Autoantibody Formation in Sickle Cell Disease Patients Receiving Multiple Blood Transfusions.
Authors: Sakhalkar Vishwas S. , Veillon Diana M. , Cotelingam James D. , McCaskill Deborah M. , Caldito Gloria C. , Hawthorne Linda M. 
Published: April 2020

Abstract
Aim: To study autoantibody (autoAB) formation in our sickle cell disease (SCD) patients before and after instituting the practice of transfusing C, E, K blood type negative (CEKneg) packed red blood cell (pRBC) units.
Material and Methods: We retrospectively reviewed blood bank records of all SCD patients that were transfused pRBCs since 1990 to date. Statistical analysis was performed using the Chi square test and Fischer’s exact test.
Results: During 1990–2004, a total 500 SCD patients (240 male, 260 female) received 16,617 pRBCs in our medical center. Of these, 387 (178m, 209f) received 7338 sickle negative ‘regular’ pRBC units crossmatched only for ABO and Rh blood types. 121 (31.3%, 56m, 65f) patients received 7338 pRBCs and developed alloantibodies (alloABs), and those patients developed 4 cold and 30 warm autoABs. 266 patients (68.7%, m, f; 6925 transfusions) never developed alloABs, but 5 patients developed cold and no warm autoABs.
16 patients developed autoABs (15 warm) simultaneously in addition to the multiple alloABs after a single pRBC transfusion. 113 patients (62m, 51f) always received 2354 CEKneg pRBCs (from 1997), 6 patients (4m, 2f; p&lt;0.01) developed one alloAB each and only 1 warm autoAB.Patients receiving CEK matched pRBCS developed autoABs at 6 times↓frequency. It was found that the technologist required 30 more minutes and $153 extra in reagent costs for this extended CEK match. It was found that most Rh negative pRBC units were also CEKneg. 90% of our donors are Caucasian.
The patients who received only ABORh matched transfusions and yet did not develop alloABs, also did not develop any warm autoABs compared to 30 warm autoABs encountered in corresponding patients that developed alloABs (p&lt;0.001).
Extended antigen matching (by an additional C,E,K antigen match) ↓ alloAB and autoAB formation. In some patients, allosensitization possibly activates the immune system into a hyperactive state leading to further, earlier, multiple and simultaneous alloAB and autoAB formation.
Conclusions: This study showed that utilizing CEK negative pRBCs dramatically ↓ autoAB formation in our SCD patients. Patients that did not develop alloABs also did not develop any warm autoABs (p&lt;0.001). AutoAB formation was more common in patients that developed multiple alloABs simultaneously, but did not result in any significant complications. These patients were also more prone to develop allergic reactions (p&lt;0.002), prompting speculation whether allosensitization possibly activates the immune system into a hyperactive state or if certain patients are gentically more predisposed to allosensitization or both. In our population, extended antigen matching made it easier to transfuse blood units due to less formation of alloABs and autoABs. However, it resulted in a significant overuse of Rh negative pRBCs and extra cost and effort to find CEKneg pRBCs for every transfusion.
Table: Incidence of autoantibody formation in patient groups Major patient groups # of pts # of pRBCs Number of autoABs (% of patients)[Incidence/1000 Tx ] Total Warm P value (CEK vs Regular) 0.005 0.02 CEKmatched Tn pts 113 2354 1 (0.88%)[0.425] 1 (1%)[0.46] Regular (ABORh) 387 14263 39 (10%)[2.73] 30 (8%)[2.1] alloAB forming pts 121 7338 34 (28%)[4.63 ] 30 (25%)[4.1] No alloAB forming pts 266 6925 5 (2%)[0.7] 0 P value(alloAB vs non-alloAB) &lt;0.001 &lt;0.001