HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies

Background: Thrombotic microangiopathies (TMA) are a group of disorders with overlapping clinical features that require urgent intervention. Treatment is based on the recognition of the TMA type, which is often challenging. The aim of this study was to identify specific HLA associations with differe...

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Main Authors: Soumya Pandey, Akul Shrivastava, Yanping Izak Harville, Michele Cottler-Fox, Terry O. Harville
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Hematology, Transfusion and Cell Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2531137924000129
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author Soumya Pandey
Akul Shrivastava
Yanping Izak Harville
Michele Cottler-Fox
Terry O. Harville
author_facet Soumya Pandey
Akul Shrivastava
Yanping Izak Harville
Michele Cottler-Fox
Terry O. Harville
author_sort Soumya Pandey
collection DOAJ
description Background: Thrombotic microangiopathies (TMA) are a group of disorders with overlapping clinical features that require urgent intervention. Treatment is based on the recognition of the TMA type, which is often challenging. The aim of this study was to identify specific HLA associations with different TMA types to aid rapid diagnosis and appropriate treatment, since the HLA assay can be completed within five hours. Methods: All 86 consecutive patients who presented to the University of Arkansas for Medical Sciences between May 2013 and January 2021 with a presumptive diagnosis of TMA were included in this study. HLA typing was performed and correlated with other clinical and laboratory studies. Results: In comparison with other types of TMA, patients with acquired thrombotic thrombocytopenic purpura (aTTP) showed increased frequencies of HLA-DRB1*11, HLA-DQB1*03:01/19, HLA-DRB1*08 and HLA-DRB3. Combining the presence of these HLA associations with a PLASMIC score of 6 or more achieved a higher positive predictive value (90%) for identifying aTTP than the PLASMIC score alone (69%). In comparison with other TMA types, patients with aTTP showed decreased frequencies of HLA-DRB4, HLA-DRB1*07, HLA-DQB1*02. The HLA-DRB1*07/DQB1*02 was not observed in any aTTP patients (negative predictive value: 100%), and thus the presence of this haplotype essentially rules out aTTP. Further, HLA-DRB1*11/DQB1*03:01/19 was absent in atypical hemolytic uremic syndrome patients. Conclusion: HLA alleles can be used as an adjunct for the rapid assessment of TMA and can help to differentiate it from other primary and secondary forms of TMA, allowing for earlier definitive therapy.
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spelling doaj-art-9fcf791741ab4e36be50db6d302f28772025-08-20T02:51:42ZengElsevierHematology, Transfusion and Cell Therapy2531-13792024-11-0146S170S18010.1016/j.htct.2023.11.016HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathiesSoumya Pandey0Akul Shrivastava1Yanping Izak Harville2Michele Cottler-Fox3Terry O. Harville4University of Arkansas for Medical Sciences, Little Rock, AR, USA; Corresponding author at: University of Arkansas for Medical Sciences, 4301W Markham St., Slot #502, Department of Pathology, Little Rock, AR 72205, USA.Little Rock Central High School, Little Rock, AR, USAUniversity of Arkansas for Medical Sciences, Little Rock, AR, USAUniversity of Arkansas for Medical Sciences, Little Rock, AR, USAUniversity of Arkansas for Medical Sciences, Little Rock, AR, USABackground: Thrombotic microangiopathies (TMA) are a group of disorders with overlapping clinical features that require urgent intervention. Treatment is based on the recognition of the TMA type, which is often challenging. The aim of this study was to identify specific HLA associations with different TMA types to aid rapid diagnosis and appropriate treatment, since the HLA assay can be completed within five hours. Methods: All 86 consecutive patients who presented to the University of Arkansas for Medical Sciences between May 2013 and January 2021 with a presumptive diagnosis of TMA were included in this study. HLA typing was performed and correlated with other clinical and laboratory studies. Results: In comparison with other types of TMA, patients with acquired thrombotic thrombocytopenic purpura (aTTP) showed increased frequencies of HLA-DRB1*11, HLA-DQB1*03:01/19, HLA-DRB1*08 and HLA-DRB3. Combining the presence of these HLA associations with a PLASMIC score of 6 or more achieved a higher positive predictive value (90%) for identifying aTTP than the PLASMIC score alone (69%). In comparison with other TMA types, patients with aTTP showed decreased frequencies of HLA-DRB4, HLA-DRB1*07, HLA-DQB1*02. The HLA-DRB1*07/DQB1*02 was not observed in any aTTP patients (negative predictive value: 100%), and thus the presence of this haplotype essentially rules out aTTP. Further, HLA-DRB1*11/DQB1*03:01/19 was absent in atypical hemolytic uremic syndrome patients. Conclusion: HLA alleles can be used as an adjunct for the rapid assessment of TMA and can help to differentiate it from other primary and secondary forms of TMA, allowing for earlier definitive therapy.http://www.sciencedirect.com/science/article/pii/S2531137924000129Thrombotic microangiopathiesHLA associationsPLASMIC scorePPV and NPV
spellingShingle Soumya Pandey
Akul Shrivastava
Yanping Izak Harville
Michele Cottler-Fox
Terry O. Harville
HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies
Hematology, Transfusion and Cell Therapy
Thrombotic microangiopathies
HLA associations
PLASMIC score
PPV and NPV
title HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies
title_full HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies
title_fullStr HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies
title_full_unstemmed HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies
title_short HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies
title_sort hla dr dq associations combined with plasmic score are reliable predictors of acquired thrombotic thrombocytopenic purpura attp and aid in differentiating attp from other thrombotic microangiopathies
topic Thrombotic microangiopathies
HLA associations
PLASMIC score
PPV and NPV
url http://www.sciencedirect.com/science/article/pii/S2531137924000129
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