Week 8 Flashcards
History Anti-D
In 1932 the three most characteristic clinical signs of Rh haemolytic disease of the fetus and newborn HDFN hydrops fetalis, severe neonatal jaundice and delayed anaemia of the newborn were identified as being caused by the same process
In the early 1940s Philip Levine identified that the cause of HDFN was antibodies to the D antigen
In 1969 postnatal anti-D immunoglobulin was first introduced
Between 1976 and 1991 this guidance was extended to include anti-D immunoglobulin administration following potentially sensitising events PSE
The 2002 guidance further extended the previous guidance to include routine antenatal anti-D prophylaxis RAADP
The widespread intro of anti-D immunoglobulin prophylaxis saw a dramatic fall in deaths attributed to RhD HDFN between 1977 and 1989. This fall in the death rate from RhD HDFN is mainly due to the introduction of anti-D immunoglobulin prophylaxis
Anti-D prophylaxis administered postnatally and following potentially sensitising events during pregnancy has reduced the UK maternal RhD sensitisation rate to 1.0-1.5%
Anti-D immunoglobulin prophylaxis
The anti-D immunoglobulin prophylaxis policy has been so successful that it is hailed as one of the major achievements in obstetrics in the twentieth century
It’s predicted that the universal introduction of RAADP will prevent a further 17 late fetal and neonatal deaths in the UK each year
Blood groups
A+
A-
B+
B-
AB+ can receive from everyone
AB-
O+
O- can be donor to everyone
RhD factor and pregnancy
Blood types can be categorised as either RhD positive or RhD negative
Being RhD negative is usually only of consequence during pregnancy
If a RhD negative woman is pregnant with a RhD positive fetus she maybe have a potentially harmful immune response resulting in the formation of anti-D antibodies
Genetic determinants of blood RhD factor
The RhD positive gene is more common than the RhD negative gene and is more dominant
If one of the two genes is RhD positive and the other RhD negative your blood type is RhD positive
It takes a pair of RhD negative genes to make your blood type RhD
Anti-D formation
If fetal red cells cross the placenta and enter the maternal blood stream the spleen is activated by the fetal RhD positive red blood cells to produce anti-D antibodies
The presence RhD positive fetal red blood cells in maternal circulation stimulates the production of anti-D antibodies
Anti-D
Anti-D immunoglobulin prophylaxis is administered to prevent maternal sensitisation with anti-D antibodies
If anti-D is not given
Anti-D antibodies can cross the placenta and bind to the fetal RhD positive red cells
If this happens without the anti-D immunoglobulin injection the maternal anti-D antibodies will become permanent and irreversible. This is known as maternal sensitisation
It’s unlikely that the first pregnancy will be affected
However in a future pregnancy if the baby is RhD positive the maternal immune response will be greater
The maternal anti-D antibodies will cross to the fetal circulation and destroy fetal red blood cells. This leads to haemolytic disease of the fetus and newborn HDFN
Maternal sensitisation
A woman is considered sensitised if she develops antibodies such as anti-D in her blood
Once sensitisation occurs its irreversible
The antibodies which are formed as a result of the sensitisation do not affect the mothers health
And only rarely affect first pregnancy
However they could affect future pregnancies where the baby is RhD positive
Impact of sensitisation on pregnancy
During the pregnancy that results in a woman becoming sensitised the anti-D antibody is rarely produced at a high enough level to cause haemolytic disease of the fetus and newborn HDFN
Any future pregnancies may however be at risk of developing HDFN if the baby is RhD positive
The anti-D antibody which resulted from the earlier sensitisation can cross the placenta and attach and destroy RhD positive fetal red cells causing HDFN
The anti-D antibody resulting from maternal sensitisation will only attack RhD positive fetal red blood cells
Fetomaternal haemorrhage
During pregnancy the placenta normally prevents maternal and fetal blood mixing
Fetomaternal haemorrhage FMH is the term used to describe any bleed from the fetus into maternal circulation
It’s the most common in the third trimester and around the time for birth
It’s often occurs with a potentially sensitising event such as vaginal bleeding but may also happen in the absence of any obvious potentially sensitising event
Sensitised
The timing, rate and severity of the maternal immune response will vary between individuals
The level of antibody present can be detected by laboratory tests on maternal blood samples
The higher the levels the greater the significance for a pregnancy
If a women is sensitised anti-D immunoglobulin will have no effect
It should therefore not be given to a women with immune anti-D in their blood even if they experience a potentially sensitising event
How maternal sensitisation occurs
Certain events during pregnancy are known to increase the risk of fetal maternal haemorrhage and maternal sensitisation these are known as potentially sensitising events PSEs
Gestation is an important factor for determining how a potentially sensitising event is managed
If anti-D immunoglobulin is required it should be given within 72hours of a potentially sensitising event occurring
