Rh Disease

Rh DiseaseRh DiseaseSokołowska MałgorzataSokołowska Małgorzata

PAm SzczecinPAm Szczecin

Isoimmunization:Isoimmunization:

Isoimmunization: refers to the Isoimmunization: refers to the development of antibodies to red blood development of antibodies to red blood cell antigens folowing exposure to such cell antigens folowing exposure to such antigens from another individual .antigens from another individual .

In the pregnancy the ,,other individual’’ is In the pregnancy the ,,other individual’’ is the foetus, 50%of whose genetic makeup the foetus, 50%of whose genetic makeup is derived from the father is derived from the father


If the mother is exposed to fetal red cells If the mother is exposed to fetal red cells during pregnancy or et delivery, she may during pregnancy or et delivery, she may develop antibodies to fetal cell develop antibodies to fetal cell antigens.antigens.


Later in that pregnancy or more Later in that pregnancy or more commonly with the subsequent commonly with the subsequent pregnancy , the antibodes can cross the pregnancy , the antibodes can cross the placenta and hemolyze fetal red cells, placenta and hemolyze fetal red cells, leading to fetal anemia.leading to fetal anemia.


Isoimmunization: can involve many of the Isoimmunization: can involve many of the several hundred blood group system.several hundred blood group system.

This disorder is frequently reffered to as Rh This disorder is frequently reffered to as Rh isoimmunization, becouse the Rhesus (Rh) isoimmunization, becouse the Rhesus (Rh) system is most frequently involved system is most frequently involved

Isoimmunization does develop with many other Isoimmunization does develop with many other blood systems such as blood systems such as Kell,Duffy,Kidd,Lewis,Lutheran,Public antigens Kell,Duffy,Kidd,Lewis,Lutheran,Public antigens & Private antigens, Diego, and others& Private antigens, Diego, and others

The Basics Of BloodThe Basics Of Blood

Appearance by 40 days of I.U. Life- Appearance by 40 days of I.U. Life- unchanged till death.unchanged till death.

Controlled by genes at unknown No. of Controlled by genes at unknown No. of chromosomal loci.chromosomal loci.

Also present in tissues & tissue fluids.Also present in tissues & tissue fluids. Blood group system: A group of antigens Blood group system: A group of antigens

controlled by a locus having a variable no of controlled by a locus having a variable no of allele genes.allele genes.

Antigens: -

The Basics Of BloodThe Basics Of Blood

> 15 blood group systems are recognised : > 15 blood group systems are recognised : ABO, Rh,ABO, Rh, Kell, Duffy, MN, P, Lewis, Lutheran, Kell, Duffy, MN, P, Lewis, Lutheran,

Xg, Li, Yt, Dombrock, Colton, Public antigens & Xg, Li, Yt, Dombrock, Colton, Public antigens & Private antigens.Private antigens.

Blood type- means individual antigen phenotype Blood type- means individual antigen phenotype which is the serological expression of the inherited which is the serological expression of the inherited genesgenes

Most of these blood group antigens have been Most of these blood group antigens have been found to be associated with hemolytic disease.found to be associated with hemolytic disease.

However– ABO & Rh account for 98%However– ABO & Rh account for 98%

Antigens: -

CDE (Rhesus) Blood CDE (Rhesus) Blood group systemgroup system

This system includes five red cell protein This system includes five red cell protein or antigens : c, C,D,e,E.or antigens : c, C,D,e,E.

No ,,d ,, antigen has been identified ,and No ,,d ,, antigen has been identified ,and Rh – or D – negativity is defined as the Rh – or D – negativity is defined as the absence of the D - antigen.absence of the D - antigen.

The CDE antigens are of considerable The CDE antigens are of considerable clinical importance because most D-clinical importance because most D-negative individuals become immunized negative individuals become immunized after a single exposureafter a single exposure


The CDE genes are located on the short arm The CDE genes are located on the short arm of chromosome 1 and are inherited as a group, of chromosome 1 and are inherited as a group, independent of other blood group genes.independent of other blood group genes.

