Anti D Immunoglobulin for Rh Prophylaxis

Anti D Immunoglobulin for Rh Prophylaxis

DR GOH CHEE SIONG

O & G Department

Kulim Hospital.

What Happen?

SOURCES-1.Green Top Guideliness. (RGOG).Revised May 2002.2. National Institute For Clinical Excellence.(NICE). Issue date May 2002.

3.Rhesus disease and non-immune

hydrops.-Current O&G Vol

13,Aug 2003.UK.

History

¨ 1938 - Ruth Darrow discover maternal Antibody against fetal blood.

¨ 1949 - Landsteiner & Weiner named this antigen in RBC called Rhesus Antigen.

¨ Levin confirmed sensitisation

Incidence of the Rh negativeBlood Group  in Various Populations

Population Incidence ¨ Chinese and Japanese 1%¨ North American Indian 1 - 2%¨ African American 4 - 8%¨ Caucasian 15 - 16%¨ Basque 30 - 35%

Pathophysiology

¨ RhD negative women carry a RhD positive fetus and if Fetal maternal hemorrhage (FMH) occurs,then AntiD antibodies being produced. These Antibodies will crosses the placenta and attack the blood cell of the unborn.

This will cause haemolysis of fetal cell then extensive hepatic erythropoiesis resulting distorted and enlarged liver leading to portal hypertension and hypoalbuminemia. This will then cause oedema, ascites and anarsarca. FMH can occur during birth, miscarriage, amniocentesis, chorionic villous sampling,

vaginal bleeding and ECV.

FETAL ASCITES

In UK, Post delivery immunoprophylaxis started in 1969. Since then death attributed to RhD alloimmunisation felt 46/1000 delivery in 1969 to 1.6/1000 delivery in 1990.

Guideliness of Rh immunoprophylaxis were updated in 1976,1981 and 1991.Since 1991, then,the death was the same.

WHY?

REASONS 1. There is clear evidence that guidelines was not fully applied.

2. Insufficient anti D being given.3. Most important cause is now immunusation during pregnancy where there has been no overt sensitising event.

(subclinical FMH) 4. Hemolytic disease results not only from Rh sensitization but other red cell AB.(non rhesus)

¨ Late immunisation during 1st pregnancy is responsible for 18-27%.

In European country, (except UK,France

and Ireland), standard post-natal dose of 1000-1500 IU were given without Kleihauer test. unfortunately0.3% of women have FMH greater than 15ml and as the effect, over 200 women in UK are receiving less protection yearly.

In England and Wales,about 500 fetuses developed haemolytic disease each year and between 25 to 30 babies die per year due to haemolytic disease and around 45 more to suffer developmental problems.

Test for the size of maternal haemorrhage

Studies have shown that 99.2-99.3 women have FMH less then 4 ml at normal delivery.

But Up to 50% of larger FMH also occurs after normal

deliveries.

Circumstances likely to be associated with larger FMH¨ traumatic deliveries including

caesarean section ¨ manual removal of the placenta ¨ stillbirths and intrauterine deaths ¨ abdominal trauma during the third

trimester ¨ twin pregnancies (at delivery) ¨ unexplained hydrops fetalis

Sensitizing events and risk of sensitization

Spontaneous vertex delivery 5-11%

Abortion 3%

Forcep delivery 33.7%

Caesarean section 52.5%

MRP 40.3%

Breech Delivery 25%

APH (all causes) 30%

Allo-antibodies capable of producing haemolytic disease of the newborn

Blood Group Alloantibody

Rhesus Anti-D,C,E,c,e Kell Anti-K,k,Kpa,Kpb. Lutheran Anti-Lua and Anti Lub

Duffy Anti Fya and Fyb Kidd Anti-Jk(a and b) MNS Anti-M,N,S,s and U. Wright Anti-Wr (a and b)

In UK ,It is a recommended policy to obtain and anticoagulated blood sample(within 2 hour) after delivery to perform Kleihauer screening to identified women with larger FMH and required additional AntiD Ig (Grade B recommendation)

GRADING

Grade A:randomised controlled trials.Grade B:other robust experimental or observational studies.Grade C:more limited evidence but the advice relies on expert opinion and has the endorsement of respected authorities

Test to investigate the size of Fetomaternal hemorrhage¨ Coomb test-Positive indirect means

pt have antibodies to D-antigen. ¨ Kleihauer test.¨ Flow cytometry-Better and more

accurate but many center have no access to it.

