Thesis defense Aukje Kreuger

On 13 September 2018 Aukje Kreuger defended her thesis 'Platelet transfusion in hematology; improving the chain' at the University of Leiden.

Promotor: Prof JG van der Bom MD PhD
Co-promotores:  R.A. Middelburg PhD and JLH Kerkhoffs MD PhD
Venue: Akademiegebouw, Leiden University

Summary

The majority of platelet transfusions are given to patients with a hematological malignancy to prevent or treat bleeding complications. Although the recommendations are clear for clinically stable patients, less evidence exists for patients who face an increased risk of bleeding. This results in a large variation in daily practice as we demonstrated with a survey among Dutch and European hematologists.

Some patients developed alloantibodies against antigens expressed on the surface of platelets, which may result in accelerated destruction of transfused platelets. These patients benefit the most from HLA split matched platelet concentrates. Although almost 20.000 donors are HLA typed in the Netherlands, adequate transfusion support cannot be guaranteed for all immunized patients, especially not for patients from a non-Caucasian background.

From a clinical perspective, major hemorrhage is the most relevant outcome to measure effectiveness of platelet transfusions. However, hemorrhages are not uniformly coded and proxies are needed to detect patients with major hemorrhage in large databases. We developed a model consisting of drop in hemoglobin, transfusion support, and CT-brain to enable the identification of major hemorrhage among leukemic patients in such databases.

In the Netherlands, the standard platelet concentrate is derived from buffy coats and resuspended in plasma or platelet additive solution (PAS) and can be stored for a maximum of seven days. In a meta-analysis, we showed that longer storage has a negative effect on safety and efficacy of platelet transfusions.  

Due to storage at room temperature, platelet concentrates carry the highest risk of infections compared to other blood products. In the ATTACH study we assembled routinely collected health care data of nine hospitals spread around the Netherlands to investigate the association of storage time with the risk of bacteremia after transfusion in hematological patients. Transfusion of platelet concentrates stored in plasma for five to seven days was associated with a lower risk of bacteremia. Similarly, we showed a lower risk of a positive blood culture after transfusion of older platelet concentrates stored in PAS in all recipients of platelet transfusions in Denmark. In these studies, we used a positive blood culture as proxy for a bacterial infection and these are not necessarily causally related to the transfused blood product. When the same microorganism is identified in the transfused product and in the patient, the infection is classified as a Transfusion Transmitted Bacterial Infection. Storage medium influences bacterial growth characteristics in the product. Using the database of TRIP, we showed an increased risk of transfusion transmitted bacterial infections for platelet concentrates stored in PAS compared to those stored in plasma.