ferrlecit)

*iron sucrose(venofer)


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` No specific rx

` In sevse form of disease RBC transfusion

` Chelation therapy

` Splenectomy(.2units/mo)


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` 5-azathitidine

` Decitabine

` Immunosupresive therapy withantthymopacyte

globulin,cyrosporin,glucocoprticoid


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` Removal of possible offending agent

` pyridoxine


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` Replace the deficient factor

` Potasium suplements

` Folic acid

` Cyanocobalamin for vit B12 deficiency


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Erythropoiesis stimulating agents(ESAs)

` Epoetin alfa

` Darbepoetin alfa

The aboe also used in` Chemotherapy induced anemia

` Anemia associated with HIV infection(IV

immunoglobulin G in suspected case of

mycobacterium avium complex Dx established inbone marrow)

` Anemia of chronic dse


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` Discontiue suspected offending drug

` Immunosuppessive Rx with

cyclosporin,glucocorticoids,antthymocyte globulin

`

Stem cell transplant` RBC transfussion kept at minimum.But platelet

transfussion recommended.


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` Transfusion has no role in RX of uncomplicated

vaso-oclusive crises

` Hydroxyurea therapy(increase level of HbF)

`

Acute chest syndrome-require aggressivetransfusion therapy including red cell exchange.

` Iron chelation therapy


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` Glucocorticoids

` IVIG less effective than ITP

` Splenectomy for steroid resistant

` Rituximab` Plasma exchange (for COLD IgM)

` RBC transfusion(for warm IgG) only in decreased

oxygen carryng capacity.,6g/dl

anaemia presentation mnh

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