Medicina Clínica 163 (2024) S4–S9

www.elsevier.es/medicinaclinica

Review

Antiphospholipid antibody testing

Savino Sciascia a,∗ , Barbara Montaruli b , Maria Infantino c
a
University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center
of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub
Hospital, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
b
S.C. Laboratory Analysis, AO Ordine Mauriziano, Turin, Italy
c
Laboratory of Immunology and Allergy, San Giovanni di Dio Hospital, Florence, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Antiphospholipid antibodies (aPL) are a family of autoantibodies targeting phospholipid-binding proteins
Received 18 January 2024 and are associated with several clinical settings, and most notably define the antiphospholipid syndrome
Accepted 26 June 2024 (APS). These antibodies can be identified using a variety of laboratory tests, which include both solid-
phase immunological assays and functional clotting assays that detect lupus anticoagulants (LA). aPLs
Keywords: are linked to a range of adverse medical conditions, such as thrombosis and complications affecting the
Antiphospholipid antibody testing placenta and fetus, potentially leading to morbidity and mortality. The specific aPL identified, along with
Antiphospholipid antibody
the pattern of reactivity, correlates with the severity of these conditions. Therefore, laboratory testing
Lupus anticoagulant
Anticardiolipin antibodies
for aPL is crucial for evaluating the risk of complications and for fulfilling certain classification criteria for
Anti-beta-2 glycoprotein I antibodies APS, which are also applied as diagnostic markers in medical practice. This review provides an overview
of the available laboratory tests currently for measuring aPL and discusses their clinical implications.
© 2024 The Author(s). Published by Elsevier España, S.L.U. This is an open access article under the
CC BY license (http://creativecommons.org/licenses/by/4.0/).

Diagnóstico de laboratorio de anticuerpos antifosfolípidos

r e s u m e n

Palabras clave: Los anticuerpos antifosfolípidos (aPL) son una familia de autoanticuerpos que se dirigen contra las pro-
Pruebas de anticuerpos antifosfolípidos teínas que se unen a los fosfolípidos y están asociados con varios contextos clínicos, y más notablemente
Anticuerpo antifosfolípido definen el síndrome antifosfolípido (SAP). Estos anticuerpos pueden identificarse mediante una variedad
Anticoagulante lúpico
de pruebas de laboratorio, que incluyen tanto análisis inmunológicos de fase sólida como análisis de coag-
Anticuerpos anticardiolipina
ulación funcionales que detectan anticoagulantes lúpicos (AL). Los aPL están vinculados a una serie de
Anticuerpos anti-beta-2 glicoproteína I
procesos médicos adversos, como la trombosis y las complicaciones que afectan a la placenta y al feto, lo
que potencialmente conduce a morbilidad y mortalidad. El aPL específico identificado, junto con el patrón
de reactividad, se correlaciona con la gravedad de estos procesos. Por lo tanto, las pruebas de laboratorio
para aPL son cruciales para evaluar el riesgo de complicaciones y para cumplir con ciertos criterios de
clasificación para el SAP, que también se aplican como marcadores diagnósticos en la práctica médica.
Esta revisión proporciona una visión general de las pruebas de laboratorio disponibles actualmente para
medir los aPL y discute sus implicaciones clínicas.
© 2024 El Autor(s). Publicado por Elsevier España, S.L.U. Este es un artı́culo Open Access bajo la
licencia CC BY (http://creativecommons.org/licenses/by/4.0/).

Introduction pholipid antibodies (aPL) that were more likely to experience

repeated pregnancy loss, neurological symptoms, arterial/venous
In the early 1980s, the antiphospholipid syndrome (APS) was thrombosis, and thrombocytopenia.1 APS was later identified as
identified as a distinct syndrome first described in patients a systemic disease in the years that followed. The main clinical
suffering from Systemic Lupus Erythematosus (SLE) with antiphos- manifestations of APS are described elsewhere in this special issue.
In this review, we aimed to describe the current and upcoming
evidence for laboratory testing in APS and their role in the man-
∗ Corresponding author. agement of this condition.
E-mail address: [email protected] (S. Sciascia).

https://doi.org/10.1016/j.medcli.2024.06.002
0025-7753/© 2024 The Author(s). Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.
0/).
S. Sciascia, B. Montaruli and M. Infantino Medicina Clínica 163 (2024) S4–S9

