Transfusion Complications in Thalassemia: A Report From the Centers for Disease Control and Prevention (CDC)
Authors: Vichinsky Elliott , Neumayr Lynne , Trimble Sean , Thompson Alexis A. , Giardina Patricia , Cohen Alan R. , Coates Thomas D. , Neufeld Ellis J. , Grant Althea M , Boudreaux Jeanne 
Published: October 2019

Abstract
Abstract 340
Transfusions are the primary therapy for thalassemia (thal) but have significant cumulative risks. The Thalassemia Clinical Research Network recently highlighted the increased rate of alloimmunization in this population1. In 2004, the CDC established a national blood safety monitoring program for thal. The goals of the program were to monitor blood safety and strategies for the management of complications. This report focuses on immune and non-immune transfusion reactions.

Methods:
The CDC Thalassemia Blood Safety Network is a consortium of thal centers that follow patients longitudinally to determine the transfusion-related complications. Serial demographic, physical, and laboratory data are collected along with blood samples analyzed at the CDC. Data collected includes ethnicity, genotype, phenotype, transfusion data, immunizations, type of red cell product, degree of antigen matching, and chelation therapy.
Chronically transfused (CT) patients were defined as requiring at least 8 transfusions annually. Intermittently transfused (IT) patients received less than 8 transfusions annually. Statistical analyses included continuous variables, logistic regression, and multivariant analysis.

Results:
There were 407 patients including 327 CT patients and 80 IT patients. The genotype of chronically transfused patients included: TM (81%), TI (6%), E-Beta-Thal (6%), and Hemoglobin H/CS (4%). The average age of CT patients was 22.3 years ± 13 and 21.4 years ± 17 in IT patients. The average units CT patients received was 149 ± 103.
Hemosiderosis occurred in both patient groups and correlated with transfusion history. The average ferritin (m/L) in each group, respectively, was 2261 and 689. 78% of the total population has received chronic chelation therapy. Multiple organ dysfunction was common in the population, including cardiac disease (13%), gonadal failure (17%), growth hormone deficiency (8%), hypothyroidism (8%), hypoparathyroidism (1.2%), diabetes (10%), and thrombotic events (5.4%). 45% of the population was splenectomized.
Transfusion reactions occurred in 48% of patients, including allergic (45%), multiple etiologies (32%), febrile (17%), and hemolytic (5%). Transfusion-associated infection included 58 cases of Hepatitis-C and 4 cases of HIV. Two Hepatitis-C cases occurred after specific blood testing was initiated. Recent cases of bacteremia, malaria, and Babesiosis have been documented. 21% of CT patients and 13% of IT patients developed an alloantibody. The most common antigen specificity included E (25%), Kell (13%), C (9%), Jka (5%), Kpa (4%), HLA (4%), V (3%), c (3%), D (2.5%), WA-1 (2.5%), and S (2.5%). 45% of alloimmunized patients had multiple antibodies. Race, transfusion burden, age and splenectomy predicted alloimmunization. Alloimmunization was found in 31% of splenectomized patients vs. 10% of non-splenectomized patients (p <.0001). The alloimmunization prevalence rose from 10% in young children compared to 54% in older patients. The average units transfused in patients with alloantibodies was 215 ± 104 vs. 126 ± 92 in patients without alloantibodies (p <.0001).
Autoantibodies occurred in 6.5% of the population and increased with age and splenectomy. Alloimmunization increased the risk of autoantibodies: 26% of patients with an alloantibody had an autoantibody whereas only 2% of patients without alloantibodies had an autoantibody (p<.0001). Overall, 81% of patients with an autoantibody had an alloantibody.
Local institutional policies were the major determinant in the type of units administered. In the last year, 32% of the units were washed and 80% radiated. 40% of patients received standard ABO matching, 47% limited phenotypic matching, and 12% full extended matching.

Conclusion:
Transfusion-related morbidity is a major problem in thal. Hemosiderosis immunologic and non-immunologic reactions are common. Transfusion-related infections have decreased but new, emerging pathogens have been noted.

Disclosures:
No relevant conflicts of interest to declare.