ABO-Rh - ABO and Rh ISOIMMUNISATION ABO Professor. Surendra...

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Unformatted text preview: ABO and Rh ISOIMMUNISATION ABO Professor. Surendra Nath Panda, M.S Professor. Dept. of Obstetrics & Gynaecology M.K.C.G.Medical College M.K.C.G.Medical Berhampur-760004, Orissa, India Berhampur-760004, The Basics Of Blood W.B.C. & Platelet R.B.C. Plasma ANTIGEN ANTIBODY >400 Agglutinogens on the cell membrane Natural & Immune Agglutinins/ Isoantibodies Antigen-Antobody reaction on the cell surface → Hemolysis 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 2 The Basics Of Blood Antigens: Controlled by genes at unknown No. of Controlled chromosomal loci. chromosomal Appearance by 40 days of I.U. Life- unchanged till Appearance death. death. Also present in tissues & tissue fluids. Blood group system: A group of antigens controlled Blood by a locus having a variable no of allele genes. by 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 3 The Basics Of Blood Antigens: > 15 blood group systems are recognised : 15 ABO, Rh, Kell, Duffy, MN, P, Lewis, Lutheran, Xg, Li, Yt, Dombrock, Colton, Public antigens & Private antigens. antigens. Blood type- means individual antigen phenotype Blood which is the serological expression of the inherited genes genes Most of these blood group antigens have been Most found to be associated with hemolytic disease. found However– ABO & Rh account for 98% 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 4 The Basics Of Blood Antibodies: - Alloantibodies / Agglutinins Natural IgM Iso / immune antobodies IgG Formed in response to foreign R.B.C. or soluble blood group substance. 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 5 The Basics Of Blood Natural Antibodies: Antibodies are formed against most of the major group Antibodies antigens & present in almost all individuals when the antigen is absent. antigen In most other minor systems, natural antibodies to the In antigens are found occassionally but as their anitgenicity is low, the immune antibodies are also rare ( except –Kell & Duffy) Mostly of them are IgM type. React poorly at body temp. ( except anti-A & anti-B), React but agglutinate R.B.C.s at 5-20°C but Usually do not cross placenta. 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 6 The Basics Of Blood Immune Antibodies: In contrast the immune or isoantibodies are IgG. Best react at body temp. & readily cross placenta. Most antibodies are complement binding notable Most exceptions being Rh & MN. exceptions 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 7 Antibodies Can Be Detected by: a. a. b. c. Saline agglutination test (SAT). Tests using cells suspended in colloid media. Tests using enzyme-treated cells- Rh & Tests occasional antobodies. occasional d. Indirect antiglobulin ( Coomb’s test) - wide Indirect spectrum. spectrum. Antibodies may be Complete / Incomplete ⇓ ⇓ IgM IgG Detected by→ SAT b, c, d 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 8 ABO Blood Group System ABO system is controlled by allelic genes A1, A2, B, O ABO located on the long arm of chromosome 9 located The loci of ABO & H are not genetically linked A1 & A2 genes perform same function but have a A1 different rate constant different The O gene is an amorph & functionaly silent The H antigen is a precursor to A & B Secretors & nonsecretors – Se & se genes control the Secretors production of a flucosyl transferase, which controls the production of H, A & B antigens in tissues production 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda A 9 ABO Blood Group System Genotype Genotype (Genes) (Genes) Phenotype (Blood type) Antigens in R.B.C. Antibody In plasma Antibody A1 A1 , A1 A2 A1 (23-25%) (23-25%) A1, (H) A2 A2, A2 O A2 (6-10%) (6-10%) A2, (H) anti-B, anti-H Anti-B, anti-A1 BB, BO B(8-17%) B,(H) Anti-A/A1 A1B A1B(3%) A,A1,B A2 B A2B(1%) A,B,H Anti-H Anti-A1 O,O H,h O(43-50%) Oh Bombay H None Anti-A,-A1,-B Anti-A,-A1,-B,-H 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 10 A ABO System & Pregnancy Majorities of hemolytic diseases are due to ABO Majorities incompatibility incompatibility Foetus inherits one gene from each parent. Foetus O + O = O, O + A= O or A, O + B= O or B, O + AB= O, A or B. There is a 20% chance of ABO incompatibility of There mother & foetus mother Only 5% chance of developing hemolytic disease Only only in type A & B infants of type O mothers, that too only of milder forms too 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 11 A ABO System & Pregnancy In foetus & newborn, RBCs have a decreased No. In of H, A & B reactive sites The foetal immunoglobulin production is low, so The the plasma contains very little of anti-A & B agglutinins agglutinins Anti-A & B produced in the mother being natural Anti-A are IgM molecules & so do not cross placenta. are In some type O adults, much of the anti-A & B and In anti-AB (a cross reacting antibody, also called antianti-AB C) isoagglutinins are of IgG class. 