Transcript 6. rh isoimmunization

Rh Factor
ISOIMMUNIZATION
• Associate Professor
Iolanda Blidaru, MD, PhD
INTRODUCTION
R.B.C.
Plasma
ANTIGEN
ANTIBODY
>400 Agglutinogens on the cell
membrane
Natural & Immune
Agglutinins/
Isoantibodies
Antigen-Antobody reaction on the
cell surface  Hemolysis
INTRODUCTION
Antigens
• controlled by genes at chromosomal
loci
• appeared by 40 days of i.u. life
• unchanged till death
• present in tissues and tissue fluids
Blood group system - a group of
antigens controlled by a locus
having a variable no. of allele genes.
INTRODUCTION
Antigens
• > 15 recognised blood group systems
ABO, Rh, Kell, Duffy, MNS, P, Lewis,
Lutheran, Xg, Li, Yt, 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.
• ABO & Rh account for 98%.
INTRODUCTION
Antibodies
Alloantibodies / Agglutinins
Pre-existent
IgM
Iso-antibodies
IgG
Formed in response to
foreign R.B.C. or soluble
blood group substances
INTRODUCTION
Pre-existent (natural) Antibodies
• Formed against most of the major
group antigens and present in
individuals.
• IgM type.
• Do not cross placenta.
• React poorly at body temperature
(except anti-A and anti-B), but
agglutinate erythrocytes at 5-20°C
INTRODUCTION
Iso-Antibodies
• The isoantibodies are IgG.
• Best react at body temperature
• Cross the placenta readily.
• Most Ab are complement binding.
Immunology of Rhesus Blood
Group System
• First demonstrated by testing human blood
with rabit anti sera against RBC of Rhesus
monkey → classifying into Rh negative / Rh
positive.
• The genotype is determined by the
inheritance of 5 closely linked allelic genes
situated on the short arm of chromosome 1,
named as D,C,c,E,e (Fisher-Race).
• No ”d” → absence of D
• The foetus inherits one gene from each group
as a haplotype such as sets of cDe, CDE, etc
from each parent.
Immunology of Rhesus Blood
Group System
• 12 sets of combinations and 78
genotypes are possible.
• For clinical and all practical
purposes it is enough to know
whether one is Rh POSITIVE or
NEGATIVE against anti D sera.
• The antigenic expressions of these
genes are 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.
Immunology of Rhesus
Blood Group System
• C/c and E/e are weak antigens.
• ‘D’ is the most immunogenic in the
Rh system.
• There is a rare type of Rh negative
called Rh null who lack all known Rh
antigens.
• ‘D’ antigen has no natural antibody.
• A single transfusion of Rh+ blood to
a Rh– person has a 50% chance of
forming anti Rh D antibodies.
Incidence of Rhesus Blood
Group System
Incidence of Rh negative varies in
different races and ethnic groups
• Mongoloids = nil
• Chinese, Japanese = 1-2%
• Indians = 5%
• Africans = 5-8%
• Causcasians = 15-17%
• Basques = 30-35%
Pathogenesis Of Rh Iso-immunization
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+ RBCs enter
maternal circulation

Non sensitized mother
Primary immune response

Fetus  unaffected
1st baby usually escapes.
Mother gets sensitised? ±

Pathogenesis Of Rh Isoimmunization
• Chances of feto-maternal hemorrhage / passage 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 10-15% 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.
Pathology Of Erythroblastosis fetalis
AFTER BIRTH

HAEMOLYSIS



Jaundice
Kernicterus
Hepatic Failure

DEATH
IN UTERO
ANAEMIA

INTRAUTERINE
DEATH

BILLIRUBIN

HEPATIC
ERYTHROPOIESIS
& DYSFUNCTION
MAT. LIV →
NO EFFECT

ERYTHROBLASTOSIS
FETALIS


PORTAL & UMBILICAL VEIN
HYPERTENSION, HEART
FAILURE, HYDROPS FETALIS

BIRTH OF AN AFFECTED INFANT - Wide spectrum of presentations. Rapid
deterioration of the infant after birth. May continue for few days to few months.