Antiphospholipid antibody assays specificity of the anticoagulants for phospholipids—that is, aPL.
Due to the nature of functional assays, no coagulation test is
Testing for lupus anticoagulant (LA), anticardiolipin (aCL), and 100% sensitive, necessitating the use of two tests with differing
beta-2 glycoprotein I (B2GPI) antibodies is integral to the current approaches to enhance sensitivity. The dRVVT and aPTT are rec-
classification criteria for APS.2 For a patient suspected of hav- ommended to increase standardization in LA testing, requiring
ing APS, identifying persistent circulating antiphospholipid (aPL) reliable, repeatable, sensitive, commercially available, and quality-
antibodies is crucial, given that the disease’s clinical manifesta- controlled assays. The mixing step is critical to avoid false positives.
tions are common in the general population and often complicated However, this step has been debated due to the time and reagents
by various underlying factors. The tests used to detect aPL must it consumes, and because it may correct coagulation in cases of
be both sensitive and specific to ensure an accurate diagnosis low antibody titers.4,6 One significant limitation of LA coagulation
of APS. This precision is vital because overdiagnosis or misdiag- tests is their vulnerability to interference by anticoagulant therapy
nosis can significantly impact the treatment pathway for these (Refs. 70–78). Elevated levels of C-reactive protein or factor VIII
patients. Therefore, the choice and efficacy of assays for aPL detec- can lead to false-positive or false-negative results, respectively.8
tion must be carefully considered, aligning with international In addition to the diluted Russell viper venom time (dRVVT) and
guidelines.3–5 activated partial thromboplastin time (aPTT), other phospholipid-
Historically, the assays commonly employed for aPL detection dependent coagulation assays are generally not recommended due
have been described as suffering from methodological limitations to variations in reagent compositions, poor reproducibility, or lim-
and lack of standardization.3–5 However, over the last decade sig- ited availability.9–11 The British Society for Haematology (BSH)
nificant improvement have been achieved in this field. To enhance includes the dilute prothrombin time (dPT) as an alternative to
laboratory testing for APS, the Scientific and Standardization Sub- aPTT in its guidelines,9–11 and the Clinical and Laboratory Stan-
committee on aPL of the International Society on Thrombosis and dards Institute (CLSI) cites it for second-line testing.9–11 The dPT
Haemostasis (ISTH) published guidelines in 2009 and subsequent is sensitive in detecting lupus anticoagulant (LAC), but its variabil-
updates for the detection of lupus anticoagulant,4,7 which have suc- ity in reagents limits its use.9,12,13 The kaolin clotting time (KCT),
cessfully improved the standardization of this test internationally. which differs from aPTT by lacking an exogenous phospholipid
Additionally, guidelines for the detection of aCL and B2GPI anti- source and uses kaolin as a contact activator, has fallen out of
bodies using different immunoassays have been issued to further favor due to standardization challenges, the absence of confirma-
elucidate the key concerns such as cut-off definition, inter and intra tory tests, and incompatibility with certain optical clot detection
assay comparability, and clinical significance.3–7 analyzers.10–14
When considering aPL testing, it is essential to emphasize that The Taipan snake venom time (TSVT) coupled with ecarin
only patients with a high likelihood of APS should be tested for time (ET) is an emerging assay for LAC assessment.5,15 It has
aPL. Today since a broader range of clinical disciplines order the demonstrated promising sensitivity for LAC detection with reduced
aPL tests we have witnessed in the real-life scenario a decrease in interference from oral anticoagulation treatments in multicen-
the percentage of the pretest probability and of the posttest prob- ter studies. The TSVT assay employs oscutarin C from Coastal
ability, as a consequence. This aspect has been properly addressed Taipan viper venom to convert prothrombin to thrombin in a
in the recently released EULAR/ACR Classification Criteria for APS.2 manner dependent on phospholipids and calcium, but indepen-
Routine screening for aPL without any clinical indications of the dent of Factor V.15,16 Meanwhile, ET, using venom from the
disease is generally not recommended to prevent the incidental Indian Saw-Scaled viper, activates prothrombin without the need
finding of aPL. Clinical scenarios that warrant a high suspicion for phospholipid cofactors.15 The TSVT/ET combination can func-
of APS include, for instance, younger patients (below 50 years tion as both a screening and confirmation assay, with ET being
of age) with unprovoked thrombotic events, thrombosis at atyp- phospholipid independent.15 These tests are less impacted by vita-
ical sites, or those with thrombotic or pregnancy complications min K antagonists (VKAs) and direct oral anticoagulants (DOACs)
associated with a secondary autoimmune condition.7 The prevail- that inhibit Factor Xa, potentially offering a reliable solution
ing guidance is to perform all aPL tests simultaneously and to for LA testing in patients on anticoagulation therapy. Recently
interpret the results collectively, considering that aPL represent automated algorithms with launch of the mixing step and con-
a diverse array of autoantibodies with overlapping yet distinct firmation step based on predefined cutoff values and calculations
features.2–7 improved the standardization process of the test interpretation
reducing the intralaboratory and interlaboratory variation.16 How-
Lupus anticoagulant ever, more standardized collaborative research is necessary before
The term ‘lupus anticoagulant’ (LA) is misleading, as it is nei- these assays can be widely recommended.4
ther a diagnostic test for lupus nor an anticoagulant. LA refers to an
in vitro phenomenon where substances behave as anticoagulants; Additional functional assays
however, the positivity for LA actually confers a pro-thrombotic While current coagulation assays for LA measurement are
state in vivo. Due to its capacity to recognize various antiphospho- subject to interference, they are also labor-intensive and com-
lipid antibodies (aPL), the LA assay is considered broadly reactive. plex to interpret. It is important to pursue further development
To detect LA, a combination of at least two coagulation tests is of functional assays or to identify solid-phase immunoassays as
employed. Commonly used tests include the diluted Russell viper alternative biomarkers to conventional LA tests. There is increas-
venom time (dRVVT) and the activated partial thromboplastin time ing interest in thrombin generation assays (TGAs), which offer a
(aPTT). These functional coagulation assays measure the ability more comprehensive view of the coagulation process than clot-
of aPL to prolong phospholipid-dependent clotting time. A posi- ting time-based assays. TGAs measure thrombin production in
tive result in at least one of these tests suggests the presence of plasma following the addition of tissue factor and phospholipids,
LA. The traditional method for LA detection is a three-step pro- capturing both procoagulant and anticoagulant activities. This gen-
cess involving screening, mixing, and confirmation phases.4,6 A erates a thrombogram that provides several derived parameters
LA-positive result is indicated by prolonged clotting time in the (reference 108). TGAs are particularly sensitive in identifying LA-
screening phase, which does not correct upon mixing the patient’s positive patients and may even measure LA intensity within a
plasma with normal plasma, and is then corrected by adding excess single test.17–20 However, TGAs are still labor-intensive, lack stan-
phospholipids during the confirmation phase. This confirms the dardization, and are not yet robust enough for routine clinical

