Management of a patient with sickle cell disease and multiple red blood cell alloantibodies in preparation for a hematopoietic stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) is currently the only widely available curative option for patients with sickle cell disease (SCD). Alloimmunization in this population is frequent and can complicate transfusion management during the HSCT period. The case of a pediatric patient with severe SCD clinical phenotype, multiple alloantibodies (9), and hyperhemolysis syndrome who underwent haploidentical HSCT is described. STUDY DESIGN AND METHODS: The patient was known for an anti-e, despite RHCE*01.01 allele, which predicts a C- c+ E- weak e+ phenotype. Donors matching the patient's extended phenotype were targeted for RHCE genotyping. RESULTS: Donors homozygotes or heterozygotes for RHCE*01.01 were selected for compatibility analyses and ranked based on strength of reactions. Discordance between zygosity and strength of reactions was observed, as the most compatible donors were heterozygotes for RHCE*01.01. In total, the patient received seven RBC units from two different donors during HSCT process without transfusion reaction or development of new alloantibodies. Six months post-HSCT, his hemoglobin level is stable at around 120 g/L and his chimerism is 100%. DISCUSSION: This case highlights the complexity of transfusion management during HSCT of alloimmunized patients with SCD. Collecting sufficient compatible units requires early involvement of transfusion medicine teams and close communication with the local blood provider. Genotyping of donors self-identifying as Black is useful for identifying compatible blood for those patients but has some limitations. HSCT for heavily alloimmunized patients is feasible and safe with early involvement of transfusion medicine specialists. Further research on the clinical impact of genotypic matching is needed.

HLA and red blood cell antigen genotyping in SARS-CoV-2 convalescent plasma donors.

Aim: More data is required regarding the association between HLA allele and red blood cell (RBC) antigen expression in regard to SARS-CoV-2 infection and COVID-19 susceptibility. Methods: ABO, RhD, 37 other RBC antigens and HLA-A, B, C, DRB1, DQB1 and DPB1 were determined using high throughput platforms in 90 Caucasian convalescent plasma donors. Results: The AB group was significantly increased (1.5×, p = 0.018) and some HLA alleles were found to be significantly overrepresented (HLA-B*44:02, C*05:01, DPB1*04:01, DRB1*04:01 and DRB1*07:01) or underrepresented (A*01:01, B51:01 and DPB1*04:02) in convalescent individuals compared with the local bone marrow registry population. Conclusion: Our study of infection-susceptible but non-hospitalized Caucasian COVID-19 patients contributes to the global understanding of host genetic factors associated with SARS-CoV-2 infection and severity.

High prevalence of weak D type 42 in a large-scale RHD genotyping program in the province of Quebec (Canada).

BACKGROUND: The determination of the RhD phenotype is crucial to avoid alloimmunization, especially in childbearing women. Following the 2015 recommendation from the Work Group on RHD Genotyping, a large-scale RHD genotyping program was implemented in the province of Quebec (Canada) and offered to women ≤45 years old with a serological weak D or discordant results. Since weak D type 42 was previously shown to be prevalent among French Canadians, genotyping for that variant was also performed. Our aim was to report the prevalence of the weak D alleles in the province of Quebec. STUDY DESIGN AND METHODS: A retrospective study of 2105 women with serological weak D referred to Hema-Quebec's immunohematology reference laboratory (IRL) between June 2016 and May 2020 was conducted. Results from the serological tests performed by the referring hospital were compiled and RHD were genotyped. RESULTS: Most patients presented at least one serological result ≤2+ before being referred to Hema-Quebec. Weak D type 42 was the most prevalent variant, representing 17.5% (368/2105) of all individuals tested. Only 15.3% (323/2105) of patients were weak D type 1, 3.3% (69/2105) were type 2, and 8.6% (180/2105) were type 3. Weak D type 42 is highly expressed in regions with low immigration rate and known for their founder effect. CONCLUSION: Our RHD genotyping program allowed for a better management of weak D. The province of Quebec presents a unique RHD genotype distribution. We confirmed that weak D type 42 is associated with a founder effect found in Caucasian French Canadians.

Adapting to supply-and-demand emerging trends for antigen-negative red blood cell units.

BACKGROUND: A global downtrend in blood usage has been observed by many countries, while the demand for antigen-negative red blood cell (RBC) units used in antigen-matched transfusions keeps increasing. The declining number of units collected exposes blood providers to a rapidly evolving supply challenge. METHODS: This study was conducted retrospectively with use of internal data analysis to weigh Québec's situation regarding global and antigen-negative RBC demand, to measure the effects of community-directed recruitment and blood drives, and to evaluate the benefits of mass-scale RBC genotyping. RESULTS: Our findings confirm a global RBC usage downtrend of over 20% total in the past 10 years with a steady antigen-negative usage and highlight the most requested negative antigen combinations. Our data also show our +39.5% progress regarding the number of Black donors recruited for antigen matching of patients with sickle cell disease in the past 3 years, as well as a constantly growing number of just-in-time blood collection for complex orders. Finally, our data summarize the efficiency of our mass-scale RBC genotyping efforts. CONCLUSION: Altogether, this study confirms the demand trends for regular and antigen-negative RBC units in Québec and the efficient effects of our recruitment and typing strategies.

A LU:-16 individual with antibodies.

CONCLUSIONS: Antibodies against Lutheran blood group antigens have been observed during first-time pregnancy. Samples from a woman of African descent were tested in our immunohematology laboratory on several occasions since 2001. Her samples were phenotyped as Lu(a+b-), and anti-Lub was suspected but not identified. She was asked to make autologous donations in preparation for her delivery, which she did. In 2010, two antibodies were identified: anti-Lea and -Lub. Six years later, a third investigation was requested. This time, an antibody directed at a high-prevalence Lutheran antigen was found in addition to the anti-Lea and -Lub previously observed. Her serum was compatible with three out of five Lu(a-b-) reagent red blood cells (RBCs). One of the incompatible Lu(a-b-) reagent RBCs was known to be In(Lu) (KLF1 mutation). The genetic background of the other reagent RBC was unknown. The LU cDNA sequence analysis revealed the presence of the c.230G>A (Lua), c.679C>T (LU:-16), and a silent polymorphism c.1227G>T. Anti-Lu16 was highly suspected. This would be the fifth case of LU:-16 with antibodies reported, all within women of African heritage with the Lu(a+b-) phenotype. Hemolytic disease of the fetus and newborn was not noted in these cases.