Like many genes , their incidence varies Like many genes , their incidence varies according to racial origin (Native according to racial origin (Native Americans ,Inuits, ,Chineseand other Asiatic Americans ,Inuits, ,Chineseand other Asiatic peoples are almost all D-positive; Basques peoples are almost all D-positive; Basques show the highest incidence of D-negativityshow the highest incidence of D-negativity


The C,c,E,and e-antigens have lower The C,c,E,and e-antigens have lower immunogenicity than D-antigen, but they immunogenicity than D-antigen, but they can cause erythroblastosis fetaliscan cause erythroblastosis fetalis

All pregnant women should be tested All pregnant women should be tested routinely for the presence or absence of routinely for the presence or absence of

D –antigen on their erythrocytes and for D –antigen on their erythrocytes and for irregular antibodes in their serum.irregular antibodes in their serum.

Rhesus incompatibilityRhesus incompatibility

The rhesus system is more commonly The rhesus system is more commonly associated with severe hemolytic disease. Of associated with severe hemolytic disease. Of all the antibodies (C,D,and E), the D antigen is all the antibodies (C,D,and E), the D antigen is associated most commonly with severe associated most commonly with severe hemolytic fetal disease, however, this can only hemolytic fetal disease, however, this can only occur if the mother is D-rhesus –negative and occur if the mother is D-rhesus –negative and the baby is D rhesus –positive. Both anti- C the baby is D rhesus –positive. Both anti- C and anti –E antibodies may also be associated and anti –E antibodies may also be associated with hemolytic disease requiring intrauterine with hemolytic disease requiring intrauterine fetal blood transfusion,but are much less fetal blood transfusion,but are much less commonly implicated. commonly implicated.

Why Does Rh Status Matter?Why Does Rh Status Matter?Fetal RBC cross to maternal circulation

Maternal immune system recognizes foreign antigens if fetus Rh + and mother Rh –

Antibodies are formed against fetal antigens

Subsequent pregnancy with Rh+ fetus, immune system activated

and large amounts of Ab formed

IgG Ab cross placenta & attack fetal RBC

Fetal anemia, hydrops, etc

Pathophysiology cont…Pathophysiology cont…

Initial IgM followed by IgG in 2 wks- 6 mthsInitial IgM followed by IgG in 2 wks- 6 mths Memory B lymphocytes activate immune Memory B lymphocytes activate immune

response in subsequent pregnancyresponse in subsequent pregnancy IgG Ab cross placenta and attach to fetal IgG Ab cross placenta and attach to fetal

RBC’sRBC’s Cells then sequestered by macrophages in Cells then sequestered by macrophages in

fetal spleen where they get hemolyzedfetal spleen where they get hemolyzed Fetal anemiaFetal anemia

General ScreeningGeneral Screening

ABO & Rh Ab @ 1ABO & Rh Ab @ 1stst prenatal visit prenatal visit @ 28 weeks@ 28 weeks PostpartumPostpartum Antepartum bleeding and before giving Antepartum bleeding and before giving

any immune globulinany immune globulin

Neonatal bloods ABO, Rh, Neonatal bloods ABO, Rh, DATDAT

Gold Standard TestGold Standard Test

Indirect Coombs:Indirect Coombs:-mix Rh(D)+ cells with maternal serum-mix Rh(D)+ cells with maternal serum-anti-Rh(D) Ab will adhere-anti-Rh(D) Ab will adhere-RBC’s then washed & suspended in Coombs -RBC’s then washed & suspended in Coombs

serum (antihuman globulin)serum (antihuman globulin)-RBC’s coated with Ab will be agglutinated-RBC’s coated with Ab will be agglutinated

Direct Coombs:Direct Coombs:-mix infant’s RBC’s with Coombs serum-mix infant’s RBC’s with Coombs serum-maternal Ab present if cells agglutinate-maternal Ab present if cells agglutinate

+ Rh(D) Antibody Screen+ Rh(D) Antibody Screen

Serial antibody titres q2-4 weeks Serial antibody titres q2-4 weeks If titre If titre ≥≥1:1:3232 - amniocentesis or MCA - amniocentesis or MCA

dopplers and more frequent titres (q1-2 dopplers and more frequent titres (q1-2 wk)wk)

Critical titre – sigCritical titre – signn risk hydrops risk hydrops U/S for dating and monitoring U/S for dating and monitoring Correct dates needed for determining Correct dates needed for determining

appropriate bili levels (delta OD450)appropriate bili levels (delta OD450)

