January, 1996


Ileana Lopez-Plaza, M.D., Assistant Medical Director of Transfusion Services,

The Institute For Transfusion Medicine, Pittsburgh, PA


Neonatal alloimmune thrombocytopenia (NAIT) accounts for approximately 20% of patients with neonatal thrombocytopenia, and has an incidence of 1 in 1000 to 1 in 2000 live births. NAIT, which can affect the fetus or the neonate, occurs when passively transmitted maternal antibodies coat the neonatal/fetal platelets, causing their removal from the circulation. The clearance of the affected platelets is analogous to the red cell clearance observed in hemolytic disease of the newborn (HDN). Transplacental transmission of fetal/paternal platelet antigens may occur before the 20th week of gestation, causing the production of maternal antibodies against the fetal/paternal antigens lacking in the mother. In contrast to HDN, up to 60% of NAIT occur in primiparae. In subsequent pregnancies the fetus carrying the implicated antigen will be at least as severely affected as the first affected pregnancy.

The most common antigen associated with NAIT, reported in 46-83% of cases, is HPA-1a (PlA1 ). HPA-5a (Brb ) is the second most common. HLA antibodies and ABO antibodies have been implicated in a few cases.



The existence of incompatibility between the mother and fetal/paternal platelets appears to be necessary but not sufficient for maternal alloimmunization to occur. Several studies have described an association between specific HLA class II types in the mother, and alloimmunization against platelet specific antigens: DR52a and alloimmunization against HPA-1a (P1a1 negative), and DR6 and alloimmunization against HPA-5b (Bra negative).

The degree of severity may be related to several factors: density of the target antigen; birth order; the ability of the antibody to fix complement; and the fact that the antigens to which NAIT antibodies bind are located in surface membrane molecules which are essential to platelet function. Changes in maternal antibody titers do not accurately predict severity.


Clinical Features

Up to 81% of affected newborns present with petechiae, purpura or overt bleeding at birth. There is evidence of central nervous system hemorrhage in 10-20% of the affected neonates. Specific antibodies associated with severe symptoms, including perinatal intracerebral hemorrhage (ICH), are anti-HPA-1a, anti-HPA-4a, anti-HPA-3a, anti-HPA-1b, and anti-HPA-5b. If untreated, the thrombocytopenia normally lasts 2-3 weeks and then resolves spontaneously. Up to 50% of ICH cases may occur prenatally.

In addition to NAIT, the differential diagnosis of neonatal thrombocytopenia includes: infection induced thrombocytopenia, maternal idiopathic thrombocytopenic purpura (ITP), maternal drug exposure, and other rare causes of neonatal thrombocytopenia.

NAIT has an overall mortality of 1-14%. Approximately one fourth of those with ICH may manifest persistent neurological damage. Second and subsequent siblings often have a better prognosis due to the identification of the platelet incompatibility during the first pregnancy.


Laboratory Diagnosis

Neonatal thrombocytopenia is uniformly present and maternal platelet count is normal. The neonate’s hemoglobin levels can be decreased secondary to bleeding.

Special platelet antibody studies are necessary to confirm the diagnosis of NAIT. Maternal and paternal platelet antigen typing is performed by serological and/or DNA-based assays. The maternal serum is screened by serological assays for platelet antibodies against the paternal platelets and/or selected donor platelets in which the specific antigen is present or absent. Up to 85% of the maternal sera tested will show antibodies specific for the implicated antigen. The absence of detectable maternal antibodies alone does not exclude the diagnosis of NAIT.



Postnatal treatment focuses on increasing the neonate’s platelet count. Platelet transfusion should be considered in severe thrombocytopenia (plt ct < 20,000/m L). The platelets to be transfused should be compatible with the maternal serum. The ideal donor is the mother in which platelets can be collected from a unit of whole blood or by plateletpheresis. Removal of the plasma present in the platelet product has been recommended to minimize the passive transfer of maternal antibodies that might prolong the fetal thrombocytopenia. Alternative platelet donors include the mother’s siblings or volunteer donors known to lack the identified platelet antigen. If an antigen negative product is not readily available and there is an urgent need to transfuse, random donor platelets should not be withheld. In fact, an adequate response to a unit of a random platelet concentrate is found in up to 40% of cases. High dose intravenous IgG has been successful in increasing platelet counts within 24-48 hours. This may eliminate the need for platelet transfusions in the less severe thrombocytopenic neonates and is adjunctive therapy for those with severe thrombocytopenia.

The primary purpose of antenatal diagnosis and treatment is to prevent intrauterine ICH which may occur in 2-7% of NAIT patients. Although screening programs are not available for detecting first-time mothers at risk for delivering infants affected with NAIT, subsequent pregnancies can be monitored for intrauterine NAIT and treated accordingly. The history of a prior delivery of a thrombocytopenic infant, including the cause of the thrombocytopenia, the response to platelet transfusion and the maternal platelet count, is important in determining the risk of NAIT in subsequent pregnancies. The gene frequency of the implicated antigen and the zygosity of the father for this antigen will also help predict the risk of NAIT.

During subsequent at risk pregnancies, the fetal platelets can be quantitated and typed for the implicated antigen by PCR as early as 18 weeks of gestation by percutaneous umbilical vein sampling (PUBS). In affected infants, maternal administration of high dose intravenous IgG with or without dexamethasone, has been shown to improve the fetal thrombocytopenia in approximately 75% of cases. Subsequent PUBS can then be used to monitor the platelet count and to treat with intrauterine platelet transfusions if needed.

The Institute For Transfusion Medicine uses solid phase red cell adherence test for the laboratory diagnosis of NAIT. The test can be ordered through the Red Cell Reference Laboratory, (412) 209-7470.


Copies of the Transfusion Medicine Update can be obtained by contacting
Deborah Small at (412) 209-7320