Rh Isoimmunization dr samira

8/9/2019 Rh Isoimmunization dr samira

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Dr.Samira alsagher Elmugharif teaching hospital

Agdabia - Libya


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Samira Alsagher Samira Alsagher RH IsoimmunizationRH Isoimmunization 22

Rh Isoimmunization: it is haemolytic disease of fetusRh Isoimmunization: it is haemolytic disease of fetusand/or neonate due to Rh Ag-Ab reaction.and/or neonate due to Rh Ag-Ab reaction.Rh antigen was discovered on rhesus monkeyRh antigen was discovered on rhesus monkeyRBCs (hence the name)RBCs (hence the name)People having Rh antigen on their RBC are namedPeople having Rh antigen on their RBC are namedRh+ve and people lacking it are named Rh ve.Rh+ve and people lacking it are named Rh ve.RH factor is lipoprotein present as component of RH factor is lipoprotein present as component of RBCs cell wall.RBCs cell wall.It is coded in 3 pairs of genes Cc,Dd,Ee ( D- isIt is coded in 3 pairs of genes Cc,Dd,Ee ( D- is

the most important because the D is dominant.the most important because the D is dominant.


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RH vemother

dd

dd dd

Rh vefather

(homozygote)dd

dd dd

All offspring Rh -veAll offspring Rh -ve


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Rh vemother

dd

dd Dd

Rh +vefather

(heterozygote)Dd

dd Dd

Half offspring Rh +veHalf offspring Rh +ve


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Rh +vr father (homozygote)

DD

Dd Dd

All offspring Rh + veAll offspring Rh + ve

Rh ve mother dd

Dd Dd


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D incompatibility developed when D veD incompatibility developed when D ve

women is pregnant with D +ve fetuswomen is pregnant with D +ve fetuswhich occure in up to 9-10 % of which occure in up to 9-10 % of pregnancy depending on the race.pregnancy depending on the race.


7/37Samira Alsagher Samira Alsagher RH IsoimmunizationRH Isoimmunization 77

PopulationPopulation incidenceincidence

chinese and japanesechinese and japanese 1%1%

North american indian and inuitNorth american indian and inuit 1-2%1-2%

indo- eurasianindo- eurasian 2%2%

african americanafrican american 4-8%4-8%

CaucasianCaucasian 15-16%15-16%BasqueBasque 30-35%30-35%


8/37Samira Alsagher Samira Alsagher RH IsoimmunizationRH Isoimmunization 88

If no preventing measures are taking0.7- 1.8% of these women will becomeisoimmunized antenatally8-17% will become isoimmunized at delivery3-6% after spontaneous or elective abortion2-5% after amniocentesis

In subsequent D +ve pregnancy of isoimmunized women 25-30% of their offspringhave some degree of hemolytic andhyperbilirubinemia20%-25% will have hydropic fetalis and often dieeither in utero or in the neonatal perio


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PathogenesisPathogenesis

Blood production in the fetus begins at about 3Blood production in the fetus begins at about 3weeks' and Rh antigen has been identifed in theweeks' and Rh antigen has been identifed in the

red cell membrane bas early as 38 days after red cell membrane bas early as 38 days after conception.conception.1- Exposure to the antigen:1- Exposure to the antigen:Minute amount of fetal RBCs pass to the maternalMinute amount of fetal RBCs pass to the maternal

circulation with placental separation,this occurecirculation with placental separation,this occureduring pregnancy and labour( the most importantduring pregnancy and labour( the most importantrisk).risk).


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During pregnancy due toDuring pregnancy due to

AbortionAbortionAntipartium haemorrageAntipartium haemorrageInvasive prenatal testing :Invasive prenatal testing :

chorion villus samplingchorion villus samplingamniocentisisamniocentisiscordocetisiscordocetisis

Accidental haemorrhageAccidental haemorrhage


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2- Antibody formation:2- Antibody formation:Foetal RBCs carrying RH antigen will induce anFoetal RBCs carrying RH antigen will induce animmunological response with formation of antibodies againstimmunological response with formation of antibodies against

RH antigen in maternal circulation.RH antigen in maternal circulation.1ry immune response IGM. Large and can,t cross the1ry immune response IGM. Large and can,t cross theplacenta. this is why the first baby not affected.placenta. this is why the first baby not affected.2ry immune response IgG. small and can cross the placental2ry immune response IgG. small and can cross the placentalbarrier.barrier.

