alloimmunisation

Question 1

Incidence of blood group antibodies

Incidence that is clinically significant

Answer 1

1. 4% of woman have BG antibodies

0. 4% of these are clinically significant

Question 2

Which blood group antigens result in severe Haemolytic disease
Occasional HDFN

Bad combination

No negative effect

Answer 2

Severe:
Anti D
Anti c moderate risk with 7.5-20
Anti K - refer once detected as severe anaemia can occur at 1:8

Sometimes 
Anti e, E anti Fya, anti Jka 
Anti S,s, deigo
Anti E rarely causes anaemia 
Kell - Anti K, kpa, Kpb, Jsa Jsb 
ABO hydrops are very rare 

Anti E and c are bad together

NO alloimmunisation
Lewis Le a/ b (IgM and not expressed on fetal RBC)
Duffy B - fy b

Question 3

How does alloimmunisation occur

Answer 3

During pregnancy 
(miscarriage, ectopic, termination, invasive procedures, abdo trauma, ECV passive)
delivery

Exposure to foreign antigens
Needle sharing and blood transfusions

Question 4

What is the indirect coombs test

aim
purpose
stends

Answer 4

Indirect coombs test

AIM: detect plasma antibodies

Purpose:
pretransfusion testing
screen for antibodies affecting HDNB

Patients plasma + Red cells with known antigens + coombs reagent (antibodies against human antigens)

Agglutination = positive test

Use Indirect coombs test for pretransfusion testing and blood type cross matching

Question 5

What is the direct coombs test

DAT

Answer 5

Aim
Detects antibodies or complement on the surface of RBC

Purpose 
autoimmune haemolytic anemia
drug induced haemolysis
HDNB
Alloimmune hemolytic transfusion 

method
add RBC from patient to coombs reagent

agglutination is positive

Question 6

why is kell so bad?

and how to manage?

Answer 6

It both causes haemolysis and suppresses erythropoiesis by destroying the progenitor cells in the bone marrow

severe anaemia can be caused at low titres

not for titres
does have MCA PSV from 16 weeks

Question 7

How many proteins in the Rh system?

What genes?

Answer 7

5 red cell proteins
C,c ,D, d, E

Rh negative is the absence of RhD

Ch 1 RHD and RHCE

Question 8

How much blood is needed for Rh neg sensitization ?

Answer 8

0.1 ml blood

after an unmatched transfusion 50% of Rh neg will develop antibodies

Question 9

What is the rate of ABO compatibility and the consequence?

Why is it not so bad?

Answer 9

If ABO is incompatible

2% alloimmunisation risk - risk less due to erythrocyte destruction before sensitization can occur

Question 10

How to prevent Rh isoimmunisation

Answer 10

Anti D
Recognise and treat sensitising events
within 72 hours but value 9-10 days
6 weekly 
9-% reduction in alloimmunisation
Post partum prophylaxis - reduces risk to 1.5% per pregnancy

Antenatal prophylaxis - reduces risk 0.2% per pregnancy

Question 11

How to manage anti D and cell saver

Answer 11

Reinfused blood can have fetal cells -
obtain a maternal blood sample 30-45 minutes after reinfusion to estimate the volume of fetal cells to dose adjust the anti D

Question 12

What if birth is within 3 weeks of antenatal dose?

does she need post partum prophylaxis?

Answer 12

no unless she has an abruption

Question 13

How to manage a woman with Rh neg blood group

Answer 13

Blood group antibody screen at booking and 28 weeks

Antenatal prophylaxis 28 + 34 weeks 625 IUI

Indicated prophylaxis
Can assess volume after sensitising event
Kleihauer, flow cytometry
Give additional anti D if needed

Directed prophylaxis in the Rh + neonate

Question 14

When to give prophylaxis?

