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Home , ABO blood group system

22 Immunohematology

Introduction ABO Group The blood group of an individual is determined by presence or Immunohematology is the study of blood group antigens and absence of two antigens, A and B, on the surface of the red cell , and their interactions in health and disease. Ehrlich membrane. Red cells of blood group A carry A, cells and Morgenroth first described blood groups in goats based on of blood group B carry antigen B, and cells of blood group AB antigens of their red cells in an article published in the Berliner have both A and B antigens. On the other hand, blood group klinische Wochenschrift in 1900. Subsequently, , O cells have neither A nor B antigens. a Viennese pathologist, successfully identified the human The blood groups are also differentiated by the presence or ABO blood groups for which he was awarded the Nobel Prize absence of two distinct isoantibodies in the . Serum of 30 years later. After this initial discovery, blood grouping was blood group A individuals have anti-B antibodies, blood group developed as a science, and many different systems of grouping B have anti-A antibodies, and blood group O have both anti-A were designed on the basis of many isoantigens on the surface and anti-B antibodies. The blood group AB does not contain of erythrocytes. The ABO and Rh systems are among the well- any anti-A and anti-B antibodies in the serum. known human blood groups described in the literature. Soluble ABO blood group substances may be found in mucous secretions of humans, such as saliva, gastric juice, ovarian cyst fluid, etc. Such persons are termed secretors, while ABO Blood Group System those without the blood group substances in their secretions are nonsecretors. ABO blood group system was the first human red-cell antigen The ABO group of a given individual is determined by test- system to be characterized. The ABO blood group substances ing both cells and serum. In this method, the subject’s red cells are glycopeptides with oligosaccharide side chains (Fig. 22-1). are mixed with serum containing known and the sub- The ABO blood group specificity is determined by the presence ject’s serum is tested against cells possessing known antigen. of terminal in an oligosaccharide structure. The terminal For example, the cells of a group A individual are agglutinated of the oligosaccharides are specific for blood groups A by anti-A serum but not by anti-B serum, and his or her serum and B. They are also immunogenic. The red cells express either agglutinates type B cells but not type A cells. The typing of A, B, both A and B, or neither, and antibodies are found in cells as group O is done by exclusion (a cell not reacting with serum to antigens not expressed by the red cells. anti-A or anti-B is considered to be of blood group O). It is

R A blood group Erythrocyte A

R H enzyme B enzyme + R R

B blood group H substance O enzyme N-acetylglucosamine R O blood group (inactive) N-acetylgalactosamine

