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2.2 Transfusion Science > Haemolytic Disease of The Newborne > Flashcards

Haemolytic Disease of The Newborne Flashcards

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1
Q

Who is responsible for discovered the process behind HDN

A

Levine and Stetson

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2
Q

When did Levine and Stetson first suggest HDN

A

1939

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3
Q

What happens in HDN
(3)

A

Foetal/maternal blood group incompatibility

Maternal transfer of IgG antibodies against foetal rbc antigens

Results in haemolysis of foetal rbcs

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4
Q

How does the mother become sensitised against the foetus
(3)

A

Small amount of foetal blood enters mothers circulation during first pregnancy

Due to foetal bleed

igG cross the placenta

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5
Q

How is HDN treated
(3)

A

As long as the foetus gets to birth then the child can be treated -> from birth no more antibodies against foetal cells will enter circulation

Baby can die even after birth if there is no intervention

Photolight therapy is often used -> involves using UV light to treat haemolysis in babies -> breaks down bilirubin in jaundiced babies

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6
Q

What antibodies are responsible for HDN

A

Anti-D
Anti-c
Anti-K

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7
Q

What is the most common cause of HDN

A

Anti-D

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8
Q

When might there be immunisation against the foetal cells in the first pregnancy
(3)

A

Due to foetal cells entering the maternal circulation

Foetal maternal haemorrhage

But mother’s antibody titre is usually too low in the first pregnancy to affect the foetus

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9
Q

What blood do we give to women of child bearing years

A

D- and K- blood to prevent antibody formation prior to pregnancy

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10
Q

What is considered the danger period of HDN

A

Soon after the birth of a RhD positive baby

72 hours after birth

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11
Q

List the steps in HDN
(7)

A

Rh negative woman before pregnancy

Pregnancy with Rh-positive fetus

Placental separation

maternal sensitisation to Rh positive blood

Maternal development of anti-Rh antibodies

Anti-Rh antibody to foetal Rh-positive red blood cells

Haemolysis of foetal RBCs

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12
Q

What are the three steps to foetal rbcs destruction in HDN
(5)

A

Foetal rbcs are coated with antibodies

Coated rbcs are removed by splenic macrophages

Foetal haematopoietic tissues increase production of rbcs

Premature release of NRBCs from bone marrow

Severe anaemia with oedema

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13
Q

What are the other names for HDN

A

Erythroblastosis foetalis

Hydrops foetalis

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14
Q

Why is HDN also known as erythroblastosis foetalis

A

It results in the premature release of NRBCs from bone marrow

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15
Q

Why is HDN also known as hydrops foetalis

A

It causes oedema through leakage of fluid into extravascular spaces

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16
Q

What are the clinical effects of HDN on the foetus
(4)

A

Excess breakdown of Hb which leads to raised bilirubin

After birth mother’s circulation no longer removes bilirubin so it builds up in fatty tissue e.g. nervous tissue e.g brain -> kernicterus

Albumin which binds bilirubin is also low in newborns

Anaemia may result in organ failure if severe

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17
Q

What is kernicterus

A

Build up of bilirubin in the brain

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18
Q

Write a note on kernicterus
(6)

A

25-30% of affected foetus are born with pallor

Progressive jaundice ensues

Brain damage occurs within 3-4 days

Death occurs in 90% of patients via respiratory arrest

Surviving 10% have severe brain damage

This rarely happens in first world countries

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19
Q

Why does bilirubin target the brain
(4)

A

Brain composed of nervous tissue

Nerves insulated with myelin

Myelin is a fatty tissue

bilirubin has an affinity for fat

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20
Q

What happens when bilirubin binds to myelin of nerves
(3)

A

Bilirubin impregnates the myelin sheet

Nerve conduction is impaired -> results in short circuits -> nerves will short

Can cause cardiac arrest

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21
Q

What are prenatal tests

A

Test to identify women at risk of HDFN

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22
Q

What are the initial tests carried out on women at risk of HDFN
(5)

A

ABO/D test
Weak D test (optional)
Screening for IgG antibodies
Further igG antibody identification if screen positive
Antibody titration for IgG antibodies to establish baseline

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23
Q

What follow up tests are carried out on women at risk of HDFN is igG positive

A

Selected reagent red cell panel is run to exclude other clinically significant antibodies

