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Diagnostic accuracy study of a factor VIII ELISA for detection of factor VIII antibodies in congenital and acquired haemophilia A

Diagnostic accuracy study of a factor VIII ELISA for detection of factor VIII antibodies in congenital and acquired haemophilia A
Diagnostic accuracy study of a factor VIII ELISA for detection of factor VIII antibodies in congenital and acquired haemophilia A

Antibody formation to factor VIII (FVIII) remains the greatest clinical and diagnostic challenge to the haemophilia-treating physician. Current guidance for testing for inhibitory FVIII antibodies (inhibitors) recommends the functional Nijmegen-Bethesda assay (NBA). A FVIII ELISA offers a complementary, immunological approach for FVIII antibody testing. It was the aim of this study to retrospectively evaluate the performance of a FVIII ELISA (index) for detection of FVIII antibodies, compared with the NBA (reference). All samples sent for routine FVIII antibody testing at two haemophilia Comprehensive Care Centres, were tested in parallel using the NBA and a solid-phase, indirect FVIII ELISA kit (Immucor). A total of 497 samples from 239 patients (severe haemophilia A=140, non-severe haemophilia A=85, acquired haemophilia A=14) were available for analysis. Sixty-three samples tested positive by the NBA (prevalence 12.7%, 95% confidence interval [CI], 9.9-15.9 %), with a median inhibitor titre of 1.2 BU/ml (range 0.7-978.0). The FVIII ELISA demonstrated a specificity of 94.0% (95%CI, 91.3-96.0), sensitivity of 77.8% (95%CI, 65.5-87.3), negative predictive value of 96.7% (95%CI, 94.5-98.2), positive predictive value 65.3% (95%CI, 53.5-76.0), negative likelihood ratio 0.2 (95%CI, 0.1-0.4), positive likelihood ratio 13.0 (95%CI, 8.7-19.3) and a diagnostic odds ratio of 54.9 (95%CI, 27.0-112.0). Strong positive correlation (r=0.77, p<0.001) was seen between the results of the NBA (log adjusted) and FVIII ELISA optical density. In conclusion, FVIII ELISA offers a simple, specific, surveillance method enabling batch testing of non-urgent samples for the presence of FVIII antibodies.

Analysis of Variance, Autoantibodies/blood, Biomarkers/blood, Coagulants/immunology, Enzyme-Linked Immunosorbent Assay, Factor VIII/immunology, Hemophilia A/blood, Humans, Likelihood Functions, London, Observer Variation, Odds Ratio, Predictive Value of Tests, Reagent Kits, Diagnostic, Reproducibility of Results, Retrospective Studies, Severity of Illness Index
0340-6245
804-811
Batty, Paul
965f536b-8873-466e-9c5f-bf8cb80f6591
Moore, Gary W
4a0d6b47-e6ba-458a-bc31-33431fef5a5a
Platton, Sean
19726aac-0456-472d-86b5-66afbefc4105
Maloney, James C
0058d884-3394-4bca-b867-5a4d320f32c2
Palmer, Ben
1fbc7935-0aa1-4a05-9abb-c38905c46362
Bowles, Louise
13f8356c-753d-46e4-a4de-526b34e5318f
Pasi, K John
3b81e0be-6e79-4b71-95c5-45fe04b8e6dc
Rangarajan, Savita
9a5e4c7e-55ba-4a3a-b5f6-f1e269d927c3
Hart, Daniel P
806f3603-67f9-4f07-a8b7-9b183eb55c98
Batty, Paul
965f536b-8873-466e-9c5f-bf8cb80f6591
Moore, Gary W
4a0d6b47-e6ba-458a-bc31-33431fef5a5a
Platton, Sean
19726aac-0456-472d-86b5-66afbefc4105
Maloney, James C
0058d884-3394-4bca-b867-5a4d320f32c2
Palmer, Ben
1fbc7935-0aa1-4a05-9abb-c38905c46362
Bowles, Louise
13f8356c-753d-46e4-a4de-526b34e5318f
Pasi, K John
3b81e0be-6e79-4b71-95c5-45fe04b8e6dc
Rangarajan, Savita
9a5e4c7e-55ba-4a3a-b5f6-f1e269d927c3
Hart, Daniel P
806f3603-67f9-4f07-a8b7-9b183eb55c98

Batty, Paul, Moore, Gary W, Platton, Sean, Maloney, James C, Palmer, Ben, Bowles, Louise, Pasi, K John, Rangarajan, Savita and Hart, Daniel P (2015) Diagnostic accuracy study of a factor VIII ELISA for detection of factor VIII antibodies in congenital and acquired haemophilia A. Thrombosis and Haemostasis, 114 (4), 804-811. (doi:10.1160/TH14-12-1062).

Record type: Article

Abstract

Antibody formation to factor VIII (FVIII) remains the greatest clinical and diagnostic challenge to the haemophilia-treating physician. Current guidance for testing for inhibitory FVIII antibodies (inhibitors) recommends the functional Nijmegen-Bethesda assay (NBA). A FVIII ELISA offers a complementary, immunological approach for FVIII antibody testing. It was the aim of this study to retrospectively evaluate the performance of a FVIII ELISA (index) for detection of FVIII antibodies, compared with the NBA (reference). All samples sent for routine FVIII antibody testing at two haemophilia Comprehensive Care Centres, were tested in parallel using the NBA and a solid-phase, indirect FVIII ELISA kit (Immucor). A total of 497 samples from 239 patients (severe haemophilia A=140, non-severe haemophilia A=85, acquired haemophilia A=14) were available for analysis. Sixty-three samples tested positive by the NBA (prevalence 12.7%, 95% confidence interval [CI], 9.9-15.9 %), with a median inhibitor titre of 1.2 BU/ml (range 0.7-978.0). The FVIII ELISA demonstrated a specificity of 94.0% (95%CI, 91.3-96.0), sensitivity of 77.8% (95%CI, 65.5-87.3), negative predictive value of 96.7% (95%CI, 94.5-98.2), positive predictive value 65.3% (95%CI, 53.5-76.0), negative likelihood ratio 0.2 (95%CI, 0.1-0.4), positive likelihood ratio 13.0 (95%CI, 8.7-19.3) and a diagnostic odds ratio of 54.9 (95%CI, 27.0-112.0). Strong positive correlation (r=0.77, p<0.001) was seen between the results of the NBA (log adjusted) and FVIII ELISA optical density. In conclusion, FVIII ELISA offers a simple, specific, surveillance method enabling batch testing of non-urgent samples for the presence of FVIII antibodies.

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More information

Published date: October 2015
Keywords: Analysis of Variance, Autoantibodies/blood, Biomarkers/blood, Coagulants/immunology, Enzyme-Linked Immunosorbent Assay, Factor VIII/immunology, Hemophilia A/blood, Humans, Likelihood Functions, London, Observer Variation, Odds Ratio, Predictive Value of Tests, Reagent Kits, Diagnostic, Reproducibility of Results, Retrospective Studies, Severity of Illness Index

Identifiers

Local EPrints ID: 443314
URI: http://eprints.soton.ac.uk/id/eprint/443314
ISSN: 0340-6245
PURE UUID: 582f9ebb-32b8-42fc-a38a-e38487f4bf74
ORCID for Savita Rangarajan: ORCID iD orcid.org/0000-0001-7367-133X

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Date deposited: 20 Aug 2020 16:33
Last modified: 09 Jan 2022 04:11

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Contributors

Author: Paul Batty
Author: Gary W Moore
Author: Sean Platton
Author: James C Maloney
Author: Ben Palmer
Author: Louise Bowles
Author: K John Pasi
Author: Daniel P Hart

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