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  1. Article ; Online: Blood group genotyping.

    Westhoff, Connie M

    Blood

    2019  Volume 133, Issue 17, Page(s) 1814–1820

    Abstract: Genomics is affecting all areas of medicine. In transfusion medicine, DNA-based genotyping is being used as an alternative to serological antibody-based methods to determine blood groups for matching donor to recipient. Most antigenic polymorphisms are ... ...

    Abstract Genomics is affecting all areas of medicine. In transfusion medicine, DNA-based genotyping is being used as an alternative to serological antibody-based methods to determine blood groups for matching donor to recipient. Most antigenic polymorphisms are due to single nucleotide polymorphism changes in the respective genes, and DNA arrays that target these changes have been validated by comparison with antibody-based typing. Importantly, the ability to test for antigens for which there are no serologic reagents is a major medical advance to identify antibodies and find compatible donor units, and can be life-saving. This review summarizes the evolving use and applications of genotyping for red cell and platelet blood group antigens affecting several areas of medicine. These include prenatal medicine for evaluating risk of fetal or neonatal disease and candidates for Rh-immune globulin; transplantation for bone marrow donor selection and transfusion support for highly alloimmunized patients and for confirmation of A2 status of kidney donors; hematology for comprehensive typing for patients with anemia requiring chronic transfusion; and oncology for patients receiving monoclonal antibody therapies that interfere with pretransfusion testing. A genomics approach allows, for the first time, the ability to routinely select donor units antigen matched to recipients for more than ABO/RhD to reduce complications. Of relevance, the growth of whole-genome sequencing in chronic disease and for general health will provide patients' comprehensive extended blood group profile as part of their medical record to be used to inform selection of the optimal transfusion therapy.
    MeSH term(s) Blood Group Antigens/analysis ; Blood Group Antigens/genetics ; Blood Grouping and Crossmatching/methods ; Genomics/methods ; Humans
    Chemical Substances Blood Group Antigens
    Language English
    Publishing date 2019-02-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2018-11-833954
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: AMIS and antigen modulation: of mice and men.

    Westhoff, Connie M

    Blood

    2016  Volume 128, Issue 26, Page(s) 3026–3028

    MeSH term(s) Animals ; Antigenic Modulation ; Humans ; Male ; Mice
    Language English
    Publishing date 2016-12-28
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2016-11-743914
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  3. Article ; Online: Red Cell Antigens and Antibodies.

    Lomas-Francis, Christine / Westhoff, Connie M

    Hematology/oncology clinics of North America

    2022  Volume 36, Issue 2, Page(s) 283–291

    Abstract: Autoimmune hemolytic anemia (AIHA) is caused by the production of "warm-" or "cold-" reactive autoantibodies directed against RBC antigens that may be of undefined specificity, reacting with all RBCs tested or may have an apparent specificity. ... ...

    Abstract Autoimmune hemolytic anemia (AIHA) is caused by the production of "warm-" or "cold-" reactive autoantibodies directed against RBC antigens that may be of undefined specificity, reacting with all RBCs tested or may have an apparent specificity. Autoantibodies may be of IgG, IgM, or rarely IgA isotypes and their production can be triggered by disease, viral infection, or drugs; from breakdown in immune system tolerance to self-antigens; or from exposure to foreign antigens that induce antibodies that cross-react with self-RBC antigens. Increasingly, AIHA is being reported in patients following allogeneic hematopoietic stem cell transplantation and treatment with anti-cancer checkpoint inhibitors. Autoantibodies, whatever their etiology, interfere with pretransfusion testing of patients requiring RBCs transfusion making compatibility testing complex and labor-intensive. The availability of extended antigen typing by DNA-based assay has made transfusion of RBCs that are selected based on the patient's extended phenotype (e.g., D, C, E, e, K, Jk
    MeSH term(s) Anemia, Hemolytic, Autoimmune/diagnosis ; Anemia, Hemolytic, Autoimmune/etiology ; Anemia, Hemolytic, Autoimmune/therapy ; Autoantibodies ; Blood Transfusion ; Erythrocytes ; Humans
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2022-03-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 93115-9
    ISSN 1558-1977 ; 0889-8588
    ISSN (online) 1558-1977
    ISSN 0889-8588
    DOI 10.1016/j.hoc.2021.12.002
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  4. Article ; Online: RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA.

    Israelyan, Narek / Vege, Sunitha / Friedman, David F / Zhang, Zhe / Uter, Stacey / Fasano, Ross M / Yee, Marianne / Piccone, Connie / Kelly, Shannon / Hankins, Jane S / Zheng, Yan / Westhoff, Connie M / Chou, Stella T

    Transfusion

    2024  Volume 64, Issue 3, Page(s) 526–535

    Abstract: Background: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, ...

    Abstract Background: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors.
    Study design and methods: We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays.
    Results: Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens.
    Discussion: These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.
    MeSH term(s) Young Adult ; Humans ; Child ; Erythrocyte Transfusion/adverse effects ; Erythrocytes ; Anemia, Sickle Cell/genetics ; Anemia, Sickle Cell/therapy ; Blood Group Antigens ; Genotype ; Anemia, Hemolytic, Autoimmune/etiology ; Isoantibodies ; Rh-Hr Blood-Group System
    Chemical Substances Blood Group Antigens ; Isoantibodies ; Rh-Hr Blood-Group System
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.17740
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  5. Article ; Online: Intricacies of GATA-ca, continued.

