Red Blood Cell Allo and Autoantibody Production in Patients in the Thalassemia Clinical Research Network.
Authors: Cunningham Melody J. , Macklin Eric A. , Singer Sylvia T. , Manno Catherine S. , Giardina Patricia J. , Olivieri Nancy F. , Thompson Alexis A. 
Published: October 2019

Introduction: The development of alloantibodies and/or autoantibodies, complicates red blood cell (RBC) crossmatching, shortens red cell survival, delays provision of safe transfusion and may accelerate tissue iron loading. Little is known about the incidence of alloimmunization or its inciting factors, essential data for strategies to provide optimal transfusion.

Aim: To determine the frequency of RBC allo- and autoantibodies in patients with thalassemia major (TM) who are regularly transfused and whether there is an association of RBC antibodies and age at initiation of transfusion, duration of regular transfusion, splenectomy status, transfusion of leukoreduced blood or ethnicity.

Methods: We utilized a cross-sectional registry of the Thalassemia Clinical Research Network (TCRN), an NHLBI-funded consortium of patients with thalassemia followed in Canada and the United States, for data on allo- and autoantibodies, splenectomy status, ethnicity and compared rates before and after 1990, when the first leukoreduction filters were introduced.

Results: 502 of the 836 subjects enrolled in the TCRN registry had been regularly transfused and reported allo- and autoimmunization status. Allo- and autoantibodies were reported in 104 (21%) and 46 (9.2%) subjects, respectively. Presence of both were reported in 26 (5.2%) individuals. The rate of alloimmunization was higher among individuals who initiated transfusions prior to 1990 (27%) versus those who initiated transfusion after that date (12.5%, p<.001). The rate of autoimmunization did not differ significantly between these two cohorts (pre-1990 11.2%, post-1990 6.3%, p=.08). Mean age at time of registry entry in these cohorts was 25.8±8.4 yrs and 9.3±6.8 yrs, respectively. Duration of regular transfusion was associated with allo- (p<.001) but not autoantibodies (p=.08). Initiation of transfusions before or after 1990 and duration of regular transfusions are confounded. Consequently, the differences in alloimmunization rates may reflect the use of leukoreduction or the total years of exposure to transfusions. Splenectomy was associated with a higher rate of alloantibodies among subjects in the post-1990 but not the pre-1990 cohort. Alloantibodies were reported in 14 of 49 (29%) splenectomized subjects who started transfusion after 1990, and only 12 of 159 (7.6%) nonsplenectomized subjects (p<.001). Rates of alloimmunization did not differ among races after controlling for age. Age at initiation of regular transfusions was not associated with allo- or autoimmunization. Rates of alloimmunization differed among treatment centers, possibly related to varying procedures for phenotypic antigen matching of RBCs.

Conclusions: RBC allo- and autoimmunization continue to develop in chronically transfused thalassemia patients although the availability of leukoreduced RBC may have resulted in the lower immunization rate observed in younger patients. The risk for RBC immunization that splenectomy imparts is concerning and deserves closer analysis.