This is why first baby affected when RH ve mother This is why first baby affected when RH ve mother previously received RH +ve B.Tpreviously received RH +ve B.TPrevious fetomaternal haemorrhage like ectopic / abortionPrevious fetomaternal haemorrhage like ectopic / abortion


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3- Foetal affection3- Foetal affectionWhen maternal antibodies cross the placenta,they becomeWhen maternal antibodies cross the placenta,they becomeattached to foetal RBCS and shorten their live span.the netattached to foetal RBCS and shorten their live span.the netresult is haemolysis which lead to these clinical pictures:result is haemolysis which lead to these clinical pictures:

1-Congenital haemolytic anaemia (mild form).1-Congenital haemolytic anaemia (mild form).2- Icterus gravidarum neonatorum( serious form)2- Icterus gravidarum neonatorum( serious form)3- Hydrops fetalis(most severe)3- Hydrops fetalis(most severe)

-severe intrauterine anaemia causing hyperdynamic circulation,-severe intrauterine anaemia causing hyperdynamic circulation,heart failure and subsequent generalized edema.heart failure and subsequent generalized edema.

Marked hematopoiesis in th liver causes hepatocellular Marked hematopoiesis in th liver causes hepatocellular damage . Portal hypertension,ascites,enlargement and edemadamage . Portal hypertension,ascites,enlargement and edemaof placental villi.of placental villi.polyhydramniospolyhydramnios


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Any women in their 1Any women in their 1 stst pregnancy should havepregnancy should haveblood group and RH type.If she is RH ve andblood group and RH type.If she is RH ve andher husband are RH +ve,so the risk exists.her husband are RH +ve,so the risk exists.

To confirm maternal immunizationTo confirm maternal immunizationIndirect coombs test- at 1Indirect coombs test- at 1 stst antenatal care visit.antenatal care visit.If ve Repeat at 28 wk, then monthlyIf ve Repeat at 28 wk, then monthlywith prophylactic treatmentwith prophylactic treatment

Screening and managementScreening and management


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Anti D antibody injection at 28 wk and 34Anti D antibody injection at 28 wk and 34wk gestation.wk gestation.Within 48-72 hour after delivery if the babyWithin 48-72 hour after delivery if the babyRH +veRH +veDose : 300 mcg of RhiG intramuscular .isDose : 300 mcg of RhiG intramuscular .isenough for feto-maternal haemorrhageenough for feto-maternal haemorrhageequal or less than 30 mlequal or less than 30 ml


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Failure of prophylaxis

1. Dose too small

2. Dose too late >72 hours

3. Patient already immunized but antibody titer too low for laboratory recognition

4. Defective immune globulin given


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If indirect coombs test + veIf indirect coombs test + ve

Identification of antibodies and its titre.Identification of antibodies and its titre.If the albumin titre below the critical level(1:16)If the albumin titre below the critical level(1:16)or anti D concentration < or = 15 IU/ml. repeator anti D concentration < or = 15 IU/ml. repeatthe titre every 2-3 weeks until the critical level isthe titre every 2-3 weeks until the critical level isreached.reached.If the titre remain below the critica level DeliveryIf the titre remain below the critica level Deliveryat 38 wk gestation.in the presence of neonatalat 38 wk gestation.in the presence of neonatalteam.team.

If the albumin titre reach the critical level or If the albumin titre reach the critical level or above (1:16) proceed to confirm foetalabove (1:16) proceed to confirm foetalhaemolysis and active management.haemolysis and active management.