U/S ParametersU/S Parameters

Non Reliable Parameters:Non Reliable Parameters: Placental thicknessPlacental thickness Umbilical vein diameterUmbilical vein diameter Hepatic sizeHepatic size Splenic sizeSplenic size PolyhydramniosPolyhydramnios Visualization of walls of fetal bowel from small Visualization of walls of fetal bowel from small

amounts intraabdominal fluid may be 1amounts intraabdominal fluid may be 1stst sign of sign of impending hydropsimpending hydrops

U/S reliable for hydrops (ascites, pleural U/S reliable for hydrops (ascites, pleural effusions, skin edema) – Hgb < 70effusions, skin edema) – Hgb < 70

AmniocentesisAmniocentesis

Critical titre/previous affected infantCritical titre/previous affected infant Avoid transplacental needle passageAvoid transplacental needle passage Bilirubin correlates with fetal hemolysisBilirubin correlates with fetal hemolysis ∆ ∆ optical density of amniotic fluid @ optical density of amniotic fluid @

450nm on spectral absorption curve450nm on spectral absorption curve Data plotted on Liley curveData plotted on Liley curve

Liley CurveLiley Curve

Zone I – fetus very low risk of severe fetal Zone I – fetus very low risk of severe fetal anemiaanemia

Zone II – mild to moderate fetal hemolysisZone II – mild to moderate fetal hemolysis Zone III – severe fetal anemia with high Zone III – severe fetal anemia with high

probability of fetal death 7-10 daysprobability of fetal death 7-10 days

Liley good after 27 weeksLiley good after 27 weeks 98% sensitive for detecting anemia in upper 98% sensitive for detecting anemia in upper

zone 2/ zone 3zone 2/ zone 3

Middle Cerebral Artery Middle Cerebral Artery DopplersDopplers

Measures peak velocity of blood flowMeasures peak velocity of blood flow Anemic fetus preserves O2 delivery to Anemic fetus preserves O2 delivery to

brain by increasing flowbrain by increasing flow Sensitivity of detecting severe anemia Sensitivity of detecting severe anemia

when MCA >1.5 MoM approaches 100%when MCA >1.5 MoM approaches 100% Not reliable > 35 weeks GANot reliable > 35 weeks GA

Fetus at RiskFetus at Risk

Fetal anemia diagnosed by: Fetal anemia diagnosed by: amniocentesisamniocentesis cordocentesiscordocentesis ultrasoundultrasound

hydropshydrops

middle cerebral artery Dopplermiddle cerebral artery Doppler

Treatment:Treatment: intravascular fetal transfusionintravascular fetal transfusion preterm birthpreterm birth

Pathogenesis Of Rh Iso-Pathogenesis Of Rh Iso-immunisationimmunisation

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

?

Pathology Of Iso-Pathology Of Iso-immunisationimmunisationHAEMOLYSIS IN UTEROAFTER 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

The aetiology of rhesus The aetiology of rhesus disease:disease:

Rhesus disease does not affect a first pregnancyRhesus disease does not affect a first pregnancy It requires that mother has had exposure to D rhesus - positive It requires that mother has had exposure to D rhesus - positive

fetal cells in previous pregnancy and then developed an immune fetal cells in previous pregnancy and then developed an immune response that has lain dormant until a following pregnancy of a D response that has lain dormant until a following pregnancy of a D rhesus-positive baby.rhesus-positive baby.

In the subsequent pregnancy , when maternal resensitization In the subsequent pregnancy , when maternal resensitization occurs ( rhesus- positive red cells pass from the baby to the occurs ( rhesus- positive red cells pass from the baby to the maternal circulation),IgG antibodies cross from the mother to the maternal circulation),IgG antibodies cross from the mother to the fetal circulation.fetal circulation.

If these antibodies are present in sufficient quantities fetal If these antibodies are present in sufficient quantities fetal hemolysis may occur leading to such severe anaemia that the hemolysis may occur leading to such severe anaemia that the fetus may die unless a transfusion is performed.fetus may die unless a transfusion is performed.

