Alloimmune hemolytic disease of the fetus. Newborn: Rh Isoimmunization презентация

Содержание

The Antibodies Arise In The Mother As The Direct Result Of A Blood Group Incompatibility Between The Mother And Fetus. The mother become Isoimmunized. In The

Слайд 1Alloimmune Hemolytic Disease Of The Fetus / Newborn:
Rh Isoimmunization
Professor Hassan A

Nasrat
Department of Obstetrics and Gynecology
Faculty of Medicine
King Abdul-Aziz University

Слайд 2The Antibodies Arise In The Mother As The Direct Result Of

A Blood Group Incompatibility Between The Mother And Fetus.

The mother become Isoimmunized.


In The Fetus: Erythroblastosis Fetalis
In The Newborn: HDN.

Alloimmune Hemolytic Disease Of The Fetus / Newborn:

Definition:
A condition in which the Red Cells Of The Fetus Or Newborn Are Destroyed By Maternally Derived Alloantibodies

Слайд 3Antibodies That May Be Detected During Pregnancy:
Innocuous Antibodies:

Most

Of These Antibody Are IgM Therefore Cannot Cross The Placental Barrier

Antibodies Capable Of Causing Significant Hemolytic Transfusion Reactions:

IgG antibodies, Their Corresponding Antigens Are Not Well Developed At Birth E.g. Lu (b), Yt (a), And VEL —

Antibodies That Are Responsible For HDN :
Anti-c, Anti-d, Anti-e, And Anti-k (Kell)

Слайд 4ISO: is a prefix means similar, equal or uniform.

Isoimmunization: is the

process of immunizing a species with antigen derived from the same subject.

Слайд 5RhD D negativity primarily occurs among Caucasians; the average incidence is

15 percent in this group.


Examples of the blood group distribution in various populations are illustrated below:

   Basques — 30 to 35 percent    Finland — 10 to 12 percent    American blacks — 8 percent    Indo-Eurasians — 2 percent    Native Americans and Inuit Eskimos — 1 to 2 percent.

Local Studies (population) + 8%

Distribution of Rh negative Blood Group

Слайд 6 The RH Antigen – Biochemical and Genetic Aspects

Mechanism of

Development of Maternal Rh Isoimmunization

Natural History of Maternal isoimmunization /HD of the Newborn

Pathogenesis of Fetal Erythroblastosis Fetalis

Diagnosis of Rh isoimmunization

Слайд 7The RH Antigen – Biochemical and Genetic Aspects

Слайд 8The Rh Antigen- Biochemical Aspects:
The Rh Antigen Is A Complex

Lipoprotein. Distributed Throughout The Erythrocyte Membrane In A Nonrandom Fashion

It Can Not Be Seen By Routine Microscopy, But Can Be Identified By Specific Antisera

Function of the Rh antigen:

Its Precise Function Is Unknown.
Rh Null Erythrocytes Have Increased Osmotic Fragility And Abnormal Shapes.

Слайд 9The RH Antigen- Genetic Aspect
The Rh gene complex is located

on the distal end of the short arm of chromosome one.

A given Rh antigen complex is determined by a specific gene sequence inherited in a Mendelian fashion from the parents. one haploid from the mother and one from the father.

Three genetic loci, determine the Rh antigen (i.e. Rh blood group).

Each chromosome will be either D positive or D negative (there is no "d" antigen), C or c positive, and E or e positive.

Слайд 10Grades Of “Positively” Due To Variation In The Degree Genetic Expression

Of The D Antigen.

Incomplete Expression May Result In A Weakly Positive Patient e.g. Du Variant Of Weakly Rh Positive Patient (They May Even Be Determined As Rh Negative).

A Mother With Du Rh Blood Group (Although Genetically Positive) May Become Sensitized From A D-positive Fetus Or The Other Way Around May Take Place.

Genetic Expression (Rh Surface Protein Antigenicity):

Слайд 11Incomplete Expression Of The D Antigen Result In A Weakly Positive

Patient e.g. Du Variant Of Weakly Rh Positive Patient.

