Neonatal Alloimmune Thrombocytopenia Overview

Neonatal alloimmune thrombocytopenia (NAIT) is a rare condition of platelet mismatch between a mother and her infant. During pregnancy, the mother produces antibodies that attack and destroy platelets, resulting in severe thrombocytopenia (low platelet count) and bleeding in the fetus. It is similar to hemolytic disease of the newborn, a disorder of the red blood cells.

NAIT should not be confused with neonatal autoimmune thrombocytopenia. Neonatal autoimmune thrombocytopenia occurs in mothers with immune thrombocytopenia (ITP) or lupus. The mother has platelet antibodies in her circulation that attack her own platelets. These antibodies transfer to the fetus via the placenta, resulting in the destruction of his or her platelets as well.

Symptoms

The symptoms of NAIT are dependent on platelet count. If a woman is pregnant for the first time, there are often no problems until the baby is born. During the first week after birth, the thrombocytopenia worsens. As the platelets drop, increased bruising, petechiae (small red dots on the skin), or bleeding may be noted.

The most serious complication of NAIT is bleeding in the brain, called intracranial hemorrhage (ICH). This occurs in 10-20% of infants. Infants with very low platelet counts are screened for ICH with cranial ultrasounds. If a woman chooses to become pregnant again, thrombocytopenia can be more severe, and ICH can occur prior to birth (while in the uterus).

Causes

Our platelets are coated with antigens, substances that induce an immune response. In NAIT, an infant inherits a platelet antigen from the father that the mother does not have. The maternal immune system recognizes this antigen as "foreign" and develops antibodies against it. These antibodies transfer from the mother to the fetus via the placenta, where they attach to platelets, marking them for destruction. Unlike hemolytic disease of the newborn, this can occur with the very first pregnancy.

Diagnosis

There is a long list of possible reasons for thrombocytopenia in a newborn. Most of these are due to infections like congenital cytomegalovirus, congenital rubella, or sepsis (severe bacterial infection). In these circumstances, usually the baby is quite ill. NAIT should be considered in a well-appearing infant with severe thrombocytopenia (platelet count less than 50,000 cells per microliter).

In NAIT, the infant receives treatment prior to diagnosis, since confirming the diagnosis takes several weeks. Confirming NAIT requires blood testing of the parents, not the infant. The mother will have a normal platelet count, since the antibodies do not attack her platelets. Blood is sent to a special lab to assess whether the mother and father have mismatching platelet antigens and whether the mother is making antibodies to platelet antigens found in the father. If NAIT is suspected, it is very important to confirm the diagnosis, since future pregnancies can be more severely affected, with more severe thrombocytopenia and intracranial hemorrhage in utero (prior to birth).

Treatment

Mildly affected infants may not require treatment. In more severely affected infants, the goal of treatment is to prevent or stop active bleeding, particularly in the brain.

• Platelet transfusions: Because the mother's platelets do not have the offending antigen and therefore will not be destroyed, ideally, platelets transfused to the infant would come from their mother or from a donor similar to the mother. This process can take a long time and is not always practical in real life. If the thrombocytopenia is severe (< 20,000 cells per microliter) or bleeding occurs, platelet transfusions from the volunteer donor system are given. These are often administered at the same time as intravenous immune globulin to prolong the life of the platelets.
• Intravenous immune globulin (IVIG): IVIG can be infused into the infant to distract the immune system. IVIG contains numerous antibodies from multiple donors. These antibodies overwhelm the immune system and slow down the destruction of the platelets, similar to treatment of ITP. This is used in conjunction with platelet transfusions.
• Counseling: Parents who have a child with NAIT should be counseled about the risk of this condition occurring in future pregnancies. Given this risk, future pregnancies should be monitored by a high-risk obstetrician. IVIG may be administered to the mother during the pregnancy or platelet transfusion may be given to the developing fetus to prevent severe bleeding. Cesarean section is recommended for delivery to prevent bleeding.