Causes of Rh Causes of Rh isoimmunizationisoimmunization

Fetus must have Rh-positive Fetus must have Rh-positive erythrocytes, mother must have Rh erythrocytes, mother must have Rh negativenegative

Sufficient number of erythrocytes Sufficient number of erythrocytes must gain access to maternal must gain access to maternal circulationcirculation

Mother must have immunogenic Mother must have immunogenic capacity to produce antibodycapacity to produce antibody

Fetomaternal Fetomaternal hemohemorrrhagerhage

Isoimmunization seems to be dose relatedIsoimmunization seems to be dose related After transfer of .1 ml, 3% will be After transfer of .1 ml, 3% will be

isoimmunizedisoimmunized 16% will be isoimmunized after first 16% will be isoimmunized after first

pregnancy if untreatedpregnancy if untreated Without treatment eventually 50% wilWithout treatment eventually 50% willl

become sensitizedbecome sensitized Can occur during pregnancy but rarely Can occur during pregnancy but rarely

before 3rd trimesterbefore 3rd trimester

Fetomaternal hemoFetomaternal hemorrrhagerhage

Can occur following abortion and Can occur following abortion and tubal pregnancytubal pregnancy

More common following late More common following late terminatiionterminatiion

Amniocentesis associated with Amniocentesis associated with significant hemmorage and significant hemmorage and isoimmunizationisoimmunization

Pathology Of Iso-Pathology Of Iso-immunisationimmunisation

HAEMOLYSIS IN UTEROAFTER 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

Management of Management of Unsensitised PregnancyUnsensitised Pregnancy

In Abortion, Ectopic, Amniocentesis, In Abortion, Ectopic, Amniocentesis, Chorionic villus Chorionic villus samplingsampling Pregnancy < 12 weeks- 50mcg Anti DPregnancy < 12 weeks- 50mcg Anti D Pregnancy >12 weeks- Pregnancy >12 weeks- 150 150 mcg Anti Dmcg Anti D

Normal labour , cordocentesis : - 150 Normal labour , cordocentesis : - 150 mcg Anti Dmcg Anti D S. C. , abnormal labour with mannual extraction of S. C. , abnormal labour with mannual extraction of

placenta, IUD : 300ug Anti D placenta, IUD : 300ug Anti D until 72 hours in one dose im. ( twins double doses)until 72 hours in one dose im. ( twins double doses) - - At birth- cord blood for ABO & Rh typingAt birth- cord blood for ABO & Rh typing Baby Rh negative – Be happyBaby Rh negative – Be happy

Management of Management of Sensitized PregnancySensitized Pregnancy

Careful planning during antepartum, Careful planning during antepartum, intrapartum & neonatal periodintrapartum & neonatal period

Father’s blood type & Rh antigen statusFather’s blood type & Rh antigen status Knowledge of maternal antibody titer to Knowledge of maternal antibody titer to

the specific antigenthe specific antigen Intrauterine foetal monitoring with Intrauterine foetal monitoring with

repeated ultrasound examination, repeated ultrasound examination, cordocetesis / amniocentesiscordocetesis / amniocentesis

Features of fetal Features of fetal anaemia:anaemia:

Note: clinical and ultrasound features of fetal anaemia do not Note: clinical and ultrasound features of fetal anaemia do not usually become evident unless fetal haemoglobin is >5g/dL less usually become evident unless fetal haemoglobin is >5g/dL less than the mean for gestation. Usually features are not obvious than the mean for gestation. Usually features are not obvious unless the fetal haemoglobin is < 6 g/dLunless the fetal haemoglobin is < 6 g/dL

1)1) PolyhydramionsPolyhydramions2)2) Enlarged fetal heartEnlarged fetal heart3)3) Ascites and pericardial effusionsAscites and pericardial effusions4)4) Hyperdynamic fetal circulation (can be detected by Doppler Hyperdynamic fetal circulation (can be detected by Doppler

ultrasound measuring increased velocities in the middle ultrasound measuring increased velocities in the middle cerebral artery or aorta )cerebral artery or aorta )

5)5) Reducted fetalmovementsReducted fetalmovements6)6) Abnormal CTG with reduced variability,eventually Abnormal CTG with reduced variability,eventually

a ,,sinusoidal,, tracea ,,sinusoidal,, trace

Rhesus incompatibility:Rhesus incompatibility:

The condition of the fetus is determined The condition of the fetus is determined by the amount of maternal antibody by the amount of maternal antibody transferred across the placena and the transferred across the placena and the ability of the fetus to replace the red ability of the fetus to replace the red blood cells that have been destroyed.blood cells that have been destroyed.