Genetic Expression (Rh Surface Protein Antigenicity):


Du Variant

Frank D Positive

Слайд 12Factors Affect The Expression Of The Rh Antigen
The Number Of

Specific Rh-antigen Sites:
- The Gene Dose,
- The Relative Position Of The Alleles,
- The Presence Or Absence Of Regulator Genes.

Interaction Of Other Components Of The Rh Blood Group. Erythrocytes Of Individuals Of Genotype Cde/cde Express Less D Antigen Than Do The Erythrocytes Of Individuals Of Genotype cDE/cde.


The Exposure Of The D Antigen On The Surface Of The Red Cell Membrane.

Слайд 13










D
c
E
e
C
d
eCd/EcD
Phenotype
Genotype
D positive
Antigenicity of the Rh surface protein:
genetic expression of the D

allele.
Number of specific Rh antigen sites.
Interaction of components of the Rh gene complex.
Exposure of the D antigen on the surface of the red cell

Слайд 14Mechanism of Development of Maternal Rh Isoimmunization

Слайд 15The Mechanism of Development of the Rh Immune Response:
Fetal RBC with

Rh +ve antigen

Maternal circulation of an Rh –ve mother

(Primary immune response)

The Rh +ve antigen will be cleared by macrophages; processed and transferred to plasma stem cell precursors (Develop an almost permanent immunologic memory)

With subsequent exposure the plasma cell line proliferate to produce humeral antibodies

(Secondary immune response).











Слайд 16The Primary Response:

Is a slow response (6 weeks to 6

months).
IgM antibodies
a molecular weight of 900,000 that does not cross the placenta.


The Secondary Response:

Is a Rapid response
IgG antibodies
a molecular weight of 160,000 that cross the placenta.

Слайд 17Exposure to maternal antigen in utero “the grandmother theory”:

Explains the development

of fetal isoimmunization in a primigravida, who has no history of exposure to incompatible Rh blood.


Rh negative Fetus and the mother is Rh positive

The Fetus is exposed to the maternal Rh antigen through maternal-fetal transplacental bleed.


The fetus immune system develop a permanent template (memory) for the Rh-positive antigen.

When the fetus becomes a mother herself and exposed to a new load of D antigen from her fetus (hence the grandmother connection) the immune memory is recalled and a secondary immune response occur.

Слайд 18
















IGM antibodies



1. Cleared by Macrophage
2. Plasma stem cells
The First Pregnancy is

not Affected

Mother

Placental

Primary Response

6 wks to 6 M.
IGM.

Слайд 19
















Anti - D



Macroph. antigen
Presenting cell
T- helper cell
B cell
Fetal Anemia
Mother
Placental
Secondary Response
Small amount
Rapid


IgG

IgG

Слайд 20

























Macroph. Antigen
Presenting Cell
T-Hellper
B-cell
Anti-D










Anti - A
Anti - B
Mother
Infant


B Rh positive
A Rh Positive

“O”

Rh positive

Group “O” Rh Negative

Placenta

Слайд 21Natural History of Maternal isoimmunization /HD of the Newborn

Слайд 22Without treatment:
less than 20% of Rh D incompatible pregnancies actually

lead to maternal isoimmunization

25-30% of the offspring will have some degree of hemolytic anemia and hyperbilirubinemia.

20-25% will be hydropic and often will die either in utero or in the neonatal period.

Cases of hemolysis in the newborn that do not result in fetal hydrops still can lead to kernicterus.

Natural History of Rh Isoimmunization And HD Fetus and Newborn

Слайд 23The Risk of development of Fetal Rh-disease is affected by:
The

Husband Phenotype And Genotype (40 % Of Rh Positive Men Are Homozygous And 60% Are Heterozygous).

The Antigen Load And Frequency Of Exposure.

ABO Incompatibility

Less than 20% of Rh D incompatible pregnancies actually
lead to maternal alloimmunization

Слайд 24 Why Not All the Fetuses of Isoimmunized Women Develop

the Same Degree of Disease?

