Thesis defense Anno Saris
Alloimmunization after platelet transfusion: mechanisms, prevention and treatment
On 21 November 2018 (14:00) Anno Saris defended his thesis 'Alloimmunization after platelet transfusion: mechanisms, prevention and treatment' at the University of Amsterdam
Promotores: Prof JJ Zwaginga MD PhD and prof SM van Ham PhD
Co-promotores: JA ten Brinke PhD and PF van der Meer PhD
Venue: University of Amsterdam, Agnietenkapel
Summary
The effectiveness of platelet transfusions, an essential supportive care for mostly hemato-oncologic patients, can be diminished due to multiple causes. HLA class I alloimmunization is by far the most common immunological cause for such ineffective transfusions. This thesis provides further understanding of the mechanisms of alloimmunization after platelet transfusions and provides suggestions how this may be reduced in the near future. To minimize the number of transfusions, one of the best known risk factors for alloimmunization, is to minimize the detoriation of platelets during storage. This thesis shows which of frequently used laboratory test has the best clinical correlation and therefore most suitable to monitor effects of storage. Furthermore and despite earlier claims that only WBCs were able to do so, alloimmune responses after platelet transfusions are shown to likely be also inducible by platelet - dependent pathways . This platelet - mediated alloimmunization is enhanced upon prolonged platelet storage by a mechanism that involves phosphatidylserine exposure. Pathogen inactivation of platelet concentrates, a technique developed to reduce the risk of transfusion-transmitted infections, does not help to reduce alloimmunization after platelet transfusions in vivo, but likely enhances it . Patients that are platelet transfusion refractory due to alloimmunization may be treated by exploiting natural variation in HLA class I expression on platelet as 9 - 33% of donors have such low specific HLA class I expression that platelets from these donors do not undergo antibody-mediated internalization. Finally, platelets are shown to be capable of inhibiting DC - mediated adaptive immune response, but further studies are needed to address the implications.
