Neonatal alloimmune thrombocytopenia
        (NAIT)
        Main and The Obgyn Clinic of Hvidovre (danish)
        Definition:
        Thrombocytopenia < 150 x 109/L in 0.9% of neonates. 1/3 will be immune thrombocytopenic. Severe thrombocytopenia (< 50 0,12-0,24%). Feto-maternal incompatibility for platelet antigens inherited from the father but do not cause maternal thrombocytopenia.
        Mother forms IgG class antiplatelet antibodies against the neonatal fetal platelets antigens inherited from the father. These antibodies cross the placenta and destroy fetal platelets resulting in fetal and neonatal thrombocytopenia. In contrat to RH immunisation NAIT often developes in first pregnancy.
        • Anti HPA-1a previous Zwa 75-80%
        • Anti HPA-5b previous Zwa 15%
        • Anti HPA-15b previous Zwa 4%

        Incidence:
        1:1000 more than half in first pregnancy
        Recurrence 75%-90% same or worse (Father can be heterozygote).Mother at increased risk if HLA-BB, DR 3 or DRW52.

        Risk:
        If fetal platelets < 50 great risk of intracranial hemorrhage. The most serious complication is intracerebral haemorrhage which occur in approximately 10-20% of affected newborns; one quarter to one half of these occur in utero.

        Screening
        Maternal antigen typing if a maternal sister had a pregnancy complicated by NAIT or a histsory suggestion of this diagnosis and demonstrate specific antibodies directed against the antigen.
        Ultrasound before labor.
        Vaginal delivery increased risk for cerebral hemorrhage.

        Vaginal delivery contraindicated if fetus is affected. However some will argue that vaginal delivery is possible if fetus has effective treatment.
        Affected infant should have cesarean section around 36 weeks.

        Management:
        Amniocentesis is prefered as CVS is associated with a theoretically increased risk of maternal sensitivity in case of affected fetus.
          If suspicion of an affected infant, check the zygocity on both parents. If husband is heterozygote, CVS/amniocentesis assess fetal DNA and determine infants antigen status (PCR). If fetus HPA-1a negative - no risk

          If fetus HPA-1a positive - great risk for thrombocytopenia
          Cordocentesis on fetus at risk from 20-24 weeks and treat if necessary with platelets or possible steroids.

          If HPA-negative mother delivers 15% of infants HPA negative.
          Antenatal ultrasound can show cerebral bleeding, porencephaly and ventriculomegaly.
          Ultrasound is the standard technique. MRI research tool.

        The most widly accepted strategy in United States is widly antinatal administration of gammaglobulin (IVIG) typically instituted at 20 weeks. No consensus of optimal protocol for managing IVIG after it is began. Can be given with prednisone 1 mg/kg/week. Platelet transfusion used as the last resort.

        Treatment Options:
        Management should be planned in a fetal medicine unit.

        Cordocentesis on fetus at risk from 20-24 weeks. If previous affected siblings, the platelets is < 20,000/mL in 50 percent of fetuses.

        The blood sampling should check success of treatment and several transfusions weekly can be necessary.

        Neonatal:
        Use HPA compatible donor platelets. When available mother platelets will not react and the maternity derived anti-platelets antibodies.

        IVG and corticosteroid not well documented and controversial.

        References:
        (1) Berhowitz RL, Bussel JB, McFarland JG. Alloimmune thrombocytopenia: state of the art 2006. Am J Obstet Gynecol 2006 Oct;195(4):907-13. Epub 2006 Jul 26.

        (2) Ghevaert C et al. Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion 2007;47(5):901-10.

        (3) www.uptodate.com 2007

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