Antibody titration in parallel with initial sample at 2-4 week intervals

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24
Q

What testing is carried out of pregnant women at 26-28 weeks pregnant

A

Confirm D typing -> can type foetus from mothers blood

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25
What tests are done when a pregnant woman first visits the hospital (3)
ABO and Rh group is checked Antibody screening Identifying antibodies as IgG or IgM
26
What tests are done when a pregnant woman is at 28 weeks (4)
Titration/Quantification of Anti-D if present Blood grouping of partner -> are they DD or Dd Blood grouping of foetus Amniocentesis to measure bilirubin of foetus Chorionic villus sampling
27
What is chorionic villus sampling (2)
Blood sample taken from chorionic villus to measure haemoglobin to see if foetus is suffering from anaemia This is not really done anymore -> as there is a 1% chance of spontaneous abortion
28
How do we measure bilirubin of foetus now?
Use amniotic fluid Use cell free foetal DNA Doppler Ultrasound used now
29
What is the chorionic vililus
The region where the placenta binds to the foetus
30
what is cffDNA
Cell free foetal DNA
31
What does measuring cffDNA give us (2)
We PCR the D- mother's blood for RhD DNA If RhD DNA present then it must be from the foetus therefore we can type the foetus as RhD+
32
What is a Doppler ultrasound (2)
Colour Doppler ultrasonography Used to detect foetal anaemia
33
How does Doppler ultrasound identify anaemia
Detects increased cardiac output and low blood viscosity Severity of anaemia is determined by evaluating the peak systolic velocity in the middle cerebral artery
34
What is amniocentesis (3)
Amniotic fluid is scanned spectrophotometrically for 350 to 700nm A change in optical density (delta OD) above baseline (450nm) is a measure of bilirubin The delta OD is plotted on a Liley Graph
35
How is a Liley graph used to pick up bilirubin (3)
Upper zone (zone 3): indicates severe HDFN Middle zone (zone 2): moderate disease Lower zone (zone 1): mild disease
36
How is HDN prevented (2)
Give mother anti-D antibodies before she can be stimulated to produce her own antibodies When a D negative mother gives birth to a D positive baby she would be given these anti-D antibodies within 72 hours
37
Where do we get anti-D antibodies for transfusion from? (3)
We haven't been able to produce a monoclonal anti-D yet so instead we use a human blood product They gave D positive blood to D negative men Good responders who produced lots of anti-D antibodies were selected to donate plasma
38
When is anti-D given to pregnant women
Given at 28 weeks Given in the 72 hours after birth
39
Why would we fail to prevent HDN (5)
Anti-D not given Anti-D not given in the 72 hours after birth of baby Silent foetal maternal haemorrhage -> possibility that anti-D will run out by delivery Incorrect timing of Routine antenatal anti-D prophylaxis (RAADP) Another antigen causes HDN e.g. anti-Fy(a)
40
What is RAADP?
Routine antenatal anti-D prophylaxis
41
What is Routine antenatal anti-D prophylaxis (RAADP)?
Administration of RhD+ blood to RhD- pregnant women
42
What's the one issue with RAADP
We can't tell the difference between anti-D from mother or anti-D administered
43
Give the name of one of the anti-D products used regularly
Rhophylac
44
What Rh Igs are not indicated -> in what scenarios does anti-D not need to be administered
Patients who are already sensitised Weak D's If the infant is Rh negative For women not capable of child bearing age
45
What is FMH?
Foeto-maternal haemorrhage
46
List the methods for estimating FMH (3)
Kleihauer Betke test Rosetting technique Flow cytometry
47
What is the Kleihauer Betke test (2)
Kleihauer Betke acid elution technique This test relies on the resistance of HbF to be eluted(removed) out of the rbc by an acid buffer solution
48
How is the Kleihauer Betke Test (KEB test) carried out? (6)
Mothers blood with EDTA Blood film Dip in acid Adult haemoglobin is acid soluble but HbF is not Only foetal cells are left on the blood film Count the foetal cells to determine how many cells are in mothers circulation and therefore how big of a bleed it was
49
What is the rosetting technique (3)
A technique used to demonstrate small numbers of D positive cells in a predominantly D negative population Detects FMH of approximately 10mls This isn't really carried out in Ireland anymore but is still done in the US
50
How is rosetting carried out
Count the rosettes seen in a blood film D-positive cells will have rosettes of cells around them
51
How is flow cytometry used to estimate FMH
Use flourescein labelled anti-D antibody
52
What is a DAT
Direct Antiglobulin test
53
What is a direct antiglobulin test (3)
DAT diagnoses the presence of antibodies on cells Cells shouldn't normally be coated in antibodies There will be maternal antibodies on foetal cells if there has been a bleed -> these indicate that the rbcs are being destroyed