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use.17–20 Recent guidelines on executing TGAs aim to standard- rejecting any that do not align or exhibit a correlation coefficient
ize methodologies, potentially aiding their integration into clinical below 0.90.27 Reference materials for assay calibration lack uni-
diagnostics and management, including for APS.17–20 The introduc- formity, with manufacturers supplying various non-standardized
tion of automated systems could revolutionize routine practice, calibrators.5,28,29 In the 1980s, Harris et al. developed polyclonal
offering time efficiency and reduced inter-laboratory variability. patient-derived calibrators for aCL, expressed in IgG and IgM
These automated TGAs could consolidate phospholipid-dependent phospholipid units (GPL/MPL), which are the precursors to the
testing into one assay, simplifying LA detection, which currently now-known “Harris standards”.30–32 The “Koike standards” or
requires multiple tests.17 “Sapporo standards,” which are monoclonal antibody (MoAb) stan-
dards, offer batch consistency and virtually limitless production,
Antibodies against ˇ2GPI and anticardiolipin antibodies albeit not reflecting the polyclonal nature of APS antibodies.30–32
Solid-phase immunoassays are utilized for the detection of aCL While aCL results can be reported in GPL/MPL if validated against
and anti-␤2GPI antibodies. The identification of these antibodies, Harris standards, a␤2GPI testing lacks a universal unit, leading
particularly the IgG or IgM isotypes at medium to high titers, is to a wide range of reporting units.30 Harmonization efforts are
considered diagnostic.2,21 LA assays have the capability to screen underway to establish WHO standards in IU/mL for both aCL
for all aPL antibodies, irrespective of the cofactor protein involved. and a␤2GPI.33,34 The current APS classification criteria regard aCL
The immunoassays measure antibodies against cardiolipin (via the IgG or IgM detection as significant at moderate to high titers
aCL antibody assay) or ␤2GPI (via the anti-␤2GPI antibodies assay), (>40 GPL/MPL or >99th percentile), with similar parameters for
with ␤2GPI being the principal cofactor protein for aPL.12,21 aCL significant a␤2GPI levels.34–36 The choice of 40 GPL/MPL as a
antibody assays that are methodologically robust and include anti- cut-off for aCL was based on its correlation with APS-related
␤2GPI in the reagents achieve similar sensitivities and specificities symptoms,35,36 but variability often exists between this and the
to those of anti-␤2GPI assays alone.12,21 99th percentile.37,38 Due to high inter-assay variability, using a
single numeric threshold is not advised, and the International
Which assay?. aCL and a␤2GPI antibodies are traditionally detected Society on Thrombosis and Haemostasis-Scientific Standardization
using solid-phase immunoassays, such as ELISA, which are stan- Subcommittee (ISTH-SSC) recommend defining laboratory-specific
dardized by the APS classification criteria.5 Over the years, cut-offs based on the non-parametric 99th percentile of reference
alternative methods like chemiluminescent, fluorescence enzyme, individuals.27 For clinical interpretation, higher titers of IgG aCL
and multiplex flow immunoassays have emerged. More recently, are more closely linked to APS events.39,40 While a semiquanti-
semi-automated analyzers for aCL and a␤2GPI testing have been tative interpretation has been proposed, numerical discrepancies
introduced, offering increased consistency and reduced variabil- across assays prevent a standardized approach.5,40 However, a
ity in diagnostics, although they’re not universally accessible.5,12,21 semiquantitative interpretation for IgG aCL and a␤2GPI may be
Fundamentally, these assays adhere to the immunoassay prin- clinically valuable, provided that assay-specific thresholds are
ciple where an antigen is immobilized on a solid phase and clearly defined.41 Harmonizing these ranges could be facilitated by