¨ Rosetting Technique.

Kleihauer test.

Kleihauer test.

Flow cytometry

Antenatal Monitoring

¨ About 1/3 of isoimmunized women do not have demonstrable antibody in the first sample test.

¨ Therefore, at least 2 to 3 samples to be tested during pregnancy( at booking, 28 and 34-36 weeks).

IF COOMB TEST SHOWED

POSITIVE RESULT.

Follow up

¨ Amniocentesis¨ Cordocenetsis¨ USG DOPPLER: Cerebral

¨ AMNIOCENETESIS:serial¨ Less risk,less invasive

Liley`s graph

¨ AF spectrophotometric analysis at delta 450 at different POG

¨ The amount of billirubin quantitated by spectrophotometrically measuring absorbance at the 450 nm wavelength in a specimen of AF that has been shielded from light.

`¨ `

`Lily`s curve

¨ Reading is directly related to severity of Hemolytic Disease

¨ Lily Curve is divided into 3 zones¨ Zone I mild or no disease¨ Amniocenesis,USG q3w¨ Zone II:Intermediate disease¨ Amniocentesis,USG q 1-2 w¨ Zone III: DELIVER OR

INTRAVASCULAR TRANSFUSION

¨ `

Pathology Of Iso-immunisation

HAEMOLYSIS IN UTEROAFTER BIRTH

BILIRUBIN

ANAEMIA

JAUNDICE

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

1.Ultrasound image of the placental cord insertion.

2.Technique used for intra-uterine transfusion.

¨ ¨

Administrations

¨ Intramuscular anti-D Ig is best given into the deltoid muscle as injections into the gluteal region often only reach the subcutaneous tissues and absorption may be delayed.

¨ anti-D Ig should be given as soon as possible after the sensitising event but always within 72 hours. Even within 10 days still provide some protection.

¨ Women who are already sensitised should not be given anti-D Ig.

Prophylaxis following abortion

¨ 250iu before 20 weeks' gestation and 500iu thereafter. A test for the size of FMH should be performed when anti-D Ig is given after 20 weeks.

¨ Therapeutic termination of pregnancy: Anti-D Ig should be given to all non-sensitised RhD negative women having a therapeutic termination of pregnancy, whether by surgical or medical methods, regardless of gestational age (Grade B recommendation).

¨ Ectopic pregnancy: Anti-D Ig should be given to all non-sensitised RhD negative women who have an ectopic pregnancy (Grade B recommendation).

¨ Spontaneous miscarriage: Anti-D Ig should be given to women with spontaneous complete or incomplete abortion after 12 weeks of pregnancy (Grade B recommendation).If before12 weeks,for spontaneous complete abortion, Anti-D Ig is not needed but for incomplete where intervention of evacuation is needed, Anti-D ig should be given.

Threatened miscarriage¨ First 12 weeks of pregnancy where the fetus

is viable, evident are scant-Routine Anti-D Ig cannot be recommended but if bleeding is heavy or repeated or associated with abdominal pain and gestational approaches 12 weeks, Anti-D Ig can be given.

¨ Anti-D Ig should be given to women with a threatened miscarriage after 12 weeks of pregnancy.Where bleeding continues intermittently after 12 weeks' gestation, anti-D Ig should be given at 6-weekly intervals (Grade C recommendation).

Prophylaxis following sensitising events before delivery

Anti-D Ig should be given to all non-sensitised RhD negative women after the following potentially sensitising events during pregnancy:

¨ invasive prenatal diagnosis (amniocentesis, chorion villus sampling, fetal blood sampling)

¨ other intrauterine procedures (e.g. insertion of shunts, embryo reduction)

¨ antepartum haemorrhage ¨ external cephalic version of the fetus ¨ closed abdominal injury ¨ intrauterine death

How much to Give?

¨ A dose of 250iu is recommended for prophylaxis following sensitising events up to 20 weeks of pregnancy.

¨ For all events after 20 weeks, at least 500iu anti-D Ig should be given followed by a test to identify FMH greater than 4ml red cells; additional anti-D Ig should be given as required (Grade B recommendation).

Postnatal prophylaxis ¨ At least 500iu of anti-D Ig must be given to

every non-sensitised RhD negative woman within 72 hours following the delivery of a RhD positive infant (Grade B recommendation). This includes women with alloantibodies other than anti-D.

