Fetal and neonatal immune thrombocytopenia caused by maternal alloantibodies and isoantibodies in Caucasian and Asian populations: a narrative review

Abstract

Objective: The aim of this review is to renew our knowledge about the role of platelet antibodies (allo- and isoantibodies) in fetal neonatal and alloimmune thrombocytopenia (FNAIT) among Caucasian and Asian populations and to provide additional new insights which may be responsible for the various clinical pictures of this serious immune disease. Background: During the pregnancy, maternal allo- and isoantibodies can cross the placenta via the neonatal Fc receptor (FcRn) and cause the clearance of fetal platelets and endothelial dysfunction, resulting in FNAIT, which is often associated with bleeding complications of the fetus and neonate. In the last years, great progress has been made in the field of alloantigen-related FNAIT, especially caused by alloantibodies against human platelet antigen (HPA)-1a located on β3 integrins (αIIbβ3 and αvβ3 integrins). However, little attention was paid to the role of isoantibodies, particularly against CD36, which turn out to be one of the most important antibodies responsible for FNAIT in Asian populations. Methods: In this review, we described the currently available information about alloantibodies and isoantibodies with respect to allele frequencies, the incidence of immunization, clinical relevance, and the pathophysiology of FNAIT. Conclusions: Apart from platelet alloantibodies, isoantibodies against platelet glycoproteins play an important role in the pathomechanism of FNAIT. In a globalized world, diagnosis and therapy of anti-HPA-1a- and anti-CD36-related FNAIT should be available, even if anti-HPA1a is uncommon in Asian populations and anti-CD36 is very rare in Caucasians. Most of these antibodies not only bind to platelets, but also react with endothelial cells and other blood cells (such as monocytes) which may contribute to the pathomechanism of FNAIT. In addition, recent evidence indicated that maternal antibodies are heterogeneous with respect to their epitopes, and their ratio may differ from one case to other. All of these facts may reflect the various clinical pictures of FNAIT and consequently require adapted treatment strategies. Therefore, further improvement on laboratory diagnostics, both on serological and functional analysis of platelet antibodies, is mandatory for the better prediction and management of FNAIT. To achieve this goal, a further understanding of the nature of the pathogenic antibodies will be necessary.