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 12 A ABO System & Pregnancy There is no adequate method of antenatal There diagnosis. diagnosis. Direct Coomb’s antiglobulin test may be negative Direct in ABO haemolytic disease. in ABO haemolytic disease is frequently seen in ABO infants of primigravidae & the chance of recurence is 87%. is The risk of stillbirth is not increased & no antenatal The treatment is necessary. treatment Only 67% of affected infants will need any Only treatment. treatment. 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 13 A Rhesus Blood Group System First demonstrated by testing human blood with First rabit anti sera against red cells of Rhesus monkey & classifying Rh negative & Rh positive. However the underlying biochemical genetics is However not well understood and the genotyping & phenotyping remains little confused phenotyping The genotype is determined by the inheritance of 3 The pairs of closely linked allelic genes situated in tanderm on chromosome 9 & named as D/d, C/c, E/e (Fisher- Race theory) E/e 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 14 A Rhesus Blood Group System The gene ‘d’ is an amorph & has no antigenic The expression. So there are only five effective antigens. expression. But Weiner postulates a series of allelic genes at a But single locus Rho (D), rh (C),rh (E), hr © & hr (e) single The updated system of Rosenfield refers these The antigens as – Rh1, Rh2, Rh3, Rh4, Rh5 antigens Subsequently less common antigens Cw, Du, Es have Subsequently been found been The foetus inherits one gene from each group as a The haplotype such as sets of Cde, cde etc from each parent 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 15 A Rhesus Blood Group System 12 sets of combinations & 78 genotypes are 12 possible. Most frequent genotypes are – possible. Cde/cde(33%), Cde/cde(33%), Cde/cDe(18%), Cde/cDE(12%) cDE/cde(11%), cde/cde(15%), cdE/cde(1%), Cde/cde(1%) Cde/cde(1%) Though several Rh genotypes and phenotypes Though have been described, for clinical & all practical purposes it is enough to know whether one is Rh POSITIVE or NEGATIVE against anti D sera. POSITIVE 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 16 A Rhesus Blood Group System Incidence of Rh negative varies in different races: MongoloidsMongoloids- nil, Chinese & Japanese- 1-2%, Indians-5%, Africans-5-8%, Causcasians-15-17% & Basques-30-35%. Basques-30-35%. The antigenic expressions of these genes are The dependent on an interaction between R.B.C. membrane protein & phospholipid molecules resulting in a set of antithelical epitopes, the coresponding antigens, consisting of C/c, D/d, E/e. coresponding The antigenic determinants form an intrinsic part of The the red cell membrane protein structure. the 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 17 A Rhesus Blood Group System C/c & E/e are weak antigens and impractical to C/c match. match. ‘D’ is by far the most immunogenic in the Rh D’ system excepting those that have the natural antibodies. antibodies. There is a rare type of Rh negative called Rh null There who lack all known Rh antigens. who ‘D’ antigen has no natural antibody while C & E D’ have the coresponding natural antibodies, though weak & found infrequently. weak 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 18 A Rhesus Blood Group System A single transfusion of + ve blood to a – ve person single has a 50% chance of forming anti Rh D antibodies (IgG) Anti Rh antibodies are of three categories 1st order – saline / bivalent / complete antibodies 2nd 2nd order - albumin active / univalent / incomplete antibodies antibodies 3rd 3rd order – atypical / antiglobulin active / incomplete antibodies antibodies 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 19 A Pathogenesis Of Rh Iso-immunisation Rh Negative Women Man Rh positive (Homo/Hetero) ⇓ Rh Neg Fetus ← No problem ⇓ ← ← Fetus → → Mother previously sensitized Secondary immune response ⇓ ↑? Iso-antibody (IgG) ⇓ Fetus ⇓ Haemolysis ←← → ⇐⇐ ← ← ?