RH ISOIMMUNIZATION DISEASE

1. RH ISOIMMUNIZATION DISEASE DR ANSAM ALMAJALI FETOMATERNAL MEDICINE CONSULTANT KSMC

2. ABO System & Pregnancy hemolytic diseases of the newborn may be due to ABO incompatibilityO + O      =      O,O + A      =      O or A,O + B      =      O or B,O + AB    =      O or A BFetus inherits one gene from each parent.

3. Rhesus Blood Group SystemFirst demonstrated in Rhesus monkeyHowever the underlying biochemical genetics is not well understood and the genotyping & phenotyping remains little confusedRhesus Blood Group SystemThe genotype is determined by the inheritance of 3 pairs of closely linked allelic genes situated on chromosome 9 named asD/d,C/c,E/e………..  (Fisher- Race theory)   

4. Rhesus Blood Group System The gene ( d ) is an amorph & has no antigenic expression. So there are only five effective antigensWeiner postulates a series of allelic genes at a single locus Rh (D), Rh (C), Rh (E), Rh (c) & Rh (e)The updated system of Rosenfield refers these antigens as – Rh1, Rh2, Rh3, Rh4, Rh5Subsequently less common antigens Cw, Du, Es have been foundRhesus Blood Group System The fetus inherits one gene from each group as a haplotype such as sets of Cde, cde etc from each parent

5. Rhesus Blood Group System Incidence of Rh negative varies in different races:Mongoloids                  > 1,Chinese & Japanese      1-2%,Indians                          5%,Africans                        5-8%,Caucasians                    15-17% &Basques                          30-35%.

6. Rhesus  Isoimmunization Rhesus  Iso immunization is an immunologic diseasethat occurs in pregnancy resulting in a serious complication affecting the fetus / or the neonateranging from… mild neonatal jaundice  … to intra uterine loss or neonatal death

7. Rhesus  Isoimmunization This immunologic disease occur whena Rh – negative patient carrying a Rh – positive fetus….. had a feto – maternal blood transfusion….. the mother immunological system is stimulated        to produce antibodies to the Rh antigen on the      fetal blood cell….. This antibodies cross the placenta and destroy      fetal red blood cells leads to fetal anemia….  Usually the 1st fetus will not be affected if this is      the 1st time that the mother has been exposed to      the rhesus positive antigen

8. During pregnancy while the fetus still in the uterus The bilirubin in the fetal blood will be removed by the placenta to the maternal circulation and part of it go to the liquorThe fetus will be anemic….. If the degree of anemia is severe      fetus may die in utero because of heart failure  After delivery The neonate will affected by…… The degree of the anemia…… The amount of bilirubin

9. Rh Negative WomenFetusRhNeg Fetus No problemRh positive FetusRh+ve R.B.C.s enter Maternal circulationpreviously sensitized 2nd  immune responseIgM…IgG antibodiesNon sensitized Mother Primary immune response1st Baby usually escapes. Mother gets sensitized? FetusHaemolysisPathogenesis Of RhIso - immunisationMan Rh positive (Hetero)

10. Antigen-Antibody reaction on the RBCs surface  HemolysisIN UTEROAnemia Hepatic erythropoesis & dysfunctionPortal & Umbilical Vein Hypertension … Heart FailureErythroblastosisfetalisIUDPolyhydramnios

11. Antigen-Antibody reaction on the RBCs surface  HemolysisAfter birthAnemia … Jaundice … KernicterusNeonatal deathHemolysisAntigen-Antibody reaction on the RBCs surfaceManagementof rhesus negative pregnant womenManagement of non sensitized PregnancyManagement of sensitized Pregnancy

12. Blood Group typing at 1st visit, If negative …… Check husband’s Blood Group typing. …… If husband is also Rhesus negative then no rhesus          complication and manage as other pregnant women …… If husband is Rh Positive then

13. Management of non sensitized Pregnancy … If husband is Rh Positive then… Check Husband being Homozygous or Heterozygous.... Check for maternal antibodies    by indirect Comb's test ( ICT )          … if  antibodies detected treat as sensitized          … If no antibodies Repeat ( ICT )              at 28 and 32 weeks  provided that no bleeding.        … If there is bleeding  then …..

14. Management of non sensitized Pregnancy Bleeding before 20 weeks of gestation  ……..  Check for fetal red blood cells in              maternal circulation by Kleihauer test……..  Check for maternal antibodies ( ICT ) … if negative……..  Give ( 250 IU / 50 mcg ) anti D  to the mother within            72 hours from the bleeding

15. Management of non sensitized Pregnancy Bleeding after 20 weeks of gestation  ……..  Check for fetal red blood cells in              maternal circulation by Kleihauer test……..  Check for maternal antibodies ( ICT ) … if negative……..  Give ( 500 IU / 100 mcg ) anti D  to the mother          within 72 hours from the bleeding ……..  The dose should be doubled or tripled if fetal            RBCs are more than 80 cells in maternal circulation

