UVC-treated PLTs stored for 5 days showed marginal changes in PLT metabolism and activation in vitro and were associated with a degree of reduction in recovery and survival similar to other pathogen inactivation systems that are licensed and in use.

Key Points• Recombinant antibody B2G1Dnab protects platelets from destruction by anti-HPA-1a in the circulation of HPA-1a1b human volunteers.• B2G1Dnab is a potential therapeutic agent for antenatal treatment of fetomaternal alloimmune thrombocytopenia due to HPA-1a antibodies.Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Dnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcg receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Dnab blocks monocyte chemiluminescence by >75%. In this firstin-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Dnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Dnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Dnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Dnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers. (Blood. 2013;122(3):313-320)