Abo and rh isoimmunisation

Содержание

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda The Basics

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

The Basics Of Blood

ANTIGEN


>400 Agglutinogens on the cell membrane

W.B.C. & Platelet

R.B.C.

Plasma

ANTIBODY
Natural & Immune Agglutinins/ Isoantibodies

Antigen-Antobody reaction on the cell surface → Hemolysis

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda The Basics

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

The Basics Of Blood

Controlled

by genes at unknown No. of chromosomal loci.
Appearance by 40 days of I.U. Life- unchanged till death.
Also present in tissues & tissue fluids.
Blood group system: A group of antigens controlled by a locus having a variable no of allele genes.

Antigens: -

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda The Basics

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

The Basics Of Blood

>

15 blood group systems are recognised :
ABO, Rh, Kell, Duffy, MN, P, Lewis, Lutheran, Xg, Li, Yt, Dombrock, Colton, Public antigens & Private antigens.
Blood type- means individual antigen phenotype which is the serological expression of the inherited genes
Most of these blood group antigens have been found to be associated with hemolytic disease.
However– ABO & Rh account for 98%

Antigens: -

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda The Basics

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

The Basics Of Blood

Alloantibodies

/ Agglutinins

Natural
IgM

Iso / immune antobodies
IgG

Formed in response to foreign R.B.C. or soluble blood group substance.

Antibodies: -

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda The Basics

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

The Basics Of Blood

Antibodies

are formed against most of the major group antigens & present in almost all individuals when the antigen is absent.
In most other minor systems, natural antibodies to the 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), but agglutinate R.B.C.s at 5-20°C
Usually do not cross placenta.

Natural Antibodies: -

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda The Basics

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

The Basics Of Blood

In

contrast the immune or isoantibodies are IgG.
Best react at body temp. & readily cross placenta.
Most antibodies are complement binding notable exceptions being Rh & MN.

Immune Antibodies: -

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Antibodies Can

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Antibodies Can Be Detected

by: -

Saline agglutination test (SAT).
Tests using cells suspended in colloid media.
Tests using enzyme-treated cells- Rh & occasional antobodies.
Indirect antiglobulin ( Coomb’s test) - wide spectrum.
Antibodies may be Complete / Incomplete
⇓ ⇓
IgM IgG
Detected by→ SAT b, c, d

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda ABO Blood

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

ABO Blood Group System

ABO

system is controlled by allelic genes A1, A2, B, O located on the long arm of chromosome 9
The loci of ABO & H are not genetically linked
A1 & A2 genes perform same function but have a different rate constant
The O gene is an amorph & functionaly silent
The H antigen is a precursor to A & B
Secretors & nonsecretors – Se & se genes control the production of a flucosyl transferase, which controls the production of H, A & B antigens in tissues
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda ABO Blood Group System

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

ABO Blood Group System

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda ABO System

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

ABO System & Pregnancy

Majorities

of hemolytic diseases are due to ABO incompatibility
Foetus inherits one gene from each parent.
O + O = O, O + A= O or A, O + B= O or B, O + AB= A or B.
There is a 20% chance of ABO incompatibility of mother & foetus
Only 5% chance of developing hemolytic disease only in type A & B infants of type O mothers, that too only of milder forms
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda ABO System

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

ABO System & Pregnancy

In

foetus & newborn, RBCs have a decreased No. of H, A & B reactive sites
The foetal immunoglobulin production is low, so the plasma contains very little of anti-A & B agglutinins
Anti-A & B produced in the mother being natural are IgM molecules & so do not cross placenta.
In some type O adults, much of the anti-A & B and anti-AB (a cross reacting antibody, also called anti-C) isoagglutinins are of IgG class.
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda ABO System

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

ABO System & Pregnancy

There

is no adequate method of antenatal diagnosis.
Direct Coomb’s antiglobulin test may be negative in ABO haemolytic disease.
ABO haemolytic disease is frequently seen in infants of primigravidae & the chance of recurence is 87%.
The risk of stillbirth is not increased & no antenatal treatment is necessary.
Only 67% of affected infants will need any treatment.
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Rhesus Blood

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Rhesus Blood Group System

First

demonstrated by testing human blood with rabit anti sera against red cells of Rhesus monkey & classifying Rh negative & Rh positive.
However the underlying biochemical genetics is not well understood and the genotyping & phenotyping remains little confused
The genotype is determined by the inheritance of 3 pairs of closely linked allelic genes situated in tanderm on chromosome 9 & named as D/d, C/c, E/e (Fisher- Race theory)
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Rhesus Blood

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Rhesus Blood Group System

The

gene ‘d’ is an amorph & has no antigenic expression. So there are only five effective antigens.
But Weiner postulates a series of allelic genes at a single locus Rho (D), rh (C),rh (E), hr © & hr (e)
The updated system of Rosenfield refers these antigens as – Rh1, Rh2, Rh3, Rh4, Rh5
Subsequently less common antigens Cw, Du, Es have been found
The foetus inherits one gene from each group as a haplotype such as sets of Cde, cde etc from each parent
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Rhesus Blood

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Rhesus Blood Group System

12

sets of combinations & 78 genotypes are possible. Most frequent genotypes are –
Cde/cde(33%), Cde/cDe(18%), Cde/cDE(12%) cDE/cde(11%), cde/cde(15%), cdE/cde(1%), Cde/cde(1%)
Though several Rh genotypes and phenotypes have been described, for clinical & all practical purposes it is enough to know whether one is Rh POSITIVE or NEGATIVE against anti D sera.
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Rhesus Blood