¨ There is no universal policy regarding the postnatal dose which varies in different countries;

¨ 1500iu is the standard dose in the USA.¨ 500-600iu in Canada.¨ 1000-1250iu in many European countries

except the UK, Ireland and France

The MRC (medical research council) dosage trial showed that 500iu (100mcg) of anti-D Ig given intramuscularly, which is capable of suppressing immunisation by 4-5 ml of RhD positive red cells, was as effective as both 1500iu and 1000iu.

A test to detect FMH greater than 4ml must also be undertaken, so that additional anti-D Ig can be given as appropriate (Grade B recommendation).

Routine antenatal prophylaxis (NICE) ¨ It is recommended that Routine Antenatal Anti-D

Prophylaxis (RAADP) is offered to all non-sensitized pregnant women who are RhD negative even already had AADP earlier in the pregnancy. She should also be offered postnatal anti-D prophylaxis whether or not she have had AADP or RAADP

¨ If you are pregnant and are RhD-negative, your midwife, obstetrician or GP should discuss RAADP and explain the options available so that patient can make an informed choice about treatment. The difference between RAADP and AADP should be clearly explained to the patient.

Routine antenatal prophylaxis

• The healthcare professional should discuss the situations where anti-D prophylaxis would be neither necessary nor cost effective. Such situations might include those where a woman:

1.has opted to be sterilized after the birth of the baby. 2. Is in a stable relationship with the father of the child, and it is certain that the father is RhD negative. 3. Is certain that she will not have another child after the current pregnancy.

Transfusion of RhD positive blood components

¨ RhD positive platelet transfusions: It should usually be possible to provide RhD negative platelets for women of childbearing age who need a platelet transfusion. Occasionally, if an appropriate product is not available, it may be necessary to use RhD positive platelets. In these circumstances, prophylaxis against possible Rh alloimmunisation by red cells contaminating the platelet product should be given (Grade B recommendation).

Transfusion of RhD positive blood components

¨ Each unit of platelets prepared according to the UK Guidelines from one whole blood donation contains less than 1 X 109 (< 0.1ml rbc). 250iu (50mcg) anti-D Ig should be given following every three adult doses of platelets.

Inadvertent transfusion of RhD positive blood:

¨ When less than 15ml of RhD positive blood have been transfused to a RhD negative woman, the appropriate dose of anti-D Ig should be given (Grade B recommendation).

¨ When more than 15ml have been transfused, it is preferable to use the larger anti-D Ig IM preparation (2500iu or 5000iu).

¨ The dose should be calculated on the basis that 500iu of anti-D Ig will suppress immunisation by 4ml of RhD positive red blood cells (rbc) (Grade B recommendation).

Inadvertent transfusion of RhD positive blood: ¨ When more than 2 units of RhD positive

blood have been transfused, consideration should be given to undertaking an exchange transfusion

¨ Immediate exchange transfusion will reduce the load of RhD positive rbc (a one-blood-volume exchange will achieve a 65-70% reduction in RhD positive cells; a two-volume exchange 85-90%).

Conclusion and summary of

recommendation ¨ RhD immunisation continues to occur.

In some cases this results from failure to adhere to previously published guidelines on RhD prophylaxis. However the most important cause of anti-D is now immunisation during pregnancy where there has been no overt sensitising event. This problem is not covered by previous guidelines.

TAKE HOME MESSAGE ¨ Following delivery, irrespective of the dose

of anti-D Ig routinely administered, postnatal prophylaxis must include a screening test to identify women with a large FMH who need additional immunoglobulin (Grade B recommendation).

¨ Anti-D Ig should be given after sensitising events before delivery and after abortion (Grade B recommendation).

¨ Anti-D Ig is no longer necessary in women with threatened miscarriage with a viable fetus and cessation of bleeding before 12 weeks' gestation (Grade C recommendation).

TAKE HOME MESSAGE ¨ At least 500iu of anti-D Ig should be given to

non-sensitised RhD negative women at 28 weeks and 34 weeks of pregnancy according to NICE guidance (RAADP) (Grade A recommendation).

¨ It is important that women have all the necessary information to enable them to make an informed choice about Rh prophylaxis. Information sources must indicate that anti-D Ig is a blood product. There is now an urgent need to address the implementation and monitoring of the new guidelines.

Thank you