The Non-responders:

ABO Incompatibility:

Expression Of The Rh Antigen:

Classes Of IgG Family

Слайд 25Pathogenesis of Fetal Erythroblastosis Fetalis

Слайд 26Rh Antibodies

Antibodies Coated Red Cells

Destruction of Fetal Cells by Fetal RES

Fetal

Anemia

Fetal Hypoxia and Stimulate of Erythropoietin

Extra Medullary Red Cells Synthesis

Hepatomegaly

Hepatic Cell Failure

Hypoproteinemia, Increased Intrahepatic Pressure, Portal hypertension


Ascites, Edema, hypoxia, Placental Thickness, Polyhydramnios, Pericardial effusion

Слайд 27Complications of Fetal-Neonatal Anemia:
Fetal Hydrops And IUFD
Hepatosplenomegaly
Neonatal

Jaundice
Compilations Of Neonatal Kernicterus (Lethargy, Hypertonicity, Hearing Loss, Cerebral Palsy And Learning Disability)
Neonatal Anemia

Слайд 28Management
- Prevention:
Treatment:

Слайд 29Prevention of Rh Isoimmunization
Screening all women for D Factor and

antibodies

Prophylaxis (Anti D Immunoglobulin) only for those who are negative for antibodies

The dose of Immunoglobulin depends the volume of Blood

Anti D Is given 72 hours after delivery, 28-32 weeks, and any other time when there is risk of Fetomaternal Bleeding

Слайд 3010 mcg of anti-D Ig should be administered for every mL

of fetal blood in the maternal circulation.

Thus, the 300-mcg dose covers hemorrhage volumes up to 30 mL of whole fetal blood.

In the less than 1% of cases where the volume of fetomaternal hemorrhage exceeds 30 mL, utilizing the Kleihauer-Betke test to quantitate the volume of fetal blood in the maternal circulation and administer the appropriate amount of anti-D.

Dose of prophylactic Anti-D Ig:

Слайд 31Most polyclonal RhiG comes from male volunteers who are intentionally exposed

to RhD-positive red blood cells.

Potential Problems:
infectious risk
solve supply problems.
ethical issues

MONOCLONAL ANTI-D

anti-D monoclonal antibody:
Although monoclonal anti-D is promising, it cannot be recommended at this time as a replacement for polyclonal RhIg.

Слайд 32The amount of fetal cells in maternal blood:
The Kleihauer-Braun-Betke Test

Слайд 33Management of cases of Rh isoimmunization
Diagnosis Of RH Isoimmunization

Evaluation of Fetal

Condition

Слайд 34Diagnosis of Rh isoimmunization
The diagnose is Based on the presence of

anti-Rh (D) antibody in maternal serum.

The Enzymatic Method
The Antibody Titer In Saline, In Albumin
The Indirect Coombs Tests.

Methods of Detecting Anti D Antibodies in Maternal Serum:

Слайд 35Antibody Titre in Saline: RhD-positive cells suspended in saline solution are

agglutinated by IgM anti-RhD antibody, but not IgG anti-RhD antibody. Thus, this test measure IgM, or recent antibody production.

Antibody Titre in Albumin: Reflects the presence of any anti-RhD IgM or IgG antibody in the maternal serum.

The Indirect Coombs Test:
First Step:
RhD-positive RBCs are incubated with maternal serum
Any anti-RhD antibody present will adhere to the RBCs.

Second Step:
The RBCs are then washed and suspended in serum containing antihuman globulin (Coombs serum).
Red cells coated with maternal anti-RhD will be agglutinated by the antihuman globulin (positive indirect Coombs test).

Diagnosis Maternal Isoimmunization

Слайд 36Is Done After Birth To Detect The Presence Of Maternal Antibody

On The Neonate's RBCs.

The Infant's RBCs Are Placed In Coombs Serum.
If The Cells Are Agglutinated This Indicate The Presence Of Maternal Antibody

The Direct Coombs Test

Слайд 37Fetal Rhesus Determination
RHD Type And Zygosity (If RHD-positive) Of The

Father

Amniocentesis To Determine The Fetal Blood Type Using The Polymerase Chain Reaction (PCR)

Detection Of Free Fetal RHD DNA (FDNA) Sequences In Maternal Plasma Or Serum Using PCR

Flow Cytometry Of Maternal Blood For Fetal Cells

Слайд 38Management of cases of Rh isoimmunization
Diagnosis Of RH Isoimmunization

Evaluation of Fetal

Condition

Слайд 39

Initially detecting fetal anemia prior to the occurrence of

fetal compromise.

