Increased Prevalence of Alloimmunization in Sickle Cell Disease? Should We Restore Blood Donation in French Guiana?

Abstract

Patients with sickle cell disease often undergo frequent blood transfusions. This increases their exposure to red blood cell alloantigens of donor units, thus making it more likely that they produce alloantibodies. This cross-sectional study aimed to describe the prevalence of allo-immunization in patients with sickle cell disease who were monitored at Cayenne Hospital in 2016. Of the 451 patients recruited during the study period, 238 (52.8%) were female. There were 262 (58.1%) homozygous sickle cell and 151 (33.5%) compound heterozygous sickle cell patients. The median age of the participants was 23.09 years (range, 0.5–68). We noted different red blood cell extended phenotypes: -in the Duffy system, the Fya- Fyb–profile was found in 299 patients (66%);—for the Kidd system, the most represented profile was Jka+ Jkb-, with 213 patients (47%). The Jka antigen was present in 355 patients;—in the MNS system, the S-s+ profile was found in 297 patients (66%);—the Lea antigen of the Lewis system was absent in 319 patients. The most frequent Rh phenotype in our patients was D+ C- E- c+ e+ K-, representing 51% of the patients. A total of 6,834 transfused packed red blood cell units were recorded. Sixty-eight patients (23%; 95% confidence interval, 20–25%) had detectable RBC alloantibodies. In multivariate logistic regression, only the mean number of single transfusions was statistically higher for the alloimmunized patients (p < 0.04). Thirteen (19%) of the patients with alloimmunization developed a delayed hemolytic transfusion reaction, thus representing 4.4% of the total number of transfused patients. Whether differences between donors from France vs. recipients from French Guiana could explain this high prevalence of alloimmunization to be examined. In conclusion, careful transfusion strategies for patients with RBC alloantibodies should allow further reduction of the rate of alloimmunization.

Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy

“…In our cohort, the antibodies identified were mainly of RhCDE and Kell systems, as reported in studies of transfused SCD patients from the United States and Brazil ( 9 ). Different antibodies systems (i.e., MNS and Kidd) and different frequencies of alloimmunization have been recently described in SCD patients in French Guiana when compared to our cohort or those from the United States or Brazil ( 18 ). These might reflect the heterogeneity of donor and recipient populations in different geographical settings, which increases the complexity of data analysis and comparison.…”

“…RBCs from Caucasian donors were used. The donor-recipient exact matching for ABO, Rhesus and Kell antigen for RBC compatibility strategy limits alloimmunization, which might further complicate clinical management of patients with SCD ( 9 , 18 , 19 , 28 ).…”

“…Over the course of a lifetime, patients with SCD might be exposed to different RBC transfusion regimens, ranging from simple transfusion on-demand or manual/automatized RBC exchange to manage acute VOCs or to limit disease progression and organ damage ( 3 , 17 ). Alloimmunization to RBC blood group antigens carries an increased risk of hemolytic transfusion reactions (DHTR), potentially delaying the identification of compatible RBC units ( 18 , 19 ). In Europe, Italy presents a distinctive epidemiologic European niche for SCD, characterized by endemic SCD population mainly in Southern Italian regions and multi-ethnic SCD population localized in Central and Northern Italian regions ( 20 – 23 ).…”

Unmasking delayed hemolytic transfusion reactions in patients with sickle‐cell disease: Challenges and opportunities for improvement

“…Although the optimal timing for DHTR detection remains to be elucidated, current recommendations suggest serologic testing up to 3–4 weeks post‐transfusion may help to identify new alloantibody formation before possible evanescence 9,13,14 . Incorporating hemoglobin studies (either hemoglobin electrophoresis or routine hemoglobin measurement on Complete Blood Count panel) and a four‐week testing window, recent studies performed in other countries found an incidence of 4.2%–4.4% DHTRs per transfusion event in patients with SCD, 15,16 significantly higher than previously believed, with an 11.5% mortality rate in patients with DHTRs 15 . Thus, under‐detection of DHTRs is a significant source of SCD patient morbidity and mortality.…”

A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia

“…Patients with SCD require regular blood transfusions, which increase exposure to foreign antigens and elevate the risk of producing alloantibodies that may cause delayed haemolytic transfusion responses and make it difficult to find suitable blood [ 18 , 19 , 20 ]. Moreover, it has been reported that multiple blood transfusions may lead to transfusion-transmitted infections, inflammation, and iron overload [ 21 , 22 ].…”