lecture 11 - 6.11.09 - patho - transfusion medicine

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    TRANSFUSION MEDICINETRANSFUSION MEDICINE

    DR.FARZANA RIZWANDR.FARZANA RIZWAN

    M,B;B,S M.Phil ( Haematology )M,B;B,S M.Phil ( Haematology )

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    Blood TransfusionBlood Transfusion

    Blood transfusion involves the infusion ofBlood transfusion involves the infusion of

    whole blood or a blood component, fromwhole blood or a blood component, from

    one individual ( the donor ) to anotherone individual ( the donor ) to another( the recipient )( the recipient )

    TheThe appropriate useappropriate use of blood and bloodof blood and blood

    products means the transfusion ofproducts means the transfusion ofsafesafe

    blood ,blood , onlyonly to treat a condition leading toto treat a condition leading to

    significant morbidity or mortality that cannotsignificant morbidity or mortality that cannot

    be managed effectively by other meansbe managed effectively by other means

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    Blood TransfusionBlood Transfusion

    TheThe safety and effectivenesssafety and effectiveness of transfusionof transfusion

    depend on two key factorsdepend on two key factors

    (1)(1) Supply of blood and blood products thatSupply of blood and blood products that

    areare safesafe, accessible at, accessible at reasonable costreasonable cost

    andand adequateadequate to meet national demandsto meet national demands

    (2)(2) TheThe appropriateappropriate clinical use of blood andclinical use of blood and

    blood productsblood products

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    Blood TransfusionBlood Transfusion

    TheThe qualityquality andand safetysafety of all blood and bloodof all blood and blood

    products must be assured throughout theproducts must be assured throughout the

    process, fromprocess, from selection of blood donorsselection of blood donorsthrough to theirthrough to theiradministration to the patientadministration to the patient

    Before prescribingBefore prescribing blood or blood productsblood or blood productsfor a patient, it is always essential to weighfor a patient, it is always essential to weigh

    up the risks of transfusion against the riskup the risks of transfusion against the risk

    of not transfusingof not transfusing

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    Red Cell AntigensRed Cell Antigens

    Approximately 400 red blood cell groupApproximately 400 red blood cell groupantigens have been describedantigens have been described

    The significance of blood groups, in bloodThe significance of blood groups, in bloodtransfusion is that individuals who lack atransfusion is that individuals who lack aparticular blood group antigen, may produceparticular blood group antigen, may produceantibodies reacting with that antigenantibodies reacting with that antigen

    TheTheABO and rhesus ( Rh ) groupsABO and rhesus ( Rh ) groups are ofare ofmajor clinical significancemajor clinical significance

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    ABO systemABO system

    The discovery of ABO system by Landsteiner, inThe discovery of ABO system by Landsteiner, in

    1901 marked the beginning of safe blood1901 marked the beginning of safe blood

    transfusiontransfusion

    The ABO antigens, although most important inThe ABO antigens, although most important in

    relation to transfusion, also have variablerelation to transfusion, also have variableexpression on most tissues and are importantexpression on most tissues and are important

    histocompatibility antigenshistocompatibility antigens

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    ABO SystemABO System

    There areThere are fourfourmain blood groups:main blood groups:

    AA,, BB,, AABB andand OO

    There isThere is racial variationracial variation in the frequency ofin the frequency ofthese groupsthese groups

    The presence of A, B or O antigens on redThe presence of A, B or O antigens on red

    cells is determined by the inheritance of thecells is determined by the inheritance of theallelic genes A, B and O onallelic genes A, B and O on chromosome 9chromosome 9,,

    which are inherited in pairs aswhich are inherited in pairs as MendelianMendelian

    dominantsdominants

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    ABO SystemABO System

    TheThe cellular expressioncellular expression of A and B antigensof A and B antigens

    is determined by a further gene, theis determined by a further gene, the H geneH gene,,

    which is inherited independentlywhich is inherited independently

    This gene encodes for an enzyme thatThis gene encodes for an enzyme thatconverts a carbohydrate precursor into Hconverts a carbohydrate precursor into H

    substancesubstance, on which the A and B gene, on which the A and B gene

    products actproducts act The A and B genes code for specificThe A and B genes code for specific

    enzymes ( glycosyl transferases )enzymes ( glycosyl transferases )

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    ABO SystemABO System These enzymesThese enzymes convertconvert H substance into AH substance into A

    and B antigensand B antigens

    TheThe O gene is silentO gene is silent (amorphic) allele,(amorphic) allele,

    which does not produce an activewhich does not produce an active

    transferase, so thattransferase, so that H substance persistsH substance persists

    unchangedunchanged in group Oin group O The A, B and H antigens areThe A, B and H antigens are detectabledetectable

    early in fetal lifeearly in fetal life, but, but not fully developednot fully developed onon

    the red cellsthe red cells at birthat birth..

