Transfusion medicine and proteomics. Alliance or coexistence?

Abstract

Transfusion of blood components is one of the most frequently performed clinical operations1,2. Beginning with the discovery of the AB0-blood group system by Karl Landsteiner3, the clinical relevance of transfusing blood, blood derived cells or proteins has increased constantly. Today transfusion medicine is a medical discipline and blood transfusion is embedded into one of the most advanced and regularized quality management systems in clinical medicine. In this system collection, production, storage, and administration of blood products are events separated in time and location, thus facilitating the existence of networks of donation sites and blood banks and the treatment of patients with human blood derived therapeutics even in far off areas. Today blood processing allows the provision of separate blood constituents such as cellular blood products e.g. red blood cell concentrates, platelet concentrates and stem cells, as well as plasma derived therapeutics such as fresh frozen plasma, coagulation factor concentrates, or immunoglobulins. Such blood products are either obtained by fractionation following donation of whole blood or they are selectively obtained from the blood donor using cell separators and apheresis procedures to obtain either cellular subfractions of the blood or plasma. These advances in the production of blood components enable storage of blood products under different conditions e.g. platelets at 20 °C and red blood cells at 4 °C. Blood fractionation also facilitates the targeted selection of specific blood components in order to provide patients with distinct blood functions. Thus, the different blood components are administered according to special indications such as the need for oxygen carriers or the maintenance of blood coagulation. Moreover, transfusion medicine achieved a remarkable reduction in the risk of pathogen transmission with blood products such as human immunodeficiency virus (HIV), hepatitis C, and hepatitis B4. While transmission of these pathogens has become a rare event in the Western world, bacterial contamination of blood products is still an issue, especially for platelet concentrates5. Despite the achievements just mentioned, transfusion medicine still faces a number of challenges with potential great impact on medical care systems. First the blood supply to demand ratio will change tremendously in the Western world due to the demographic changes with a growing older population and a declining birth rate2. This will require further reduction of waste of blood products e.g. by improvement of storage conditions and prolongation of storage time. Second, new emerging pathogens, which may not necessarily be known today or considered as a relevant transfusion transmissible agent, could easily thwart the blood supply. Prions causing variant Creutzfeld-Jacob-Disease (vCJD) are one recent example illustrating the need for ongoing activities to prevent pathogen transmission via blood products6. All approaches to reduce pathogen transmission or to extend storage of blood components have to maintain the integrity and function of blood cells and plasma proteins. In view of the complex composition of blood products and the constantly increasing regulatory requirements in transfusion medicine, monitoring of the effects of different maneuvers and interventions on the integrity of a blood product is becoming an issue of increasing importance. This will likely also require the application of more sensitive technologies. Technology advancements in the field of proteomics but particularly mass spectrometry have provided an entirely new view on the protein inventory of cells and cellular compartments by allowing fast and highly sensitive identification and analysis of thousands of proteins, both qualitatively and quantitatively. Such a comprehensive monitoring of dynamic changes of the protein levels but also of post-translational modifications7 is particularly useful for blood plasma and cells without a nucleus such as red blood cells and platelets. Although de novo protein synthesis has been convincingly demonstrated in platelets8 it occurs to a limited extend and is confined to pre-existing RNA. Application of proteomic technologies to different blood cells and plasma proteins has been subject of some excellent review articles9–12. Most of these studies have been performed for research questions not directly related to transfusion medicine. Only within the last five years, researchers in transfusion medicine have started to adopt proteomics to a larger extent to analyze blood products for patient care13. This review does focus on the potential of proteomics to address some of the current issues in transfusion medicine and provides a current status of proteomics in transfusion medicine.