Rhesus incompatibility:Rhesus incompatibility:

In subsequent pregnancies , with Rh + fetus, the In subsequent pregnancies , with Rh + fetus, the proces of antibody production and transfer may be proces of antibody production and transfer may be accelerated, leading to the development of more accelerated, leading to the development of more significant anaemia. significant anaemia.

In such cases, the fetal liver can manufacture In such cases, the fetal liver can manufacture additional red cells. However, this activity reduces the additional red cells. However, this activity reduces the amount of protein manufactured by the fetal liver. In amount of protein manufactured by the fetal liver. In turn, the reduced protein production can lead to a turn, the reduced protein production can lead to a decreased oncotic pressure within the fetal vascular decreased oncotic pressure within the fetal vascular system, resulting in fetal ascites and subcutaneous system, resulting in fetal ascites and subcutaneous edema. At the same time , the severe fetal anaemia edema. At the same time , the severe fetal anaemia can lead to high output cardiac failure. This can lead to high output cardiac failure. This combination of findings is referred to as HYDROPS combination of findings is referred to as HYDROPS FETALIS.FETALIS.

Risk of Rh sensitization:Risk of Rh sensitization: Event Incidence%Event Incidence% Early pregnancy loss 3-5Early pregnancy loss 3-5 Elective abortion 6-20Elective abortion 6-20 Ectopic pregnancy 5-8Ectopic pregnancy 5-8 Amniocentesis 4-11Amniocentesis 4-11 Chorionic villous sampling 8-15Chorionic villous sampling 8-15 Cordocentesis 30-50Cordocentesis 30-50 Antepartum trauma variableAntepartum trauma variable Placental abruption lowPlacental abruption low Fetal demise variableFetal demise variable Manual placental extraction variableManual placental extraction variable External version variableExternal version variable

Immune hydropsImmune hydrops

The abnormal collection of fluid in more The abnormal collection of fluid in more than one area of the fetal body, such as than one area of the fetal body, such as ascites and pleural effusion, is termed ascites and pleural effusion, is termed hydrops.hydrops.

Its causes usually are categorized as Its causes usually are categorized as immune – such as isoimmunization- and immune – such as isoimmunization- and nonimmune.nonimmune.


In immune hydrpos , excessive and In immune hydrpos , excessive and prolonged hemolysis causes anaemia , prolonged hemolysis causes anaemia , which stimulates marked erythroid which stimulates marked erythroid hyperplasia of the bone marrow as well hyperplasia of the bone marrow as well as extramedullary hematopoesis in the as extramedullary hematopoesis in the spleen and liver with eventual hepatic spleen and liver with eventual hepatic dysfunction.dysfunction.


There may be cardiac enlargement and There may be cardiac enlargement and pulmonary hemorrhage.pulmonary hemorrhage.

Fluid collects in the fetal thorax, Fluid collects in the fetal thorax, abdominal cavity, or skin. The placenta is abdominal cavity, or skin. The placenta is markedly edematous, enlarged, and markedly edematous, enlarged, and boggy, with large , prominent cotyledons boggy, with large , prominent cotyledons and edematous villi.and edematous villi.


Hydrothorax may be so severe as to Hydrothorax may be so severe as to restrict lung development, which causes restrict lung development, which causes pulmonary compromise after birth.pulmonary compromise after birth.

Ascites, hepatomegaly, and Ascites, hepatomegaly, and splenomegaly may lead to severe splenomegaly may lead to severe dystocia.dystocia.

HYDROPIC CHANGES ARE EASILY HYDROPIC CHANGES ARE EASILY SEEN BY SONOGRAPHY!!!!SEEN BY SONOGRAPHY!!!!

Fetuses with hydrops may die in utero from Fetuses with hydrops may die in utero from profound anaemia and circulatory failure.profound anaemia and circulatory failure.

One sign of severe anaemia and impending One sign of severe anaemia and impending death is the sinusoidal fetal heart rate pattern.death is the sinusoidal fetal heart rate pattern.

