Deciphered coagulation profile to diagnose the antiphospholipid syndrome using artificial intelligence

Kremers, Romy; Wahl, Denis; Zuily, Stéphane; Ninivaggi, Marisa; Chayouâ, Walid; Régnault, V.; Musiał, Jacek; Groot, Philip G. de; Devreese, Katrien; Laat, Bas de

doi:10.1016/j.thromres.2021.05.008

Cited by 7 publications

(22 citation statements)

References 26 publications

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“…TGAs can be used to assess hypo-and hypercoagulability, including APS [109,110]. TGAs show high sensitivity for detection of LAC-positive patients, and could potentially quantify LAC potency in a single assay [111][112][113]. Unfortunately, TGAs are labor intensive, poorly standardized so far, and not robust enough to include in routine setting [44,110].…”

Section: Alternative Assays For Lac Measurementmentioning

confidence: 99%

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Vandevelde

Devreese

2022

JCM

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Diagnosis of antiphospholipid syndrome (APS) requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL). Currently, laboratory criteria aPL consist of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM. Diagnosis and risk stratification of APS are complex and efforts to standardize and optimize laboratory tests have been ongoing since the initial description of the syndrome. LAC detection is based on functional coagulation assays, while aCL and aβ2GPI are measured with immunological solid-phase assays. LAC assays are especially prone to interference by anticoagulation therapy, but strategies to circumvent this interference are promising. Alternative techniques such as thrombin generation for LAC detection and to estimate LAC pathogenicity have been suggested, but are not applicable yet in routine setting. For aCL and aβ2GPI, a lot of different assays and detection techniques such as enzyme-linked immunosorbent and chemiluminescent assays are available. Furthermore, a lack of universal calibrators or standards results in high variability between the different solid-phase assays. Other non-criteria aPL such as anti-domain I β2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies have been suggested for risk stratification purposes in APS, while their added value to diagnostic criteria seems limited. In this review, we will describe laboratory assays for diagnostic and risk evaluation in APS, integrating applicable guidelines and classification criteria. Current insights and hindrances are addressed with respect to both laboratory and clinical implications.

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Section: Alternative Assays For Lac Measurementmentioning

confidence: 99%

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Vandevelde

Devreese

2022

JCM

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“…Four studies included thrombotic APS patients ( n = 102) only ( 35 , 37 , 43 , 47 ). Four studies specified the proportion of APS patients with thrombotic manifestations ( n = 200), obstetric manifestations ( n = 37), or both ( n = 14) but did not analyse the subgroups separately ( 40 , 41 , 45 , 46 ). In four studies, no clear differentiation between thrombotic and obstetric APS patients could be derived from the publications ( n = 172) ( 39 , 42 , 44 , 48 ).…”

Section: Resultsmentioning

confidence: 99%

“…The presence of AID was not specified in 212 APS patients ( 39 , 41 – 43 , 46 , 47 ). Furthermore, in the remaining studies 42 secondary APS and 192 primary APS patients were investigated, but no subgroup analysis was performed in these studies ( 35 , 38 , 40 , 45 ).…”

Section: Resultsmentioning

confidence: 99%

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Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature

Gehlen

Vandevelde²,

Laat³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundThe antiphospholipid syndrome (APS) is classified by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or adverse obstetric outcomes. The diagnosis and risk assessment of APS is challenging. This systematic review investigated if the thrombin generation (TG) assay could be helpful for APS diagnosis and risk assessment.MethodsA systemic review was performed by searching two databases (MEDLINE and Embase) until March 31, 2022, using a search strategy with two concepts: APS and TG, and related keywords. Two reviewers independently screened the articles based on predefined inclusion and exclusion criteria. Data extraction and quality assessment with the Newcastle-Ottawa Scale (NOS) were performed independently. Synthesis Without Meta-analysis guidelines were followed for data synthesis reporting.ResultsFourteen studies with 677 APS and 1,349 control subjects were included with variable quality according to the NOS. Twelve studies measured TG via the calibrated automated thrombogram (CAT) method using a fluorogenic substrate, whereas two used a chromogenic substrate-based TG assay. One study compared the CAT assay to the fully-automated ST Genesia® (Stago, France). Two studies initiated TG using platelet-rich plasma, whereas the rest of the studies used platelet-poor plasma. Resistance to activated protein C (aPC) was examined in ten studies. They reported a significant increase in aPC-resistance in APS patients compared to healthy controls, aPL-carriers, and thrombotic controls. Based on two studies, the prevalence of aPC-resistance was higher in APS patients compared to healthy controls and thrombotic controls with odds ratios of 5.9 and 6.8–12.8, respectively (p < 0.05). In contrast, no significant difference in aPC-resistance was found between APS patients and autoimmune disease controls. Furthermore, 7/14 studies reported TG-parameters including peak height, endogenous thrombin potential, lag time, and time to peak, but these outcomes were highly variable between studies. Furthermore, TG methodology between studies differed greatly, impacting the comparability of the studies.ConclusionaPC-resistance measured with TG was increased in APS patients compared to healthy and thrombotic controls, but the diagnostic and prognostic value is unclear compared to current diagnostic strategies. Studies of other TG-parameters were heterogeneous and more research is needed to identify their potential added value in APS diagnosis.Systematic Review Registrationhttps://www.PROSPERO/, identifier: CRD42022308363

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“…A clear difference between patients and controls can be detected (11), although more research is needed to determine the diagnostic and prognostic value of TG in diagnostic strategies. Indeed, previous studies have shown that an imbalance of pro-and anticoagulant processes could be indicative of clinical outcomes in APS (12,13). Therefore, the availability of the TG assay in the clinical laboratory is an important opportunity for TG-based personalized treatment.…”

Section: Editorial On the Research Topic Advances In Thrombin Generationmentioning

confidence: 99%