Role of lupus anticoagulants in immediate acting inhibitor positivity in congenital haemophilia A patients
Abstract
Objectives Presence of lupus anticoagulants (LA) in haemophilia and their interference in coagulation assays is well-known. Factor VIII (FVIII) inhibitors are generally time and temperature dependent whereas LAs are immediate acting inhibitors (IAIs). The present study reports the challenges in laboratory detection of both progressive and non-progressive, specific FVIII inhibitors in the presence of LA.Methods From 2012 through 2015, 4900 HA patients were screened for inhibitors. APTT based inhibitor screening tests and Nijmegen-modified Bethesda assay (NBA) were done in all samples. LA test and FVIII inhibitors by ELISA were done in patients with IAIs.Results Out of 451 patients positive for inhibitors in the initial screening tests, classical and progressive FVIII inhibitors were observed in 398 patients while 53 had IAIs showing no/partial correction in 1:1 mixtures of NPP and patient plasma. In 27 patients, both FVIII and FIX activity levels were <1%, resulting in difficulty in diagnosis. In 48 HA patients with IAIs, 42 were LA positive. 4 patients were found to have only LA with false positive results in NBA while 38 had a combination of LA and FVIII inhibitors. Six patients were LA negative and had only FVIII IAIs. Five (62.5%) of 8 HA patients initiated on immune tolerance induction (ITI) also were positive for IAIs.Conclusion The findings emphasizes the presence of specific FVIII inhibitors in congenital HA with absence of time dependent inactivation kinetics in a small proportion of cases. ELISA or chromogenic assays along with LA testing can offer accurate laboratory diagnosis in patients with coexisting LA.
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A previous study examining patients with both hemophilia and LA showed split results (non-correction in some patients but not in others).
“A previous study examining patients with both hemophilia and LA, in which mixing tests were performed without incubation, showed split results (non-correction in some patients but not in others) [11].”
From Performance characteristics of 5 numerical indexes in mixing test interpretation under coexistence of lupus anticoagulant and coagulation factor deficiency (2023) · cites this paper as [11]
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Matsuda, M., Hoshiyama, Y., Ogawa, K., Emmi, M., Terai, S., & Moriyama, M. (2023) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2023.100065 · Cited by 4 · see citing works
“However, this is not always the case [10,11].”
BackgroundResultThe coexistence of antiβ2 glycoprotein 1 antibody antibody has no effect on hemophilia A patient
Yu, X., Kong, D., Wang, Z., Yin, J., & Yu, Z. (2022) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000001137
- Authors
- Patil, R., S., C., Parihar, A., Mohite, A., & Shetty, S.
- Affiliations
- Indian Council of Medical Research (IN)
- King Edward Memorial Hospital and Seth G.S. Medical College (IN)
- Corresponding author
- Shetty, Shrimati
- ORCID
- Shetty, Shrimati
- Venue
- Thrombosis Research
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 172
- Pages
- 29-35
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W2897538183
- Cited by
- 2
- References
- 19
- Citations by year
- 2023: 1 · 2022: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research (27(0334)/18/EMR-II)
- Topics
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Keywords
- lupus anticoagulant, factor VIII inhibitors, immune tolerance induction, factor IX activity, inhibitor screening
- MeSH terms
- Adolescent, Adult, Blood Coagulation, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Factor VIII, Hemophilia A, Humans, Middle Aged, Partial Thromboplastin Time, Lupus Coagulation Inhibitor, Blood Coagulation Factor Inhibitors, Young Adult
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