In heart transplant patients receiving leukoreduced red cells, is there evidence to support washing of the cells to remove soluble HLA antigens that might contribute to HLA alloimmunization and organ rejection?

A physician who is medical director for a blood center in the Midwest also co-directs the transfusion service for one of their metropolitan area medical centers. This medical center provides solid organ transplants, including heart transplants. The transplant cardiologist has requested washed leukoreduced red cells for transfusion for some of his pre-heart transplant patients. (Since nearly 2000, universal leukoreduction policy was adopted by all metropolitan hospitals supplied by her blood center.) In the past it was an infrequent request, but recently it has become more routine, occuring on red cell orders for all of these patients. From limited phone conversations with this surgeon, his rationale is to decrease the risk of HLA alloimmunization due to the presence of soluble HLA antigens in the plasma. Although this medical director has discussed with him the lack of clinical evidence of such transfusion practice, he is quite persistent on the use of washed cells in these patients.

She has the following questions:

• Is this standard practice at other tranplant centers?
• Have others of the e-Network Forum members at transplant centers have had similar requests for pre-heart transplant patients?
• Is there any literature to justify such orders? (She has been unsuccessful in finding any such reports.

The following comments have been received.

ADDENDA Apr. 23, 2004

1. A transfusion medicine physician in New York reports that in his opinion there may be many reasons that washed red cells and platelets might benefit patients on ventricular assist devices (VADs), but he does NOT believe HLA allosensitization is one of them. He and his colleagues believe that use of leukoreduced blood and only ABO identical platelet (and red cell) transfusions are sufficient to prevent de novo sensitizations in the vast majority of patients. HLA allosensitization rates are very high in patients on VADs receiving non-leukoreduced transfusions. Leukoreduction obviously works in this regard in patients receiving myeloablative chemotherapy. The question has been does it work in patients who are more immunologically more intact. There are data in the literature suggesting that giving ABO mismatched platelets boosts the likelihood of HLA allosensitization (Hutton R et al. Br J Haematol. 1990 Jul;75(3):408-13 Transfusion of ABO-mismatched platelets leads to early platelet refractoriness.)
   
   The responding New Yorker's group now has a series of about 25 previously unsensitized patients awaiting transplant who have received only leukoreduced blood components and only ABO identical platelets. Despite receiving dozens of unwashed red cell and platelet transfusions each, none have become allosensitized.
   
   The first fifteen of these patients were reported in the abstract presented at ASH in December 2003. Blood 102 (11): 562 a(2003). Abrogation of HLA allosensitization in patients on ventricular assist devices (VAD) receiving leukoreduced, ABO identical blood components. Myra Coppage MS,CHS *, Neil Blumberg MD , Leway Chen MD,MPH *, H Todd Massey, MD *, Jean Huether RN,NP *, Martin Zand MD,PhD *, Nufatt Leong BS,CHS * and Thomas Shanahan PhD *. Surgery, Transfusion Medicine, and Medicine, University of Rochester, Rochester, NY, United States, 14642.

ADDENDA Apr. 25, 2004

2. A transfusion medicine physician in North Carolina reports that this question is somewhat similar to a question about the risk of HLA alloimmunization following with plasma infusions. This is relevant as even if a cellular product is leukocyte reduced and washed, it would be expected that the residual white cell may still approximate that found in plasma.  The North Carolina physician reports "plasma, although generally thought of as a cell free product, does contain variable small amounts of WBCs. In one study of post freeze-thaw plasma prepared from whole blood (N=10) the residual WBCs were reported as mean (range) 4.9 (0.6-16.3) x 10⁶ WBCs. Similarly in post freeze-thaw plasma collected by apheresis (N=10) the residual intact WBCs were reported as mean (range) 8.3 (<0.6-36.2) x 10⁶. In addition, soluble HLA antigens are present in plasma. Such antigens are not removed with leukocyte reduction filters. Although there are reports of patients transfused with plasma, but no cellular blood products who have become HLA alloimmunized, it is not clear if this alloimmunization occurred as a result of soluble HLA antigens or from the residual WBCs present in the plasma. It is generally felt that wbc-associated transfusion complications are rare or absent with FFP, as is HLA alloimunization so that there is no immediate medical mandate to produce leukoreduced FFP."
   
   References: Greene CJ, Paglieroni TG, Moss CB, Ward JM, Hill L, MacKenzie, Holland PV. WBC populations in thawed fresh frozen plasma. Transfusion 1999;39 Supplement 99S.
   
   Stringham JC. Bull DA. Fuller TC. Kfoury AG. Taylor DO. Renlund DG. Karwande SV. Avoidance of cellular blood product transfusions in LVAD recipients does not prevent HLA allosensitization. Journal of Heart & Lung Transplantation. 18(2):160-5, 1999.
   
   Modified from Brecher ME. Collected Questions and Answers. 7th edition AABB Press, 2001.

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