Minimize fetal morbidity and mortality by correcting this anemia until fetal lung maturity and delivery can be achieved.

Goals of managing Fetal Alloimmunization:

Слайд 40Evaluation of Fetal Condition
Measurements Of Antibodies in Maternal Serum
Determination

of Fetal Rh Blood Group

Ultrasonography

Amniocentesis

Fetal Blood Sampling

Past Obstetric History

Слайд 41
Although not reliably accurate in predicting severity of fetal disease, past

obstetrical history can be somewhat prognostic

Past Obstetric History:

Слайд 42Maternal Anti-D Titer
Antibody Titer Is A Screening Test.

A

Positive Anti-d Titer Means That The Fetus Is At Risk For Hemolytic Disease, Not That It Has Occurred Or Will Develop.

Variation In Titer Results Between Laboratories And Intra Laboratory Is Common.

A Truly Stable Titer Should Not Vary By More Than One Dilution When Repeated In A Given Laboratory.

Слайд 43Ultrasound Image of Transabdominal Chorion Villus Sampling

Слайд 44 To Establish The Correct Gestational Age.

In Guiding Invasive

Procedures And Monitoring Fetal Growth And Well-being.

Ultrasonographic Parameters To Determine Fetal Anemia:
Placental Thickness.
Umbilical Vein Diameter
Hepatic Size.
Splenic Size.
Polyhydramnios.
Fetal Hydrops (e.g. Ascites, Pleural Effusions, Skin Edema).

Ultrasonography:

Слайд 45Anemic Fetus Preserves Oxygen Delivery To The Brain By Increasing Cerebral

Flow Of Its Already Low Viscosity Blood.

Doppler Velocimetry Of The Fetal Middle Cerebral Artery (MCA)

To Predict The Timing Of A Second Intrauterine Fetal Transfusion.

For Predicting Fetal Anemia

Слайд 46

Previous Seriously Affected Fetus Or Infant
(e.g. Intrauterine Fetal Transfusion,

Early Delivery, Fetal Hydrops, Neonatal Exchange Transfusion).

A Critical Anti-D Titer:
I.E. A Titer Associated With A Significant Risk For Fetal Hydrops. Anti-D Titer Value Between 8 And 32

Invasive Techniques
( Amniocentesis and Fetal Blood Sampling):

Indications:

Слайд 47Amniocentesis
Normally Bilirubin In Amniotic Fluid Decreases With Advanced Gestation.

It

Derives From Fetal Pulmonary And Tracheal Effluents.

Its Level Rises in Correlation With Fetal Hemolysis.

Determination Of Amniotic Fluid Bilirubin:

By The Analysis Of The Change In Optical Density Of Amniotic Fluid At 450 nm On The Spectral Absorption Curve (delta OD450)

Procedures Are Undertaken At 10-15 Days Intervals Until Delivery Data Are Plotted On A Normative Curve Based Upon Gestational Age.

Слайд 48Ultrasound image of amniocentesis at 16 weeks of gestation

Слайд 49Extended Liley graph.

Слайд 50Queenan curve (Deviation in amniotic fluid optical density at a wavelength

of 450 nm in Rh-immunized pregnancies from 14 to 40 weeks' gestation)

Слайд 51Interpretation Of Amniotic Fluid Bilirubin:

    A Falling Curve: Is Reassuring: i.e.

An Unaffected Or RhD-negative Fetus.

A Plateauing Or Rising Curve: Suggests Active Hemolysis (Require Close Monitoring And May Require Fetal Blood Sampling And/Or Early Delivery).

A Curve That Reaches To Or Beyond The 80th Percentile Of Zone II On The Liley Graph Or Enters The “ Intrauterine Transfusion" Zone Of The Queenan Curve:

Necessitates Investigation By Fetal Blood Sampling

Слайд 52Is the gold standard for detection of fetal anemia.

