Pathogenesis of Anti-integrin αIIb-mediated Fetal and Neonatal Alloimmune Thrombocytopenia: Establishment of Novel Murine Models in αIIb Deficient and Human αIIb Transgenic Mice

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder caused by maternal antibodies targeting fetal/neonatal platelets. The incidence is approximately 1:1000 live births, but the frequency of FNAIT associated miscarriage has not been adequately investigated. FNAIT targeting the β3 subunit of integrin αIIbβ3 occurs in approximately 85% of reported cases, whereas αIIb-mediated-FNAIT only accounts for approximately 5% of reported cases although frequencies of polymorphisms in αIIb and β3 polypeptides are similar in the human population. It is unknown whether immune responses to these two subunits differ and currently no animal model exists to address this question. We hypothesize that αIIb-mediated-FNAIT causes a severe form of FNAIT (e.g. miscarriage), which may account for this discrepancy. Here, two new murine models of αIIb-mediated-FNAIT were established. Severe FNAIT (e.g. miscarriage and intracranial hemorrhage) is frequently observed, and we conclude that the severity of anti-αIIb-FNAIT may mask the clinically reported incidence of disease.M.Sc