16. Prophylactic Management of non sensitized Pregnancy During antenatal periodProphylactic (500 IU / 100 mcg ) Anti Dare recommended to be given to allnegative non sensitized mothers married to  Rh positive husband at28weeks and 34 weeks to protect andovercome any asymptomatic or un noticed  antenatal feto maternal blood transfusion

17. Prophylactic Management of non sensitized PregnancyIndications for prophylaxisAt 28weeks to a Rhesus –ve non sensitized woman whose husband is Rhesus +vePostpartum if the woman remains non sensitized and delivers a Rhesus +ve fetusFollowing amniocentesis or chorionic villus samplingFollowing evacuation of a molar pregnancy or termination of pregnancyFollowing an ectopic pregnancyFollowing abruptio placenta orundiagnosed uterine bleeding

18. Prophylactic Management of non sensitized PregnancyFailure of prophylaxisDose too smallDose too late >72 hoursPatient already immunized but antibody titer too low for laboratory recognitionDefective immune globulin given

19. Management of non sensitized Pregnancy Precaution should be taken to prevent the possibility of increased chance of feto - maternal blood transfusion At birthDuring labor… No fundal pushing in 1st or 2nd stage of labor… No uterine massage or uterine grasp and squeeze    in 3rd stage… Let the placenta to be delivered spontaneous  … A void avulsions of the cord… Protect the vaginal and perineal wounds and laceration    from being exposed to the fetal blood spilled from cord

20. Management of non sensitized PregnancyDuring cesarean section… Use abdominal packs in the sides of the uterus      before opening the lower segment to prevent    spilled blood from the placenta to inter the    peritoneal cavity.… Let the placenta to be delivered spontaneous using    control cord traction without squeezing the uterus… A void avulsions of the cord

21. Management of non sensitized PregnancyAt birth …….  Maternal blood sample for          …….. antibodies by indirect Comb's test ( ICT )          …….. fetal red blood cells in maternal circulation…….  Cord blood sample ( Neonatal blood sample ) for          …….. antibodies by Direct Comb's test ( DCT )          …….. Infant blood group          …….. Infant bilirubin level          …….. Infant Hb & Hct level

22. Management of non sensitized Pregnancy …….  If fetal blood group is rhesus positive…….  No antibodies detectedDon’t give Anti D…….  If fetal blood group is rhesus negative……. If Antibodies detected

23. Causes of sensitization Misinterpretation of maternal Rh typeRh positive blood transfusionUnprotected pregnancy & labourInadequate dose Anti D on previous occasionsSensitized  Rh Negative mothersFactors affecting immunization and severityAmount of Antigen …… ( amount of fetal RBCs)ABO-incompatible Rh- positive cells will be hemolysed before Rh antigen  can be recognized by the mother’s immune system

24. Management of Sensitized Pregnancy… Check quantitative antibodies level @ 1st visit… Recheck the level every 2 weeks… Serial U/S Scan monitoring every 2 weeks… If antibodies level continuo at the same level        and no fetal compromise … deliver at termSensitized  Rh Negative mothersManagement of Sensitized PregnancyIf antibodies level start to increase  … Arrange for amniocenteses… Spectrophotometer to study the optical density      of the amniotic fluid  ( i.e. bilirubin level which reflect RBCs haemolysis )… U/S Scan evaluation of the fetal will beings… Use LILY’ s Curve to determine the fetal condition

25. USS can detect …..…. Fetal Skin and scalp edema,……... Fetal Ascites,……... Fetal Pericardial or pleural effusion…….. Polyhydramnios…….. Fetal hepatosplenomegaly…….. Fetal Cardiomegaly…….. Placental hypertrophy and enlargements…….. Abnormal fetal posture (Buddha stance)Ultrasound  scan (USS)

26. Term pregnancy ( mild or Severely affected ) …Deliver Suitability of the place and its facility  Experience of the teamType of DeliveryExtra uterine Blood exchangePhoto therapyMedicationManagement of Sensitized PregnancyPreterm fetus with      Zone I in …..Cordocentesis blood sample Hb > 10g/dl      No U / S Scan evidence of Hydropic changesConsider conservative management with regular follow up of fetal and maternal conditions till the fetal lung maturity is assured …. Then deliver

27. Regular cheek of the fetal Hb and Hct values if the facilities available  Serial U / S Scan for fetal growth and amniotic fluid  Daily C T GBiophysical ProfileDaily maternal clinical assessmentsPreterm fetus withZone II or IIICordocentesis blood sample Hb less than 10g/dlUltrasound evidence of Hydropic changes ConsiderIntra uterine therapyDelivery + extra uterine mang.Transfer to suitable placeManagement of Sensitized Pregnancy

28. Dexamethazone to enhance lung maturityClinical assessments + C T G + U / S Scan + B P PLung maturity …..  If  certain … deliver  Consider repeating the intrauterine blood transfusionManagement of Sensitized PregnancyIntra peritoneal blood transfusionThrough the umbilical vein “ Cordocentesis80 % of packed cell “ o “ rhesus negative Blood Cross matched against maternal blood groupFree of  infectionFreshIntra uterine therapyManagement of Sensitized Pregnancy