    Lomas-Francis, Christine / Stone, Elizabeth F / Westhoff, Connie M / Shi, Patricia A

    Haematologica

    2022  Volume 107, Issue 8, Page(s) 1988

    MeSH term(s) DNA-Binding Proteins ; Humans ; Transcription Factors
    Chemical Substances DNA-Binding Proteins ; Transcription Factors
    Language English
    Publishing date 2022-08-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2022.280876
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  6. Article ; Online: Variant RHD alleles and Rh immunization in patients with sickle cell disease.

    Takasaki, Kaoru / Friedman, David F / Uter, Stacey / Vege, Sunitha / Westhoff, Connie M / Chou, Stella T

    British journal of haematology

    2023  Volume 201, Issue 6, Page(s) 1220–1228

    Abstract: RH diversity among patients and donors contributes to Rh immunization despite serologic Rh-matched red cell transfusions. Anti-D can occur in D+ patients with RHD variants that encode partial D antigens. Anti-D has also been reported in patients with ... ...

    Abstract RH diversity among patients and donors contributes to Rh immunization despite serologic Rh-matched red cell transfusions. Anti-D can occur in D+ patients with RHD variants that encode partial D antigens. Anti-D has also been reported in patients with conventional RHD transfused primarily with units from Black donors who frequently have variant RHD. We report 48 anti-D in 690 D+ transfused individuals with sickle cell disease, categorized here as expressing conventional D, partial D or D antigen encoded by RHD*DAU0. Anti-D formed in a greater proportion of individuals with partial D, occurred after fewer D+ unit exposures, and remained detectable for longer than for those in the other categories. Among all anti-D, 13 had clinical or laboratory evidence of poor transfused red cell survival. Most individuals with anti-D were chronically transfused, including 32 with conventional RHD who required an average of 62 D- units/year following anti-D. Our findings suggest that patients with partial D may benefit from prophylactic D- or RH genotype-matched transfusions to prevent anti-D. Future studies should investigate whether RH genotype-matched transfusions can improve use of valuable donations from Black donors, reduce D immunization and minimize transfusion of D- units to D+ individuals with conventional RHD or DAU0 alleles.
    MeSH term(s) Humans ; Alleles ; Rh-Hr Blood-Group System/genetics ; Blood Transfusion ; Anemia, Sickle Cell/genetics ; Anemia, Sickle Cell/therapy ; Genotype ; Immunization ; Phenotype
    Chemical Substances Rh-Hr Blood-Group System
    Language English
    Publishing date 2023-04-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18774
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  7. Article ; Online: A novel P1PK allele in two Bangladeshi sisters with a history of spontaneous abortion: A4GALT*02N(951C).

    Floch, Aline / Lomas-Francis, Christine / Vege, Sunitha / Chai, Jamie / Cai, Connie / Westhoff, Connie M

    Transfusion

    2021  Volume 61, Issue 10, Page(s) E71–E72

    MeSH term(s) Abortion, Spontaneous/genetics ; Alleles ; Antigens, CD/genetics ; Female ; Galactosyltransferases/genetics ; Globosides/genetics ; Humans ; Lactosylceramides/genetics ; Pedigree ; Polymorphism, Single Nucleotide ; Pregnancy
    Chemical Substances Antigens, CD ; Globosides ; Lactosylceramides ; galactopyranosyl-1-4-paragloboside ; CDw17 antigen (4682-48-8) ; Galactosyltransferases (EC 2.4.1.-) ; UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase (EC 2.4.1.-)
    Language English
    Publishing date 2021-09-03
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.16649
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  8. Article ; Online: Three new XK alleles; two associated with a McLeod RBC phenotype.

    Floch, Aline / Lomas-Francis, Christine / Vege, Sunitha / Westhoff, Connie M

    Transfusion

    2021  Volume 61, Issue 10, Page(s) E69–E70

    MeSH term(s) Adult ; Aged ; Alleles ; Amino Acid Substitution ; Erythrocytes/metabolism ; Female ; Humans ; Kell Blood-Group System/blood ; Kell Blood-Group System/genetics ; Male ; Middle Aged ; Neuroacanthocytosis/blood ; Neuroacanthocytosis/genetics ; Phenotype ; Young Adult
    Chemical Substances Kell Blood-Group System
    Language English
    Publishing date 2021-09-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
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    ISSN 0041-1132
    DOI 10.1111/trf.16650
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  9. Article ; Online: Shining a light on AHG "blind" spot(s).

    Branch, Donald R / Westhoff, Connie M

    Transfusion

    2016  Volume 56, Issue 12, Page(s) 2913–2915

    Language English
    Publishing date 2016-12
    Publishing country United States
    Document type Editorial
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.13921
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  10. Article ; Online: Five novel FY null alleles associated with typing discrepancies.

    Vege, Sunitha / Floch, Aline / Lomas-Frances, Christine / Clarke, Gwen / Westhoff, Connie M

    Transfusion

    2021  Volume 61, Issue 11, Page(s) E80–E82

    MeSH term(s) Alleles ; Duffy Blood-Group System ; Genotype ; Humans ; Phenotype
    Chemical Substances Duffy Blood-Group System
    Language English
    Publishing date 2021-09-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
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    ISSN 0041-1132
    DOI 10.1111/trf.16676
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