What is Neonatal Alloimmune Thrombocytopenia?

An overview

Physician examining newborn
Physician examining newborn. Blend Images - ERproductions Ltd/Creative RF/Getty Imagea

Defintion

Neonatal alloimmune thrombocytopenia (NAIT) is a rare condition of platelet mismatch between 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 destruction of his/her platelets as well.  

How does this present?

The symptoms are dependent on the platelet count.  Often in the first pregnancy, there are no problems until the baby is born.  During the first week, 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.  In future pregnancies the thrombocytopenia can be more severe and ICH can occur prior to birth (while in the uterus).

 

Why does this occur?

Our platelets are coated with antigens, substances that induce an immune response.  In NAIT, the 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.  

How is it diagnosed?

There is a long list of possible reasons for thrombocytopenia in a newborn.  Most of these are due to infections like congenital CMV, 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 for prior to diagnosis as 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 as 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 if the mother is making antibodies to platelet antigen found in the father.

 If NAIT is suspected, it if very important to confirm the diagnosis as future pregnancies can be more severely affected with more severe thrombocytopenia and intracranial hemorrhage in utero (prior to birth).

How is this treated?

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 come from the volunteer donor system are given.  These are often administered 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 in 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 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.  

Reference

Karen S. Fernandez and Pedro de Alarcon.  Neonatal Thrombocytopenia.  NeoReviews. 2013.

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