Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1075121/full |
| _version_ | 1797858971003912192 |
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| author | Rachel Gehlen Rachel Gehlen Arne Vandevelde Arne Vandevelde Bas de Laat Bas de Laat Katrien M. J. Devreese Katrien M. J. Devreese |
| author_facet | Rachel Gehlen Rachel Gehlen Arne Vandevelde Arne Vandevelde Bas de Laat Bas de Laat Katrien M. J. Devreese Katrien M. J. Devreese |
| author_sort | Rachel Gehlen |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-04-09T21:22:01Z |
| format | Article |
| id | doaj.art-c410d81e4ca248d0add1c31388386192 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T21:22:01Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-c410d81e4ca248d0add1c313883861922023-03-28T05:28:05ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-03-011010.3389/fcvm.2023.10751211075121Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literatureRachel Gehlen0Rachel Gehlen1Arne Vandevelde2Arne Vandevelde3Bas de Laat4Bas de Laat5Katrien M. J. Devreese6Katrien M. J. Devreese7Department of Functional Coagulation, Synapse Research Institute, Maastricht, NetherlandsDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, NetherlandsCoagulation Laboratory, Ghent University Hospital, Ghent, BelgiumDepartment of Diagnostic Sciences, Ghent University, Ghent, BelgiumDepartment of Functional Coagulation, Synapse Research Institute, Maastricht, NetherlandsDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, NetherlandsCoagulation Laboratory, Ghent University Hospital, Ghent, BelgiumDepartment of Diagnostic Sciences, Ghent University, Ghent, BelgiumBackgroundThe 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: CRD42022308363https://www.frontiersin.org/articles/10.3389/fcvm.2023.1075121/fullanitphospholipid antibodiesantiphospholid syndromepregnancy outcomethrombin generationthrombosis |
| spellingShingle | Rachel Gehlen Rachel Gehlen Arne Vandevelde Arne Vandevelde Bas de Laat Bas de Laat Katrien M. J. Devreese Katrien M. J. Devreese Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature Frontiers in Cardiovascular Medicine anitphospholipid antibodies antiphospholid syndrome pregnancy outcome thrombin generation thrombosis |
| title | Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature |
| title_full | Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature |
| title_fullStr | Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature |
| title_full_unstemmed | Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature |
| title_short | Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature |
| title_sort | application of the thrombin generation assay in patients with antiphospholipid syndrome a systematic review of the literature |
| topic | anitphospholipid antibodies antiphospholid syndrome pregnancy outcome thrombin generation thrombosis |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1075121/full |
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