Hydropic changes in the placenta, leading to Hydropic changes in the placenta, leading to placentomegaly, can cause preeclampsia.placentomegaly, can cause preeclampsia.

Hyperbilirubinemia:Hyperbilirubinemia:

Less severely affected infants may Less severely affected infants may appear well at birth, only to become appear well at birth, only to become jaundiced within a few hours.jaundiced within a few hours.

Marked hyperbilirubinemia, if untreated , Marked hyperbilirubinemia, if untreated , can cause kernicterus, a from of central can cause kernicterus, a from of central nervous system damage that specifically nervous system damage that specifically affects the basal ganglia and can lead to affects the basal ganglia and can lead to cerebral palsy.cerebral palsy.

Mortality:Mortality:

Perinatal deaths from hemolytic disease Perinatal deaths from hemolytic disease caused by D-isoimmunization have decreased caused by D-isoimmunization have decreased dramatically since adoption of the policy of dramatically since adoption of the policy of routine administration of D- immunoglobulin to routine administration of D- immunoglobulin to all D-negative women during or immediately all D-negative women during or immediately after pregnancy.after pregnancy.

Survival also has been increased by advances Survival also has been increased by advances in antenatal and neonatal therapy : the in antenatal and neonatal therapy : the seriously affected fetus can be identified and seriously affected fetus can be identified and treated by antenatal transfusion or delivered treated by antenatal transfusion or delivered preterm if necessary.preterm if necessary.

Identification of the Identification of the Isoimmunized PregnancyIsoimmunized Pregnancy

1)The first step is identifying the woman 1)The first step is identifying the woman at risk by performing a blood type and at risk by performing a blood type and antibody screen at first prenatal antibody screen at first prenatal appointment during every pregnancy. appointment during every pregnancy. Because the antibodies in maternal Because the antibodies in maternal serum are unbound, they are detected by serum are unbound, they are detected by the indirect Coombs test.the indirect Coombs test.


In the fetus or neonate, however, the In the fetus or neonate, however, the anti- red cell antibodies produced by the anti- red cell antibodies produced by the mother are absorbed to the D-positive mother are absorbed to the D-positive fetal erythrocytes, and thus are identified fetal erythrocytes, and thus are identified primarily by the direct Coombs test.primarily by the direct Coombs test.


If the maternal antibody screen reveals the If the maternal antibody screen reveals the presence of red cell antibodies, they should be presence of red cell antibodies, they should be identified and their subtype- either IgG or IgM- identified and their subtype- either IgG or IgM- determined.determined.

Only IgG antibodies are of concern because Only IgG antibodies are of concern because IgM antibodies cannot cross the placenta.IgM antibodies cannot cross the placenta.

If antibodies are IgG and are known to cause If antibodies are IgG and are known to cause fetal hemolytic anemia, the antibody titer fetal hemolytic anemia, the antibody titer sholud be quantified.sholud be quantified.

A titer above a critical level requires further A titer above a critical level requires further evaluation .evaluation .


The critical titer for anti-D antibodies is The critical titer for anti-D antibodies is usually 1:32 ; a titer equal to or higher usually 1:32 ; a titer equal to or higher than this indicates the possibility of than this indicates the possibility of severe hemolytic disease. severe hemolytic disease.


If this is not the first sensitized pregnancy , maternal If this is not the first sensitized pregnancy , maternal antibody titers may not be helpful because they may be antibody titers may not be helpful because they may be elevated simply as a result of the amnestic response. elevated simply as a result of the amnestic response.

In these cases fetal anemia can be predicted In these cases fetal anemia can be predicted noninvasively using middle cerebral artery Doppler – noninvasively using middle cerebral artery Doppler – the anemic fetus shunts blood preferentially to the the anemic fetus shunts blood preferentially to the brain to mantain adequate oxygenations.brain to mantain adequate oxygenations.

This response can be identified by measuring peak This response can be identified by measuring peak blood flow velocity in the MCA PSV blood flow velocity in the MCA PSV

If the antibody titer or MCA PSV (when > 1,5 MoM) If the antibody titer or MCA PSV (when > 1,5 MoM) flow indicate that the fetus is likely to be anemic then flow indicate that the fetus is likely to be anemic then further evaluation is appropriate – fetal cordocentesis further evaluation is appropriate – fetal cordocentesis and fetal transfusions .and fetal transfusions .


