Dr. Enass Saleh Al-Khayat
ObstetricsRheusus iso-Immunization
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Definition :
It is an immunological disorder that occur in a pregnant Rh-ve patient carrying an Rh+ve fetus . The immunological system in the mother is stimulated to produce antibodies to Rh-antigen , which then cross the placenta and destroy fetal RBCs .Pathophysiology :
The human blood group is extremely complex and it is determined by a number of antigenes on the surface of RBCs ( ex. ABO , Rheusus ( C, c , D, E, e , d ) , dufffy, kidd , kell , . etc ). Clinically the most impotent antigens are : ABO & Rh ( 3 antigenes are dominant ( C , D, E ) and 3 are recessive ( c , d , e ) , the person possessing the D-dominant gene described as Rh + ve , When D-dominant gene is absent from both chromosomes the individual is termed as Rh-ve .The mode of inheritance of Rh-factor is by :
Mandelian law :
CDe* CDE ---------- homozygous Rh +ve .
CDe* cde ------------ heterozygous Rh+ve
cde * cde ------------ Rh-ve
The pathophysiolog of Rh- isommunization occur as following :
During normal pregnancy the fetal blood may enter the maternal circulation ( fetomaternal hg ) in small amount , it is demonstrated throughout normal pregnancy and at the time of delivery occurs ( in large amount ( 15 30 ml )) .
And the critical sensitization volume is 0.1 ml of fetal RBCs to stimulate maternal immune system .
Potential sensitizing events for Rh disease : (i.e. these events increase fetomaternal hemorrhage ) are :
1. miscarriage .
2. termination of pregnancy .
3. Anterpartum haemorrhage .
4. Delivery ( normal vag. Delivery or C/S ) .
5. External cephalic version , invasive prenatal testing ( chorion villous sampling , amniocentesis and cordocentesis )
6. Fetal loss ( IUD ) .
7. Fetal reduction .
8. Ectopic pregnancy .
9. Abdominal trauma .
10. Rh+ve platelet transfusion .
11. Manual delivery of placenta .
- When Rh-ve patient are exposed to Rh+ve antigen , they may become sensitized . Two mechanisms are proposed for this sensitization : The most likely mechanism is the occurrence of undetected placental leak of fetal RBCs into maternal circulation during pregnancy and other mechanism is the " grand mother theory " this suggest that Rh-ve woman may have sensitized from the birth by receiving enough Rh+ve cells from her mother during her own delivery to produce an antibody response .
- The initial response to exposure to Rh+ve antigen is production of IgM antibody for a short term ( which can't pass the placenta ) followed by the production of IgG antibody , that capable crossing the placenta , if the fetus has the Rh+ve Ag , these antibodies will coat the fetal RBCs and cause haemolysis , if the haemolysis is mild , the fetal can compensate by increasing the rate of erythropoiesis is mild, if it severe profound anemia and extramedullary erythropoiesis in :
placenta enlarged and congested .
spleen enlarged and congested .
liver enlarged and congested .
and may result in hydrops fetalis ( Hb% < 5g/dl ) from congested cardiac failure(CHF) and IUD may result .
- In subsequent pregnancies -------- this response may be --------- more aggressive and may occur earlier than in the previous pregnancy .
Note : Hydrops fetalis ( generalized edema and ascitis and hydrothorax and pericardial effusion ) due to C H F and hypoproteinemia .
- Destruction of the fetal RBC increase bilirubin cleaned into amniotic fluid and cord blood and through the placenta and metabolized by mother ( so during fetal life there is no jaundice ) .
After the delivery accumulation of bilirubin in neonatal circulation
hyperbilirubinemia if not managed it will be deposited in a basal ganglia kernicterus ( lethargic , hypertonic hyperextension of neck, apnea) ,
death , if survive cerebral palsy .
Factors determined the occurrence of Rh-Isoimmuization :
1. Presence of Rh+ve fetus inside Rh-ve mother .2. Whether the process of immunization is initiated in the mother or not .
3. ABO blood group compatibility between the fetus and the mother , if incompatible the fetal cells will be destroyed rapidly and no immunization will occur .
4. Variable antigenicity and variable maternal response to Ag.
5. Efficacy of placental passage .
6. Quantity and subclasses of antibodies screated .
* So not all females with Rh-ve develop Rh Iso immunization or hydrops
fetalis .So the incidence of Rh-ve to develop Th-iso immunization is 16% and decrease to 2% if the fetus has ABO incompatible .
Clinical features of fetus with Rh-iso immunization
1. Hydropis fetalis .2. Large placenta and oedematous .
3. Polydramnious .
4. Large fetal heart .
5. Decrease fetal movement .
6. Abnormal fetal cardiotocography(CTG) with reduced variability and eventually a sinusoidal trace .
7. Hyper dynamic fetal circulation ; can be detected by Doppler U/S by measuring increasing velocity in middle cerebral artery and aorta .
8. Hepato-spleenomegaly .
9 . Mid-trimester recurrent miscarriage or still birth .
10. The baby has jaundice within the first 24 hrs post delivery and may kernicterus , cerebral palsy and convulsions .
Note : The clinical and U/S features of fetal anemia do not usually become evident unless fetal Hb is < 6g/dl .
Prevention :
1. By administration of anti-D Ig to a non-sensitized Rh-ve woman within 72 hrs following the delivery of Rh +ve infant . The standard dose ( 1500 IU ) ( 300 microgram ) . ( I.M. ) can be suppress immunization by 4 5 ml of Rh+ve RBCs .* If the fetal maternal hg> 4 5 ml , additional dose of anti D-Ig .