Antenatal Diagnosis Of Rh Isoimmunization
• the history and physical exam.
• the maternal and paternal Rh blood type
• anti-Rh Ab screen (monthly after 20-th
week) – by indirect Coombs test; if positive
as 1/8-1/32, there is needed further
assessment
• ultrasound exams
• fetal anemia and hyperbilirubinemia – by
ultrasound guided amniocentesis
→ spectrophotometry of amnionic fluid
(Liley chart)
→ CORDOCENTESIS – fetal blood tests
Antenatal Diagnosis Of Rh Isoimmunization - ultrasound exams
Antenatal Diagnosis Of Rh
Iso-immunization
• Liley chart
Antenatal Diagnosis Of Rh
Iso-immunization
Postnatal Diagnosis Of Rh Isoimmunization
Hemolytic disease of the newborn
• Hemolytic anemia (Hb = 13-14g%;
bilirubin < 3.5mg%)
• Icterus gravis neonatorum (Hb =
7-12g%; bilirubin > 10mg%)
• Kernicterus (bilirubin > 18mg%)
• Hydrops fetalis (Hb < 7-12g%;
bilirubin > 10mg%)
Postnatal Diagnosis Of Rh
Iso-immunization
Hydrops fetalis
Hydrops fetalis
Postnatal Diagnosis Of Rh
Iso-immunization
Laboratory tests (newborn)
• ABO and Rh blood group test
• Hb and Ht
• Reticulocyte count
• Bilirubin level
• Direct Coombs test
Prevention of Rh Isoimmunization
• Premarital counseling.
• Blood grouping for every
woman, before 1st pregnancy.
• Proper management of
unsensitised Rh negative
pregnancies.
Prevention of Rh Isoimmunization
 Blood typing at 1-st visit, If negative → husband’s typing.
 Anti-Rh Ab screen (indirect Coomb’s test) of Rh–negative
mother.
 At about 28 weeks – negative → 300μg anti D
immunoglobulin.
 In abortion, ectopic pregnancy, abruption of placenta,
placenta praevia, molar pregnancy, abdominal trauma,
chorionic villi sampling, amniocentesis = foetal-maternal
hemorrhage → 150-300μg anti D
 At birth- cord blood for ABO and Rh typing → Baby Rh
positive → 300μg anti D within 72 hours of delivery
Prevention of Rh Isoimmunization
In case of large fetal-maternal
hemorrhage:
1. the Kleihauer-Betke test estimates
the amount of fetal blood in
circulation
2. the indirect Coombs test
3. an additional dose of anti-D, if
needed
The Kleihauer-Betke test
Prevention of Rh Isoimmunization
Errors - Causes of sensitization
• Misinterpretation of maternal Rh
type
• Rh+ blood transfusion
• Unprotected pregnancy and labour
• Inadequate dose / improper use of
IgG on previous occasions
• Immunization to cross-reacting
antigen
Management of Rh Isoimmunized Pregnancy
ANTEPARTUM
• Careful planning during antepartum,
intrapartum and neonatal period
• Known repeated maternal anti-D Ab
titer
• Intrauterine fetal monitoring with
repeated US examinations,
cordocentesis & fetal blood sampling /
amniocentesis, the measurement of
the fetal middle cerebral artery peak
velocity (Doppler)
Management of Iso-
immunized Pregnancy
• Fetus Rh Positive + anemia
• Intrauterine transfusion of Rhnegative blood in selected cases
• Planned preterm delivery any time
after 34 weeks or as soon as the
lung maturity is documented by
inducing the labor or cesarean
section (for the severely affected
fetuses)
Management of Iso-
immunized Pregnancy
POSTPARTUM
Management of the infant
• Monitoring up to 8 weeks
• Exchange-transfusion in the newborn
in the umbilical vein
• Phototherapy
• In cases of severely sensitized
women, consider medical termination
of pregnancy and sterilization.