Advances in Transfusion Medicine
This article was published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.
Blood transfusions are an important part of hematologic care. Transfusion is the transfer of blood, its components, or products from one person (donor) into another person's bloodstream (recipient). Every year in the U.S., more than 20 million units of red blood cells, platelets, and plasma are transfused to treat hematologic conditions such as severe anemia, leukemia, and sickle cell disease. Transfusions have long been associated with some risk to patients. The HIV epidemic during the 1980s was a major cause of fear; regular transfusions, especially of clotting factor concentrates, spread the virus quickly and nearly undetected. That outbreak prompted the development of biovigilance or hemovigilance: tracing and tracking transfusion-related adverse events and incidents, both infectious and non-infectious, that affect blood donors and recipients. Another of the most significant issues complicating transfusion safety has been bacterial contamination of blood products, particularly of platelets. However, steps have been taken in the last decade to avoid, detect, and eliminate this complication through improved donor selection, specialized preparation of the arm before needle insertion, and special screening techniques.
Despite ongoing improvements in the collection, processing, testing, delivery, and monitoring of transfusions during the past several decades, concerns over the safety of these therapies and the process in general continue today.
Historically, there was concern about transmitting infectious diseases from a donor to a recipient. Now blood is regularly tested for infectious disease transmission, particularly for viruses such as Hepatitis B and C, HIV, and West Nile Virus. Traditionally, serum has been tested to look for the body's response to past infectious exposure, but many serum tests have been replaced by molecular testing called nucleic acid amplification testing (NAT), which finds active viruses in the donor's blood to determine infection risk. If an active virus is found, the donor unit is discarded. Experts anticipate that new methods, including new molecular and microarray testing, which can identify many infectious agents rapidly and accurately, will replace or augment serum studies and NAT in the near future. Blood transfusion has never been safer from known infectious risk than it is today.
In addition to infectious disease risks, doctors must also manage other risks, such as post-transfusion reactions. These include transfusion-related lung injury (TRALI), during which the donor's immune antibodies cause breathing problems in the recipient; transfusion associated cardiac overload (TACO), which is swelling caused by the increased blood volume; and post-transfusion iron overload, which is a buildup of iron in the body, usually caused by multiple or regular transfusions.
Immune reactions, which happen when the body's immune system is affected by the donor blood, also pose several risks to transfused patients. Alloimmunization occurs when the recipient develops an allergic reaction to the donor's red blood cells: transfusion-related immune modulation (TRIM) can lead to increased risk of infections and cancer recurrence, post-transfusion graft-versus-host disease (GVHD, when the donor's immune system attacks the recipient's blood cells), and microchimerism (when a small amount of donor blood persists in the recipient's body, causing ongoing low-grade GVHD).
To minimize these risks, researchers studying the body's immune response to transfusions have found that modifying the blood prior to transfusion can reduce reactions. In particular, removing white blood cells or radiating blood to prevent white blood cell growth can reduce the likelihood that the recipient will reject the donor blood. Recently, studies found that using male plasma and platelets may eliminate the transmission of certain antibodies that can cause reactions and are found only in previously pregnant women and transfused males. However, using these techniques has reduced the amount of blood available for transfusions, so researchers are working to identify better ways to safely increase available blood sources. For example, new technologies can collect large amounts of red cells and platelets from a single donor, improving collection efficiency and decreasing the number of different donors to which a transfused patient is exposed. Some studies have suggested that blood transfusion may be related to higher death rates in critically ill patients; researchers suggest that aged bank blood may be the reason.
While the hematology community continues to improve current processes, the last decade has also seen dramatic developments in innovative approaches, particularly in high-tech cellular therapies and bio-engineering. New techniques can isolate specialized cell populations from blood - most importantly, hematopoietic progenitor cells (HPCs) that are used for stem cell transplantation. Because HPCs are easier to extract and the process is safer for donors, HPC transplantation has replaced bone marrow transplantation for many cancers and other diseases.
Researchers are also using umbilical cord stem cells (UCSCs) as a source of HPCs. UCSCs are collected and processed in a method similar to whole blood and are a rich resource for transplantation therapy in pediatric and some adult patients. In the future, these cells may be grown and expanded for clinical use. Furthermore, researchers have isolated specialized cell types other than HPCs that play an important role in cellular therapy because they can modify proliferation and immune responses during the engraftment of transplanted cells.
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Today, the hematology community continues to advance its transfusion systems, guided by the AABB, American Red Cross, American Society of Hematology, U.S. Food and Drug Administration, and other federal and professional organizations. Researchers are also establishing new surveillance systems that record data and transfusion outcomes to better understand and manage the risks associated with transfusion. They are offering more personalized treatment, limiting transfusions based on careful assessment of need, and ultimately improving patient care.
Transfusion medicine today is using lessons learned from the past to dramatically improve outcomes in the future. Areas of study include technologies that will more precisely identify blood components to increase patient safety and simplify blood inventory; improved automation to increase efficiency and decrease error; and screening methods that will help reduce the risk of infection. In addition, novel cellular therapies continue to be developed and tested to offer more effective treatment options. These innovations will help hematologists not only to reduce the risks associated with blood transfusions, but also to provide new therapies for a wide range of diseases.