“Maybe, future research will bring us tailor made treatment”

Paula Ypma is a hematologist in The HagaZiekenhuis in The Hague for over ten years now. Although, during her study Ypma was never much involved in research, the drive to be part of a scientific study was still there. So, since two years now, she spends one day a week on research; a clinical trial study performed by Sanquin.

Can you tell us something about your current research?
My research is part of the PREPAReS Study which is a large international randomized clinical trial. In this trial two platelet products are compared. Hematology patients are supported with either standard plasma stored platelets or Mirasol treated platelets, which are pathogen reduced by the addition of riboflavin and subsequent UVB treatment. The aim of the study is to demonstrate that Mirasol platelets do just as well in patients as standard platelets with regard to bleeding prevention. We study and compare the intensity of the bleeding events in the two patient groups to investigate the effectiveness of the platelet transfusion. Observing patients is a challenge because comparing bleeding intensity demands clear standards. You need to make sure that everyone involved in the study interprets and describes a bleeding event in the same way. Another issue in the PREPAReS trial will be the development and/or validation of several in vitro tests which might be of value in the prediction of clinical efficacy.
My role in the trial focuses on the clinical efficacy of transfused platelet products. I make sure that all the different centers involved have a benchmark to score and registrar bleeding events in a uniform manner. After registration, we score the bleedings in level of severity. Eventually we will analyze these degrees of bleeding in both groups which will indicate the effectiveness of the platelet transfusions.
My personal research question in this whole project is aimed at the understanding of why hematology patients with (hypoproliferative) thrombocytopenia bleed. Generally it is assumed that bleeding severity is related to the depth of the platelet deficit. This is, however, a matter of debate as bleeding events also occur in patients with higher platelet levels. This indicates that there are probably other factors involved. We think that the chemotherapy causes endothelial damage which causes the bleeding events. By studying markers for endothelial damage markers we hope to elucidate the mechanism, which in turn might aid in recognizing susceptible patients and improve measures to prevent bleeding.

What are the most important lines of research/approaches that have developed in your field over the past 5 or 10 years?
Five to ten years ago a lot of increment studies were done. In these studies we looked at the average increase of platelets in a patient after transfusion. However, in recent years the trend of focusing on the clinical effects of a transfusion, i.e. bleeding prevention, as an end point developed. This is also a greater challenge, partly due to the differences in the way bleeding events are evaluated and graded.
In the practice of hematologists there have been no major changes in the transfusion area. We are still are using a transfusion trigger of 10 ∙ 109 platelets/L blood above which you want to keep a patient. But maybe, future research will bring us tailor made treatment for patients who are more susceptible for bleeding events and we will no longer make use of a standard limit.

What is, according to you, the biggest challenge in current research in your field?
My own challenge is to continue making sure the different centers score the bleeding events properly. Eventually, I not only want the study to contribute to the knowledge about the working of the Mirasol product, but also to the treatment of a patient on an individual level. However, finding the specific parts of the PREPAReS trial results that will make a difference for the clinical practice will be challenging.

Why does your line of research matter? Why should people put money into it?
I think that pathogen reduction is of importance, because I do not ever want to see a patient get infected after a transfusion anymore. Nevertheless, in the clinic this is not a life threatening problem. We hardly see infections due to platelet transfusions. However, we do see patients that suffer massive bleeding events while others never bleed. This might be due to the fact that we transfuse in a general manner. Therefore, much more research needs to be done to understand why people bleed.
In addition, the kind of progress that is made in the treatment of leukemia in comparison to the progress in the area of supportive care, does not differ that much. I think that doing large randomized trials in the broad area of supportive care will provide more information.

Who or what will benefit from your research?
Leukemia patients. Moreover, other patients that need to be transfused for other hematological diseases will benefit.

How does your research suits Sanquin?
It especially fits the clinical transfusion part of Sanquin and is therefore placed at the department of Clinical Transfusion Research in Leiden. Besides, it is also linked to preclinical research due to the laboratory tests.

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