exposed to patient antibodies. The binding is then detected by paired analysis using standard materials or patient samples across
conjugated anti-human IgG or IgM antibodies, eliciting a mea- different assays, including those traceable to the original Harris
surable response.5,12,21 Despite using similar principles, assays standards.41
vary in materials and methodologies, leading to significant
inter-assay variability.5,12,21 Thus, it’s crucial to maintain assay
consistency for patient follow-up and consider retesting with dif- Antibody profile
ferent platforms in cases of high clinical suspicion but negative When evaluating the antibody profiles in patients, the presence
results. of LA is considered a primary risk factor for thrombotic events asso-
ciated with APS.42 However, since patients may test positive for
Which isotype?. It is noteworthy that the detection of identical only one type of aPL antibody, it is essential to conduct tests for all
isotypes of both aCL and anti-␤2GPI antibodies increases the prob- three antibodies—LA, aCL, and anti-␤2GPI)—to establish a complete
ability of the APS diagnosis.22–24 Although IgG-type antibodies are antibody profile. The initial guidelines for aPL profiling were estab-
more closely associated with thrombosis than the IgM isotype, lished in the 2006 Sydney APS classification criteria, which included
recent literature reviews have not conclusively determined how patient classification based on single or multiple aPL positivity.
many APS cases would be overlooked if IgM testing were omitted.22 These criteria support the concept that the aPL profile influences
The relevance of IgA antibodies for anti-␤2GPI and aCL remains the probability of APS-related clinical events.2,42 A subsequent revi-
controversial, and thus, routine measurement of this isotype is not sion has suggested taking into account the diversity and quantity
currently recommended.2,5 IgA testing may not be widely useful for of positive test results.2
initial diagnostic screening but could be considered in confirming Research indicates that patients with multiple positive aPL tests,
APS or in patients with a high clinical suspicion of APS who are neg- especially those who are ‘triple positive’ for LA, aCL (IgG or IgM), and
ative for the criterion aPL.22–24 Variability in calibration and assay anti-␤2GPI antibodies (IgG or IgM), have the strongest association
properties leads to inter-assay differences in the results of aCL and with thrombotic expressions of APS.43–45 Furthermore, ‘triple pos-
anti-␤2GPI antibody tests.22–24 This variation is partly due to dif- itivity’ is associated with recurrent thrombosis, and when detected
ferent solid-phase coatings in the assays, which can influence the in asymptomatic individuals, it is linked to a heightened risk of a
amount of antigen available for antibody binding.5,21–26 However, primary thrombotic event.43–45 Patients with triple-positive APS
advancements in technology, such as the adoption of automated typically retain this profile over time and demonstrate consistent
systems that standardize operating procedures, have also reduced outcomes three months following initial testing.43–45 Nevertheless,
interlaboratory discrepancies over the years.25,26 it is common practice to recommend retesting for aPL after three
months to avoid misdiagnosis, such as mistaking transient anti-
From calibration to cut-off choice. Calibration curves are manda- body elevations—possibly due to infections—as chronic APS.46,47 It
tory in each ELISA run or for new reagent lots in automated is also critical to validate the reliability of positive results through
systems to accurately determine aPL titers. Recalibration may be confirmation testing, particularly in light of suboptimal standard-
necessitated by internal quality control outcomes. Evaluations of ization and potential interferences that may affect the accuracy of
each calibration must adhere to the manufacturer’s specifications, test outcomes.46,47