± Rh positive Fetus ⇓ Rh+ve R.B.C.s enter Maternal circulation ⇓ Non sensitized Mother Primary immune response ⇓ Fetus → unaffected, 1st Baby usually escapes. Mother gets sensitised? ± ⇐ 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 20 A Pathogenesis Of Rh Iso-immunisation Chances of T.P.H/F.M.H. are only 5% in 1st Chances trimester but 47% in 3rd trimester, many conditions can increase the risk. can Chances of primary sensitization during 1st Chances pregnancy is only 1-2%, but 10 to 15% of patients may become sensitized after delivery. may ABO incompatibility and Rh non-responder status ABO may protect. may Amount of antibodies that enter the fetal circulation Amount will determine the degree of haemolysis will 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 21 A Pathology Of Iso-immunisation AFTER BIRTH ⇐ HAEMOLYSIS ⇒ ⇓ ⇓ Jaundice Kernicterus Hepatic Failure ↑ DEATH ANAEMIA ⇓ ⇓ ↑ ↑ ↑ ↑ IUD ↑ ERYTHROBLASTOSIS FETALIS ⇓ IN UTERO ⇓ ↑BILLIRUBIN ⇓ ↑ HEPATIC ERYTHROPOESIS & DYSFUNCTION MAT. LIV NO EFFECT ⇓ PORTAL & UMBILICAL VEIN ⇐ HYPERTNSION, HEART FAILURE ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ BIRTH OF AN AFFECTED INFANT - Wide spectrum of presentations. Rapid deterioration of the infant after birth. May contiune for few days to few months. Chance of delayed anaemia at 6-8 weeks probably due to persistance of anti Rh antibodies. 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 22 A Prevention of Rh Incompatibility Premarital counseling? Ambitious? Proper matching of blood particularly in women Proper before childbearing. before Blood grouping must for every woman, before 1st Blood pregnancy. pregnancy. Rh+ve Blood transfusion- 300mcg Immunoglobulin Rh+ve (minimum). (minimum). Proper management of unsensitised Rh negative Proper pregnancies. pregnancies. 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 23 A Management of Unsensitised Pregnancy Blood typing at 1st visit, If negative husband’s Blood typing. If husband is also negative then no treatment treatment If husband is positive, if possible, Homo/Hetero? Do Indirect Coomb’s test of mother – Do Negative-good. Negative-good. Repeat Repeat ICT at 28 weeks – Negative- ICT at 35 weeks - Negative- Observe Positive→ Sensitised - 300mcg Rh immunoglobulin 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 24 A Management of Unsensitised Pregnancy In Abortion, Ectopic, CVSIn Pregnancy < 12 weeks- 50mcg Anti D Pregnancy >12 weeks- 300mcg Anti D APH, IUD, Amniocentesis, Abdominal trauma, APH, Foetal-maternal hemorrhage -300mcg Anti D Foetal-maternal At birth- cord blood for ABO & Rh typing Baby Rh negative – Be happy 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 25 A Management of Unsensitised Pregnancy If Rh positive- Test mother’s blood for ICT & If Infant’s for DCT Infant’s Negative Negative or weakly reactive- 300mcg immunoglobulin immunoglobulin Positive Positive – Sensitised–Hb & Bilirubin Estimation of the infant -Treat the infant the ?Prophylactic Anti D administration during ?Prophylactic antenatal period to all negative mothers at 28weeks and again at 34 / 36 weeks. 28weeks 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 26 A Management of Sensitized Pregnancy Causes of sensitizationCauses Misinterpretation Rh +ve of maternal Rh type blood transfusion Unprotected preg. & labour Inadequate Inadequate dose / improper use of IgG on previous occasions previous Immunization to cross-reacting antigen 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 27 A Management of Sensitized Pregnancy Careful planning during antepartum, intrapartum & Careful neonatal period neonatal Father’s blood type & Rh antigen status Knowledge of maternal antibody titer to the specific Knowledge antigen antigen Intrauterine foetal monitoring with repeated Intrauterine ultrasound examination, cordocetesis / amniocentesis amniocentesis 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 28 A Management of Sensitized Pregnancy Fetus Rh Negative: - Observation Fetus Rh Positive: Fetus Intrauterine Intrauterine transfusion of ‘Rh Neg’ blood as indicated indicated Timely delivery any time after 32 weeks Management of the infant up to 8 weeks In cases of severely sensitized women, consider In medical termination of pregnancy and sterilization . 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 29 A THANK YOU 15th Agust, 2002 BO & Rh Isoimmunisation - Prof.S.N.Panda 30 A ...
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