Diagnostic Challenges on the Laboratory Detection of Lupus Anticoagulant
Open accessAbstract
Lupus anticoagulant (LA) is one of the three laboratory parameters (the others being antibodies to either cardiolipin or β2-glycoprotein I) which defines the rare but potentially devastating condition known as antiphospholipid syndrome (APS). Testing for LA is a challenging task for the clinical laboratory because specific tests for its detection are not available. However, proper LA detection is paramount for patients’ management, as its persistent positivity in the presence of (previous or current) thrombotic events, candidate for long term anticoagulation. Guidelines for LA detection have been established and updated over the last two decades. Implementation of these guidelines across laboratories and participation to external quality assessment schemes are required to help standardize the diagnostic procedures and help clinicians for appropriate management of APS. This article aims to review the current state of the art and the challenges that clinical laboratories incur in the detection of LA.
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In clinical practice, enrolment of 120 subjects is difficult; an alternative could be the use of manufacturer-provided cut-offs, assuming that these derive from a correct procedure in terms of population selection, statistical method, etc.
“In clinical practice, the enrolment of 120 subjects is difficult (especially for small laboratories); an alternative could be the use of manufacturer-provided cut-offs (assuming that these derive from a correct procedure in terms of population selection, statistical method, etc.).”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [8]
Section 7, “Cut-Off Values,” says enrolling 120 or more healthy subjects is impractical, especially for small laboratories, and identifies manufacturer cut-offs as a possible alternative. But it requires those cut-offs to be checked locally for accuracy using 20 or 40 subjects; assuming the manufacturer used a correct procedure is not the condition the paper gives. The section also cautions against using cut-offs determined elsewhere without local validation. (LLM, conf=0.90)
Experimental — accuracy not yet measuredEven if factor VIII inhibitors require incubation to express their activity, if present at very high titre, they immediately neutralize factor VIII of NPP in the aPTT mixing procedure, making them indistinguishable from LA.
“Even if these inhibitors require incubation to express their activity (2 h at 37 °C), if they are present at very high titre, they immediately neutralize factor VIII of NPP in the aPTT mixing procedure, thus making them indistinguishable from LA [8].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [8]
Section 11 says factor VIII inhibitors generally exert their activity after incubation for 2 hours at 37 °C, but high-potency inhibitors are likely to inhibit factor VIII in pooled normal plasma immediately during mixing, making them indistinguishable from LA. The citing sentence states immediate neutralization as certain, whereas the source qualifies it as likely. (LLM, conf=0.85)
Experimental — accuracy not yet measuredReagents containing a low concentration of phospholipids are more sensitive to LA.
“a general principle is that reagents containing a low concentration of phospholipids are more sensitive to LA [8].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [8]
LA detection is based on functional coagulation assays that are characterized by poor standardization, difficulty in interpreting the results, and interference by several drugs commonly used in the clinical setting in which LA search is appropriate.
“In contrast, LA detection is based on functional coagulation assays that are characterized by poor standardization, difficulty in interpreting the results, and interference by several drugs commonly used in the clinical setting in which LA search is appropriate [8].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [8]
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- Authors
- Tripodi, A.
- Affiliations
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Corresponding author
- Tripodi, Armando
- ORCID
- Tripodi, Armando
- Venue
- Biomedicines
- Publisher
- MDPI AG
- Published
- 2021-07-20
- Volume
- 9
- Issue
- 7
- Pages
- 844
- ISSN
- 2227-9059 (ISSN-L)
- PMC
- PMC8301384
- OpenAlex
- W3185090855
- Cited by
- 14
- References
- 20
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- lupus anticoagulant, antiphospholipid syndrome, laboratory diagnosis, diagnostic challenges, external quality assessment, test standardization, anticoagulation, thrombosis, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies
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