Foetal and neonatal alloimmune thrombocytopenia and HLA class I alloimmunisations

Abstract

Background: Foetal and neonatal alloimmune thrombocytopenia (FNAIT) is estimated to occur at an incidence of 1:1-2000 live borns, while maternal immunisation against HLA class I is a common finding during pregnancy and after delivery. Whether anti-HLA antibodies can cause FNAIT in some cases is debateable. Aim: This study aims to give a background to FNAIT, and to describe cases of suspected or anticipated FNAIT referred to the thrombocyte and leukocyte laboratory at Karolinska University Hospital, with a focus on cases that could be due to anti-HLA class I antibodies. In an experimental part, anti-HLA class I antibody specificities in selected cases were analysed and the expression of HLA class I antigens on adult and umbilical cord blood platelets was determined. Results: Out of 260 patients referred from January 2007 until March 2012, alloantibodies were detected in 43%, and anti-HLA class I antibodies were most common. 35 patients were diagnosed with FNAIT with HPA incompatibilities between the parents and detectable antibodies. Sera from 23 anti-HLA class I immunised mothers were analysed further, and most of them had antibodies reactive with several specificities. The most common specificities were of the HLA-B type, against rare alleles. Flow cytometry analysis of HLA-A,B,C and HLA-B,C on platelets indicated that platelets from neonates had a higher HLA-A expression and lower HLA-BC expression. Conclusion: FNAIT is rare, and is probably even more rarely caused by HLA class I immunisation, although it remains a possibility. Maternal anti-HLA class I antibodies have been shown to be associated with complications related to pregnancy, and it is not clear how the presence of these antibodies affects the foetus. In cases of suspected HLA alloimmunisation, most of the mothers had broadly reacting antibodies. The expression of HLA class I on platelets seems to be different in adult and umbilical cord blood.