W11L8 - Haemolytic Disease of the Newborn Flashcards
What is HDN Characterised by?
Jaundice, significantly elevated (> 300 µM) and/or rapidly rising (> 8.5 µM/hr) serum bilirubin within 24 hours or >14 days post partum
Positive DAT
Maternal antibody
Severe HDN → kernicterus, hydrops fetalis
HDN Mechanism
- Ag neg mother carrying ag pos child (Ag pos father)
- Mother is exposed to child RBCs (during amniocentesis, delivery, etc)
- Mother’s immune system mounts immune response against foreign antigen → IgG aby produced
- During subsequent pregnancy, maternal IgG aby crosses the placenta and enters foetal circulation
- Maternal IgG aby binds to foetal RBCs (if Ag pos)
- Aby coated foetal RBCs destroyed by foetal reticuloendothelial system
Which Antibodies Cause HDN?
IgG antibodies reactive in the IAT Rhesus - anti -D, -c, -C, -e, -E Kell - anti -K, -k Duffy - anti-Fya MNS, Kidd ABO
Tests for Foetal Anaemia
Performed if quantitation/titration suggests risk of HDN
Middle cerebral artery (MCA) doppler ultrasound
- non-invasive
- velocity of blood flow in middle cerebral artery is measured
- ↑ blood flow = anaemia
Antenatal and Postnatal Practice at Delivery
Mother
- ABO and Rh(D) group, screen and aby ID (if not performed already)
- determine degree of foetomaternal haemorrhage (FMH) by Kleihauer or flow cytometry, only in Rh(D) neg mother delivering Rh(D) pos baby
Baby
- if mother is Rh(D) neg or has a clinically significant antibody
- ABO/Rh(D) group, DAT, Elution studies, Hb, bilirubin
HDN Treatment
Phototherapy
Exchange Transfusions
Exchange Transfusions
Can be performed in utero (intrauterine) or in a newborn
Intrauterine allow the lungs to develop until baby can be delivered
Blood should be:
- < 5 days old (for intrauterine)
- ABO and Rh compatible w/ mother and foetus. O Rh(D) neg if foetal status is
unknown.
- K neg (for intrauterine)
- Ag neg for the relevant maternal aby
- matched to the maternal phenotype
- CMV negative
- Irradiated
- Hct of at least 70%
- X-match compatible with maternal or infant plasma
Modifications of Blood Components
- Paediatric units of RBCs (and platelets/plasma, too!)
- CMV-negative RBCs and platelets
- CMV = cytomegalovirus
- carried by WBC’s
- self-limiting in healthy, can cause morbidity and mortality in at-risk groups
- fever, malaise, lymphadenopathy, rash, pharyngitis through hepatitis, meningoencephalitis, nephritis, leukocytosis, leukopenia, thrombocytopenia, haemolytic anaemia
Indication
- CMV-seronegative, at-risk patients
- at-risk patients include: transplant recipients, immunosuppressive chemotherapy, intrauterine transfusion, neonates, pregnant women
Irradiation
RBCs, platelets
Products are treated w/ 25-50 Gy γ-radiation
To prevent transfusion associated graft-vs-host disease
- prevents proliferation of donor T lymphocytes
When this is used:
- directed donation
- HLA-matched transfusions
- intrauterine transfusion
- newborns
- immunodeficiency
RBCs - irradiated within 14 days, used within 14 days
Prophylactic Anti-D
Can’t be distinguished from immune anti-D
Clinical history is crucial
If anti-D quant is low and falling, probably prophylactic
If anti-D quant is stable, probably immune
Treatment w/ prophylactic anti-D should continue until it’s confirmed that anti-D is immune
Anti-C+D vs Anti-G
G antigen
- an antigen in the Rh blood group
- present on C and D antigens, and therefore C+ and/or D+ RBCs
Individuals who are G- can produce an anti-G antibody
- most Rh(D) neg individuals are rr, and therefore are also G-
- sensitised to G antigen after exposure to r’r cells (via transfusion or pregnancy)
Anti-G will react to C+ D+ cells on ID
Is the antibody present anti-G, or are two aby’s present (i.e. anti-C+D)?
-anti-C+D - anti-D component is usually stronger than anti-C
- anti-G - apparent anti-C component (i.e. reactivity against D-C+ cells) is stronger than apparent anti-D component (i.e. reactivity against D+C- cells)
Important to differentiate, because someone producing anti-G (or anti C+G) is eligible for Rh(D)Ig, whereas someone producing anti-D+C is not
Anti-K HDN
Anti-K HDN differs to anti-D HDN in that:
- previous history is not indicative of disease severity
- poor correlation between aby titre and disease severity
- haemolysis is not a dominant feature
Elevated bilirubin is not a feature in newborns
Anaemia is due to insufficient erythropoiesis
- erythroid progenitors express Kell antigen
- aby binding prevents proliferation
Anti-K HDN - If Mother has Anti-K Aby
Refer to specialist foetal medicine unit, irrespective of aby titre
Phenotype/genotype father
If father is K+, genotype foetus using foetal DNA from maternal plasma
If foetus is K+, perform MCA Doppler and perform intrauterine transfusion if necessary
To help prevent HDN due to anti-K, all K- (or unknown phenotype) females of childbearing potential are transfused with K- units wherever possible
ABO HDN
Is currently the most common cause of HDN
Pregnant women can produce high-titre IgG ABO aby’s
Can occur in first pregnancy
Most common in maternal group O, foetal group A
Elevated bilirubin w/o significant anaemia
- foetal RBCs have relatively low ABO Ag’s, so sensitised cells remain in circulation longer
DAT positive, though not always
Spherocytes
Not usually severe - treat with phototherapy
ABO incompatibility appears to protect against alloimmunisation to other blood group incompatibilities
HDN Due to Low Incidence Antigens
In some instances, the father may produce a low incidence antigen that is subsequently produced by the foetus and results in sensitisation of the mother
Remember, aby’s against low incidence antigens are commonly missed on aby screens
Consider when the foetus exhibits signs of HDN w/ positive DAT, but with neg maternal aby screen and ABO compatibility between mother and foetus
Detected by performing IAT XM with maternal plasma and paternal RBCs