The decision to give anti-D immunoglobulin in response to a potentially sensitising event should not affect or be affected by routine ante or post natal anti-D immunoglobulin prophylaxis
Potentially sensitising events
Any vaginal bleeding
Blunt abdominal trauma
Invasive antenatal testing (amniocentesis, CVS)
External cephalic version
Miscarriage or termination of pregnancy
Ectopic pregnancy
Intrauterine death
Stillbirth and birth of a RhD positive baby
Management of potentially sensitising events
The management of a potentially sensitising even varies according to gestation
Prior to 12 weeks gestation anti-D immunoglobulin is only occasionally indicated following a potentially sensitising event
Between 12 and 20 weeks gestation a minimum dose of anti-D immunoglobulin 1500iu is recommended
At 20 weeks gestation and onwards a minimum dose of anti-D 1500iu is also required however more anti-D immunoglobulin may be required depending upon the size of FMH this will be determined by laboratory tests
management of potentially sensitising events 2
Anti-D immunoglobulin is most effective if given within 72 hours of a potentially sensitising event. However if a woman has not received anti-D immunoglobulin within this time it may still offer some protection if given up to 10 days after the potentially sensitising event occurred
Before the 12 weeks gestation, anti-D immunoglobulin should be considered if PV bleeding is heavy or persistent and/or associated with severe pain, particularly when approaching 12 weeks gestation
Anti-D immunoglobulin is always indicated following surgical intervention to remove products of conception (miscarriage and termination of pregnancy)
Anti-D immunoglobulin should always be given in cases of termination of pregnancy whether by surgical or medical means. In some cases anti-D immunoglobulin is also offered if early pregnancy loss, due to miscarriage or ectopic pregnancy if managed medically
Sensitisation
Is irreversible there’s no treatment for it
Anti-D immunoglobulin should not be given to sensitised woman in the event that it is inadvertently administered the only consequence is the unnecessary exposure of the woman to a blood product
Sensitisation is only likely to cause problems for a women should she become pregnant with a RhD positive baby or require blood transfusion. It may be difficult to cross match blood and transfusion reactions could occur if RhD positive blood is given inadvertently eg during an emergency
This will usually mean regular monitoring of the anti-D antibody level in the woman’s blood. Usually the higher the antibody level the greater the risk of harm to the baby
There is no effective treatment that can change the levels of antibody produced and levels are likely to rise during the pregnancy if the fetus is RhD positive
Management of pregnancies at increased risk due to maternal sensitisation
Some RhD negative women will be known to be sensitised before their first visit or it will be discovered during pregnancy. Although this does not affect woman’s health the baby is at risk of developing HDFN
Sensitised women require specialised care during pregnancy to monitor the health of their baby. They should be referred to a consultant obstetrician/fetal medicine department and have a haematologist or transfusion specialist involved in planning their care
Specialist investigations such as serial ultrasound including middle cerebral artery Doppler scanning can be used to monitor the health of the developing baby. Repeated testing of the woman’s antibody levels during pregnancy can help to predict the risk to the baby from HDFN
Babies of women known to have anti-D antibodies should be delivered in a hospital with neonatal care facilities it should be recognised that a future pregnancy with a RhD positive baby is likely to be at even greater risk of HDFN
Management continued
Middle cerebral artery:
-measurement of Doppler flow through MCA can help identify babies with anaemia. Babies with anaemia have increased blood flow and should be referred to a fetal medicine unit
Fetal medicine unit:
-in the most serious cases intrauterine blood sampling may be indicated to determine the fetal haemoglobin level. If a fetus is found to be very anaemia a intrauterine blood transfusion may be required
Neonatal care:
-babies born to sensitised women are at risk of HDFN. They need to be assessed at birth by a paediatrician and may require treatment
Future pregnancies:
-women should be counselled about the likely risk of HDFN. In future pregnancies this should include follow up appointments with an obstetrician and/or haematologist/transfusion specialised and liaison with their general practitioner
Booking visit
A maternal blood sample should be taken early in pregnancy ideally at the first antenatal clinic visit and before 16 weeks of gestation. This is to establish ABO and RhD type of the woman and to screen for the presence of red cell antibodies
If known the gestation of the fetus and any transfusion or anti-D administration history should be included on the request form to assist the effective interpretation of results
Fetal DNA testing
We can now test whether the fetus of a women who is Rh negative is Rh positive or Rh negative
This test can be done from 11+2 weeks up to 24 weeks
The test is sent in a normal group and save bottle, the bottle must be handwritten.
