Jens Kjeldsen-Kragh1, Heyu Ni, Bjørn Skogen. 1. Department of Clinical Immunology and Transfusion Medicine, University and Regional Laboratories Region Skåne, Lund, Sweden. Jens.Kjeldsen-Kragh@skane.se
Abstract
PURPOSE OF REVIEW: The purpose of the review is to show the similarities between haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) and to describe the background and challenges related to the current endeavours of developing a prophylaxis against FNAIT. The rationale for this prophylaxis is similar to the prophylaxis which has been used with great success for the last 40 years against RhD-associated HDFN. The idea is to prevent human platelet antigen (HPA)-1a-associated FNAIT by administering anti-HPA-1a immunoglobulin G (IgG) to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. RECENT FINDINGS: Results from a Norwegian screening and intervention study on FNAIT have indicated that about 75% of women with antibodies against HPA-1a are immunized in relation to delivery. This observation leads to the possibility of preventing HPA-1a-associated FNAIT in the same way as today's prevention of HDFN. Results from a proof-of-concept study in a murine FNAIT model have shown that the production of alloantibodies against platelets can be suppressed by administrating antiplatelet antibodies after the antigenic challenge. Even more interesting, the prophylactic antiplatelet antibodies could also significantly reduce the clinical consequences of FNAIT in this FNAIT model. SUMMARY: These novel observations have paved the way for clinical studies. Production and testing of anti-HPA-1a IgG for clinical use will be carried out by a European Union-funded consortium. If the results from the clinical trial are favourable, there is a chance that a medicinal product for the prevention of FNAIT will be available within this decade.
PURPOSE OF REVIEW: The purpose of the review is to show the similarities between haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) and to describe the background and challenges related to the current endeavours of developing a prophylaxis against FNAIT. The rationale for this prophylaxis is similar to the prophylaxis which has been used with great success for the last 40 years against RhD-associated HDFN. The idea is to prevent human platelet antigen (HPA)-1a-associated FNAIT by administering anti-HPA-1a immunoglobulin G (IgG) to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. RECENT FINDINGS: Results from a Norwegian screening and intervention study on FNAIT have indicated that about 75% of women with antibodies against HPA-1a are immunized in relation to delivery. This observation leads to the possibility of preventing HPA-1a-associated FNAIT in the same way as today's prevention of HDFN. Results from a proof-of-concept study in a murine FNAIT model have shown that the production of alloantibodies against platelets can be suppressed by administrating antiplatelet antibodies after the antigenic challenge. Even more interesting, the prophylactic antiplatelet antibodies could also significantly reduce the clinical consequences of FNAIT in this FNAIT model. SUMMARY: These novel observations have paved the way for clinical studies. Production and testing of anti-HPA-1a IgG for clinical use will be carried out by a European Union-funded consortium. If the results from the clinical trial are favourable, there is a chance that a medicinal product for the prevention of FNAIT will be available within this decade.
Authors: Jens Kjeldsen-Kragh; Dean A Fergusson; Mette Kjaer; Lani Lieberman; Andreas Greinacher; Michael F Murphy; James Bussel; Tamam Bakchoul; Stacy Corke; Gérald Bertrand; Dick Oepkes; Jillian M Baker; Heather Hume; Edwin Massey; Cecile Kaplan; Donald M Arnold; Shoma Baidya; Greg Ryan; Helen F Savoia; Denise Landry; Nadine Shehata Journal: Blood Adv Date: 2020-07-28
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