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    ABO SystemABO System

    TThe number of antigen sites reaches adulthe number of antigen sites reaches adult

    levels at about 1 year of age and remainslevels at about 1 year of age and remains

    the same throughout lifethe same throughout life

    ANTIBODIESANTIBODIES

    AntiAnti-- A and antiA and anti--BB. A feature of the ABO. A feature of the ABOsystem is the regular occurrence of antisystem is the regular occurrence of anti--AA

    and antiand anti--B in the absence of correspondingB in the absence of corresponding

    red cell antigensred cell antigens

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    ABO SystemABO System

    The regular occurrence of antiThe regular occurrence of anti--A and antiA and anti--B,B,

    allows for theallows for the reverse (serum) grouping,reverse (serum) grouping, asas

    a means ofa means ofconfirmingconfirming the red cellthe red cellphenotypephenotype

    AntiAnti A and antiA and anti--B are always to someB are always to some

    extent,extent, naturally occurringnaturally occurring and ofand ofIgMIgM classclass

    They react best at low temperatures but areThey react best at low temperatures but are

    potentially haemolytic at 37potentially haemolytic at 37ooCC

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    ABO SystemABO System

    Hyperimmune antiHyperimmune anti--A and antiA and anti--BB occur lessoccur less

    frequently, in response to transfusion orfrequently, in response to transfusion or

    pregnancypregnancy They are predominantly ofThey are predominantly ofIgGIgG class and areclass and are

    usually produced by group Ousually produced by group O

    Hyperimmune IgG antiHyperimmune IgG anti--A and/or antiA and/or anti--B fromB fromgroup O mothers, may cross the placentagroup O mothers, may cross the placenta

    and cause haemolytic disease of theand cause haemolytic disease of the

    newbornnewborn

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    ABO SystemABO System

    Hyperimmune antiHyperimmune anti--A , antiA , anti--B react over aB react over a

    wide thermal rangewide thermal range and areand are more effectivemore effective

    haemolysinshaemolysins than the naturally occurringthan the naturally occurringantibodiesantibodies

    Group O donorsGroup O donors should always be screenedshould always be screened

    for hyperimmune antifor hyperimmune anti--A and antiA and anti--BB

    antibodies, which may cause haemolysisantibodies, which may cause haemolysis

    when group O whole blood is transfused towhen group O whole blood is transfused to

    recipients with A and B phenotypesrecipients with A and B phenotypes

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    ABO SystemABO System

    These dangerous universal donorsThese dangerous universal donorsshould bereserved forgroup Oshould bereserved forgroup O

    recipientsonlyrecipientsonly

    The antibodies are a potential cause ofThe antibodies are a potential cause ofdangerous haemolytic reactions, ifdangerous haemolytic reactions, iftransfusions are given without regard totransfusions are given without regard toABO compatibilityABO compatibility

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    Rh SystemRh System

    The rhesus (Rh) system was so namedThe rhesus (Rh) system was so named

    because the original antibody that wasbecause the original antibody that was

    raised by injecting red cells of rhesusraised by injecting red cells of rhesus

    monkey into rabbits and guineamonkey into rabbits and guinea--pigs,pigs,reacted with most human red cellsreacted with most human red cells

    The clinical importanceThe clinical importance of this system is dueof this system is dueto the fact that Rh negative individuals areto the fact that Rh negative individuals are

    easily stimulated to form Rh antibodies, ifeasily stimulated to form Rh antibodies, if

    transfused with Rh positive bloodtransfused with Rh positive blood

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    Rh SystemRh System

    In case ofIn case ofpregnant womenpregnant women, if exposed to, if exposed to

    Rh positive fetal red cells which haveRh positive fetal red cells which have

    crossed the placenta, Rh antibodies arecrossed the placenta, Rh antibodies areproduced in the motherproduced in the mother

