Neonatal alloimmune thrombocytopenia (NATP)

Fetal and/or neonatal alloimmune thrombocytopenia (NATP) occurs when a pregnant woman produces an alloantibody that reacts with a paternal platelet-specific antigen carried on fetal platelets. The mother is sensitised following a blood transfusion or during pregnancy. The maternal immunoglobulin G (IgG) antibodies cross the placenta and react with the corresponding antigen(s) on fetal platelets resulting in neonatal thrombocytopaenia.

• NATP occurs at a frequency of approximately 1:1000 live births (1,2)
  • NATP accounts for 3% of all neonatal thrombocytopenias and 27% of severe cases (platelets <50 x10^9 /l)
• twenty-three different platelet antigens have been implicated as targets for antibodies in NATP (4)
  • platelet antigen PLA-1 (HPA-1a) is the causative antigen in 85% of cases
• the thrombocytopenia is generally self-limiting after delivery; appropriate platelet transfusions - e.g. PLA-1 negative - may be necessary to treat or prevent bleeding
• risk of intracranial haemorrhage (ICH) and death associated with NATP
  • fetal and/or neonatal thrombocytopenia results in ICH in 10% to 20% of cases (5,6) and death in 1% to 3% (5)
    • the study by Radder et al (6) revealed that:
      • in 52% of the ICH cases, a previous sibling suffered from ICH
      • recurrence rate of ICH in the subsequent offspring of women with a history of fetal or NATP with ICH was 72%[CI: 46-98%] without inclusion of fetal deaths and 79% (CI: 61-97%) with inclusion of fetal deaths
      • in 48% of the ICH cases, the previous sibling had thrombocytopenia but not ICH
      • the risk of ICH in a subsequent pregnancy following a history of fetal or NATP without ICH, was estimated to be 7% (CI: 0.5-13%)
• 60% of NATP cases occur in first pregnancies
  • diagnosis is usually not made until after birth of an affected infant

Reference:

1. Williamson LM et al.The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening, Blood 1998;92: 2280–2287
2. Kaplan. Alloimmune thrombocytopenia of the fetus and the newborn. Blood Rev 2002;16: 69–72
3. Saino S et al. Thrombocytopenia in term infants: a population-based study, Obstet Gynecol 2000;95: 441–446.
4. Metcalfe P et al. Nomenclature of human platelet antigens. Vox Sang 2003;85: 240–245
5. Udom-Rice I, Bussel JB. Fetal and neonatal thrombocytopenia. Blood Rev 1995;9:57–64
6. Radder CM et al. Will it ever be possible to balance the risk of intracranial hemorrhage in fetal or neonatal alloimmune thrombocytopenia against the risk of treatment strategies to prevent it?. Vox Sang 2003;84: 318–325