Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME)

Abstract

Background and Study Objectives Transfusions are the primary therapy for thalassemia but have significant cumulative risks. In 2004, the Centers for Disease Control and Prevention (CDC) established a national blood safety monitoring program for thalassemia. The purpose of this report is to summarize the patient population as well as previous non-immune and immune transfusion complications at the time of enrollment into the program. A focus on factors associated with allo- and auto-immunization in chronically transfused patients and a description of blood product preparation and transfusion practices at the participating institutions are included. Study Design and Methods The CDC Thalassemia Blood Safety Network is a consortium of thalassemia centers, longitudinally following patients to determine transfusion-related complications. Enrollment occurred from 2004 through 2012 and annual data collection is ongoing. Demographic data, transfusion history, and previous transfusion and non-transfusion complications were summarized for patients enrolled between 2004 and 2011. Logistic analyses of factors associated with allo- and auto-immunization were developed. Summary statistics of infections reported at the time of enrollment were also calculated. Results The race/ethnicity of the 407 thalassemia patients enrolled in the Network was predominantly Asian or Caucasian and 27% were immigrants. The average age was 22.3 years ± 13.2 and patients received an average total number of 149 ± 103.4 units of red blood cells. Iron-induced multi-organ dysfunction was common despite chelation. At study entry, 86 patients had previously been exposed to possible transfusion-associated pathogens, including Hepatitis-C (61), Hepatitis B (20), Hepatitis A (3), Parvovirus (9), HIV (4), malaria (1), staphylococcus aureus (1) and babesia (1). As 27% of the population was born outside of the United States (India, Pakistan, Thailand, China, Vietnam and Iran accounting for 57%), the source of infection cannot be unequivocally tied to transfusion. In total, 24% of transfused patients were reported to have possible transfusion-associated pathogens. Transfusion reactions occurred in 48% of patients, including allergic, febrile, and hemolytic; 19% of transfused patients were alloimmunized (defined as a having an antibody to a foreign red blood cell antigen). The most common antigens were E, Kell and C. One hemolytic reaction to an anti-Mia antibody was noted. Years of transfusion was the strongest predictor of alloimmunization. However, initiating transfusions in infancy may induce immune tolerance. Autoantibodies occurred in 6.5% and were predicted by previous alloimmunization (p < .0001). Local institutional transfusion policies, rather than patient characteristics, were the major determinants in the preparation of red-blood cells for transfusion. Conclusion Hemosiderosis and immunologic and non-immunologic transfusion reactions are major problems in thalassemia patients. Infections continue to be a problem in thalassemia and new pathogen...

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

“…RBC transfusions also prove to be life saving for acute sickle-related complications, such as acute ischaemic stroke, acute chest syndrome (ACS), splenic sequestration and aplastic crisis. However, transfusion of RBCs is complicated by development of allo-and auto-antibodies, which occur much more frequently in patients with SCD than in any other heavily transfused patient population (alloimmunization rates 18-47% for SCD vs. 7-19% for thalassaemia major (Rosse et al, 1990;Heddle et al, 1995;Hoeltge et al, 1995;Aygun et al, 2002;Castro et al, 2002;Azarkeivan et al, 2011;Thompson et al, 2011;Vichinsky et al, 2014).…”

Thalassemia 2016: Modern medicine battles an ancient disease

“…Transfusion reactions (some fatal) due to alloantibodies were well documented in the older literature. Unfortunately due to differences in ethnicity in donors and recipients of transfusions, alloimmunization will undoubtedly continue to persist even in modern times [26]. A recent survey found that, even in the industrialized world, the practice of transfusion medicine is still variable and could be improved and standardized to reduce alloimmunization [27].…”

“…Transfusion transmitted diseases have dealt a lifelong blow to patients who began receiving transfusions prior to testing for hepatitis and/or HIV. In the industrialized world, these are either the oldest patient cohort or immigrants who began their transfusion history in countries where testing for pathogens is not yet standard practice [26]. Besides their immediate impact on the patient's health, transfusion transmitted infections can lead to late complications such as cirrhosis and/or hepatocelluar carcinoma (HCC).…”

Factors Influencing RBC Alloimmunization: Lessons Learned from Murine Models

“…It must also be appreciated that splenectomy has many potential adverse immunologic and hematologic/vascular sequelae [109,110] beyond RBC immune responses to RBC antigens, especially over the long term. The human literature concerning the spleen's role in RBC alloimmunization is mixed: some studies have found that splenectomy has no statistically significant impact on RBC alloimmunization rates, or that it decreases alloimmunization [13,111,112,113], while others suggest that splenectomy may increase RBC alloimmunization rates [32,33,114,115]. Such findings are likely due in part to the large number of confounding variables involved and, as above with animal studies, may be affected by the history of RBC transfusion and whether the recipient was first exposed to foreign RBCs before or after splenectomy.…”

“…Young recipient age at the time of initial RBC exposure has been shown to influence rates of RBC alloimmunization in patients with sickle cell disease [14,79] and thalassemia major [115], leading to a hypothesis that relative ‘tolerance' to RBC antigens may be possible in young transfusion recipients. To date, only one animal study has been published investigating the relationship between recipient age at initial RBC exposure and RBC alloimmunization, with no or very low levels of anti-HOD alloantibodies observed in juvenile animals (3 weeks of age) compared to adult animals [80].…”