    ANTIGENSANTIGENS

    The Rh antigens are present only on redThe Rh antigens are present only on redcells and are a structural part of the cellcells and are a structural part of the cell

    membranemembrane

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    Rh AntigensRh Antigens

    Rh antigens areRh antigens are well developed before birthwell developed before birth

    and can be demonstrated on the red cells ofand can be demonstrated on the red cells of

    very early fetusesvery early fetuses

    Rh system is represented as a single geneRh system is represented as a single gene

    complex oncomplex on chromosome 1chromosome 1, which gives rise, which gives riseto various combinations of three alternativeto various combinations of three alternative

    antigensantigens C/c, D/d and E/eC/c, D/d and E/e

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    Rh AntigensRh Antigens

    It is convenient to classify individuals as RhIt is convenient to classify individuals as Rh

    positive or negative depending on thepositive or negative depending on the

    presence of thepresence of the D antigenD antigen

    Rh D antigen is the most immunogenic redRh D antigen is the most immunogenic red

    cell antigencell antigen afterafterA and BA and B Rh antigens are restricted to red cells andRh antigens are restricted to red cells and

    Rh antibodies are due to alloRh antibodies are due to allo --immunizationimmunization

    by previous transfusion or pregnancyby previous transfusion or pregnancy

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    Rh AntibodiesRh Antibodies

    They are usuallyThey are usually IgGIgG, react best at 37, react best at 3700CC

    and do not fix complementand do not fix complement

    Anti D is the most important clinically, it mayAnti D is the most important clinically, it may

    causecause haemolytic transfusionhaemolytic transfusion reactions andreactions and

    was common cause of fetal death resultingwas common cause of fetal death resultingfromfrom haemolytic disease of the newbornhaemolytic disease of the newborn,,

    before the introduction of antibefore the introduction of anti--D prophylaxisD prophylaxis

    in 1970in 1970

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    ABO GroupingABO Grouping

    Correct interpretation of the patientsCorrect interpretation of the patientsABOABO

    groupgroup requiresrequires confirmationconfirmation, whenever, whenever

    possible, by tests on thepossible, by tests on the patients serumpatients serum

    Except for the newborn infants up toExcept for the newborn infants up to

    4 months of age in whom naturally occurring4 months of age in whom naturally occurringantianti--A and antiA and anti--B are normally absentB are normally absent

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    ABO GroupingABO Grouping

    SampleSample: 1 ml EDTA blood in a vial: 1 ml EDTA blood in a vial

    3 ml clotted blood in a test tube3 ml clotted blood in a test tube

    Both vials should be labeled with the numberBoth vials should be labeled with the numbergiven to the samplegiven to the sample

    TechniqueTechnique: (A) FORWARD (cell) grouping: (A) FORWARD (cell) grouping

    (B) REVERSE (serum) grouping(B) REVERSE (serum) grouping

    (A) FORWARD GROUPING (cell grouping)(A) FORWARD GROUPING (cell grouping)

    (1)(1) Make 5% cell suspension of blood in a test tubeMake 5% cell suspension of blood in a test tube

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    ABO( Forward) GroupingABO( Forward) Grouping

    (2)(2) take 3 test tubes in a rack and labeltake 3 test tubes in a rack and label

    (a)(a)AA (b)(b) BB (c)(c) DD

    Also write the donor /recipient identificationAlso write the donor /recipient identificationnumbernumber

    (3)(3) add one drop of anti seraadd one drop of anti sera

    A in tube marked as AA in tube marked as A B in tube marked as BB in tube marked as B

    D in tube marked as DD in tube marked as D

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    ABO (Forward) GroupingABO (Forward) Grouping

    (4)(4) Then add 2 drops of donor / recipients 5% redThen add 2 drops of donor / recipients 5% redcell suspension and mixcell suspension and mix

    (5)(5) Centrifuge all the test tubes for 1 minute atCentrifuge all the test tubes for 1 minute at

    1000rpm or at 3400 rpm for 15 seconds1000rpm or at 3400 rpm for 15 seconds (6)(6) InterpretationInterpretation: after centrifugation, see for: after centrifugation, see for

    agglutination (result)agglutination (result)

    (a) if agglutination in tube A, it means blood group(a) if agglutination in tube A, it means blood groupAA

