Rhesus (rh) isoimmunization

Содержание

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Blood groups (1900): Antigens: Antibodies: O (45%) AntiA+Anti B A (40%)

Blood groups (1900):
Antigens: Antibodies:
O (45%) AntiA+Anti B
A (40%) Anti B
B (10%)

Anti A
AB (5%)
A and B : dominant
O : recessive

Rh ISOIMMUNIZATION

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Rhesus factor (1940): Agglutinogen (C,D,E) - mainly D C,D,E - dominant

Rhesus factor (1940):
Agglutinogen (C,D,E) - mainly D
C,D,E - dominant antigen
d,e -

recessive antigen

Rh ISOIMMUNIZATION

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Rh positive (85%) - homozygous (DD) (35%), or heterozygous (Dd) (50%)

Rh positive (85%) - homozygous (DD) (35%), or heterozygous (Dd) (50%)
Rh

negative (15%)
Incidence of Rh-ve in far east is about 1%
Examples of Rh factor: (CDe=R1) , (Cde=r) (cDE=R2)
Other systems:
kell-antikell,
luther,
Duffy, etc.

Rh ISOIMMUNIZATION

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Rh ISOIMMUNIZATION So in response to introduction of foreign protein (antigen)

Rh ISOIMMUNIZATION

So in response to introduction of foreign protein (antigen) ?

production of antibody to neutralize the antigen
In ABO and other non Rh-incompatibility: It usually causes mild anaemia, mainly as there is no intrapartum boosting
In Rhesus isoimmunization: mainly (D), but C, E can produce antibodies
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Rh ISOIMMUNIZATION Feto-maternal haemorrhage: during pregnancy leakage of fetal cells in

Rh ISOIMMUNIZATION

Feto-maternal haemorrhage: during pregnancy leakage of fetal cells in the

maternal circulation (Rh+ fetal cells in Rh- maternal circulation
Examples:
- Spontaneous abortion
- Induced abortion
- APH
- E.C.V.
- Cordocentesis, CVS, amniocentesis
- Severe preeclampsia
- Ectopic pregnancy
- Caesarean section
- Manual removal of placenta
- Silent feto-maternal hage
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Rh ISOIMMUNIZATION Development of Rhesus antibodies: depends on factors: 1- Inborn

Rh ISOIMMUNIZATION

Development of Rhesus antibodies: depends on factors:
1- Inborn ability to

respond
2- protection if ABO incompatible 1\10
3- Strength of Rh antigen stimumlus (CDe=R1)
4- Volume of leaking feta blood (0.25ml)
IgM (7 days) doesn’t cross placenta, then IgG 21 days - crosses placenta
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1- If ABO is incompatible: Red blood cells is easily destroyed,

1- If ABO is incompatible:
Red blood cells is easily destroyed, so

not reaching enough immunological component to cause antibody response and reaction
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IgM antibodies 1. Cleared by Macrophage 2. Plasma stem cells The

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

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Anti-D Macroph. antigen Presenting cell T- helper cell B cell Fetal

Anti-D

Macroph. antigen
Presenting cell

T- helper cell

B cell

Fetal Anemia

Mother

Placental

Secondary Response

Small amount
Rapid


IgG

IgG

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2 - If ABO is compatible: Rh+ fetal cells ? remain

2 - If ABO is compatible:
Rh+ fetal cells ? remain in

circulation (life span) until removed by (R.E.S) ? destroyed ? liberating antigen (D) ? isoimmunization
It takes time:
1st pregnancy is almost always not affected:
1% - during labour or 3rd stage)
10% - 6 months after delivery
15% by the 2nd pregnancy
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Mild Cases: fetal (RBC) destruction ? from anti-D (IgG): ? anaemia

Mild Cases:
fetal (RBC) destruction ? from anti-D (IgG): ? anaemia

? compensating haemopoiesis ? excess of unconjugated bilirubin
Severe Cases:
excessive destruction of fetal (RBC) ? severe anaemia ? hypoxia the tissues ? cardiac or circulatory failure ? generalized edema ? (H. failure) ? ascitis ? IUFD
When excess of unconjugated bilirubin > (310-350 mol/L) ? It passes brain barrier ? (kernicterus) ? permanent neurological and mental disorders

Rh ISOIMMUNIZATION

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Rh ISOIMMUNIZATION Kleihauer-Betke technique: (acid elution test) - measure amount of

Rh ISOIMMUNIZATION

Kleihauer-Betke technique:
(acid elution test) - measure amount of feto-maternal haemorrhage
If

