Thesis defense Anno Saris: Alloimmunization after platelet transfusion

Mechanisms, prevention and treatment

anno Saris

On 21 November 2018 Anno Saris  defended his thesis at the University of Amsterdam. He investigated the mechanisms of alloimmunization after platelet transfusions and provides suggestions how this may be reduced in the near future.

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. In this thesis, Anno Saris provides further understanding of the mechanisms of alloimmunization after platelet transfusions and provides suggestion how this may be reduced in the near future. One of the best known risk factors for alloimmunization is the number of transfusions. To reduce this, deterioration of platelets during storage should be minimized. This thesis shows which of the frequently used laboratory test has the best clinical correlation and is therefore most suitable to monitor effects of storage.

Furthermore, Saris found that contrary to previous claims, not only white blood cells but also platelets can induce alloimmune responses. 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.

Treatment and prevention

Patients that are platelet transfusion refractory due to alloimmunization may be treated by exploiting natural variation in HLA class I expression on platelets, 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 dendritic-cell-mediated adaptive immune response, but further studies are needed to address the implications

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: Agnietenkapel (14:00)