Fetal and neonatal alloimmune thrombocytopenia (FNAIT)

A healthy neonate is born after an uneventful pregnancy. The cord platelet count is 12 × 10⁹ per L. Twelve hours later he has a seizure, and the cranial ultrasound shows a large parenchymal haemorrhage. The diagnosis that was missed antenatally — because there is no routine screening programme — is FNAIT, and the registrar who knows this disease protects the next pregnancy. FNAIT rewards the candidate who knows the antibody, the feared complication, the antenatal treatment, and the delivery plan.^[1][8]

Overview and definition

FNAIT is the platelet alloimmune disease of the fetus and newborn. Maternal sensitisation to a paternally inherited fetal human platelet antigen (HPA) produces an IgG alloantibody that crosses the placenta and is cleared by the fetal reticuloendothelial system along with the antibody-coated fetal platelets. The result is isolated fetal and neonatal thrombocytopenia — and, in a minority, devastating intracranial haemorrhage.^[1][7]

Two features make FNAIT unlike haemolytic disease of the fetus and newborn, and examiners test them:^[7][8]

• The first affected pregnancy is usually the index presentation. There is no routine antenatal HPA screening programme in current practice, so the disease is typically recognised only when a neonate presents with severe thrombocytopenia, bleeding, or — worst case — an intracranial haemorrhage.
• The severity rises with each successive antigen-positive pregnancy. Antibody titres and disease severity typically climb, so the next pregnancy is the opportunity for prevention — and one obstetric team can influence.^[1][6]

^{[8] [10]}

References12ShowHide

1. [1]Kamphuis MM, Tiller H, van den Akker ES, et al. Fetal and neonatal alloimmune thrombocytopenia: management and outcome of a large international retrospective cohort Fetal Diagn Ther, 2017.PMID 27728915
2. [2]Kamphuis M, Paridaans N, Winkelhorst D, et al. Lower-dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study Transfusion, 2016.PMID 27383293
3. [3]Paridaans NP, Kamphuis MM, Taune Wikman A, et al. Low-dose versus standard-dose intravenous immunoglobulin to prevent fetal intracranial hemorrhage in fetal and neonatal alloimmune thrombocytopenia: a randomized trial Fetal Diagn Ther, 2015.PMID 25896635
4. [4]Berkowitz RL, Kolb EA, McFarland JG, et al. Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia Obstet Gynecol, 2006.PMID 16394045
5. [5]Berkowitz RL, Lesser ML, McFarland JG, et al. Antepartum treatment without early cordocentesis for standard-risk alloimmune thrombocytopenia: a randomized controlled trial Obstet Gynecol, 2007.PMID 17666597
6. [6]Bussel JB, Berkowitz RL, Hung C, et al. Intracranial hemorrhage in alloimmune thrombocytopenia: stratified management to prevent recurrence in the subsequent affected fetus Am J Obstet Gynecol, 2010.PMID 20494333
7. [7]Bussel JB, Vander Haar EL, Berkowitz RL New developments in fetal and neonatal alloimmune thrombocytopenia Am J Obstet Gynecol, 2021.PMID 33839095
8. [8]de Vos TW, Winkelhorst D, Porcelijn L, et al. Natural history of human platelet antigen 1a-alloimmunised pregnancies: a prospective observational cohort study Lancet Haematol, 2023.PMID 38407610
9. [9]de Vos TW, Winkelhorst D, Árnadóttir V, et al. Postnatal treatment for children with fetal and neonatal alloimmune thrombocytopenia: a multicentre, retrospective, cohort study Lancet Haematol, 2022.PMID 36108655
10. [10]de Vos TW, Winkelhorst D, de Haas M, Lopriore E, Oepkes D Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia Transfus Apher Sci, 2020.PMID 31974030
11. [11]Winkelhorst D, Kamphuis MM, de Kloet LC, et al. Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature Transfusion, 2016.PMID 26996515
12. [12]Winkelhorst D, de Vos TW, Kamphuis MM, et al. HIP (HPA-screening in pregnancy) study: protocol of a nationwide, prospective and observational study to assess incidence and natural history of fetal/neonatal alloimmune thrombocytopenia and identifying pregnancies at risk BMJ Open, 2020.PMID 32690731