Antibody profiles comprising anti phosphatidylserine/prothrombin differently affect thrombin generation and protein C resistance in antiphospholipid antibody carriers

Cheng, Chun‐Yan; Pontara, Elena; Tonello, Marta; Cattini, Maria Grazia; Bison, Elisa; Denas, Gentian; Pengo, Vittorio

doi:10.1016/j.cca.2020.09.025

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…Recently, our group reported the induction of APC-R both by aβ2GPI and aPS/PT immunoaffinity purified from plasma of tetrapositive APS patients. 58 59 60 However, aPS/PT induction of APC-R was much stronger than that of aβ2GPI antibodies. A summary of these findings is presented in Table 2 .…”

Section: Interference In Protein C Activation Of Specific Antibodiesmentioning

confidence: 95%

Interaction between Antiphospholipid Antibodies and Protein C Anticoagulant Pathway: A Narrative Review

Pengo

2022

Semin Thromb Hemost

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Thrombotic antiphospholipid syndrome (APS) is a condition in which thrombosis in venous, arterial, and/or small vessels is ascribed to the presence of antiphospholipid antibodies (aPL). Among the various proposed pathogenic theories to explain thrombotic APS, those involving the interaction between aPL and the protein C system have gained much consensus. Indeed, robust data show an acquired activated protein C resistance (APC-R) in these patients. The role of aPL in this impairment is clear, but the mechanism of action is uncertain, as the type of aPL and to what extent aPL are involved remains a gray area. Lupus anticoagulant (LA) is often associated with APC-R, but antibodies generating LA comprise those directed to β2-glycoprotein I and antiphosphatidylserine/prothrombin. Moreover, the induction of APC-R by aPL requires the presence of phospholipids and is suppressed by the presence of an excess of phospholipids. How phospholipids exposed on the cell membranes work in the system in vivo is unknown. Interestingly, acquired APC-R due to aPL might explain the clinical phenotypes of thrombotic APS. Indeed, the literature reports cases of both venous and arterial thromboembolism as well as skin necrosis, the latter observed in the severe form of protein C deficiency and in catastrophic APS.

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Section: Interference In Protein C Activation Of Specific Antibodiesmentioning

confidence: 95%

Interaction between Antiphospholipid Antibodies and Protein C Anticoagulant Pathway: A Narrative Review

Pengo

2022

Semin Thromb Hemost

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“…Other aPL subtypes, such as anti-phosphatidylserine/prothrombin antibodies (aPS/PT), are currently excluded from the routine laboratory tests for aPL positivity, being therefore defined "non-criteria" antibodies. However, data from recent studies showed that positivity to aPS/PT could be considered a supplementary risk factor for thromboembolic events beyond the conventional aPL panel [24], given their contribution to LA activity [25]. Probably, evaluation of such antibodies could allow for a more accurate risk stratification in selected cases.…”

Section: Apl Profile and Risk Stratificationmentioning

confidence: 99%

Risk Assessment and Antithrombotic Strategies in Antiphospholipid Antibody Carriers

et al. 2021

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Antiphospholipid antibodies (aPL) are a cluster of autoantibodies directed against plasma proteins with affinity for membrane phospholipids. The most frequently tested aPL are lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-β2GPI). aPL play a key pathogenic role in the development of the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by recurrent thrombotic and/or pregnancy complications in patients with persistent aPL. However, aPL positivity is occasionally documented in patients with no previous history of thrombotic or pregnancy morbidity. LA activity, multiple aPL positivity, high-titer aPL, and a concomitant systemic autoimmune disease are recognized risk factors for future thrombotic events in asymptomatic carriers. Moreover, an accelerated atherosclerosis with increased cardiovascular (CV) risk has also been associated with aPL positivity, thus exposing aPL carriers to fatal complications and chronic disability requiring cardiac rehabilitation. Overall, an accurate risk stratification is recommended for aPL-positive subjects in order to prevent both venous and arterial thrombotic complications. In this review, we provide an overview of the main antithrombotic and risk assessment strategies in aPL carriers.

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“…Used in the context of antiphospholipid antibody testing, TG can be applied beyond this field, as a suitable assay to investigate hypo-or hypercoagulability. [32][33][34]…”

Section: Introductionmentioning

confidence: 99%

“…Our main aim is to reach a reduced interlaboratory variation by following this guidance protocol, which will be helpful to further integrate TG assay for patient management. Used in the context of antiphospholipid antibody testing, TG can be applied beyond this field, as a suitable assay to investigate hypo‐ or hypercoagulability 32‐34 …”

Section: Introductionmentioning

confidence: 99%

Recommendations for the measurement of thrombin generation: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

Ninivaggi

Laat-Kremers

Tripodi

et al. 2021

Journal of Thrombosis and Haemostasis

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Antibody profiles comprising anti phosphatidylserine/prothrombin differently affect thrombin generation and protein C resistance in antiphospholipid antibody carriers

Cited by 7 publications

References 26 publications

Interaction between Antiphospholipid Antibodies and Protein C Anticoagulant Pathway: A Narrative Review

Interaction between Antiphospholipid Antibodies and Protein C Anticoagulant Pathway: A Narrative Review

Risk Assessment and Antithrombotic Strategies in Antiphospholipid Antibody Carriers

Recommendations for the measurement of thrombin generation: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

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