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Active management duringActive management duringpregnancypregnancy

1- U/S.SAVE ACCURATE NON INVASIVE1- U/S.SAVE ACCURATE NON INVASIVEWhen the fetus is moderatly to severly affectedWhen the fetus is moderatly to severly affectedsigns of hydrops fetalis(Buddha attitude)signs of hydrops fetalis(Buddha attitude)

polyhydraminspolyhydraminscardiomegalycardiomegalyPericardial effusionPericardial effusionAscitis and oedemaAscitis and oedemaincrese placental thicknessincrese placental thickness

Are readily detectable by u/sAre readily detectable by u/s


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2- Middle cerebral artery (MCA) peak2- Middle cerebral artery (MCA) peaksystolic velocity.systolic velocity.

The major advantage of MCA doppler study isThe major advantage of MCA doppler study isthat non invasive means of detecting fetalthat non invasive means of detecting fetalanemia and indecated when transfusion isanemia and indecated when transfusion is

necessarlynecessarlySensitivity 100% for prediction of moderate toSensitivity 100% for prediction of moderate tosevere fetal anaemia either in the presence or severe fetal anaemia either in the presence or absence of hydrops fetalis.absence of hydrops fetalis.False +ve 12%False +ve 12%


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MCA-PSV


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3- Cordiocentesis3- CordiocentesisIndications:Indications:

- when fetal haemolysis is expected befor 20 weeks- when fetal haemolysis is expected befor 20 weeks-when intrauterine transfusion is decided.-when intrauterine transfusion is decided.

Procedure:Procedure:Percutaneous umblical blood sampling( PUBS)Percutaneous umblical blood sampling( PUBS)

-sampling of blood from the umblical cord using-sampling of blood from the umblical cord usingultrasound - directed needle aspiration.ultrasound - directed needle aspiration.

It is done to testIt is done to test

1- ABO and RH typing1- ABO and RH typing2- haemoglobin and haematocrite values2- haemoglobin and haematocrite values3- bilirubin level3- bilirubin level4- direct coombs test4- direct coombs test


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4- amniocentesis4- amniocentesis

Done after 20 wk for AF DNA RH typing andDone after 20 wk for AF DNA RH typing and F delta.O.D.450F delta.O.D.450

Aspirated AF is tested for bilirubin concentrationAspirated AF is tested for bilirubin concentration

by spetrophotometry at wave length 450 nm.by spetrophotometry at wave length 450 nm.The optical density reading (delta.O.D.450) isThe optical density reading (delta.O.D.450) isdirectly related to the severity of haemolysis.directly related to the severity of haemolysis.When plotted against GA on LileysWhen plotted against GA on Lileys

curve.degree of the haemolysis are obtained.curve.degree of the haemolysis are obtained.


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The curve is divided into 3 prognostic zonesThe curve is divided into 3 p rognostic zones ::

Zone I (Lowest zone)Zone I ( Lowest zone)The fetus usually unaffectedThe fetus usually unaffectedRepeated every 4 wksRepeated every 4 wksContinue maternal antibody titre to detect rise in titre.Continue maternal antibody titre to detect rise in titre.Delivery at term with prophylactic treatment.Delivery at term with prophylactic treatment.


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Zone II (MID ZONE)Zone II (MI D ZONE)

The fetus moderatelly affectedThe fetus moderatelly affectedRepeat 1-2 WKsRepeat 1-2 WKs

Termination of the pregnancy is advisedTermination of the pregnancy is advisedonce the L/S ratio is mature.once the L/S ratio is mature.


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ZONE III ( highest zone)ZONE III ( highest zone)

Fetus is severly affectedFetus is severly affectedOptions include:Options include:

Intra-uterine BT (CORDOCENTESIS)Intra-uterine BT (CORDOCENTESIS)OROR

Immediate termination of the pregnancy,Immediate termination of the pregnancy,

and arrange for extra uterine exchangeand arrange for extra uterine exchangetransfusiontransfusion


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Zone I

Zone II

Zone III

Lileyscurve


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Intra uterine transfusionIntra uterine transfusion

Indications:Indications:- Delta O D 450 within lileys zone III.- Delta O D 450 within lileys zone III.- to treat the fetus 10 WKs earlier than in previous- to treat the fetus 10 WKs earlier than in previouspregnancy loss or hydrops.pregnancy loss or hydrops.

