A blood banker from Tennessee wants to know what other institutions do regarding the transfusion of sickle trait donor RBC units to sickle cell patients. Her facility currently transfuses sickle cell patients with donor RBC units that are negative for sickle cell trait and matched for ABO/D as well as the following antigens based on the patient's phenotype: C, E, K. The inquiring blood banker's facility wants to change their local policy to allow the use of sickle trait donor RBC units and to drop the screening of donor units for sickle trait. She points out that an AABB standard (21st edition) states that there shall be a policy defining the patients who are to receive red cells and whole blood known to lack hemoglobin S (5.16.3); the standard does not require that sickle cell disease patients must receive sickle test negative units. She also points out that in the 13th edition of the AABB Technical Manual, there is a statement that "Patients with sickle cell disease need sickle-cell-negative blood." (page 473). However, she reports that her institution has had sickle cell disease patients with multiple antibodies whose transfusion could be further delayed because a rare compatible donor RBC unit was sickle trait positive and their current policy limits them to use only donor RBC units that test sickle negative. She wants to know if transfusion of sickle trait units actually causes harm to a sickle cell patient. She also wants to know if other institutions are considering or actually employ a more flexible policy that allows the transfusion of sickle trait donor RBCs to sickle cell patients.

A note from the e-network forum Editor: The e-Network Forum may find the following earlier e-Network discussions to be of interest as you consider the query from the Tennessee blood banker:

• What is your policy regarding the collection of blood from a person with sickle cell trait, and what is your policy regarding transfusion of such blood?
• Implications of Sickle Trait Blood for Leukocyte Reduction and Transfusion
• Should We Irradiate Red Cells Transfused to Patients with Sickle Cell Anemia?
• Red Blood Cell Phenotype-matched Donor RBCs and Transfusion for Sickle Cell Anemia

Before sharing the above discussion with the full e-Network, the input of selected experts was solicited. Here is what they had to say:

1. In the opinion of a New York physician blood bank expert, "sickle trait testing for transfusions to patients with sickle cell anemia is usually an unnecessary inconvenience and expense unless there is some reason for very closely monitoring the per cent hemoglobin S, which is obviously interfered with by giving sickle trait blood, although not much. Sickle trait donors are only a few out of every thousand donors in the USA in most communities so the likelihood of getting a trait unit is quite low and of getting more than one extremely low. Even if one had a strictly African American donor pool, the frequency is only about 8-10%. Sickle trait blood transfusion is benign and there is virtually no evidence that transfusion of sickle trait blood to any patient is deleterious per se. The likelihood of sickling has to do with the concentration of sickle hemoglobin in the red cell, and the concentration in trait cells is below the sickling threshold except under extreme hypoxic conditions. Early studies of sudden death in sickle trait patients in military basic training have been questioned as to whether they had much to do with the hemoglobin phenotype. Antigen matching is a controversial area. About 20-30% of patients with sickle cell disease will be sensitized, mostly to C, c, E, e and K, if transfused. This is only modestly higher than the rate in many other patient groups (10-20%). However, the problem comes in sickle cell disease because there is a high incidence of requiring life time transfusion for prophylaxis of stroke, acute chest syndrome, etc. Most studies suggest that avoiding Rh and K antigens that the recipient lacks decreases the alloimmunization rate to close to zero. We have about 15 such patients I have followed for about 20 years and none of them have made any Rh or K antibodies, and interestingly, none have made any Duffy, Kidd, Ss etc. antibodies either. All of our extremely difficult to transfuse patients have been sensitized elsewhere. So while I am reluctant to endorse antigen matching for these patients (we also do it for thalassemics on transfusion prophylaxis) it does seem to work and is not a major burden in our setting. If we had hundreds of patients, we would probably restrict antigen matching to female children and females under the age of 50."

2. In the opinion of a physician blood bank expert from Minnesota, "in the transition to an ISO format, useful guidance has been lost from the Standards, and should, in the ideal world, now appear in the Technical Manual. (Standards are Standards and the Technical Manual is a book of good ideas on how to do stuff...). Hence, we simply wanted to ensure that as the Standards got less proscriptive and that people still were aware that it is a good idea to avoid using sickle trait blood in neonatal exchanges, ECMO etc. As a former sickle cell clinician, the major reason to avoid sickle trait blood for transfusion to patients with sickle cell anemia is that we often use residual sickle hemoglobin content as a measure of the adequacy and end point for our transfusion therapy. I have had the experience of having a pediatric patient with profound alloimmunization who typed as homozygous ee but had a demonstrable anti-e antibody! Marilyn Mould wrote him up with a collection of other variant little e antigens. I bring this case up simply because the only person we could find compatible with him (by radioactively labeling her cells and following survivals) was his mother, who, by definition had sickle cell trait. Hence, of course it is OK to use it, but certainly you should know it so that when the clinicians do the exchange or transfusion and the Hb S doesn't fall as far as expected that you don't start chasing exotic subclinical alloimmune hemolysis theories. Another superb reference that gives lots of guidance is the AABB text "Transfusion Support for Patients with Sickle Cell Disease" by Rosse, Telen and Ware.

3. A third physician blood bank expert from North Carolina agreed wholeheartedly with the blood bank expert from Minnesota.

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator