Transfusion related immunomodulation

Project leader: Jaap-Jan Zwaginga MD PhD

A study further evaluating transfusion related immunomodulation by gene array (GE) expression evaluation (project leaders JA van Hilten) shows only minor effect of leukocyte-depleted RBC transfusion on cytokine gene expression profiles in a wide range of transfusion recipients (cardiac surgery, orthopedic surgery, anemia of prematurity). However, increased GE of TGF-α, TNFSF10 and -13B transcripts were observed after cardiopulmonary bypass surgery. A relationship with post-operative complications is further explored.

Platelet transfusions

The possibility to predict the need for platelet transfusions in acute myeloid leukemia patients (Ex vivo Determination of Bleeding risk; project leaders: R Middelburg, JJ Zwaginga) is of great importance to establish appropriate indications for platelet transfusions for these patients. Within this project a flowcytometry based assay for the assessment of platelet function ex vivo in whole blood, has been validated in 2010. Correlation with clinical bleeding (within the PREPAReS study) starts in 2011.

Predictive value of platelet product characteristics and clinical efficacy regarding bleeding and transfusion increment of platelet transfusions (project leader: PF van de Meer) will correlate a composite score of stored and/or pathogen-treated platelet products within the randomized PREPAReS study. In 2010 the technique of platelet product scoring was validated.

Preventing surface sialic acid loss of the platelet GPIbα receptor increases platelet lifespan in vivo and after transfusion (pilot study) (project leader: G Jansen). The study aims to investigate the relationship between sialic acid loss and loss of the vWFR complex in human platelets and platelet life span. Preliminary results showed a relationship between loss of GPIbα after activation with neuraminidase in human platelets. This, however, has to be investigated further. The current study is divided into three sections. The first part is focused on validation of the tests. Secondly we would like to investigate the relationship between platelet storage and loss of sialic acid and loss of platelet receptors. The third part is to investigate platelet characteristics of patients with thrombocytopenia with special interest in sialic acid.

RBC alloantibodies

The mechanism of HLA restriction in RBC allo-antibody formation (project leaders: H Schonewille, IIL Doxiadis) is further explored. An (IgG) antibody response generally requires initial activation of antigen-specific T helper (CD4) cells via the indirect (by self-HLA class II) pathway through effective presentation by antigen-presenting cells. By the end of 2010, more than 1000 patients with various (multiple) antibody specificities were HLA class-II typed. This study will reveal whether the role of HLA antigens in RBC immunization is of such extent that they have to be taken into account for preventive matching strategies.

Double cord transplantation

Understanding single cord blood dominance after double cord transplantation (project leader: Y van Hensbergen, A Brand). After double cord transplantation in most instances one of the two cords dominates. We validated a method using monoclonal HLA-single allele specific antibodies to follow the development of cells in the early post-transplantation period with the aim of early detection of (the mechanism of) a winning UCB.

Key publications