lecture 11 - 6.11.09 - patho - transfusion medicine
TRANSCRIPT
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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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