FIG. 22-1. ABO blood group system. Chapter 22 Section II antibodies, hencearenot compatible withmostoftheredcells. anti-B,andanti-H with “Bombay” bloodgrouphave anti-A, gens aswell asHantigens areabsentintheblood.Individuals suchasin“Bombay,”instances, orOHblood,both AandBanti- inbloodgroupingortransfusion.However,important inrare and galactose,respectively, to nated bytheantibodytoRhredcellswere termed antibody.as theneonatal Thedonorswhosecellswere aggluti- rhesus (Rh)redcells,whichappearedtohave thesamespecificity guinea pigs,anddiscovered theresultingantibody agglutinated antigen D(RhD) ismostimportant. and both refer totheRhDantigen only. OfalltheRhantigens, Rh antigens.The termsRhfactorand antigenaresimilar, antigens (C,c,D,E,ande)as well asmany other less frequent mainRh The termRhbloodgroup system refers tothefive Rh BloodGroupAntigens those whosecellswere not agglutinatedwere termed injected bloodfromthemonkey red cellsof85%Caucasians.In1940,LandsteinerandWiener antibody thatreactedwiththeredcellsofinfantand an who gave toinfantswithhemolyticdiseasecontained birth Philip Levine,in1939,discovered thattheseraofmostwomen A andBantigensareformed byadditionof ◗ inherited fromthemother andonefromthefather. two ,one into A1andA2),any individualwillcarry B,andO(Acanbesubdivided three commonallelicgenes:A, oftheABOgroupsfollowstance simple Mendelianrules,with of tolerancetohisorherown bloodgroupantigens.Theinheri- todevelop anti-B,butwillnot because produceanti-A will start theinfant eventually colonizedbythenormalmicrobialflora, tunity toundergocross-immunization.Whentheintestineis have anti-Binhisorherserum,sincetherehasbeennooppor- the humanbody. For example, anewbornwithgroupAwillnot theAandBantigensin strikingly similartothosethatdefine gut. Thesebacteriahave outermembraneoligosaccharides teria ofthefamilyEnterobacteriaceaethatcolonizeinfants’ synthesized asaconsequence ofcross-immunizationwithbac- in all individuals includingthosethathave hadnotransfusions. noteworthy thattheseantibodiestotheisoantigensarefound an Hantigen isaglycoprotein gen, orHsubstance. andstructurally is cellsofallABOgroupspossessacommonantigen,theHanti- Red but nevertheless theRhnomenclature isstillretained. but nevertheless related totheonethatis recognized inhumanhemolyticdisease, Wiener reactswithanantigen(LW) butisclosely isdifferent It isnow known byLandsteinerand thattheantibodyobtained 168 Rh BloodGroupSystem H antigen L The Hantigen,duetoitsuniversal distribution,isnot that It isbelieved andanti-Bisoagglutininsare thattheanti-A -fucose. It is a precursor for the production of A and B antigens. -fucose. Itisaprecursorfor theproductionofAandBantigens. IMMUNOLOGY L -fucose ofHantigen. Macacus rhesus N- acetylgalactosamine acetylgalactosamine into rabbits and into rabbitsand Rh negative Rh positive ; . mother bloodbyindirectCoombs’test. be detected innewbornbloodbydirectCoombs’testand few IgMantibodies.Theseareincomplete antibodiesandcan transfusion. MostoftheseantibodiesareIgGantibodies,and situations,suchasinRhincompatible pregnancyor certain Rh antigens.Antibodiesagainstantigensdevelop onlyin Unlike ABOsystem,thereare nonaturalantibodiesagainst ◗ Basically, those procedures try: Basically, thoseprocedurestry: theproperselectionofbloodfor thepatient. done toestablish Before abloodtransfusion, aseriesofproceduresneedtobe below: mentioned of another. Bloodtransfusionshave many indicationsas based productsfromonepersonintothecirculatory system Blood transfusionistheprocessoftransferring bloodorblood- nants withintheRhsystem. obscured accidentally. Thereareseveral alloantigenicdetermi- research ormedicalsituations,becauseitcanbealtered neg,” or to“Dpos”/“Dneg,”“RhDpos”/“RhD shortened isoften suffix totheABObloodtype.This (does not have theantigen)suffix “RhD positive” (doeshave theRhDantigen)or“RhDnegative” oftheirredbloodcells.Thisisusuallyindicatedby surface Individuals eitherhave ordonot have theRhDantigenon ■ ■ ■ ■ ■ ■ ■ D antigen of parturition. Rh (D)immunoglobulintothesewomen within72hours cies. Thiscannow beprevented bytheadministrationof hemolytic diseaseofthenewborninsubsequent pregnan- munization againsttheRhDantigen.Thismay cause pregnancy (suchasinamniocentesis)canleadtoalloim- ortraumaduringthematernal circulation atparturition intothe offetal erythrocytes from thefather. Theentry ers whobearachildwithRhD-positive redcellsinherited The DantigenalsoposesaprobleminRhD-negative moth- RhD-positive blood. that may transfusionsof leadtosevere reactionswithfurther bytransfusioncandevelop tive erythrocytes alloantibodies is becauseRhDnegative individualswhoreceive RhDposi- Clinically, This theDantigenhasalot ofmedicalimportance. serum, which could reactwithtransfused red cells. to ruleoutthe existenceofantibodies in therecipient’s recipient and ABOandRhcompatibility betweento establish donorand require frequent bloodtransfusions. People fromhemophiliaorsickle-celldiseasemay suffering or thrombocytopeniacausedbyablooddisease. Blood transfusionsmay alsobeusedtotreatasevere anemia replace bloodlostduringsurgery. such asmassive bloodlossduetotrauma,orcanbe usedto Blood transfusionscanbelife-saving insomesituations, ϩ / Ϫ . Thelattersymbolisgenerallynot preferred in Section II Chapter 22 − + /Rh /Rh − − fetus 169 Rh Rh fetal RBCs − . /Rh antigens − + Mother not sensitized by Rh on fetal RBCs Production of IgG against Rh . When the disease is moderate or severe, or severe, disease is moderate . When the erythroblastosis fetalis erythroblastosis