The form can have a sticker on it but there must be a EDD from a scan on the form otherwise the sample will. Be rejected
The results will be put as an alert of Badgernet and a copy sent to woman
If the fetus is predicted Rh negative then the woman doesn’t need to have any antenatal or post natal anti-D—A cord sample needs to be sent at delivery for confirmation of blood group
If the fetus is predicted Rh positive then antenatal and post natal anti-D must be continued- A cord sample and Kleihauer must be sent at delivery
Routine antenatal care
At the 28 week antenatal clinic visit a maternal blood test must be taken to recheck the ABO and RhD type and to screen for presence of any clinically significant antibodies the woman should then be offered routine antenatal anti-D prophylaxis RAADP
RAADP is given as a single dose at 28 weeks
The blood test must be taken before the woman is given RAADP
If anti-D immunoglobulin has previously been given for a potentially sensitising event, antibody screening should still be undertaken and the 28 week dose of RADDAP should still be given
Routine postnatal care
Women who do not receive RAADP at 28 weeks eg. As a result of a missed appointment may still benefit from treatment at a later stage of gestation
The individual circumstances should be discussed with medical staff
Should the woman decline RAADP this should be recorded in her case notes
Postnatal care:
-at birth a cord blood sample should be taken from the baby to check for:
—the ABO and RhD type
A maternal blood sample should be taken no sooner than 30-45 minutes after the placenta has separated. Anti-D immunoglobulin is never administered to a baby
Anti-D informed decision making
Health care professionals have a responsibility to support RhD negative women to make a fully informed decision about the use of anti-D immunoglobulin in pregnancy
Administration of anti-D immunoglobulin and RAADP in particular will benefit a small number of women and may carry some risks. Both health care professionals and the woman herself should be aware that the decision to accept or reject anti-D is hers
Notes
Fit for purpose
Information provided should use readily understandable language and include:
-the reason anti-D immunoglobulin is offered
-the potential benefits
-the potential risks
-the option to decline anti-D immunoglobulin
-a list of potentially sensitising even and action to be taken in relation to them
-sources of further information about anti-D immunoglobulin
-a statement offering the opportunity to discuss anti-D immunoglobulin prophylaxis further
Potential benefits of anti-D immunoglobulin
Although there are some theoretical concerns about anti-D immunoglobulin crossing the placenta entering the fetal circulation and causing harm to the unborn baby this has never been observed clinically
Known side effects of anti-D immunoglobulin occur infrequently and include: localised pain at the injection site, fever and/or malaise and allergic reaction
There are some RhD negative women who do not need or will not benefit from receiving anti-D immunoglobulin. However for these women the decision to decline anti-D immunoglobulin maybe difficult
Examples of such circumstances:
-women who are certain that the father is also RhD negative
-women who are certain this will be their final pregancy
Level of information
HCP should ensure that all women understand the information they have been given.some women will require more detailed info. Provision of this information is the responsibility of the healthcare professional
The overall chance of a woman benefitting from RAADP is around 1 in 5790 this represents the risk of her becoming sensitised and going on to have a pregnancy affected by HDFN
The chance of benefitting through avoiding sensitisation alone is around 1 in 228
In most sensitised pregnancies the baby will not develop clinically significant HDFN. However HDFN can be very serious and in around 10-12% of sensitised pregnancies the fetus will require one or more intrauterine blood transfusions. At present RhD HDFN causes about 37 fetal and neonatal deaths each year in the UK and around same number babies are born with developmental problems caused by HDFN
Level of information continues
All human plasma use in the manufacture of anti-D immunoglobulin is screened for viruses known to be transmitted by blood. Anti-D immunoglobulin is only manufactured from plasma donated in countries outside the UK. This is to minimise any potential risk of vCJD. The risk of viral transmission by anti-D immunoglobulin is considered to be exceptionally low
Transmission of Hep C via contaminated anti-D immunoglobulin is known to have occurred in the Republic of Ireland and in Germany between 1977 and 1979 prior to the introduction of hep c screening of blood donors and following intravenous administration of the product
Level of information 3