    (b) If in tube Bblood group B(b) If in tube Bblood group B (c) Both A and Bblood group AB(c) Both A and Bblood group AB

    (d) No agglutination blood group O(d) No agglutination blood group O

    (e) In tube D. Rh factor positive(e) In tube D. Rh factor positive

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    ABOABO (Reverse)(Reverse) GroupingGrouping

    Prepare 3 times washed 5% cell suspensionPrepare 3 times washed 5% cell suspension

    from known A +ve, B +ve, and O +ve bloodfrom known A +ve, B +ve, and O +ve blood

    inin 3 tubes3 tubes separately and label themseparately and label themproperly asproperly asA +veA +ve,, B +veB +ve andand O +veO +ve cellcell

    suspensionsuspension

    Take 3 test tubes in a rack and label them asTake 3 test tubes in a rack and label them as

    SASA,, SBSB andand SOSO, along with identification, along with identification

    numbers of donor / recipientnumbers of donor / recipient

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    ABOABO (Reverse)(Reverse) GroupingGrouping

    Put 2 drops of known 5% red cellPut 2 drops of known 5% red cell

    suspension in test tubes as undersuspension in test tubes as under

    A +ve cell suspension in tube marked as SAA +ve cell suspension in tube marked as SA

    B +ve cell suspension in tube marked as SBB +ve cell suspension in tube marked as SB

    O +ve CS in tube marked as SOO +ve CS in tube marked as SO

    Then add 2 drops of donor/ recipientsThen add 2 drops of donor/ recipients

    serum in all the 3 test tubes and mixserum in all the 3 test tubes and mix

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    ABOABO ( Reverse)( Reverse) GroupingGrouping

    InterpretationInterpretation

    Centrifuge all these 3 test tubes and see forCentrifuge all these 3 test tubes and see foragglutinationagglutination

    The results in tubes SA and SB should beThe results in tubes SA and SB should beexactly reverse from that of direct groupingexactly reverse from that of direct grouping

    If agglutination in tube SA..blood group BIf agglutination in tube SA..blood group B

    If in tube SB..blood group AIf in tube SB..blood group A Sa and SB .blood group OSa and SB .blood group O

    If no agglutination in SA and SB.bloodIf no agglutination in SA and SB.bloodgroup ABgroup AB

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    Compatibility TestingCompatibility Testing

    SamplesSamples:: Patient/ recipient serumPatient/ recipient serum

    5%v suspension of5%v suspension ofdonor red blood cellsdonor red blood cells

    Technique: First of all do blood grouping of both theFirst of all do blood grouping of both the

    donor and the recipientdonor and the recipient

    Take 2 test tubes, and label one asTake 2 test tubes, and label one as SalineSalinephasephase and other asand other as Albumin phase.Albumin phase. WriteWrite

    the identification numberthe identification number

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    Compatibility TestingCompatibility Testing

    PutPut 2 drops of recipients serum2 drops of recipients serum in both thein both the

    tubestubes

    Add 2 drops ofAdd 2 drops ofdonors 5% celldonors 5% cell suspensionsuspensionin both the tubesin both the tubes

    AddAdd 2 drops of bovine albumin2 drops of bovine albumin in the tubein the tube

    marked as Albumin phasemarked as Albumin phase Centrifuge both the tubes and see forCentrifuge both the tubes and see for

    agglutination or haemolysisagglutination or haemolysis

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    Compatibility TestingCompatibility Testing

    If there is agglutination/ haemolysis, itIf there is agglutination/ haemolysis, it

    means donors cells are not compatible withmeans donors cells are not compatible with

    recipients serumrecipients serum IfIfnono agglutination/ haemolysis, thenagglutination/ haemolysis, then

    incubateincubate both the tubes at 37both the tubes at 37oo C for 45C for 45

    minutesminutes

    Centrifuge both the tubes and see forCentrifuge both the tubes and see for

    agglutination/ haemolysisagglutination/ haemolysis

    If its there, means blood is not compatibleIf its there, means blood is not compatible

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    Compatibility TestingCompatibility Testing

    IfIfno reactionno reaction, then give, then give 3 saline washings3 saline washings toto

    the tube marked asthe tube marked as Saline phaseSaline phase

    AddAdd 2 drops of anti2 drops of anti --human serum, andhuman serum, andcentrifugecentrifuge

