Neonatal alloimmune thrombocytopenia

Neonatal Alloimmune Thrombocytopenia (NAITP or NAIT or NAT for short; or

feto-maternal alloimmune thrombocytopenia, FMAITP or FMAIT) is a disease
that affects fetuses and newborns. Genetic differences between the fetus and mother
may result in the expression of certain antigens by fetal platelets, not expressed by the
mother. Fetomaternal transfusions result in the recognition of these antigens by the
mother's immune system as non-self, with the subsequent generation of allo-reactive
antibodies which cross the placenta. NAIT, hence, is caused by transplacental passage
of maternal platelet-specific alloantibody and rarely human leukocyte antigen (HLA)
allo-antibodies[citation needed] (which are expressed by platelets) to fetuses whose platelets
express the corresponding antigens. NAIT occurs in somewhere between 1/800 [1] and
1/5000 [2] live births (more recent studies of NAIT seem to indicate that it occurs in
somewhere between 1/800 and 1/1000 live births).

Causes

About 80% of cases of NAIT are caused by antibodies against platelet antigen HPA-
1a, 15% by anti-HPA-5a, and 5% by other antibodies. Unlike the hemolytic disease,
NAIT occurs during the first pregnancy in up to 50% of cases, and the affected fetuses
may develop severe thrombocytopenia (<50,000 /μL) very early during pregnancy.
Usually, the thrombocytopenia increases as gestation progresses. In utero intracranial
hemorrhage occurs in about 10% of affected cases. This complication may also take
place before 20 weeks of gestation. The recurrence of NAIT been estimated to be
more than 80% in subsequent pregnancies with incompatible fetuses.

Treatment
During Pregnancy

The use of Intravenous immunoglobulin (IVIG) during pregnancy and immediately

after birth has been shown to help reduce or alleviate the effects of NAIT in infants
and reduce the severity of thrombocytopenia. The most common treatment is weekly
IVIG infusions at a dosage of 1g/kg beginning at 20 weeks of pregnancy and
continuing until the birth of the child[3]. In some cases this dosage is increased to
2g/kg and/or combined with a regiment of prednisone depending on the exact
circumstances of the case. Although this treatment has not been shown to be effective
in all cases it has been shown to reduce the severity of thrombocytopenia in some.
Also it is suspected that (though not understood why) IVIG provides some added
protection from ICH (intercranial hemorrhage) to the fetus.

After Birth

The most rapidly effective treatment in infants with severe hemorrhage and/or severe
thrombocytopenia (<30x109/L) is the transfusion of compatible platelets (i.e. platelets
from a donor who, like the mother lacks the causative antigen). Additionally if the
thrombocytopenia in the infant at birth is not severe enough to warrant a transfusion
of platelets (>30x109/L) an infusion of IVIG (1g/kg/day for two days) in the infant has
been shown to rapidly increase platelet count and reduce the risk of related injury.
HLA-matched platelets
Indications. HLA-matched platelets are indicated for patients who have become
refractory to random donor platelets. Such patients have no significant increase in
platelet count following transfusion. HLA-matched platelets survive better than
random donor platelets in approximately half of refractory patients. Patients who do
not have improved survival of HLA-matched platelets probably have platelet-specific
antibodies instead of or in addition to HLA antibodies.

Use on our campus. We generally suggest one of two other alternatives rather than
HLA-matched platelets. The best alternative is to collect platelets from blood
relatives, especially siblings. These donors are more likely to be matched for platelet-
specific antigens as well as HLA antigens. If no siblings or other relatives are
available (or if transfusion from relatives must be avoided because of potential future
bone marrow transplantation), the other option is platelet crossmatching. If the
clinicians insist on HLA-matched platelets rather than these other two options, it is
probably best to consult with blood bank faculty or fellows. Remember, HLA-
matched platelets must be irradiated.

NOTE: Prior to pursuing any special platelet products, please make sure that the
patient is not responding poorly to platelet transfusions for reasons other than platelet
antibodies. See Thrombocytopenia or Appendix 4 in paper supplement for a listing of
nonimmune causes of low platelet count. For example, if the patient is septic or has
DIC, platelets will survive poorly in circulation even if they are antigen matched;
therefore, expenditure of extra time, effort and money to find matched platelets is not
justified. Other causes of poor platelet survival are fever, bleeding, and splenomegaly.
If the patient has any of these underlying conditions, please do not approve HLA-
matched or crossmatched platelets.

Crossmatched platelets
Crossmatching of potential donor apheresis platelets against patient’s serum to detect
in vitro incompatibility.
Test Indications: Platelet crossmatching is indicated for patients with a poor response to
platelet transfusions due to recipient HLA or platelet reactive antibodies.
Alloimmunization can be a result of previous blood transfusions and/or pregnancy.
Refractoriness (poor response) could be caused by an antibody to either HLA-A, HLA-B, or
platelet specific antigens.