Currently , however, using molecular genetic Currently , however, using molecular genetic techniques , fetal D-antigen type can be techniques , fetal D-antigen type can be determined by testing fetal DNA obtained determined by testing fetal DNA obtained from blood sample of mother – real time PCR. .from blood sample of mother – real time PCR. .

This technique is invaluable , especially for This technique is invaluable , especially for pregnancies in which the father is a presumed pregnancies in which the father is a presumed heterozygote for the D-antigen ( 50% chance heterozygote for the D-antigen ( 50% chance of having positive infant , a50% chance of of having positive infant , a50% chance of having positive infant , 50% chance of having having positive infant , 50% chance of having D-negative infant – no treatment and dgn. D-negative infant – no treatment and dgn.

Management:Management:

Amniotic fluid assessment is of great value in Amniotic fluid assessment is of great value in managing the isoimmunized patient– the level managing the isoimmunized patient– the level of bilirubin in the amniotic fluid accurately of bilirubin in the amniotic fluid accurately reflects the condition of the fetus – the level of reflects the condition of the fetus – the level of bilirubin in the amniotic fluid is determined bilirubin in the amniotic fluid is determined using a spectrophotometer .using a spectrophotometer .

Normal amniotic fluid subjected to Normal amniotic fluid subjected to spectrofotometric analysis has a characteristic spectrofotometric analysis has a characteristic curve , based on optical density (OD); the curve , based on optical density (OD); the presence of bilirubin causes a characteristic presence of bilirubin causes a characteristic deviation in this curve , at 450 nm.deviation in this curve , at 450 nm.

Amniotic fluid is obtain from the patient Amniotic fluid is obtain from the patient by amniocentesis at periodic intervals by amniocentesis at periodic intervals between the twentieth and thirtieth weeks between the twentieth and thirtieth weeks of pregnancy .of pregnancy .

OD (optical density) values are than OD (optical density) values are than plotted on a curve , which allows plotted on a curve , which allows estimation of the degree of severity of the estimation of the degree of severity of the anaemia in the fetus.anaemia in the fetus.

Blood transfused to the Blood transfused to the fetus must be:fetus must be:

when the HGB is at least 3g% below the when the HGB is at least 3g% below the mean for normal fetuses of mean for normal fetuses of corresponding gestational agecorresponding gestational age

when fetal HCT is below 30% , which is 2 when fetal HCT is below 30% , which is 2 standard deviations below the mean at all standard deviations below the mean at all gestational agesgestational ages

Blood transfused to the Blood transfused to the fetus must be: fetus must be:

Blood may be given :Blood may be given :

a) intravasculary : PUBS: under ultrasound a) intravasculary : PUBS: under ultrasound quidance, the umbilical cord can be sampled quidance, the umbilical cord can be sampled directly ( per cutaneus umbilical blood directly ( per cutaneus umbilical blood sampling)sampling)

b) intravasculary : into heartb) intravasculary : into heart

c) intraperitoneally(when technical difficulty, or if c) intraperitoneally(when technical difficulty, or if the gestation less then 22 Hbd)the gestation less then 22 Hbd)


The most severely affected fetuses may The most severely affected fetuses may require repeat transfusions every 7-10 require repeat transfusions every 7-10 days; days;

After 34Hbd the risk of cordocentesis After 34Hbd the risk of cordocentesis ( fetal bradycardia, cord tamponade, ( fetal bradycardia, cord tamponade, haemorrhage, fetal death )outweigh the haemorrhage, fetal death )outweigh the risk of prematurity and delivery of the risk of prematurity and delivery of the baby is normally undertaken.baby is normally undertaken.


Transfusion of Rh (-) red blood cells Transfusion of Rh (-) red blood cells ( fetus is in significant jeopardy for ( fetus is in significant jeopardy for hydrops or fetal death), Kell(-)hydrops or fetal death), Kell(-)

concentraced ( Hb normally 22-24 g/dl)concentraced ( Hb normally 22-24 g/dl) cytomegalovirus-negativecytomegalovirus-negative irradiated ( to reduce the risk of graft irradiated ( to reduce the risk of graft

versus host disease)versus host disease) filteredfiltered

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Rh Disease

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