0,1-0,25 ml of fetal blood leakes (critical volume) ? isoimmunization represented by 5 fetal cells in 50 low power microscopic field of peripheral maternal blood
So 1 ml is represented by 20 fetal cells
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Rh ISOIMMUNIZATION Fetal and Neonatal Effects: Haemolytic anaemia of newborn Hb=14-18g/dl

Rh ISOIMMUNIZATION
Fetal and Neonatal Effects:
Haemolytic anaemia of newborn Hb=14-18g/dl
Icterus gravis neonatorum

Hb=10-14g/dl
Hydrops fetalis (Erythroblastosis fetalis)
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MANAGEMENT OF Rh ISOIMMUNIZATION I) PROPHYLAXIS 1 - Prevention of Rhesus

MANAGEMENT OF Rh ISOIMMUNIZATION

I) PROPHYLAXIS
1 - Prevention of Rhesus isoimmunization:

Anti D (RhoD IgG)
Standard dose for > 20 wks, and ½ standard dose for < 20 wks - given within 72hours of the incident
SD: i.m. injection: 500 iu = 100 ugm (UK),
1500iu = 300 ugm (USA)
1500iu = 300 ugm ? neutralize 15ml
500 iu = 100 ugm ? neutralize 5ml (4ml+1ml)
4ml = 4x20 f.cells = 80 fetal cells
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MANAGEMENT OF Rh ISOIMMUNIZATION K-B test if large amount of leaking

MANAGEMENT OF Rh ISOIMMUNIZATION
K-B test if large amount of leaking ?

another SD if mother is Rh-, baby Rh+ with no isoimmunization (checked by indirect or direct Coombs test)
2 - A.P. administration of anti-D
SD at 28 wks or at 28 and 36 wks will reduce Rh isoimmunization
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MANAGEMENT OF Rh ISOIMMUNIZATION II) 1- Antibody Screening: for all pregnant

MANAGEMENT OF Rh ISOIMMUNIZATION
II) 1- Antibody Screening:
for all pregnant women in

ANC for irregular antibodies (mainly for Rh- women), then start at 20 wks , and every 4 weeks
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MANAGEMENT OF Rh ISOIMMUNIZATION 2 - Management following detection of Rh

MANAGEMENT OF Rh ISOIMMUNIZATION

2 - Management following detection of Rh antibodies
Should

be treated in specialized centres
Quantitative measures of antibodies + husband genotype
Repeat titration (indirect Coombs, detecting of antibodies) titre or specific enzymes for antibodies IU
Amniocentesis once necessary
Obstetrical management based on timing of I.U. transfusion (now cordocentesis + fetoscopy) versus delivery
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3 - Amniocentesis: Should be performed under ultrasound guidance if titre

3 - Amniocentesis:
Should be performed under ultrasound guidance if titre >

1\16 = 0.5-1 ugm ? 2.5-5 I.U
Timing: 1st amniocentesis - 10 weeks before previous IUFD
Start from 20-22 weeks, 2-4 weekly or more frequent if needed
Amniotic fluid analysis - spectrophotometry: optical density at the height of optical density deviation at wave length 450 nM

MANAGEMENT OF Rh ISOIMMUNIZATION

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CORDOCENTESIS

CORDOCENTESIS

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IU transfusion (cordocentesis, in the past intraperitoneal transfusion) versus delivery of

IU transfusion (cordocentesis, in the past intraperitoneal transfusion) versus delivery of

the baby:
Using Liley’s chart
Prediction chart (Queenan curve)
Whitefield’s action line

MANAGEMENT OF Rh ISOIMMUNIZATION

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LILEY’S CHART

LILEY’S CHART

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WHITEFIELD’ ACTION LINE

WHITEFIELD’ ACTION LINE

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MANAGEMENT OF Rh ISOIMMUNIZATION Alternatively follow up with Doppler study for

MANAGEMENT OF Rh ISOIMMUNIZATION

Alternatively follow up with Doppler study for the

fetal middle cerebral artery
Prognosis depends on:
obstetrical history
paternal genotype
maternal history (blood transfusion, antibody titre)
amniocentesis results
Delivery: Vaginal versus C-Section
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Intensive plasmaphoresis: when severe cases anticipated, using continous flow cell separator,

Intensive plasmaphoresis: when severe cases anticipated, using continous flow cell separator,

as early as 12 wks
Postnatal management: for the neonate:
Direct Coombs test, blood group, Rh type, Hb, bilirubin
Mild cases: phototherapy - correction of acidosis
Severe cases: exchange transfusion

MANAGEMENT OF Rh ISOIMMUNIZATION