54
Why might there be antibodies on cells (4)
Occurs in pregnancy Occurs in autoimmune reaction Occurs in transfusion Used for demonstration of in vivo sensitisation of red cells with antibodies
55
How is a DAT carried out (4)
Cells are coated with antibodies in vivo We wash the cells to remove unbound globulins We add anti-human globulin (AHG) which promotes agglutination after centrifugation If there has been in vivo sensitisation then the cells will clump after addition of AHG
56
What is an indirect antiglobulin test (3)
Serum with specific antibody mixed with reagent red cells Washed 3x after incubation to remove unbound globulins Anti-human globulin is added to promote agglutination on centrifugation
57
What is the direct antiglobulin test also called?
Direct Coombs test
58
How do we carry out a direct antiglobulin test (4)
Blood sample taken from patient with haemolytic anaemia Antibodies are shown attached to antigens on the RBC surface The patients washed RBCs are incubated with antihuman antibodies (Coombs reagent) RBCs agglutinate: antihuman antibodies form links between RBCs by binding to the human antibodies on the RBCs
59
How do we carry out an indirect coombs test/antiglobulin test (5)
Recipient's serum contains antibodies Donors blood sample is added to the tube with serum Recipient's Ig's that target the donors red blood cells form antibody-antigen complexes Anti-human Ig's are added to the solution Agglutination of red blood cells occurs, because human Ig's are attached to rbcs
60
How do we treat affected babies (5)
We measure anti D and anti C to see how severe the disease is Prenatal: - Intra-uterine transfusions can be done - Plasma exchange Postnatal: - exchange transfusions - phototherapy to break down bilirubin pigment
61
What is considered mild, moderate and severe anti-D ?
mild < 4 Moderate = 4 -> 15 Severe = 15+
62
What is considered mild, moderate and severe anti c?
Mild = < 8 Moderate to severe = 8+
63
What is an intra-uterine transfusion (5)
Transfusion guided by ultrasound via the placenta Highly concentrated rbc pack is used 1 in 100 risk of spontaneous abortion Transfuse about 20 units a year Medical scientists will actually come out of the lab and see the patient for this
64
What is plasma exchange
This is done on the mother -> removes anti-D antibodies from mothers circulation
65
What tests may be done on a HDN baby
Haemoglobin Bilirubin DAT
66
How is Hb affected by HDN?
Babies born will have low Hb
67
How is bilirubin affected by HDN?
babies born will have raised bilirubin
68
What will a DAT reveal in HDN babies
May reveal babies have in vivo coating of red cells with maternal antibody
69
Why might an exchange transfusion be carried out on a baby
Take out some of the babies blood and give D negative blood -> only transfuse very small volumes approx 50mls
70
How do intrauterine transfusions work
Foetus receives transfusion through the umbilical vein in the placenta
71
What blood is given to newbornes in need of transfusion (7)
Blood must be less than 5 days old Must be packed red cells Must be leucocyte depleted Must be irradiated Must be from a cytomegalovirus negative donor Must be a small volume - approx 50 mls Must be HbS negative
72
Why must blood be less than 5 days old to be given to a baby (4)
Stored blood is fine for an adult But rbcs leak potassium when in storage High potassium can cause heart attack in newborns New borns aren't able to regulate salts and electrolytes as easy as adults
73
Why are rbc packs for babies leucocyte depleted
Leucocytes will continue to live in the patient if their body can't kill them Leucocytes will colonise baby's circulation
74
Why are rbc packs irradiated (2)
This ensures no nuclear material -> leukocytes can be found in the newborn If this is not done Graft versus host disease will result which is nearly always fatal in newborns
75
What is graft versus host disease (2)
White blood cells of the donor's immune system which remain within the donated tissue recognize the recipient as foreign. The white blood cells present within the transplanted tissue then attack the recipient's body's cells
76
What happens if a group O mother has a group A or B baby (7)
Disease state usually mild 1st pregnancy can be affected -> already have anti-A or anti-B antibodies Anti A or Anti B antibodies are IgG and can cross the placenta Mild disease as ABO antigens are mildly expressed by the foetus DAT will be positive Phototherapy can be used to treat Transfusion can be given if required
77
Why might a premature baby need a transfusion (3)
Premature babies need a lot of monitoring so a lot of tests are carried out Even though only small volumes of blood are taken this all adds up if baby is being tested multiple times a day Baby might need a transfusion to top up

2.2 Transfusion Science (22 decks)

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