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Non criteria antiphospholipid antibodies Table 1

The Global AntiPhospholipid Syndrome Score (GAPSS) is a risk assessment tool
In clinical practice, when screening for aPL, standard test pan-
designed to evaluate the risk of thrombotic/obstetric events in patients with
els typically include only those antibodies specified in the current antiphospholipid syndrome (APS).
classification criteria. Non-criteria tests refer to a group of assays
Risk factor Points
that are largely non-standardized, and there is no international
agreement on their utility for patients with APS.48–51 Nevertheless, Anticardiolipin antibodies (IgG/IgM) 5
specifically, the SSC-ISTH recommendations did not encompass the Lupus anticoagulant 4
Anti-␤2 glycoprotein I (IgG/IgM) 4
testing for anti-domain 1 (anti-D1) antibodies, a subset of IgG anti-
Anti-phosphatidylserine/prothrombin (IgG/IgM) 3
␤2GPI antibodies, due to the lack of appropriate clinical trials and Hyperlipidemia 3
the absence of a standardized commercial assay at that time.48–51 Arterial hypertension 1
However, research using specialized assays53 has shown a note-
worthy association between anti-D1 antibodies and thrombosis.
With advancements in laboratory technology, a commercial chemi-
current classification criteria.52 In a systematic review analyzing
luminescence immunoassay has been developed to detect anti-D1
data from over 7000 patients and controls across 38 studies on aPT
antibodies. This assay has been employed in various studies, con-
and 10 studies on aPS/PT, we found that aPS/PT was associated with
firming a significant odds ratio for thrombosis and underscoring
both arterial and/or venous thrombosis, with a stronger correlation
the relevance of anti-D1 antibodies in risk stratification for APS
than aPT55 and was confirmed in a subsequent analysis.56 Ongoing
patients. These antibodies, particularly the IgG isotype of anti-D1,
research aims to further delineate aPS/PT and their mechanisms.
are predominantly detected in patients with triple-positive aPL
Nonetheless, further laboratory and clinical studies are imperative
profiles and tend to appear at high titers.50,51
to definitively determine the significance and prognostic value of
Despite these findings, anti-D1 antibodies are not considered
these antibodies in routine clinical practice. The potential inclu-
an independent risk factor for APS clinical manifestations, as evi-
sion of aPS/PT as an additional serological diagnostic tool for APS
denced by a limited number of studies.48–51 Thus, they are viewed
is actively debated, particularly regarding the identification of APS
more as a confirmation of increased thrombotic risk rather than as
patients who test negative for classical aPL.
an alternative to anti-␤2GPI antibodies.
However, excluding triple/tetra-positive APS in which high-risk
patients are clearly identified, a␤2GPI-D1 antibodies might be use- Risk assessment in antiphospholipid syndrome
ful in the incomplete aPL profiles when deciding the type and length
of anti-thrombotic treatment. Similarly, the ratio of anti-D1 to anti- The clinical symptoms associated with aPL may range consider-
D4/5 antibodies as a tool to identify those subjects carrying the “less ably among individuals. While some individuals carrying aPL may
pathogenic” anti-b2GPI antibodies should be explored.51 remain asymptomatic, others may experience pregnancy complica-
tions, thrombotic events, or both. Research is ongoing to ascertain
Antibodies to prothrombin. Antibodies to prothrombin can be the significance of different aPL profiles in predicting the risk of
detected by ELISA, utilizing either prothrombin coated onto irradi- thrombosis or obstetric complications. Notably, triple positivity,
ated plates (aPT) or the phosphatidylserine/prothrombin complex persistently isolated medium-to-high titers of aCL, and LA presence
as antigen (PS/PT). Both tests have been associated with the clini- have been identified as significant risk factors for thrombosis.43–47
cal manifestations of APS. Current evidence indicates they originate This is corroborated by data suggesting that adverse pregnancy
from distinct populations of autoantibodies, yet they can be simul- outcomes are also associated with the presence of LA and triple
taneously detected in a single patient. positivity.43–47
The link between APS and antibodies to prothrombin, identified The Global Antiphospholipid Syndrome Score (GAPSS), estab-
