HDFN detection and treatment- amanda Flashcards
Laboratory based diagnostic testing
-pregnant women ABO and RhD grouped and screened for presence of red cell antibodies during early and late pregnancy
-when present, antibody specificity is identified and when antibody poses HDFN risk, levels are determined and monitored to identify sudden changes which would indicate problems for the foetus.
—monitor antibody levels by antibody quantitation (anti-D,-c) and antibody titration for all other antibodies
- paternal sampling- phenotype and zygosity testing when appropriate (Rhc, RhD, K)
Alternative methods
-foetal blood type: chronic villus sampling, cell free fetal DNA (cffDNA) from maternal blood sample
-amniotic fluid sampling for rising bilirubin levels
-ultrasound (hydrops, and mid cerebral velocity MCV)
Anti-D in HDFN
-Anti-D most common cause of HDFN due to its high immunogenicity
-despite anti-D prophylaxis program, maternal sensitisation occurs in approx. 1000 RhD negative pregnancies annually
-rarely effects 1st pregnancies
Anti-K in HDFN
-Anti-K 2nd most common cause
-characterised by severe HDN at low antibody concentrations due to the haemolysis of sensitised foetal red cells as well as erythroblasts which impacts compensatory erythropoiesis
-over 50% of antibodies are produced as a result of multiple transfusions with the remainder produced as a result of a previous pregnancy
Anti-c in HDFN
-anti-c = 3rd most common cause
-policy of providing R1R1 blood to c negative women of child bearing age by Welsh blood service who undertake large scale antenatal testing
How might we predict there’s a risk of HDFN?
-antibody levels
Quantitation:
-anti-D (mild <4iu/ml, severe >15iu/ml)
-anti-c (mild <7iu/ml, severe >20iu/ml)
Titration:
-anti-K: no cut off titration but highlight increasing titres
-antibodies other than -D, -c, -K -no problems if titre score <32 but increasing titration scores referred for further investigation)
Invasive procedures for detection
-amniocentesis: indirect surrogate marker for haemolysis except where alloantibody is anti-K: used to measure OD450 as a measure of bilirubin in amniotic fluid., 1% risk of pre-term labour, miscarriage and foetal demise
-foetal blood sampling from the placental cord insertion or the intrahepatic vein gives a direct marker for foetal anaemia, however procedure associated with 1-3% foetal loss which can be as great as 20% for hydropic foetuses
Non-invasive procedures for detection
Ultrasonography to detect early features of hydrops such as subcutaneous scalp oedema, pleural and pericardial effusions, ascites and a thickened hydropic placenta
Velocimetry of foetal middle cerebral artery by Doppler ultrasonography. Anaemic foetuses have a hyper dynamic circulation which can be assessed by measuring the maximum or mean velocity in the middle cerebral artery- MCA velocity correlates with increasing levels of bilirubin in amniotic fluid
Treatment
Transfusion:
-interuterine transfusion- manage severe anaemia in utero
-exchange- reduce unconjugated bilirubin concentration usually required within a few days of delivery and increase RBC count, Hb, and Hct
-top up- correct anaemia when bilirubin levels are not significantly high
Requirements of RBC donations for foetal and neonate transfusions
-cytomegalovirus negative (CMV)
-stored for less than 5 days due to potassium levels
-irradiated to prevent TaGVHD
-low concentrations of anti-A and anti-B in the donor plasma
Alternate treatments
-treatment with intravenous immunoglobulin in severe cases of RhD incompatibility, not uniformly effective in inhibiting haemolysis but when successful serum bilirubin concentrations fall
-early delivery with the possible administration of antenatal steroids to assist foetal lung maturity
-UV light treatment of infants to breakdown unconjugated bilirubin deposited in the skin for those not severely affected
Prevention
-provision of antigen negative blood to women of child bearing age: RhD negative blood to RhD negative women- universal, R1R1 blood to c negative women- WBS region, K negative blood to all women of child bearing age
-anti-D prophylaxis: following potential sensitising events I.e. antenatal trauma, delivery, miscarriage etc.- anti-D works by a negative feedback mechanism or by blocking RhD antigenic determinants on red cells
Characteristics of cffDNA
-fragmented with average DNA fragment size of 200bps, mainly derived from apoptosis rather than necrosis
-rapidly removed from the maternal circulation after delivery and therefore relevant to current pregnancy only
-unable to separate maternal from foetal DNA so current NIPD testing relies upon the detection or exclusion of gene sequences that are not present in the mother
-1 in 1 billion foetal cells need mechanical separation and may exist in maternal circulation for many years
Non-invasive prenatal testing
- Lo et al, 1997 reported the detection of cffDNA in maternal plasma/serum
-NIPT involves analysis of cell free foetal DNA circulating in maternal blood
-cffDNA represents extracellular DNA which originates from trophoblastic cells
Application of NIPT
Possible to sequence and genotyping foetal DNA in maternal plasma.
- foetal DNA thought to be derived from foetal trophoblasts constitutes as much as 3% of maternal plasma DNA in early pregnancy rising to 6% in the 3rd trimester
NICE approved NIPT testing
Individual testing:
Foetal genotyping
Foetal gender
Aneuploidy
Haemoglobinopathies
Other single gene disorders such as cystic fibrosis, haemophilia etc.
- High throughout NIPT for foetal RHD genotype to guide antenatal prophylaxis with anti-D immunoglobulin to those RhD negative women who need it
RHD genotyping from maternal plasma
- manage pregnancies in previously sensitised antenatal patients (who have made anti-D)
- avoidance of invasive procedures which Cary an associated risk of miscarriage and stimulate further antibody production
- All RhD negative women
- avoidance of administering un-necessary blood product - approximately 40% of all RhD negative pregnancies - and the associated cost savings