IMMUNOHEMATOLOGY − + /Rh /Rh − − fetus fetal RBCs Rh Rh + Hemolytic diseases of newborn. and persist after delivery (Fig. 22-2). /Rh (hydrops fetalis) (hydrops − attacks fetal RBCs Rh Mother sensitized by Maternal anti-Rh IgG crosses placenta and Immunological destruction of fetal and/or newborn eryth- and/or newborn of fetal Immunological destruction is exposed to an Antibodies are produced when the body rocytes is likely to occur when IgG antibodies are present in the to occur when IgG antibodies rocytes is likely antigen(s) present on directed against the maternal circulation This is because only IgG antibodies can red blood cells. the fetal cross the placenta Anti-D and circulation. the fetal and reach most usually types of antibodies anti-A or anti-B are the two Anti-A in hemolytic disease of the newborn. or anti- involved IgM, but, in some circumstances,B antibodies are usually IgG This can O mothers). (usually in group develop antibodies may be secondary (some vaccines contain to immune stimulation blood group substances or polysaccharides), or cross-reactive reasons. unknown apparent cause for occur without may is If a mother of the body. to the make-up antigen foreign IgG (as opposed exposed to an alien antigen and produces cross the placenta),to IgM which does not the IgG will com- affect it and may fetus, bine with the antigen, if present in the in utero attack result- circulation, in the fetal the red blood cells and lyse varies condition in fetus and anemia. This ing in reticulocytosis occur due to heart to veryfrom mild may death and fetal severe, failure erythroblastsmany blood, and this form in the fetal are present of the disease is called FIG. 22-2.