Character:Character:Transfusion with fresh bloodTransfusion with fresh bloodHt% > 75%Ht% > 75%

Cytomegalo virus ve.Cytomegalo virus ve.RH ve blood that is compatible with mother RH ve blood that is compatible with mother serum.serum.


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Fetal Hemoglobin (g/dl) by Gestational Age

Weeks

Gestation 18 12.3 10.6 8.9 6.9 5.820 12.9 11.1 9.3 7.2 6.122 13.4 11.6 9.7 7.5 6.4

24 13.9 12.0 10.1 7.8 6.626 14.3 12.3 10.3 8.0 6.828 14.6 12.6 10.6 8.2 6.930 14.8 12.8 10.8 8.3 7.132 15.2 13.1 10.9 8.5 7.2

34 15.4 13.3 11.2 8.6 7.336 15.6 13.5 11.3 8.7 7.438 15.8 13.6 11.4 8.9 7.5 40 16.0 13.8 11.6 9.0 7.6

mild moderate severeanemia anemia anemia

Multiples of the Median

1.16 1.00 0.84 0.65 0.55

HgbValues


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Mode of deliveryMode of deliveryVaginal delivery versus clsVaginal delivery versus cls

Management during labour Management during labour No cord milking,cut the cord about 30 cm away from the fetus.No cord milking,cut the cord about 30 cm away from the fetus.Cord blood examination for Cord blood examination for ABOABORH typingRH typingHBHBHaematocriteHaematocriteSerum bilirubinSerum bilirubinDirect coomb,s test.Direct coomb,s test.

Exchange transfusion If HB < 100 g/lExchange transfusion If HB < 100 g/l


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Management during C/SManagement during C/S

Use abdominal packs in the sides of the uterus before opening the lower segment to prevent spilled blood from

the placenta to inter the peritonealcavity.Let the placenta to be deliveredspontaneous using control cordtraction without squeezing the uterus.


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Other red cells antibodiesOther red cells antibodies

Anti kellAnti kellAnti cAnti c

Anti fy and fybAnti fy and fybAnti Ra and RbAnti Ra and Rb


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Anti kellAnti kell

90% of population are kell ve90% of population are kell veMost kell antibodies developed because of Most kell antibodies developed because of icompatible transfusion.icompatible transfusion.

Management of anti kell in pregnancy:Management of anti kell in pregnancy:Antibodies screen:if antikell isAntibodies screen:if antikell ispresent,genotype the father:if he is kell ve present,genotype the father:if he is kell ve No further investigationNo further investigationIf the father is kell +ve>>> Do antibodiesIf the father is kell +ve>>> Do antibodiestitre( if the titre> 1:64 amniocentesis or titre( if the titre> 1:64 amniocentesis or cordiocentesis is indacated.cordiocentesis is indacated.


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ABO IncompatibilityABO Incompatibility

The mother is group O and the fetus A or BThe mother is group O and the fetus A or Bblood group.blood group.Occure in 15% of all pregnancyOccure in 15% of all pregnancy

Antibodies IgM, sometimes IgG.Antibodies IgM, sometimes IgG.Its occure in 1Its occure in 1 stst pregnancy with no tendency topregnancy with no tendency toincrease in severity with subsequent pregnancy.increase in severity with subsequent pregnancy.

1 in 30 fetus = mild jaundice1 in 30 fetus = mild jaundice1 in 50 fetus = mild anemia1 in 50 fetus = mild anemia1 in 3000 fetus require exchange transfusion.1 in 3000 fetus require exchange transfusion.


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Liley CurveOD450

Timeline: hemolytic disease of the newborn

1 9 4 0

1 9 5

0

1 9 6

0

1 9 7

0

1 9 8

0

1 9 9

0

2 0 0

0

Discovery of Rh factor Landsteiner & Weiner

PostnatalExchangeTransfusions

Prevention-RhD Ig

QueenanModificationOD450

Maternal

serumantibody titers

MCA

Doppler Noninvasive

detection

HDN

described

Fetal RhD

MaternalPlasma

Amniotic fluid

bilirubinmeasurement


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Rh Isoimmunization dr samira