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Rhesus Blood Group System

Incidence

of Rh negative varies in different races:
Mongoloids- nil, Chinese & Japanese- 1-2%, Indians-5%, Africans-5-8%, Causcasians-15-17% & Basques-30-35%.
The antigenic expressions of these genes are 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.
The antigenic determinants form an intrinsic part of the red cell membrane protein structure.
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Rhesus Blood

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Rhesus Blood Group System

C/c

& E/e are weak antigens and impractical to match.
‘D’ is by far the most immunogenic in the Rh system excepting those that have the natural antibodies.
There is a rare type of Rh negative called Rh null who lack all known Rh antigens.
‘D’ antigen has no natural antibody while C & E have the coresponding natural antibodies, though weak & found infrequently.
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Rhesus Blood

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Rhesus Blood Group System

A

single transfusion of + ve blood to a – ve person 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 order - albumin active / univalent / incomplete antibodies
3rd order – atypical / antiglobulin active / incomplete antibodies
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Pathogenesis Of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Pathogenesis Of Rh Iso-immunisation


Rh

Negative Women

Man Rh positive (Homo/Hetero)

⇓ ⇓

← ← Fetus → →

Rh Neg Fetus No problem

Rh positive Fetus




Rh+ve R.B.C.s enter Maternal circulation



Mother previously sensitized Secondary immune response


↑? Iso-antibody (IgG)


Non sensitized Mother Primary immune response


Fetus → unaffected, 1st Baby usually escapes. Mother gets sensitised? ±


Fetus

Haemolysis






±

?

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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Pathogenesis Of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Pathogenesis Of Rh Iso-immunisation

Chances

of T.P.H/F.M.H. are only 5% in 1st trimester but 47% in 3rd trimester, many conditions can increase the risk.
Chances of primary sensitization during 1st pregnancy is only 1-2%, but 10 to 15% of patients may become sensitized after delivery.
ABO incompatibility and Rh non-responder status may protect.
Amount of antibodies that enter the fetal circulation will determine the degree of haemolysis
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Pathology Of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Pathology Of Iso-immunisation

HAEMOLYSIS



IN UTERO

AFTER

BIRTH

↑BILLIRUBIN


ANAEMIA



MAT. LIV NO EFFECT


↑ HEPATIC ERYTHROPOESIS & DYSFUNCTION


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.


Jaundice Kernicterus Hepatic Failure


DEATH

ERYTHROBLASTOSIS FETALIS




IUD






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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Prevention of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Prevention of Rh Incompatibility

Premarital

counseling? Ambitious?
Proper matching of blood particularly in women before childbearing.
Blood grouping must for every woman, before 1st pregnancy.
Rh+ve Blood transfusion- 300mcg Immunoglobulin (minimum).
Proper management of unsensitised Rh negative pregnancies.
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Management of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Management of Unsensitised Pregnancy

Blood

typing at 1st visit, If negative husband’s typing. If husband is also negative then no treatment
If husband is positive, if possible, Homo/Hetero?
Do Indirect Coomb’s test of mother –
Negative-good.
Repeat ICT at 28 weeks – Negative- ICT at 35 weeks - Negative- Observe
Positive→ Sensitised - 300mcg Rh immunoglobulin
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Management of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Management of Unsensitised Pregnancy

In

Abortion, Ectopic, CVS-
Pregnancy < 12 weeks- 50mcg Anti D
Pregnancy >12 weeks- 300mcg Anti D
APH, IUD, Amniocentesis, Abdominal trauma, Foetal-maternal hemorrhage -300mcg Anti D
At birth- cord blood for ABO & Rh typing
Baby Rh negative – Be happy
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Management of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Management of Unsensitised Pregnancy

If

Rh positive- Test mother’s blood for ICT & Infant’s for DCT
Negative or weakly reactive- 300mcg immunoglobulin
Positive – Sensitised–Hb & Bilirubin Estimation of the infant -Treat the infant
?Prophylactic Anti D administration during antenatal period to all negative mothers at 28weeks and again at 34 / 36 weeks.
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Management of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Management of Sensitized Pregnancy

Causes

of sensitization-
Misinterpretation of maternal Rh type
Rh +ve blood transfusion
Unprotected preg. & labour
Inadequate dose / improper use of IgG on previous occasions
Immunization to cross-reacting antigen
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Management of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Management of Sensitized Pregnancy

Careful

planning during antepartum, intrapartum & neonatal period
Father’s blood type & Rh antigen status
Knowledge of maternal antibody titer to the specific antigen
Intrauterine foetal monitoring with repeated ultrasound examination, cordocetesis / amniocentesis
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15th Agust, 2002 ABO & Rh Isoimmunisation - Prof.S.N.Panda Management of

15th Agust, 2002

ABO & Rh Isoimmunisation - Prof.S.N.Panda

Management of Sensitized Pregnancy

Fetus

Rh Negative: - Observation
Fetus Rh Positive: -
Intrauterine transfusion of ‘Rh Neg’ blood as indicated
Timely delivery any time after 32 weeks
Management of the infant up to 8 weeks
In cases of severely sensitized women, consider medical termination of pregnancy and sterilization .