Diagnosis and treatment of immunological platelet refractoriness by histocompatibility

Fagundes, Iara dos Santos; Franz, Juliana M.; Jobim, Mariana; Arend, Ana Cristina; Merzoni, Jóice; Cardone, Jacqueline Moraes; Gil, Beatriz Chamun; Sekine, Leo; Jobim, Luiz Fernando Job

doi:10.1016/j.humimm.2020.02.005

Cited by 6 publications

(11 citation statements)

References 32 publications

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“…Since HPA antibodies or platelet autoantibodies can also cause a positive PXM result independent of class I HLA‐Abs, patients with detectable non‐HLA serum platelet antibodies were analyzed separately 8,17 . For these four study patients, one study patient had Glanzmann thrombocythemia with a GpIIb/IIIa platelet alloantibody, one study patient had an HPA‐1a alloantibody, one study patient had both an HPA‐1b alloantibody and a platelet autoantibody, and one study patient had a platelet autoantibody (Figure 6).…”

Section: Resultsmentioning

confidence: 99%

“…A positive PXM HLA‐Ab MFI zone was defined as above the 90% specificity cutoff and a negative PXM HLA‐Ab MFI zone was defined as below the 90% sensitivity cutoff. Study patients with a positive serum platelet antibody test (HPA alloantibody or platelet autoantibody) were analyzed separately as these non‐HLA anti‐platelet antibodies have been reported to cause a positive PXM result 8,17 …”

Section: Methodsmentioning

confidence: 99%

“…While only the cause of 20%–25% of cases, immune‐mediated platelet transfusion‐refractoriness can be successfully mitigated by selecting platelet units that avoid recipient anti‐platelet antibodies 3,4,7–11 . Multiple in vitro approaches exist for the identification of compatible platelet inventory for such patients, including solid‐phase platelet crossmatches, class I HLA antibody (HLA‐Ab)/antigen testing, and HPA antibody/antigen testing 8–18 . Each approach has diagnostic limitations, however, so algorithms integrating multiple approaches have been proposed 17,19 …”

Section: Introductionmentioning

confidence: 99%

“…Multiple in vitro approaches exist for the identification of compatible platelet inventory for such patients, including solid‐phase platelet crossmatches, class I HLA antibody (HLA‐Ab)/antigen testing, and HPA antibody/antigen testing 8–18 . Each approach has diagnostic limitations, however, so algorithms integrating multiple approaches have been proposed 17,19 …”

Section: Introductionmentioning

confidence: 99%

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Prozone rates in the solid‐phase platelet crossmatch assay and correlation with class I HLA antibody levels

et al. 2021

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Background Solid‐phase platelet crossmatch (PXM) testing is used to help manage patients with platelet transfusion‐refractoriness. Recently, we published the first report of false‐negative PXM results from prozone effect that was mitigated using sample dilution. This study aimed to describe the prevalence of PXM prozone effect and the levels of class I HLA antibodies (HLA‐Abs) associated with positive PXM results and with false‐negative PXM results from prozone effect. Study Design and Methods A cross‐sectional study of patients undergoing PXM testing from July 2019 through December 2020 was performed. All PXM tests were run simultaneously using undiluted and 1:4 diluted patient plasma. Prozone effect was defined as a negative PXM result using undiluted patient plasma but a positive PXM result using 1:4 diluted patient plasma. Results Among 59 patients, 830 individual ABO‐compatible PXM results yielded an overall positivity rate of 25.8% (214/830) and a false‐negative rate from prozone effect of 4.7% (10/214). Among the 28 patients with class I HLA‐Ab testing and no other anti‐platelet antibodies, maximum HLA‐Ab mean fluorescence intensity (MFI) was significantly associated with a positive PXM result (p < .0001; AUC approx. 0.9) and categorized into negative (<3700), indeterminate (3700–10300), and positive (>10300) maximum HLA‐Ab MFI zones. Maximum HLA‐Ab MFI, however, was not associated with prozone effect (p = .17; AUC approx. 0.6). Discussion While there is a strong predictive association between class I HLA‐Ab levels and positive PXM results, PXM prozone effect is a common occurrence not associated with class I HLA‐Ab levels, so additional testing with diluted samples should be considered.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prozone rates in the solid‐phase platelet crossmatch assay and correlation with class I HLA antibody levels

et al. 2021

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“…15 Although not routinely done in Indonesia, HLA-typing is recommended American transfusion guidelines. 16 It would guide the next diagnostic workup and required treatment strategy. In addition, implementation of HLA typing is a stepping stone before proceeding to more sophisticated matching, such as human platelet antigen (HPA) matching.…”

Section: Discussionmentioning

confidence: 99%

Donor HLA Genotyping using Polymerase Chain Reaction- Sequence Specific Primers (PCR-SSP) as Method for Acquiring Donor Panel in Platelet Refractoriness

Atmakusuma

Rachman

Ritchie³

2021

Mol Cell Biomed Sci

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Background: Evaluation and identification of HLA antibodies in the recipient’s serum is of utmost importance prior to transplantation and transfusion. HLA typing is a steppingstone in proposing a donor panel. In order to obtain the HLA typing, Polymerase Chain Reaction-Sequence Specific Primers (PCR-SSP) can be performed.Materials and method: This is a preliminary study to determine HLA polymorphism by HLA genotyping in 43 blood donors. DNA from the samples was isolated using commercial kits according to the standard protocol. The DNA then was amplified using PCR-SSP methods and analyzed using the provided set in the kit.Results: This study found that the most frequent HLA-A alleles was HLA-A*24 (41.9%). For HLA-B alleles, the most common was HLA-B*15 (28%). Most frequent HLA-A-B haplotypes was HLA-A*24-B*15 (11.3%). The results from this study concurs with that of previous study. However, some alleles might vary due to difference in study population. Determining HLA-typing is of paramount importance in an ethnically diverse country such as Indonesia. In contrast to homogenous caucassian country, difference in ethnicity might cause platelet refractoriness due to incompatibility. HLA-typing would also guide the diagnostic workup and required treatment strategy for platelet refractoriness.Conclusion: From the HLA typing using PCR-SSP in blood donors in Jakarta, we found that the most frequent alleles were HLA-A*24 and HLA-B*15; and the most frequent haplotypes were HLA-A*24-B*15. This study should be upscaled to include larger population and ethnic groups to obtain complete profile of Indonesian population.Keywords: platelet refractoriness, HLA, donor, PCR-SSP, transfusion medicine

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The relevance of a bank with genotyped platelets donors

Barbagallo¹,

Costa

Bastos

et al. 2022

Hematology, Transfusion and Cell Therapy

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Diagnosis and treatment of immunological platelet refractoriness by histocompatibility

Cited by 6 publications

References 32 publications

Prozone rates in the solid‐phase platelet crossmatch assay and correlation with class I HLA antibody levels

Prozone rates in the solid‐phase platelet crossmatch assay and correlation with class I HLA antibody levels

Donor HLA Genotyping using Polymerase Chain Reaction- Sequence Specific Primers (PCR-SSP) as Method for Acquiring Donor Panel in Platelet Refractoriness

The relevance of a bank with genotyped platelets donors

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