Severe allergic reactions caused by anti-D immunoglobulin are rare
Paternal RhD blood group testing is not usually offered routinely but if requested must be determined by formal lab tests
If father is RhD negative all babies born to couple will be RhD- and woman cannot become sensitised to the RhD antigen. Sensitive counselling may be required to establish that women is certain of identity of this babies father prior to paternal RhD blood group testing
Sensitisation is only likely to impact on future pregnancy women who seem certain that this will be their last pregnancy should be counselled on the risk should an unplanned pregnancy occur
For those who will be sterilised at birth or soon afterwards anti-D immunoglobulin is of no benefit
Ordering and administration of anti-D
Anti-D immunoglobulin is given as a standard dose
It’s requested from blood bank on a named patient basis
To request anti-D you must send a pink transfusion request form and tick the box for anti-D
If the request is urgent hand the form to biomedical scientist and state that its urgent and patient is waiting and they’ll issue anti-d soon as
Before administering anti-D it’s imperative to ensure the women has been confirmed as RhD-
Anti-D made from human plasma and is subject to same ID checks and stringent documentation that are applied to the administration of other blood products
In order to be effective it must be given as intramuscular injection
Late administration, omission or administration of anti-D to wrong patient must all be reported via DATIX and the SHOT reporting system
Management continued
Decline RAADP
Some women may not accept RAADP:
-personal choice
-women who choose to be sterilised following delivery
-women sure that father is RhD negative
-where women is sure she wont have another child
Difficult for women to be certain about these factors and the decision to decline should only be made after careful consideration and counselling
Adverse reactions and drug interactions
As with any blood product occasional undesirable effects may occur all adverse effect must be recorded and the patients GP informed
If anti-D given in community setting it’s recommended that where practicable the woman should be observed for 20 mins after admin
Passively acquired antibody (present in anti-D preparation) can interfere with the maternal responses to live virus vaccines such as MMR
Live vaccines such as MMR should not be given within 3 months of injection
In postpartum period MMR may be given with anti-D provided that separate syringes are used and products are administered to separate limbs
If not given simultaneously MMR given 3 months after
Notes 2
Any muscle can be used for administration , care when injecting gluteal area and to women with higher BMI to ensure its intramuscular not subcutaneous
Muscle more vascular so it’s absorbed more effectively
Record must include:
-first and last name women, DOB, unique ID/hospital number and whether consent was given
-name of product, dose, batch number, route, site , time and date of admin
-name and signature of staff who administered it
Accurate documentation important to enable clinicians to plan future treatment. It also allow s lab staff to accurately interpret test results to help determine whether any anti-D present is passive or active
Adverse events relating to anti-D administration
SHOT (serious hazards of transfusion) advise that improving HCP knowledge and understanding of guidance on anti-D immunoglobulin is key to changing practise and improving patient outcomes
SHOT data shows a steady increase over the last 10 years in reported incidence involving anti-D immunoglobulin administration
There is evidence to suggest that poor compliance with guidelines for anti-D immunoglobulin administration is a contributing factor to maternal sensitisation in the UK
Evidence shows a consistent failure to recognise potentially sensitising events in pregnancy and a failure to manage them appropriately when they do occur
For RAADP to be effective it must be administered in the third trimester of pregnancy
The fetal period
Growth and physiological maturation of the structures created during the embryonic period
Period involving preparation for the transition to independent life after birth
From fertilisation to birth
Preembryonic period- 1-2 weeks
Embryonic period- 3-8 weeks
Fetal period 9 to 38 weeks
Pregnancy weeks calculated from date of LMP. I.e conception weeks +2 so term is pregnancy 40 weeks
Respiratory system
The lungs develop relatively late
Embryonic development creates only the bronchopulmonary tree
Functional specialisation occurs in the fetal period
Important implications for pre term survival
Lung development in the foetal period
Weeks 8-16: pseudoglandular stage bronchioles
Weeks 16-26: canalicular stage respiratory bronchioles
Weeks 26-term: terminal sac stage. Alveoli type I and type II cells. Surfactant