    NowNow seesee both the saline and albumin phaseboth the saline and albumin phase

    tubes macroscopically and microscopicallytubes macroscopically and microscopically If agglutination/ haemolysis, blood is notIf agglutination/ haemolysis, blood is not

    compatible .If none, blood is compatiblecompatible .If none, blood is compatible

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion Complications may be divided into twoComplications may be divided into two

    groups, early and lategroups, early and late

    EarlycomplicationsEarlycomplications

    HaemolyticHaemolytic reactionsreactions

    Reactions due toReactions due to infected bloodinfected blood Allergic reactionsAllergic reactions to white cells, platelets orto white cells, platelets or

    proteinsproteins

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion Early complicationsEarly complications

    Pyrogenic reactionsPyrogenic reactions

    Circulatory overloadCirculatory overload Air embolismAir embolism

    ThrombophlebitisThrombophlebitis

    Citrate toxicityCitrate toxicity

    HyperkalaemiaHyperkalaemia

    Clotting abnormalitiesClotting abnormalities

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    Complications of blood transfusionComplications of blood transfusion

    LatecomplicationsLatecomplications

    Transmission of diseasesTransmission of diseases

    (1)(1) Viruses :Viruses : hepatitis A, B C , HIV, CMVhepatitis A, B C , HIV, CMV

    (2)(2) Bacteria:Bacteria: Treponema pallidum, Brucella,Treponema pallidum, Brucella,salmonellasalmonella

    (3)(3) Parasites:Parasites: malaria, Toxoplasma, microfilariamalaria, Toxoplasma, microfilaria

    Transfusional iron overloadTransfusional iron overload

    Immune sensitization, e.g. to Rh D antigenImmune sensitization, e.g. to Rh D antigen

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion Haemolytic transfusion reactions, may beHaemolytic transfusion reactions, may be

    immediate or delayedimmediate or delayed

    ImmediateImmediate lifelife--threatening reactions,threatening reactions,associated with massiveassociated with massive intravascularintravascular

    haemolysis are the result of complementhaemolysis are the result of complement--

    activating antibodies of IgM or IgG classesactivating antibodies of IgM or IgG classes

    The severity of the reaction depends on theThe severity of the reaction depends on the

    recipients titre of antibodiesrecipients titre of antibodies

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion Reactions associated withReactions associated with extravascularextravascular

    haemolysis are generally less severe, buthaemolysis are generally less severe, butstill may be lifestill may be life threateningthreatening

    Clinical FeaturesClinical Features::

    Major haemolytic transfusion reactionMajor haemolytic transfusion reaction

    Haemolytic shock phaseHaemolytic shock phase

    The oliguric phaseThe oliguric phase

    Diuretic phaseDiuretic phase

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion Febrilereactions:Febrilereactions: HLA antibodies areHLA antibodies are

    usually the result of sensitization byusually the result of sensitization by

    pregnancy or a previous transfusion. Theypregnancy or a previous transfusion. Theyproduce rigours, pyrexia and in severeproduce rigours, pyrexia and in severe

    cases pulmonary infiltratescases pulmonary infiltrates

    AllergicreactionsAllergicreactions

    Usually due to hypersensitivity to donorUsually due to hypersensitivity to donor

    plasma proteins, if severe can causeplasma proteins, if severe can cause

    anaphylactic shockanaphylactic shock

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion Allergic reactions can cause urticaria, feverAllergic reactions can cause urticaria, fever

    and in severe cases dyspnoea, facialand in severe cases dyspnoea, facial

    oedema and rigoursoedema and rigours PostPost--transfusion circulatoryoverloadtransfusion circulatoryoverload

    Causes pulmonary oedema, fullness in theCauses pulmonary oedema, fullness in the

    head and dry coughhead and dry cough

    Can be prevented by a slow transfusion ofCan be prevented by a slow transfusion of

    packed red cellspacked red cells

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion PostPost-- transfusion hepatitistransfusion hepatitis

    May be due to one of the hepatitis viruses,May be due to one of the hepatitis viruses,

    i.e. types B and C and other types of noni.e. types B and C and other types of non--AAnonnon--B and nonB and non--C and occasionally CMV andC and occasionally CMV and

