Genetics play an important role in fetal and neonatal alloimmune thrombocytopenia (FNAIT). This rare autoimmune disease occurs when a fetus inherits a human platelet antigen (HPA) from its father that the mother doesn’t possess.
This genetic incompatibility causes the mother’s immune system to develop antibodies against her baby’s blood platelets, which cross the placenta and destroy them. Genetic testing is key to diagnosis and disease management.
What is FNAIT?
FNAIT is a rare but serious hematological autoimmune disease that can occur in pregnancy when the fetus’s genetically incompatible blood comes into contact with the mother’s blood, triggering the maternal immune response. It can be potentially life-threatening for the fetus.
Learn more about FNAIT causes and risk factors
Platelets are small blood cells and their main function is to prevent or stop bleeding, so when the fetus or neonate platelet count drops there is a significant risk of internal bleeding. This can occur in the brain (intracranial hemorrhage or ICH), the stomach or spinal cord. If bleeding occurs on the brain and is not treated urgently with platelet transfusion, the baby risks long-term neurological damage or death.
Genetic screening for FNAIT
Screening for FNAIT is not part of standard prenatal screening procedure. Testing is therefore only performed if there is a family history of FNAIT or if bleeding has been detected in the fetus.
During pregnancy, the genetic test for FNAIT involves identifying the HPA types of both parents to understand the risk factor. A diagnosis of FNAIT can be confirmed by determining the fetus’s HPA type by testing DNA extracted from fetal cells that have been obtained via amniocentesis.
This is an invasive test and comes with a certain level of risk of bleeding and potential miscarriage. A newborn who is suspected of a low platelet count (thrombocytopenia) or FNAIT will also have his/her HPA type tested to confirm the diagnosis of FNAIT.
As a rare disease, FNAIT is not well-known to all doctors, and the HPAs associated with FNAIT differ according to the population. For example, in White people, FNAIT is usually associated with anti-HPA-1a antibodies, while in African Americans, it’s more likely to occur in babies with HPA-2 and HPA-5 antigens. In Japanese populations, FNAIT is more common in babies with HPA-4 and HPA-5 antigens.
Genetic testing is performed to ensure the correct diagnosis and guide treatment but also to inform the care protocol for subsequent pregnancies.
FNAIT in subsequent pregnancies
Once FNAIT is confirmed by genetic testing in a pregnancy or in a newborn, subsequent pregnancies are at higher risk of being affected. Future pregnancies will require close monitoring and possible proactive treatment with intravenous immunoglobulin (IVIG) of the pregnant woman at risk of developing FNAIT.