; and donovani, donovani,

Leptospira interrogans Leptospira and It is an ABO blood group individualIt is an ABO blood Toxoplasma gondii, Leishmania Toxoplasma Treponema pallidum Treponema individ- a blood group O RhD-negative It is species. Plasmodium Transmission of HIV I and II, HBV, and HCV, which is a and HCV, of HIV I and II, HBV, Transmission major concern. Protozoa, such as Protozoa, Viruses, such as human immunodeficiency viruses I and C virus hepatitis II (HIV I and II), hepatitis B virus (HBV), (CMV); and cytomegalovirus (HCV), hepatitis D virus (HDV), Bacteria, such as It is best if the universal recipient is Rh positive, i.e., has the is Rh positive, recipient It is best if the universal and ■ ■ ■ ■ Hemolytic Disease of Newborn Hemolytic Disease of Newborn (Erythroblastosis Fetalis) Hemolytic disease of the newborn, also known as HDN, is an Hemolytic disease of the newborn, also known which contains the in a fetus, alloimmune condition. It develops and have mother been produced by the IgG antibodies that have passed through the placenta. These antibodies subsequently Transfusion reaction is the major immunological complication reaction is the major immunological complication Transfusion transfusion. Other transfusion blood incompatible following than incompat- be caused due to factors other reactions may allergens to some such as a person being hypersensitive ibility, agents through of infectious present in the blood. Transmission blood is the most important These include: complication. Complications of Blood Transfusion To establish the ABO and Rh compatibility between donor and establish between ABO and Rh compatibility the To be transfused are and the blood to the recipient both recipient, ient’s in the recip antibodies to detect most direct way typed. The red cells is of the transfused could cause serum that cross- serum with the donor’s cells (major to test the patient’s a cross-match, which consists of testing match). The minor serum is of little significancepatient’s cells with donor and rarely be greatly diluted antibodies would donor performed, since any it causes clinical problems. and rarely, in the recipient’s plasma, recipient:Universal serum express antigens A and B, but whose whose red blood cells containdoes not anti-A blood and anti-B antibodies. Thus, red i.e., from an individ- of the ABO antigens, cells containing any ual with type A, be transfused to the universal B, AB, or O, may transfusion reaction.recipient without inducing a hemolytic RhD antigen on the erythrocytes a hemo- developing to avoid blood group systems other lytic transfusion reaction. However, recipi- in a universal induce hemolytic reactions than ABO may ent. Thus, it is best to use type-specific transfusions. blood for donor:Universal ual whose erythrocytes express neither A nor B surface antigens. a hemolytic transfusion This type of fails to elicit A,reaction in recipients with blood group AB, or O. However, B, group O individuals serving express donors may as universal erythrocytes blood group antigens on their other that may to use type-specificinduce hemolysis. It is preferable blood for in cases of disaster or emergency. transfusions, except Chapter 22 Section II bloodtypes areasfollows:particular sensitized (i.e.,producesIgGantibodiesagainst)toward ine transfusionorearlyinductionoflaborwhen( infant’s redcellsandtestingtheelutewithABcells. byelutingantibodiesfromthe positive andmay beconfirmed incompatibility, thedirectantiglobulintestisusuallyweakly is invariably positive incasesofRhincompatibility. InABO A positive directCoombs’(antiglobulin)testwithcordRBC 3. 2. 1. nary maturity has been attained, ( maturity hasbeenattained, nary blood cells,typecompatible withboth theinfantandmother. and/or assistedventilation andexchangetransfusionwitha istration ofsodiumbicarbonatefor correctionofacidosis, transfusion withcompatible packed redbloodcells,admin- phototherapy,tion. Theseincludetemperature stabilization, antibody byasmuch75%. administered withplasmatoreducethecirculating levels of ( 170 c ) 35–37 weeks of gestation have) 35–37weeks ofgestation passed.Themother isalso The threemostcommonways inwhichawoman becomes Before birth, treatmentofthe conditionincludeintrauter-Before birth, After birth, treatmentdependsonthe severity ofthecondi- birth, After from exposure to environmental antigens. from exposuretoenvironmental contrast, Rhesusantibodiesaregenerallynot produced in life. Onrareoccasions, IgGantibodiesareproduced.In andIgManti-Bantibodiesearly production ofIgManti-A are widespreadintheenvironment, usuallyleadstothe type O.TheimmuneresponsetoAandBantigens,which The thirdsensitizationmodelcanoccurinwomen ofblood uneconomical toscreenfor thesebloodgroups. to avoid possiblesensitization. However, itisconsidered transfusion withRhc-positive bloodorKell-positive blood of childbearingageoryoung girlsshouldnot begiven a to transfusion.Suggestionshave beenmadethatwomen tem andRhbloodgroupsystemtypingareroutineprior with anincompatible bloodtype.ABOgroupsys- The woman may receive atherapeuticbloodtransfusion afetusaffect withRhD-positive blood. anRhD-positive fetus, these antibodieswillonly carrying major Rhantigen)IgGantibodiesasaresultofpreviously lysis. Inother words, ifamother hasanti-RhD(Dbeingthe causehemo- combine withtheredbloodcells,andfinally intothefetal bloodstream, bodies thencrosstheplacenta there isasimilarincompatibility inthefetus, theseanti- that breachtheuterinewall.Insubsequent pregnancies,if nancy, ormedicalprocedurescarriedoutduringpregnancy duringpreg- ruptures intheplacenta childbirth, abortion, Fetal–maternal hemorrhagecanoccurduetotrauma, IMMUNOLOGY b ) fetal distress ispresent,or a ) pulmo- delivery; hence the first childescapes. hencethefirst delivery; child.Thisisbecausesensitizationoccursonlyduringthe first new bornismoreinsecondandsuccessive child,butnot in Number ofpregnancies: 3. nological unresponsiveness, however, isnot known. are known reasonfor asnonresponders.Theexact suchimmu- Rh-positive cellsfailtoform Rhantibodies.Suchindividuals Rh-negative repeatedinjectionsof individualseven after 2. Immune unresponsivenesstoRh antigen: form theRhantibodies. are destroyed rapidlybytheABOantibodiesbefore they can this condition,thefetal cellsenteringthematernalcirculation rare.In ibility coexist,Rhsensitizationfromthemother isvery more likely tooccur. However, whenRhandABOincompat- and fetus possessthesameABOgroup,Rhimmunizationis Mother–fetus ABOincompatibility: 1. due toeitherofthefollowing causes: fromhemolyticdiseasesofnewborn.Thismaydo not suffer be produce animmuneresponseandform anti-DIgG. fetal redcellswiththeDantigenbefore themother isableto sensitization totheDantigen.TheRhIGactsbybindingany toprevent delivery globulin (RhIG)duringpregnancyandafter pregnant withanRh-positive infantaregiven Rhimmuno- spherocytosis. Coombs’ test.Peripheral bloodsmearcharacteristicallyshows made byapositive indirectCoombs’testbutanegative direct of theRhdisease.ThediagnosisABOincompatibility is naturally occurringmaternalisoantibodies. immunization. ThisisbecausetheABOdiseasecaused by childeven withoutprior lytic diseasescanoccureven infirst andsensitizethefetus.does not crosstheplacenta B becausenaturalantibodiesaremainlyIgMinnature,which Itdoesnot occurinmothersplacenta. withbloodgroupsAor the isoantibodiesarelargelyIgGinnature,whichcancross group AorBfetus. Itoccurslargely inOgroupmothers The conditionisusuallyseeninOgroupmothers bearingblood even common. thoughmaterno-fetal ABOincompatibility isvery lessnumberofcases, ABO hemolyticdiseasesoccurinavery ABO HemolyticDiseases All the offsprings ofRh-incompatible marriages,however,All theoffsprings Rh-negative mothers whohave hadapregnancywithorare ABO hemolyticdiseaseismuchmilderconditionthanthat Unlike hemolyticdiseaseofthenewborn,ABOhemo- Theriskofhemolyticdisease When the mother because Some