    EpsteinEpstein--Barr virusBarr virus

    HIVHIV the cause of AIDS, and relatedthe cause of AIDS, and related

    syndromes is transmitted both in cellularsyndromes is transmitted both in cellular

    and plasma components of bloodand plasma components of blood

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion OtherinfectionsOtherinfections: CMV, infectious: CMV, infectious

    mononucleosis, toxoplasmosis, malaria andmononucleosis, toxoplasmosis, malaria and

    syphilis may all be transmitted by bloodsyphilis may all be transmitted by bloodtransfusiontransfusion

    PostPost-- transfusional iron overloadtransfusional iron overload::

    repeated blood transfusions over manyrepeated blood transfusions over many

    years, in the absence of blood loss causeyears, in the absence of blood loss cause

    deposition of iron initially in in RE tissuedeposition of iron initially in in RE tissue

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    Complicationsof bloodComplicationsof blood

    transfusiontransfusion Iron is deposited initially in the RE tissue atIron is deposited initially in the RE tissue at

    the rate of 200the rate of 200--250mg / unit (450ml) of250mg / unit (450ml) of

    whole bloodwhole blood

    AfterAfter50 units in adults50 units in adults, and, and lesserlesseramountsamounts

    in children, the liver, myocardium andin children, the liver, myocardium and

    endocrine glands are damaged with clinicalendocrine glands are damaged with clinical

    consequencesconsequences

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    Bone marrow transplantationBone marrow transplantation

    BMT involvesBMT involves eliminatingeliminating an individualsan individuals

    bone marrowbone marrow stem cellsstem cells and all the cellsand all the cells

    derivedderived from them, including haemopoietic,from them, including haemopoietic,lymphoid and histiocytic / macrophagelymphoid and histiocytic / macrophage

    systemssystems

    These areThese are replacedreplaced with bone marrow stemwith bone marrow stem

    cells either from another individual or with acells either from another individual or with a

    previously harvested portion of thepreviously harvested portion of the

    individuals own bone marrow cellsindividuals own bone marrow cells

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    Bone marrow transplantationBone marrow transplantation

    Syngeneic BMTSyngeneic BMT: a transplant from an: a transplant from an

    identical twinidentical twin

    Allogeneic BMTAllogeneic BMT: a transplant from an: a transplant from anHLAHLA--matched brother or sister, or from anmatched brother or sister, or from an

    HLAHLA-- matching close relative other than amatching close relative other than a

    sibling, or from an unrelated but HLAsibling, or from an unrelated but HLA--

    matching individualmatching individual

    Autologous BMTAutologous BMT: from the patients own: from the patients own

    marrowmarrow

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    Bone marrow transplantationBone marrow transplantation

    Allogeneic BMTAllogeneic BMT is most frequentlyis most frequently

    performed for patients with theperformed for patients with the malignantmalignant

    diseases like acute leukaemia or chronicdiseases like acute leukaemia or chronic

    myeloid leukaemia and formyeloid leukaemia and foraplasticaplastic anaemiaanaemia

    andand thalassaemiathalassaemia majormajor

    Autologous BMTAutologous BMT is frequently used foris frequently used for

    malignantmalignant lymphomalymphoma and also forand also forAML, ALLAML, ALLandand multiple myelomamultiple myeloma

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    Bone marrow transplantationBone marrow transplantation

    PreparationPreparation

    For BMT, matching of class I and class IIFor BMT, matching of class I and class II

    HLAHLA genes, between recipient and donor isgenes, between recipient and donor is

    essentialessential toto preventprevent ororreducereduce allograftallograft

    reactions of rejection and GVHDreactions of rejection and GVHD

    Identification of class I and class II antigensIdentification of class I and class II antigens

    is usually performed by serological methodsis usually performed by serological methods

    The chance of a sibling being fully HLAThe chance of a sibling being fully HLA

    matching with a patient with the samematching with a patient with the same

    parents is theoretically 25%parents is theoretically 25%

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    Bone marrow transplantationBone marrow transplantation

    PreparationPreparation

    HLA matching is independent of sex andHLA matching is independent of sex and

    blood groupblood group

    The chance of an unrelated potential donorThe chance of an unrelated potential donormatching is 1: 30,000matching is 1: 30,000

    THE RECIPIENTTHE RECIPIENT

    The patient is nursed in a protectiveThe patient is nursed in a protectiveenvironment with barrier nursingenvironment with barrier nursing