Reserved for

cases with: - With an increased MCA-PSV
- Increased ΔOD 450

Complications:
Total Risk of Fetal Loss Rate 2.7% (Fetal death is 1.4% before 28 weeks and The perinatal death rate is 1.4% after 28 weeks).
Bleeding from the puncture site in 23% to 53% of cases.
Bradycardia in 3.1% to 12%.
Fetal-maternal hemorrhage: occur in 65.5% if the placenta is anterior and 16.6% if the placenta is posterior.
Infection and abruptio placentae are rare complications

Fetal blood sampling:

Слайд 53Diagram of cordocentesis procedure
Cordocentesis

Слайд 54Cordocentesis

Слайд 55 Suggested management of the RhD-sensitized pregnancy
Monthly Maternal Indirect Coombs Titre
Below

Critical Titre

Complicated History and / or Exceeds Critical Titre

Paternal Rh Testing

Rh Positive

Rh-negative

Amniocentesis for RhD antigen status

Routine Care

Fetus RhD positive

Fetus RH D Negative

Serial Amniocentesis

Weekly MCA-PSV

< 1.50 MOM

Cordocentesis or Deliver

> 1.50 MOM

Слайд 56Suggested management after amniocentesis for ΔOD 450
Serial Amniocentesis
Lily zone I
Lower

Zone II

Upper Zone II

Zone III
Hydramnios & Hydrops

Repeat Amniocentesis every 2-4 weeks

Delivery at or near term

Repeat Amniocentesis in 7 days or FBS

Hct < 25%

Hct > 25%

Intrauterine
Transfusion

Repeat Sampling
7 to 14 days

< 35 to 36 weeks
And Fetal lung immaturity

> 35 to 36 weeks Lung maturity present

Intrauterine
Transfusion

Delivery

Слайд 57Ultrasound-guided transabdominal fetocentesis

Слайд 58
Titers greater than 1:4 should be considered Rh alloimmunized. However, the

threshold for invasive fetal testing varies at different institutions and generally is 1:16 or greater because these titers have been associated with fetal hydrops

Antibody Titer in maternal blood

Слайд 59
Because the wavelength at which bilirubin absorbs light is 420-460 nm,

the amount of shift in optical density from linearity at 450 nm (D OD 450) in serial amniotic fluid samples can be used to estimate the degree of fetal hemolysis.

Modification of the Liley curve to adjust for the relative inaccuracy of D OD 450 readings in early-to-middle second trimester and the use of serial measurements has improved its accuracy.

spectrophotometric measurements of bilirubin in amniotic fluid

Слайд 60Changes Since Introduction of Anti-D

Слайд 61DIAGNOSIS
Blood and Rh(D) typing and an antibody screen should always

be performed at the first prenatal visit

Слайд 62Liver lengths plotted against gestation for 18 fetuses with anemia with

ultrasonographic measurement during week before delivery, shown in reference to normal values Open circles, Cord hemoglobin level <90 g/L; solid circles, cord hemoglobin level 90 to 130 L.

Слайд 63Liver length measurements made within 48 hours of fetal blood sampling

in all fetuses with anemia at first fetal blood sampling, shown in reference to normal values.

Похожие презентации

Иммунная система человека 507
Открытый прикус. Виды. Этиология, патогенез. Клиника 478
Доброкачественные заболевания молочных желез. Классификация, клиника различных форм, диагностика, лечение 861
Неионизирующие методы диагностики 753
Сведения о медицинской организации. Форма № 30 593
Раны и раневой процесс 319

Обратная связь

Если не удалось найти и скачать презентацию, Вы можете заказать его на нашем сайте. Мы постараемся найти нужный Вам материал и отправим по электронной почте. Не стесняйтесь обращаться к нам, если у вас возникли вопросы или пожелания:

Email: Нажмите что бы посмотреть 

Что такое ThePresentation.ru?

Это сайт презентаций, докладов, проектов, шаблонов в формате PowerPoint. Мы помогаем школьникам, студентам, учителям, преподавателям хранить и обмениваться учебными материалами с другими пользователями.

Для правообладателей

Яндекс.Метрика