Thrombin generation assay and lupus anticoagulant synergically distinguish populations of patients with antiphospholipid antibodies

Radin, Massimo; Barinotti, Alice; Cecchi, Irene; Foddai, Silvia Grazietta; Rubini, Elena; Roccatello, Dario; Menegatti, Elisa; Sciascia, Savino

doi:10.1136/jcp-2022-208199

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…In addition, PH and ETP values were highly variable and inconsistent results were reported between studies. This discrepancy may partially be explained by the hypothesis that distinct aPL profiles may be associated with different TG profiles ( 60 ). Furthermore, to fairly evaluate the predictive ability of TG in relation to the risk of thrombotic or obstetric manifestations, it is necessary to calculate an OR, or to investigate the sensitivity, specificity, and positive and negative predictive values of the assay.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…In the diagnosis of LA, the dRVVT test has the highest diagnostic value [55,58]. By combining the dRVVT test and a modified TGA test sensitive to one of the most potent inhibitory systems of APC coagulation, the diagnosis of APS can be further refined [15,57].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, this modified TGA test could also be used to detect the sensitivity of different aPL to APC. Similarly, Radin et al performed TGA in 108 patients with LA positivity and concomitant positivity of other aPLs and found the most severe findings with LA and TGA tests in patients who were tetrapositive (LA, anti-PS/PT, aβ2GPI, and aCL), and these patients also had significant clinical manifestations of APS [15].…”

Section: Introductionmentioning

confidence: 93%

Determining Thrombogenicity: Using a Modified Thrombin Generation Assay to Detect the Level of Thrombotic Event Risk in Lupus Anticoagulant-Positive Patients

Bradáčová,

Slavík,

Úlehlová

et al. 2023

Biomedicines

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The aim of this study was to determine the thrombogenicity of lupus anticoagulant (LA) antibodies using a modified thrombin generation assay (TGA) with the addition of activated protein C (APC) in a group of 85 patients with LA-positive samples. Of these, 58 patients had clinical manifestations of antiphospholipid syndrome (APS) according to the Sydney criteria classification, i.e., each patient had thrombosis or foetal loss, and 27 patients did not show any clinical manifestations of APS. A comparison of the two groups’ TGA results revealed statistically significant differences (Fisher’s test p = 0.0016). The group of patients exhibiting clinical manifestations of APS showed higher thrombogenicity in 56.9% of patients, while the group of patients not yet exhibiting clinical manifestations of APS showed higher thrombogenicity in 25.9% of patients. There were no significant differences in the specificity of the TGA test between the groups of patients exhibiting similar clinical manifestations. Receiver operating characteristic curve analysis showed a more significant relationship (p = 0.0060) for TGA than for LA titre (p = 0.3387). These data suggest that the determination of LA thrombogenicity with the TGA assay leads to an increased prediction of the manifestation of a thromboembolic event. Our findings appear to be particularly relevant for the prediction of thrombotic events in patients with laboratory-expressed APS and no clinical manifestations.

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Thrombin Generation Assay in Antiphospholipid Antibodies Positive Subjects as a Personalized Thrombotic Risk Assessment: State of the Art and Perspectives

Foret,

Dufrost,

Lagrange

et al. 2024

Curr Rheumatol Rep

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Thrombin generation assay and lupus anticoagulant synergically distinguish populations of patients with antiphospholipid antibodies

Cited by 3 publications

References 35 publications

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

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

Determining Thrombogenicity: Using a Modified Thrombin Generation Assay to Detect the Level of Thrombotic Event Risk in Lupus Anticoagulant-Positive Patients

Thrombin Generation Assay in Antiphospholipid Antibodies Positive Subjects as a Personalized Thrombotic Risk Assessment: State of the Art and Perspectives

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