Answer 14

First trimester 
CVS 
Miscarriage 
Termination  
Ectopic  
Not enough evidence for threatened miscarriage before 12 weeks 

Second and third trimester 
APH 
Amniocentesis. Cordocentesis 
ECV (successful or not) 
Abdo trauma or other suspective intrauterine bleeding

Question 15

What is the initial work up if antibodies are found

Answer 15

Maternal antibody titres and quantification

Anti D, c, K monthly until 28 weeks then every 2 weeks

If other antibodies consider paternal testing

Fetal risk assessment
Fathers blood phenotype and genotype if certain of paternity

If father is Rh + but heterozygous 50% of children will be Rh neg

NIPT
Assess fetal genotype – if doesnt have Antigen then not at risk
Indicated if father is heterozygous

Amniocentesis and PCR of amniocytes

CVS is not used may worsen alloimmunisation and increased FMH

Maternal hx

Monitoring antibody
Quantitation is more reliable then titre
Referral 1:16/32 = 4-6 quant

Refer to MFM 
Hx of haemolytic disease  
High titres, abnormal USS 
Critical titre reached 
MCA PSV approaching / 1.5 MoM

Question 16

How to monitor ongoing pregnancies

Answer 16

MCA PSV (peak systolic velocity)

Increased velocity due to increased cardiac output, vasodilation of the brain, decreased blood viscosity

Technique
Resting fetus
Circle of Willis imaged in axial image using colour doppler

Entire length of MCA
Close to origin of internal carotid artery

Gestation dependent
Measure from 18-20 weeks, to 36 weeks

Not as efficacious after 36 weeks

Levels <1.5Mom = 100% not anaemic

Measure 2 weekly
Levels >1.5 Mom = 65% anaemic 12% false +
Repeat in 24 hours – if the same then FBS +/- transfuse

After IUT MCA maybe unreliable

Liver length is a helpful adjunct

Assess for signs of hydrops
Ascites
Pericardial effusion, skin oedema, hydramnios
Hydrops required Hb 6 SD below normal level

If signs of hydrops then perform a cordocentesis with transfusion

Question 17

What is the treatment if raised PSV?

treatment risks?

Answer 17

Treat anaemia 
IU transfusions  
1% fetal loss rate per procedure 
Peritoneal vs placental cord insertion vs hepatic vein  
IPT - ? Interplacental transfusion  
Perform earlier gestations  

Intravenous IUT
Survival 84%
70% if hydropic
95% if not

can be performed from 20 weeks up until 32 weeks

Balance how long to continue (when to pack it in and deliver)

Complications 1.2% PPROM, infection, EMLSCS, fetal loss

Ensure CMV free, irradiated 0 neg X matched cells, leukocyte deplete, packed hct 80 (prevent volume overload)

When
4 weeks earlier then previous pregnancy transfused
10 week prior to prev hydropic fetus / IUFD
As clinically indicated by USS

How much and how often 
AIm for hct 40-50% 
Hb over 120 
Volume based on Hb and GA 
Can transfuse 1-2 weekly until erythropoesis is suppressed then 3-4 weekly  

Maternal IVIG
High titre or early hydrops
Reduces titre and blocks placental antibody receptors
Delay need for transfusion

Notify blood bank

Consider weekly cross match if high risk maternal delivery

Cord bloods for bilirubin, Hb , DAT

Question 18

What is the advice for future pregnancy

Answer 18

Anaemia occurs earlier in future pregnancies

consider sperm donor / surrogate

Question 19

When does ABO incompatibility affect the fetus?
How common is it?
How can it be managed?

Answer 19

Incompatible for blood group A and B is the most common cause for haemolytic disease of the new born

20% of infants have incompatibility but only 5% are clinically affected

Often seen in first born

Most O woman have anti A and B from exposure to bacteria with similar antigens

Rarely progressive

Not an obstetric problems but a paediatric one – this is because

Antibodies are IgM and do not cross the placenta

Fetal red cells have fewer antigenic sites and thus are less immunogenic

No need to monitor antenatally

Monitor neonatal as hyperbilirubinaemia may need phototherapy or occasionally transfusion

Question 20

What is the dosing for prophylaxis Rh Ig (RANZCOG)

Answer 20

first trimester 250 IU
If multiple pregnancy 625 IU

T2/3 625 IU

28/34 week prophylaxis 625 IU
Post natal - FHM quantified and Rh Ig given accordingly within 72 hours