as aPT or aPS/PT, has been evaluated with varying outcomes.52,53 lished in 2013, incorporates various risk factors alongside the
Nevertheless, recent evidence supports the clinical relevance of presence of aPL, acknowledged as a risk factor for APS.57 GAPSS
aPS/PT in diagnosing APS.52,53 Atsumi and colleagues made early amalgamates independent predictors of pregnancy morbidity and
strides in elucidating the clinical significance of aPS/PT, finding thrombosis, including autoimmune antibody profiles such as anti-
that its presence increased the risk for APS 3.6-fold in a cohort nuclear antibodies (ANA), extractable nuclear antigen antibodies
of 265 Japanese patients with systemic autoimmune diseases.54 (ENA), and anti-double stranded DNA antibodies (dsDNA), among
Subsequent studies have corroborated the association of aPS/PT others. Independent risk factors within the GAPSS include both cri-
with APS clinical manifestations.56,57 Among the retrieved stud- teria and non-criteria aPL, such as aCL, a-␤2GPI), aPS/PT, LA, and
ies mentioned in the available systematic review,55,56 Zigon et al. the IgG/IgM isotypes of these antibodies, all linked to an elevated
reported that aPS/PT is a strong independent risk factor for aPL- risk of thrombosis and/or pregnancy morbidity PM. In GAPSS, each
related obstetric complications in a cohort of 156 patients with risk factor is assigned specific points: IgG/IgM a␤2GPI (4 points),
systemic autoimmune diseases.55,56 Furthermore, Sanfelippo et al. IgG/IgM aPS/PT (3 points), LA (4 points), hyperlipidemia (3 points),
demonstrated the utility of testing for aPS/PT in a large cohort of 728 and arterial hypertension (1 point) (Table 1). Higher GAPSS scores
patients suspected of APS, even in the absence of aCL or anti-␤2GPI have been associated with an increased incidence of thrombosis
antibodies. They found that 41 individuals with elevated levels of and/or pregnancy loss, particularly in patients with SLE, where
aPS/PT experienced thrombotic events in 50% of the cases where the GAPSS model was initially developed.57 Subsequently, a study
medical histories were available.55,56 This suggests that aPS/PT involving 62 patients with primary APS applied the GAPSS scoring
testing can help identify APS in patients who might otherwise system.58 It was observed that APS patients with a history of throm-
remain undetected using current testing protocols. Bertolaccini bosis alone exhibited higher GAPSS scores compared to those with
team’s assessed various aPL specificities to identify the profile with only prior pregnancy losses. Additionally, patients with a GAPSS
the highest diagnostic accuracy for APS. This investigation included score of 11 or higher were found to have an elevated risk of future
230 patients with SLE, testing for six aPLs in 23 possible combi- thrombotic events. Another investigation highlighted a relation-
nations. The combination of LA, anti-␤2GPI, and aPS/PT showed ship between GAPSS and a history of APS manifestations, especially
the highest diagnostic accuracy for APS overall, and specifically thrombosis, suggesting its potential as a quantitative measure for
for thrombosis and pregnancy loss, with the greatest specificity APS.58 More recent research involving patients with APS and SLE
compared to other combinations, including those defined by identified that a GAPSS score above 16 predicted an increased

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Determine the necessity for more aggressive management and/or more antibody immunoassays: survey of participants in the college of Ameri-
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Funding 24. Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero
R, et al. 14th International Congress on Antiphospholipid Antibodies Task
Force. Report on antiphospholipid syndrome laboratory diagnostics and trends.
None. Autoimmun Rev. 2014;13:917–30.
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quality control and external quality assurance in testing for antiphospholipid
Conflict of interest
antibodies: Part I—Anticardiolipin and anti-beta2-glycoprotein I antibodies.
Semin Thromb Hemost. 2012;38:390–403.
None. 26. Pelkmans L, Kelchtermans H, de Groot PG, Zuily S, Regnault V, Wahl D, et al.
Variability in exposure of epitope G40-R43 of domain i in commercial anti-
beta2-glycoprotein I IgG ELISAs. PLoS ONE. 2013;8:e71402.
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