Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs due to a genetic incompatibility between the mother and baby due to inherited paternal platelet antigens.
FNAIT is a rare blood disorder affecting 0.1% of births, and there is no standard prenatal screening test. Unless FNAIT was diagnosed in a previous pregnancy or there is a family history of the disorder, more specifically in the mother’s sister, then there is little warning that a pregnancy will be affected.
What is FNAIT?
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare but serious condition that affects 0.1% of pregnancies in which a pregnant mother’s immune system produces antibodies against the platelets of her fetus. This occurs when a fetus inherits platelet antigens from the father that are not compatible with the mother, typically involving a protein called human platelet antigen (HPA). The mother’s immune system recognizes the fetal platelets as foreign, attacking and destroying them, leading to low platelet levels (thrombocytopenia) in the fetus or newborn.
Platelets and human platelet antigens (HPAs)
Platelets are cells in the bloodstream. Their role is to stop or prevent bleeding caused by injury in the body by clotting the blood. The surface membrane of platelets contain natural proteins, called antigens. There are 35 different platelet-specific antigens, with some rarer than others, and only a few are implicated in FNAIT.
The fetus inherits half the antigens from the mother and half from the mother. FNAIT occurs when the fetus inherits a human platelet antigen (HPA) from the father that is not present in the mother, creating a genetic mismatch between mother and baby. During pregnancy, if the fetus’s blood platelets come into contact with the mother’s blood–known as alloimmunization–the maternal immune system classifies them as a foreign entity.
This causes the mother’s immune system to respond by creating antibodies that cross the placenta and attack the fetal platelets. The consequences of severe thrombocytopenia, in particular intracranial hemorrhage (ICH) can cause long-term neurological damage or death to the fetus or newborn.
Accounting for approximately 75% of FNAIT cases in the White population, the most common HPA affected in FNAIT is HPA-1, when the fetus inherits HPA-1a from the father and the mother is HPA-1a negative. The next most common is HPA-5b, with 20% of cases. In the Asian population, HPA-4b is more common.
Diagnosing FNAIT
If FNAIT is suspected during pregnancy, the mother will undergo an HPA antibody screen to identify whether or not she is producing alloantibodies to a specific HPA. HPA genotyping of the mother and father will also be performed via a blood test. This will determine potential genetic maternal-fetal incompatibilities. The most critical procedure is non-invasive fetal genotyping using next generation sequencing of cell-free fetal DNA in the mother’s plasma, which is key in confirming diagnosis.
Diagnosis often occurs post-delivery when the newborn presents with bruising, bleeding under the skin known as petechiae and purpura, hematoma and a low platelet count. Urgent platelet transfusions are required to treat FNAIT in newborns, without waiting for a confirmed diagnosis of FNAIT. A diagnosis of FNAIT in the newborn can also be determined via HPA genotyping of the mother, father and baby.
