Red Cell Alloantibodies and Autoantibodies in Thalassemia Patients at Childrens’ Hospital Boston: Incidence and Influential Factors.
Authors: Cserti Christine M. , Braunstein Jennifer , Cunningham Melody J. 
Published: April 2020

Introduction: Alloantibodies [alloAb] or autoantibodies [autoAb] may represent complications of, and pose relevant barriers to, transfusion in thalassemia patients. A high incidence of alloAb (21%) and autoAb (9.2%) was noted in the Thalassemia Clinical Research Network (TCRN), with an apparent but unresolved association with factors such as the transfusion of nonleukoreduced products, or status post splenectomy. [ASH 2005]

Methods: To learn more about the specific types and timing of serologic abnormalities, the histories of all 44 patients living with thalassemia, born between 1951 and 2005, and treated regularly at this institution, were reviewed.

Results: The ethnic composition of the 44 patients was Caucasian (23; 52.3%), Asian (15; 34.1%), Latin (4; 9.1%), or mixed (2; 4.5%). Sex distribution was evenly male (24; 54.5%) and female (20; 45.5%). The hemoglobinopathy was most commonly β-thalassemia major (31; 70.5%), followed by β-thalassemia intermedia (6; 13.6%); E/β- thalassemia (2; 4.5%); Hb Lepore/ β-thalassemia (1; 2.3%); α-thalassemia major (3; 6.8%); and α-thalassemia intermedia (1; 2.3%). Many patients had been, or continued to be, transfused at other institutions (18; 40.9%). The majority were chronically transfusion dependent (39; 88.6%) and on chelation therapy, with others either never transfused (3; 6.8%) or only intermittently transfused (1; 2.3%). The median age at the first of a patient’s chronic transfusions was 1.1 (range 0.1 to 32) years. Roughly half of the patients had undergone splenectomy (23; 52.3%), at a median age of 6.0 (range 1.3–49) years. There were a total of 914 thalassemia-years, and 659 chronic transfusion-years in this cohort. Twenty patients had been either born or exclusively transfused after universal prestorage leukoreduction, which began in 1990 at this institution. The overall number of chronic transfusion years incorporating prestorage leukoreduction was 457 (69.3% of the total). Alloimmunization occurred in 11/40 chronically transfused patients (27.5%), and 3/11 developed multiple sensitivities (27%, or 7.5% of the total), giving a total of 19 alloAb, 8 of which were clinically significant (E, e, Le(a), or S), 8 of which were clinically insignificant (Bg[a], Sci[2], HTLA Ab, or an alloAb against a low frequency antigen), and 3 of which were persistently unidentifiable due to inconclusive reactivities. The median age of alloAb onset was 4.5 (range 0.8–35.4) years. The median time to first alloimmunization after the initiation of chronic transfusion was 3.7 (range 0 to 33.4) years. Warm autoAb formed in 6 patients, and were discovered only among the chronically transfused (15%), at a median age of onset of 15 (range 3–30) years. The incidence rates of alloAb and autoAb, per hundred chronic transfusion years, overall, or according to leukoreduction (LR) or splenectomy (SP), are listed in the Table:

Rate, per hundred chronic transfusion years pre-leukoreduction post-leukoreduction pre-splenectomy post-splenectomy rate of new alloAb formation 4.5 2.2 1.9 2.2 rate of warm autoAb formation 0.5 1.1 0.3 0.9

Conclusions:

In chronically transfused thalassemia patients, alloAb occurred in 28% and autoAb in 15%, with the former appearing twice as often before prestorage leukoreduction.