Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

Ewa Brojer,Małgorzata Uhrynowska,Anne Husebekk,Romuald Dębski,Krystyna Maślanka,Katarzyna Guz,Agnieszka Orzińska,Marzena Dębska

doi:10.1007/s00005-015-0371-9

Abstract

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000–1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway.

Highlights

Fetal/neonatal alloimmune thrombocytopenia (FNAIT), caused by maternal alloantibodies against fetal human platelet antigens (HPA) is a relatively rare condition (1/ 800–2000 live newborns) but its consequences may be severe (Kjeldsen-Kragh et al 2007; Uhrynowska et al 2000; Williamson et al 1998)
A thrombocytopenic fetus or newborn is at risk of intracranial hemorrhage that may result in lifelong disability or death
Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy

Summary

Introduction

Fetal/neonatal alloimmune thrombocytopenia (FNAIT), caused by maternal alloantibodies against fetal human platelet antigens (HPA) is a relatively rare condition (1/ 800–2000 live newborns) but its consequences may be severe (Kjeldsen-Kragh et al 2007; Uhrynowska et al 2000; Williamson et al 1998). It has recently been suggested that the presence of two HLA alleles (DRB3*01:01 and DRB4*01:01) in the mother increases the risk and severity of FNAIT and reduces the success of preventive IgG treatment (Loewenthal et al 2013) In those pregnant women with detectable anti-HPA-1a antibodies, the disease severity widely varies (Maslanka et al 2003; Tiller et al 2013, 2014; Uhrynowska et al 1997, 2000). Prospective studies on NAIT in nonselected newborns with thrombocytopenia, as those summarized by Kamphuis et al (2014) (see above), give the best possible incidence estimates of NAIT and NAIT-related ICH When comparing these studies, it is clearly shown that ICH due to FNAIT in nonscreened population is much higher (24/59,425) than that found in the group of women who were antenatally screened for FNAIT risk (HPA-1a determination and antibody detection in HPA-1a negatives) (7/176,084 cases).

FNAIT accidentally discovered in a neonate after delivery

Screening methods

Findings

Compliance with ethical standards