Fetal and neonatal alloimmune thrombocytopenia

December 31, 2014

Overview

Neonatal Alloimmune Thrombocytopenia (NAIT) is a blood-related disease that affects expectant mothers and their babies.

Most people are familiar with the red blood cells that make up the majority of the blood in our bodies, but may not be aware of a second type of cell in our blood stream called platelets. These small cells are responsible for stopping bleeding in the human body.

Neonatal Alloimmune Thrombocytopenia is a disease that develops when platelets in the pregnant mother and her baby become incompatible and cannot exist together.

Causes

Neonatal Alloimmune Thrombocytopenia is caused when the mother’s and baby’s platelets become incompatible, a condition known as platelet alloimmunization. To understand platelet alloimmunization, you must first understand about different platelet types. Platelet types are defined by antigens, substances or “factors” that exist on the surface of the cell. The most common of these is the HPA-1 antigen, which is present in 98% of people. These patients are referred to as HPA-1 positive. When their blood is tested, the test will return as HPA-1a/1a or HPA-1a/1b. About 2% of the population is HPA-1 negative; these patients are called HPA-1 negative. A blood test on one of these patients will return as HPA-1b/1b.

There are other platelet antigen systems found in humans that are associated with Neonatal Alloimmune Thrombocytopenia, including HPA-3, HPA-4 (present in people of Asian descent), HPA-5, HPA-9 and HPA-15. If an antigen is present, the person is called positive for the antigen; if it is absent, the person is called negative for the antigen.

When a woman becomes pregnant, genes (inherited traits) from her egg are combined with genes from her partner’s sperm. Together a unique embryo (future baby) is formed. This embryo carries with it genes from both the mother and the father. These genes include things such as hair and eye color, body build, blood type and platelet type.

Platelet alloimmunization happens when a mother’s body forms antibodies (a protein substance that reacts to unrecognized proteins in the body) in reaction to antigens that are different from her own.

These antibodies are usually formed when the mother’s blood circulation comes in contact with blood from another person that is different from her own. This can happen with blood transfusion, or during a miscarriage, abortion, or after the delivery of a child, when the baby’s blood mixes with the mother’s. It can also happen during pregnancy, as the baby’s blood can cross the placenta and come in contact with the mother’s. If the mother’s platelet type is negative for a certain antigen and the baby’s platelets are positive for that antigen, the mother may form antibodies against the baby’s platelets.

During pregnancy, these antibodies cross the placenta (afterbirth) and attach to the platelets in the baby’s blood.

The antibodies can cause the unborn baby’s platelets to disappear from his or her blood stream, resulting in a low platelet count. This is called thrombocytopenia. The disease process that happens in the fetus or baby is known as Neonatal Alloimmune Thrombocytopenia. It is a direct result of the platelet alloimmunization in the mother. In about one fourth of cases, the baby can experience spontaneous bleeding into the brain; in about one third of these cases, this leads to fetal death.

Prevention

No, there is currently no medication to prevent the development of platelet antibodies that occurs with Neonatal Alloimmune Thrombocytopenia.

Diagnosis

There is no routine blood test that is performed in pregnancy to see if a mother has antibodies to platelets. Most mothers do not even know they have this disease unless they give birth to a baby with a low platelet count or if their sister gives birth to an affected baby.

Physicians take several steps to diagnose this disease. They can:

Check the mother's platelet type
Check the father’s platelet type
Check the mother's blood for antibodies
Perform an amniocentesis (the process of getting a fluid sample from the amniotic sac) to check the baby’s platelet type
Perform several ultrasounds
If necessary, conduct a cordocentesis (the process of getting a blood sample from the unborn baby’s umbilical cord) for more information.

Checking the Mother’s Platelet Typ

One of the first steps in finding out whether platelet alloimmunization is present is to check the mother’s platelet type. This involves drawing a special blood sample and sending it to a reference laboratory. If the mother is HPA-1 negative, the test result will return HPA-1b/1b.

Treatment

In an effort to prevent a low platelet count in the baby, a medication called intravenous immune globulin is often prescribed. This medication is made from antibodies from many people. The exact way that intravenous immune globulin prevents thrombocytopenia in the baby is unknown. It may cause the mother to make less anti-platelet antibodies, it may block her antibodies from crossing the placenta (afterbirth) to get to the fetus or it may prevent the platelets in the fetus that have antibodies attached to them from being destroyed.

The major side effects of this medicine appear to be severe headache, nausea and rash. Patients may take two extra-strength acetaminophen tablets (Tylenol®) and an anti-histamine (Benadryl) before receiving intravenous immune globulin. Typically the first one or two doses are given in the hospital over six to eight hours. Subsequent doses are given weekly and can be administered by a home health care agency. Intravenous immune globulin is very expensive, however most insurance companies pay for its use in Neonatal Alloimmune Thrombocytopenia after it has been pre-approved.

(Note: Medication brand names will differ according to country, as will treatment costs, place and time taken for IVIG administration.)

The dose and the timing for the start the intravenous immune globulin typically depend on how severely a previous child was affected by Neonatal Alloimmune Thrombocytopenia.

If a previous child had only a low platelet count after birth, then intravenous immune globulin is usually started at a low dose (usually one gram/kilogram of maternal body weight) at 20 weeks of the pregnancy. This is repeated weekly. At around 32 weeks into the pregnancy, prednisone, a steroid pill that is taken by mouth, may be added. This medication is usually taken once or twice daily. Prednisone is usually well-tolerated, although it can be associated with diabetes in pregnancy, weight gain, mood changes and an increase in appetite.
If a previous unborn child had bleeding into the brain before seven months of pregnancy, then intravenous immune globulin is started as early as 12 weeks of pregnancy at a higher dose (two grams per kilogram of body weight). The dose is usually given over two separate days to reduce the rate of complications; this is repeatedly weekly. Prednisone is usually added at around 20 weeks of the pregnancy.
If bleeding occurred into the brain of a previous unborn child after seven months of the pregnancy and before 36 weeks’ gestation, intravenous immune globulin is usually started by 12 weeks of pregnancy at a dose of one gram/kilogram and repeated weekly. Prednisone is added at around 20 weeks and the dose of intravenous immune globulin is increased to two grams/kilogram at around 28 weeks of the pregnancy. The increase in the dose of intravenous immune globulin will required two infusions each week.
If bleeding occurred into the brain of a previous unborn child after 36 weeks of the pregnancy or after the child was born, intravenous immune globulin (one gram/kilogram/week) is started at around 12 weeks of the pregnancy. At 24 weeks of gestation, the dose of intravenous immune globulin may be increased to two grams/kilogram/week OR prednisone may be prescribed.

Platelet transfusions to the baby in the womb are not typically used as the primary treatment for Neonatal Alloimmune Thrombocytopenia during pregnancy. Giving platelets to the unborn baby is associated with a risk of bleeding from puncture of the umbilical cord. In addition, platelets do not last more than seven to ten days in the baby once they are given.