Abstract
Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).
Financial & competing interests disclosure
ND Avent is a member of the Transfusion Medicine Advisory Board of Grifols SA. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Free fetal DNA based testing for most blood group alleles that cause hemolytic disease of the fetus & newborn and HPA-1A platelet antigens are in widespread use.
The use of amniotic fluid as a source of fetal DNA has largely been eliminated, and should be actively discouraged in preference to maternal plasma testing.
Mass scale application of fetal RHD genotyping has led to the focused and reduced use of prenatally administered prophylactic anti-D.
Whilst the economic value of applying prophylactic anti-D as directed by prenatal diagnosis is debated, there is no doubt that ethically wasteful use of a blood product obtained from male volunteers should be avoided.
A preliminary trial of the efficacy of prophylactic treatment of HPA-1b1b mothers with anti-HPA-1a is being considered in Norway, and has shown to be effective in human volunteers. This may pave the way to the routine prophylaxis in these mothers in the future.