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

Abstract
Aim: To study allosensitization 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: See table 1.
Table I: General data of various patient groups Major patient groups Total pt # (%) Sex (m/f) Pt age in yrs, Median (range) Total pRBC units Median Tn #/pt(range) 121 (31.3%, 56m, 65f) developed alloantibodies (alloABs). Grand total of all patients 500 240/260 22 (0.7–79) 16617 14 (1–524) CEK (& ABO) matched tn pts 113 62/51 8 (0.5–35) 2354 10 (1–143) Regular (ABORh) matched Tn pts 387 (100) 178/209 26 (0.7–79) 14263 18 (1–524) AlloAB forming patients 121 (31.3) 56/65 29 (5–70) 7338 26 (1–500) Non-alloAB forming pts 266 (68.7) 122/144 25 (0.7–79) 6925 12 (1–524) Table II: Transfusion characteristics of patients forming alloantibodies Data on pts forming alloantibodies CEK matched patients CEK unmatched pRBC Transfusion (Tn) patients(387) &gt;0 ABs &gt;1 ABs &gt;2 ABs &gt;3 ABs &gt;4 ABs Number of patients 6/113 121/387(31%) 57/121 (47%) 29/57 (51%) 16/29 (55%) 11/29 # of Transfusions before AB formation 9.5 (0–106) 7 (0–270) 2 (0–106) 0 (0–89) 0 (0–180) 0 (0–16) # of pts with &gt; 5 Tn before alloAB formed 4/6(67%) 68/121(56%) 21/57(37%) 5/29(17%) 4/16(25%) 1/11(9%) # of pts with &gt;30 Tn before AB formed 1 12 4 2 1 0
There were 33 patients with anti-C, 74 with anti-E, and 57 with anti-K ABs (a total of 164, incidence of 2.235 CEK alloABs/100 transfusions{Tn}). 266 patients (6925 Tn, 68%) did not develop any alloABs.
21 patients developed multiple alloABs simultaneously after a single transfusion. pRBC Tn was 1½ times more likely to lead to alloAB formation in adult females (p=0.006) and children (p=0.011) over adult males. &gt;13% patients transfused with CEK unmatched units developed ABs to C, E, K and other antigens. 2/3 patients never developed ABs. Once allosensitized, there was an sustained ↑ chance of developing a 2nd (& later) AB (50% Vs 31% for first timers) with fewer Tn (usually &lt;5). A small number of patients developed alloABs later (&gt;30 pRBCs). Patients receiving CEK matched pRBCs developed non-CEK ABs at 2½ times lower frequency than the corresponding group of patients. It was found that the technologist required 30 more minutes and $153 extra in reagent costs for this extended CEK match. Most Rh negative pRBC units were also CEKneg. 90% of our donors are Caucasian.
Conclusions: This study showed that utilizing CEK negative pRBCs dramatically ↓ alloAB(p&lt;0.01) formation in our SCD patients, including C, E, and K and other minor blood group antigens. Patients transfused without C, E, K antigen match developed ABs to C, E, K, and other antigens. In some patients, allosensitization possibly activates the immune system into a hyperactive state leading to further, earlier, multiple and simultaneous alloAB and autoAB formation. Though unlikely, Rh negative and CEKneg pRBCs may also be negative for other minor antigens. Extended antigen matching made it easier to find proper blood units due to less formation of alloABs. However, it resulted in overuse of Rh negative pRBCs and effort to find CEKneg pRBCs for every transfusion.