Gary Edward Stack MD, PhD
Professor of Laboratory Medicine; Chief, Pathology and Laboratory Medicine at VA Connecticut
blood group alloimmunization; pharmacogenetics; blood bank storage of platelets; pro-inflammatory cytokines; blood transfusion
We have focused on finding ways to improve transfusion safety. We have studied blood group alloimmunization, i.e. the development of antibodies to red blood cells that occurs in some patients after transfusion. These antibodies are important since they can make it difficult to find compatible blood. They also mediate destruction of transfused red blood cells and transfusion reactions. We found that these antibodies are more dangerous than previously thought due to their higher rate of disappearance over time than previously thought. Their disappearance causes them to become undetectable during transfusion compatibility testing, yet their levels increase dramatically following transfusion of incompatible red blood cells. We have also studied the tendency of some patients to develop more than one blood group antibody. Currently, we are investigating ways to better detect and prevent blood group antibodies.
We have also studied how to better prepare and store platelets for transfusion. Platelets are small blood particles that are important in the early stages of blood clotting. Some patients develop dangerously low platelet counts and require platelet transfusions to prevent bleeding. However, we have found that platelets leak substances during blood bank storage that can mediate adverse inflammatory reactions when transfused. We are attempting to understand what causes this leakage and how to prevent it.
We also have recently been investigating the use of genetic testing to better predict correct doses of anticoagulant and anti-platelet drugs. Our initial focus has been on determining the advantages and disadvantages of different testing methods.
Extensive Research Description
We have investigated the role of pro-inflammatory cytokines in mediating adverse effects of blood transfusion. We have shown that leukocyte-derived cytokines such as interleukins-1, -6, - 8, as well as MIP-1 alpha, GRO-alpha, and TNF-alpha are present in the plasma portion of stored platelet concentrates and are generated in vitro during blood bank preparation and storage. Some cytokines were also detected in the supernatant portion of red blood cell units. These cytokines are generated in direct proportion to the leukocyte content of the component, the storage temperature, and the storage time. Bacterial contamination of blood components, as might occur in the setting of a septic transfusion reaction, further stimulates cytokine generation. Pre-storage leukoreduction of blood components prevents the generation of leukocyte-dereived cytokines.