    High doses of chemotherapy with or withoutHigh doses of chemotherapy with or without

    total body irradiation are giventotal body irradiation are given

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    Bone marrow transplantationBone marrow transplantation

    PreparationPreparation

    This is aimed at eliminating the patientsThis is aimed at eliminating the patients

    bone marrowbone marrow stemstem andand progenitorprogenitorcells andcells and

    if present, the bone marrowif present, the bone marrow diseasedisease

    Total body irradiation (TBI) is usually used inTotal body irradiation (TBI) is usually used in

    cases with malignant diseasecases with malignant disease

    TheThe conditioningconditioning eliminates the patientseliminates the patients

    immune system, and so reduces the risk ofimmune system, and so reduces the risk of

    failure due to rejection of donor stem cellsfailure due to rejection of donor stem cells

    by the recipients immune cellsby the recipients immune cells

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    Bone marrow transplantationBone marrow transplantation

    PreparationPreparation

    At leastAt least 36 hours36 hours are allowed for theare allowed for the

    elimination of the drugs from the circulationelimination of the drugs from the circulation

    The patient is givenThe patient is given parenteralparenteral nutrition,nutrition,prophylactic antibiotics and antiprophylactic antibiotics and anti-- fungalsfungals

    THE DONORTHE DONOR About 500About 500-- 1200 ml of marrow is harvested1200 ml of marrow is harvested

    under general anaesthesia, mainly from theunder general anaesthesia, mainly from the

    pelvispelvis

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    Bone marrow transplantationBone marrow transplantation

    PreparationPreparation

    The marrow isThe marrow is heparinizedheparinized,, filteredfiltered and theand the

    lymhocytes are removedlymhocytes are removed

    ForForautologous BMTautologous BMT, the harvested marrow, the harvested marrowmay be stored inmay be stored in liquid nitrogenliquid nitrogen indefinitelyindefinitely

    Autologous peripheral blood stem cells mayAutologous peripheral blood stem cells may

    be usedbe used

    The marrow cells are infused intravenouslyThe marrow cells are infused intravenously

    via anvia an indwelling central venous catheterindwelling central venous catheter

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    PostPost -- transplant coursetransplant course

    22 -- 33 weeks of severe pancytopeniaweeks of severe pancytopenia

    The first signs of successful engraftment areThe first signs of successful engraftment are

    the appearance ofthe appearance ofmonocytesmonocytes followed byfollowed byneutrophilsneutrophils in the blood with a subsequentin the blood with a subsequent

    increase in platelet countincrease in platelet count

    ReticulocytosisReticulocytosis also begins in the 2also begins in the 2ndnd and 3and 3rdrd

    weekweek

    The marrow cellularity gradually returns toThe marrow cellularity gradually returns to

    normalnormal

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    BMT complicationsBMT complications

    EarlyEarly ( usually100 days) complications

    Earlycomplications:Earlycomplications:

    Infections, especially bacterial, fungal,Infections, especially bacterial, fungal,

    herpes simplex virus, CMVherpes simplex virus, CMV Haemorrhage due to severeHaemorrhage due to severe

    thrombocytopeniathrombocytopenia

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    BMT ComplicationsBMT Complications

    Acute graft versus host diseaseAcute graft versus host disease ( GVHD )( GVHD ) isis

    caused by donorcaused by donor--derived immune cells,derived immune cells,

    particularly T lymphocytes, reacting againstparticularly T lymphocytes, reacting against

    recipient tissues.recipient tissues.

    The skin, liver and GIT are affected (GVHD)The skin, liver and GIT are affected (GVHD)

    Graft failureGraft failure

    Haemorrhagic cystitisHaemorrhagic cystitis

    Interstitial pneumonitis, cardiac failureInterstitial pneumonitis, cardiac failure

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    BMT ComplicationsBMT Complications

    LatecomplicationsLatecomplications ( usually > 100 days)( usually > 100 days)

    Relapse of the original diseaseRelapse of the original disease

    Infections, vericella zoster, fungal, bacterialInfections, vericella zoster, fungal, bacterial

    Chronic GVHDChronic GVHD

    Chronic pulmonary diseaseChronic pulmonary disease

    Autoimmune disordersAutoimmune disorders CataractCataract

    Infertility and second malignancies ( NHL)Infertility and second malignancies ( NHL)

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