Red Cell Antibodies in Pregnancy - GT65

Question 1

Which red cell antigens can be tested for using non-invasive fetal genotyping?

Answer 1

D, C, c, E, K antigens

Question 2

When would invasive testing be considered for red cell antigens?

Answer 2

If antibodies other than D, C, c, E, K are present

If testing being carried out for other reasons, e.g. karyotyping

Question 3

When (generally) should patients be referred to FMU if the fetus is at risk of anaemia?

Answer 3

Rising antibody levels/titres
Level/titre above certain threshold (see separate question)
USS suggestive of anaemia
Unexplained severe neonatal jaundice
Neonatal anaemia requiring transfusion or exchange transfusion

Question 4

When should referral to FMU be taken for patients with antibodies other than anti- D, c and K?

Answer 4

Hx of previous significant HDFN or intrauterine transfusion

Titire >= 32 (especially if rising)

Question 5

At what level should patients with anti-D antibodies be referred to FMU?

Answer 5

> 4iu/ml

Question 6

At what level should patients with anti-c antibodies be referred to FMU?

Answer 6

> 7.5iu/ml

Question 7

At what level should patients with anti-K antibodies be referred to FMU?

Answer 7

At any level - severity does not correlate with titre level

Question 8

At what level should patients with anti-E antibodies be referred to FMU?

Answer 8

If anti-c also present - potentiates effect; then at lower levels

Question 9

How often should antibody levels be monitored during pregnancy once anti D, c, and K detected?

Answer 9

Every 4/52 until 28/40
Then every 2/52 until delivery
(Even though K doesn’t correlate)

Question 10

How often should antibody levels be monitored during pregnancy (Other than D c and K) ?

Answer 10

Retest at 28/40
Unless previous hx of HDFN
Discuss with bloodbank re: testing if crossmatch isssues anticipated (usually weekly if high risk for blood transfusion)

Question 11

How often should fetal monitoring occur if it has the corresponding antigen or antibody titres reach the required threshold?

And when should invasive treatment be considered?

Answer 11

Weekly ultrasound, especially looking at MCA PSV (peak systolic velocity)
(100% sensitivity - decreases at 36/40 - FPR 12%)

Invasive treatment once MCA PSV rises above 1.5 MoM

Question 12

What type of donor blood should be used for intrauterine transfusion?

Answer 12

• O or ABO typed
• Negative for the antigens corresponding to maternal antibodies
• K neg
• CMV neg and irradiated last 24 hrs - large vol = GVHD
• <5/7
• In CPD anticoagulant

Question 13

What type of donor blood should be used for maternal transfusion?

Answer 13

• ABO and D typed
• K neg
• CMV neg

Question 14

For women with multiple antibodies requiring rare donation - where does frozen blood come from?

Answer 14

National Frozen Blood bank in Liverpool

Question 15

What type of donor blood should be used for neonatal exchange?

Answer 15

• ABO typed with fetus AND mother
• Rh neg (or typed to fetus)
• K neg and neg for antigen causing anaemia
• <5/7 old
• CMV neg and irradiated (if no time delay for latter)
• Plasma reduced, haematocrit 0.5-6

Question 16

What type of donor blood should be used for neonatal small volume top up transfusion?

Answer 16

• ABO typed with fetus AND mother
• Rh neg (or typed to fetus)
• K neg and neg for antigen causing anaemia
• <35/7 old
• CMV neg, irradiated if previous IUT (prevent GVHD)
• Stored in SAGM

Question 17

What cord blood samples should be taken if mum has clinically significant antibodies?

Answer 17

Direct antiglobulin test (DAT)
Hb
BR levels

Question 18

How many pregnancies have antibodies, and what is the prevalence of clinically significant antibodies?

Answer 18

Antibodies 1.2% pregnancies (1 in 80)

0.4% clinically relevant (1 in 300)

Question 19

How many cases of anti D alloimmunisation were accounted for by late immunisation in a first pregnancy, prior to routine anti-D prophylaxis?

Answer 19

18-27%

Similar proportion in 2nd/subsequent pregnancies

Question 20

Which antibodies other than D, c and K can cause significant fetal anaemia?

Answer 20

Anti E,
Fy
Jk
C
Ce

Question 21

What is the perinatal survival for pregnancies with antibodies causing severe anaemia following treatment (hydropic and non-)?

Answer 21

84% overall
Hydropic 74%
Non hydropic 94%

Question 22

How does anti-K cause fetal anaemia and how does it differ from other antibodies?

Answer 22

Erythroid suppression and immune destruction of early erythroid progenitor cells
Hyperbilirubinaemia not a feature, can occur at relatively low titres

Question 23

From what gestation can genotyping (cfDNA) be determined?

Answer 23

16/40 for C, c, E, e
20/40 for K
Can’t determine twins

Question 24

What is the risk of fetal loss following in utero fetal blood sampling?

Answer 24

1-3%, higher if hydropic

Question 25

If ABO, K, D typed blood not matched for other antibodies is the only option for a life threatening haemorrhage, what other measures can be taken?

Answer 25

Give 1g IV methylpred and resuscitate if necessary, including adrenaline
No implications for plts, FFP, cryoprecipitate or fractionated products

Question 26

When should women with clinically significant antibodies be delivered?

Answer 26

If stable throughout pregnancy - aim 37-38/40
If IUT performed will depend on how recent - ie deliver when anaemia avoided (not indication for C/S)
CEFM

Question 27

Why is sensorineural hearing loss more common in infants complicated by haemolytic disease of the newborn?

Answer 27

Toxic effect of prolonged exposure of bilirubin on CNVIII