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Comparison of prophylactic genotypic matchingwith phenotypic matching for reducing the rate of

alloimmunization and hemolytic transfusionreactions in patients with Sickle Cell Disease (SCD)

Ianca leal, Maria Rita M Miranda, Tamires D Santos, Simone Gilli, Lilian Castilho

Date: 10/19/2021

Faculty Disclosure

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In compliance with ACCME policy,

AABB requires the following

disclosures to the session audience

I have no conflict of interest to declare

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Red blood cell alloimmunization

Transfusion of patients with SCD represents a significant challenge in clinical transfusion medicine with RBC alloimmunization a primary and serious complication

The rates of RBC alloimmunization in patients with SCD (18-52%) are considerably higher than rates reported in general transfused population (0.2–2.8%)

Alloimmunization often makes finding compatible RBC products difficult and is also associated with:

Delayed hemolytic transfusion reactions (DHTRs)

Production of autoantibody

Decrease in red blood cell survival

Increased transfusion requirement

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Red blood cell alloimmunization

Prophylactic serologic matching

Prophylactic genotypic matching

Transfusion strategies proposed to mitigate alloimmunization in SCD

Transfusion protocols with limited or extended RBC antigen matching reduces antibody formation

No consensus to the best practical approach

Cost effectiveness is controversial

Provision of RH genotype-matched RBCs

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serologic matching x genotypic matching

Transfusion strategies proposed to mitigate alloimmunization in SCD

Evaluate the effect prophylactic genotypic matching and serologic

matching have on alloimmunization and hemolytic transfusion

reactions in patients with SCD receiving regular transfusions

Objective

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Prospective study

March/2016-March/2021 (5 years)

29 patients with SCD

(HgbSS)

15 patients received prophylactic RBC transfusions serologicmatched for ABO, Rh, K, Fya/Fyb, Jka/Jkb and S/s antigens

Number of transfusions, RBC phenotype/genotype of the patient and received unit and presence of antibodies were registered for all patients

Antibodies were classified as allo-antibodies based on the

serologic testing, RBC phenotyping and RBC genotyping

The clinical significance of the antibody was accessed by

comparison of the hemoglobin (Hb) levels recorded before and

after transfusion at time of antibody detection

14 patients received prophylactic RBC transfusions genotypicmatched for ABO, Rh, K, Fya/Fyb, Jka/Jkb, S/s, Dia, Doa/Dob antigensand Rh variants

Patients and donors were from Hemocentro

Unicamp, Campinas, SP, Brazil

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Methods

Serology

Phenotyping and antibody screening were performed by gel test

Adsorption onto autologous RBC was performed to aid the

differentiation of auto and alloantibodies

D C E Jkb sSc e K Fya Fyb Jka Dia

Molecular biology

Performed by LDTs, HEA BeadChip , RHD BeadChip, RHCE BeadChip

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Results

29 patients with

SCD

Median age: 36

15-407 RBC units

5 years

Antigen profile Rh variants

Most common

phenotypes/genotypes

C-E-K-, Fy(a-), Jk(b-),S-

C-E-K-, Fy(a-), Jk(a-), S-

Most common Rh variants

RHD*DAR, RHD*DIIIa-CE(4-7)-D,

RHCE*ceAR, RHCE*ceMO,

RHCE*ceS, RHCE*ce733G

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15/29 patients

receiving

prophylactic

serologic

matching

6/15 (40%)

with antibodies

1 anti-D

1 anti-Fya, -Doa

1 anti-S

1 anti-e, -hrB

1 anti-e, -hrS

1 anti-C, -Dia

3 patients with Rh variants

RHCE*ceMO, RHCE*ceAR

RHD*DIIIa-CE(4-7)-D

3 patients with discrepancies

previous phenotype and the

genotype

Results

Three patients with Rh antibodies and the patient with anti-Fya

presented laboratory evidence compatible with a DHTR at time of

antibody detection

The other 2 patients had a good survival of the transfused RBCs

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14/29 patients

receiving prophylactic

genotypic matching

5/14 with Rh variants

1RHD*DAR/RHCE*ceAR

2 RHCE*ce733G

2 RHD*DIIIa-CE(4-7)-D

receiving RH matched

RBC units

2 (14.3%) with

conventional RH alleles

made antibodies

Rh antibodies as a

result of altered Rh

epitopes on

transfused red cells

RHD*DIIIa

RHCE*ceMO

1 anti-D

1 anti-e

Results

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Conclusions

Prophylactic genotypic matching

Superior to phenotypic matching in patients with SCD

Reduction of antibodies to KEL, FY, JK, MNS, DI and DO antigens

RBC transfusions in chronically transfused patients with SCD

RH molecular matching

Significant effects on Rh alloimmunization rates

Potential to decrease risk of transfusion reactions and to prevent

alloimmunization

Transfused RBCs should be tested for Rh variants

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IMPACT OF PROPHYLACTIC RBC TRANSFUSION WITH EXTENDED GENOTYPIC

MATCHING INCLUDING RH VARIANTS IN PATIENTS WITH SCD

Challenges

Transfusion of non-matched RBC units in another hospital

Presence of RH variant alleles in blood donors and risk of alloimmunization

Increased racial admixture of African and European genomes in blood donors

Antigenic differences in relation to patients with SCD

Finding good approaches for screening donors with homozygous

genotypes and RH variants

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castilho@unicamp.br

Thank you for your attention!

Acknowledgments