Note : 5 fetal RBCs = 0.25 ml .
2. A dose of 250 IU is recommended for prophylaxis following sensitization events up to 20 wks of gestation , at least 500 IU anti D Ig should be given followed by a test to identify a FMH greater than 4 ml red cells , for all events after 20 wks of gestation .
3. Give anti-D Ig (300 microgram ( I.M. ) as a prophlyaxis ) at 28 34 wks of gestation . To a non sensitized female ( because , there may be occult FMH during the pregnancy sensitize the female .
4. Proper cross matching at any blood transfusion .
5. ABO grouping and Rh factor should be known for every pregnant for her and her partner .
If father was Rh+ve we must check if he is heterozygous or homozygous , If is homozygous that means that there is 100% chance to have a baby with Rh+ve , and if heterozygous there is 50% chance of have a baby with Rh+ve .
6. 250 IU of anti D Ig if Rh D+ve platelet transfusion ( each unit of platelet contain < 0.1 ml RBC ) .
7. Abortion and Rh-ve of : ( < 20 wks Anti- D Ig 250IU , > 20 wks >= 500 IU )
A- Therapeutic termination of pregnancy ( medical or surgical ) ( risk of about 5.5% ) regardless of GA , give anti- D Ig .
B- Ectopic pregnancy. Anti- D Ig .
C- Spontaneous abortion ( risk of 3.5 ) :
- If < 12 wks ------ of no instrumentation was done for evacuation of the uterus --- no Anti D Ig .
- If > 12 wks ------- give anti- D Ig.
D- Threatened abortion :
- If < 12 wks : either :
1. no Anti- D if small amount of bleeding , a viable fetus .
2. Give anti- D if missed abortion or heavy bleeding and abdomenal . pain or repeated bleeding .
- If > 12 wk : ----- give anti D Ig .
If the gestational age > 12 wk we can repeat the dose of Anti D Ig if the bleeding continue at 7 days interval + estimation of FMH .
The spectrum of Rh diseases :
( Wide spectrum from mild sever )
1. Normal delivery at term , mild jaundice requiring phototherapy .
2. Preterm delivery of an anemic fetus requiring exchange transfusion .
3. Delivery of fetus at 34 wks of gestation following fortnightly blood transfusion from 26 wks of gestation .
4. Still birth or neonatal death .
Detection of fetal RBCs in maternal circulation :
1. Kleihauer Betke test : ( to estimate FMH )Is dependent on the fact that adult Hb ( HbA ) is readily eluted through the cell membrane in the presence of acid , while fetal Hb ( HbF ) is more resistant to elusion by acid , then follow this equation :
No. of fetal cells counted / No. of maternal cells counted = estimated fetal volume ( ml ) / estimated maternal blood volume ( ml ) .
2. Detection of Abs in maternal circulation :
A- Agglutination test ------- to detect IgG , IgM .B- Coomb's test ( direct and indirect ) .
* Direct coomb's ( patients serum and antiglobulin )
* Indirect : patients serum + RBCs of specific Ag + antiglobulin ). Then expressed in titer ( 1/2 , 1/4 , 1/8 , ) , 1/16 is the critical level . It has been found that titrations of anti-D do not correlate well with development of haemolytic disease of the fetus& newborn(HDFN).
* Rh-ve mother with +ve coombs test ------ called Rh-ve sensitized patient .
If comb's test ve ----- called Rh-ve non sensitized patient .
3- Measurement of Anti- D antibody level in IU / ml in maternal blood with critical level >= 4IU/ ML :is a standard quantification method &gives more clinically relevant levels .
Management of Pregnant lady that is Rh-ve
- History of present pregnancy and previous pregnancy ( any previous Rh disease and it's severity and the time of it's occurrence ( GA ) and neonatal outcome , BL. Group of her husband and Rh and the zygostiy if possible , any basal records of indirect coomb's test you can depend on it , and according to his result can divide the pat. To :
a. Rh-ve non-immunized ( comb's test ve )
b. Rh-ve immunized ( comb's test + ve ) .
1. Management of Rh-ve non-immunized :
The aim of management is to prevent the formation of Abs in maternal circulation , by giving Anti D Ig injections antinatally before or shortly after the exposure to Rh+ve fetal RBCs ( sensitized event ) and prophylactically at 28-34wks of gestation , and postnatal with 72 hr of birth of Rh+ve baby300 microgram = standard dose ) if suspected more than 30 ml FMH ---- so do Kleihauer test ., and repeat Ab titer after 1st one at monthly interval , to ensure the ongoing status of a non-sensitization , also repeat the titer 3-6 months after birth to detect any failure of protection .Need Anti- D Ig after each delivery of each subsequent Rh+ ve baby
(Q) Why we give Anti D at 28-34 wks ?
To avoid isoimmunization from occult FMH ( which more in 3rd trimester ) about 29% of pregnancy .
Objective
The students should know about :1. Definition of Rh-Iso immunization .
2. Pathophysiologyof Rh-Iso immunization .
3. Potential sensitizing events for Rh-disease .
4. Factors determined the occurrence of Rh-Isoimmunization .
5. Clinical features of fetus with Rh-Isoimmunization .
6. Prevention .
7. Detection of fetal RBCs in maternal circulation .
8. Mamagement of Rh-ve non-immunized pregnant .
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