Winter 2013
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Sickle Cell Q&A: Use of technology in providing transfusions to sickle cell patients

By Dr. Mark Yazer, Associate Professor of Pathology, University of Pittsburgh and Medical Director, Centralized Transfusion Service is an Associate Professor of Pathology at the University of Pittsburgh and is the medical director of the red blood cell serology reference laboratory at the Centralized Transfusion Service in Pittsburgh. Dr. Yazer was not compensated for writing this article and he is on the scientific advisory boards or speaker’s bureau of Novartis, Grifols, Octaplas, Ortho J&J.
Sickle Cell Q&A: Use of technology in providing transfusions to sickle cell patients

Q: What is Sickle Cell Disease?

Sickle cell disease (SCD) is a hereditary blood disorder that affects about 100,000 Americans and many millions more worldwide. SCD is characterized by red blood cells (RBC) that can assume an abnormal, sickle shape. This sickling results when an individual inherits two copies of the sickle hemoglobin gene.

Hemoglobin is the substance that carries oxygen inside an RBC. Under certain conditions of stress, such as when the patient has an infection, the sickle hemoglobin causes the RBCs to change their shape from a round disc into that of a sickle.

The RBCs that take this sickle shape do not flow in the blood stream properly and can get trapped in the small blood vessels of the brain, lungs, and kidneys, causing pain and potentially organ damage. These episodes are called “sickle crises.” How often these sickle crises occur varies from person to person with sickle cell disease.

Q: Is there a cure for SCD?

A bone marrow or stem cell transplant from a donor without the SCD gene is the only known cure for SCD. However, stem cell or bone marrow transplants are dangerous procedures and can have severe complications. SCD can also be managed with medication that reduces the relative amount of the sickle hemoglobin inside the RBC.  RBC transfusions are also used to manage SCD patients. Transfusions decrease the number of abnormal RBCs while adding normal, healthy red blood cells – thereby reducing the likelihood that a crisis will occur.

Q: Why do some people have the sickle cell gene or trait, but never suffer from the disease?

The sickle cell trait is usually a much less severe form of SCD that results when a person inherits one gene for normal hemoglobin and one gene for sickle hemoglobin. It is estimated that approximately two million Americans have sickle cell trait. Sickle crises rarely occur in people with sickle cell trait because these people produce some normal hemoglobin that prevents the RBCs from sickling in the blood vessels. However, sometimes under conditions of severe stress crises can occur. For example, Ryan Clark, a Pittsburgh Steeler football player with sickle cell trait, experienced a significant crisis while playing in Denver. Although he only has one gene for sickle hemoglobin, the physical stress of playing professional sports in a high altitude city was enough to cause a crisis. 

Q: What role do transfusions play in the care of SCD patients?

Transfusing RBCs from normal donors is one of the most important treatments in SCD. Transfusing normal RBCs reduces the amount of sickle hemoglobin and number of cells that could sickle and disrupt blood flow to vital organs. RBC transfusion, combined with fluids and pain control medications, is a mainstay of SCD treatment. The past 20 years have seen significant progress in reducing the likelihood of transmitting viruses like HIV and hepatitis through transfusion. This is welcome news for SCD patients who often require hundreds of RBC transfusions over their lifetime. Another area of transfusion safety that is gaining widespread attention is the formation of antibodies to transfused RBCs by SCD patients. The formation of antibodies is the immune system’s natural response to a foreign substance – it is how one becomes “immune” after receiving a flu vaccine. Normally, antibodies are useful because they help the body recognize and destroy foreign particles. However, if an SCD patient forms an antibody to a transfused RBC, it becomes difficult to find compatible blood for future transfusions.

Q: What’s being done to prevent antibody formation in SCD patients?

Every RBC has hundreds of proteins and sugars on its surface. If a donor and recipient’s RBC proteins or sugars do not match, the recipient may develop antibodies. It is estimated that between 30% to 50% of transfused SCD patients produce at least one of these antibodies, which can potentially result in the destruction of the transfused RBCs. Thus, when RBC antibodies are identified in a recipient, the blood bank must carefully select only compatible donor RBC units. The traditional method of locating compatible units for transfusion is to randomly select donated RBC units in the blood bank and test them one-by-one to see if they are compatible.  Thus, it really is “the luck of the draw” when selecting units to test, and in some cases dozens of units have to be tested before a compatible unit is found. This process for finding donated RBC units that are compatible for SCD patients is both time consuming and expensive in terms of a blood bank’s resources, and it can delay the availability of blood for patients.

Q: Can technology be used to change the way compatible RBCs are selected for SCD patients? 

New technology, known as blood group genotyping (BGG), is being increasingly used in the search for compatible donated RBC units. As all of the proteins and sugars on the RBCs are ultimately determined by genes, BGG techniques use the blood donor’s DNA to predict which proteins or sugars will be on their RBCs. With only a few exceptions, if a donor has a gene for a specific protein or sugar, then it will be on their RBC surface. BGG techniques allow the transfusion service to provide RBC units that are extensively matched between the donors and the SCD patients thereby reducing the chances that the recipient will form an antibody. BGG techniques overcome many of the limitations of the traditional way of searching for compatible RBC units by providing information on the presence or absence of many of the most important proteins and sugars on the RBCs using one test, rather than randomly screening units with expensive reagents. Although BGG testing is subject to its own limitations, it is becoming a useful adjunct in providing compatible RBCs for SCD patients.

Q: What should legislators know about the management of SCD patients?

By being aware of the latest developments in SCD research and transfusion therapy, legislators will understand the impact of improvements in transfusion safety that are occurring now and those that are planned in the future. Legislative solutions may then be developed to support these innovations in research and therapy if they are shown to be clinically effective.
Dr. Mark Yazer

Associate Professor of Pathology, University of Pittsburgh and Medical Director, Centralized Transfusion Service is an Associate Professor of Pathology at the University of Pittsburgh and is the medical director of the red blood cell serology reference laboratory at the Centralized Transfusion Service in Pittsburgh. Dr. Yazer was not compensated for writing this article and he is on the scientific advisory boards or speaker’s bureau of Novartis, Grifols, Octaplas, Ortho J&J.

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