Thrombin generation in subjects with lupus anticoagulant without prior thrombosis or gestational morbidities

Velasco-Rodríguez, Diego; Laso, Rosa Vidal; García-Raso, Aránzazu; Mahíllo‐Fernández, Ignacio; Guzmán-López, Karina; Martín-Herrero, Sara; Barral, Elena Jiménez; Vegas-Sánchez, María del Carmen; Martínez-Becerra, Maria José; Plaza, Reyes de la; Romero, Luisa Fernanda López; Mínguez, Dolores; Blas, Carlos; López, Almudena Fernández; Fernández, M. Soledad Sánchez; Llamas-Sillero, Pilar

doi:10.1016/j.thromres.2020.09.025

Cited by 5 publications

(3 citation statements)

References 37 publications

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“…aPC resistance is thought to be one of the ways through which LA is associated with a pro‐thrombotic phenotype in APS 17,19 . Fluorogenic thrombin generation measurements have shown that the presence of LA is associated with a decreased aPC‐induced inhibition of the ETP and peak thrombin 15,34‐36 . In this study, we have shown that, in high‐risk tetra‐positive APS patients, aPS/PT antibodies with LA activity are those responsible for most of aPC resistance.…”

Section: Discussionmentioning

confidence: 58%

See 1 more Smart Citation

Insight into the hypercoagulable state of high‐risk thrombotic APS patients: Contribution of aβ2GPI and aPS/PT antibodies

Pontara

Cattini

Cheng

et al. 2021

Journal of Thrombosis and Haemostasis

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Objective Most high‐risk thrombotic antiphospholipid syndrome (APS) patients test positive for anti‐β2‐glycoprotein I (aβ2GPI) and anti‐phosphatidylserine/prothrombin (aPS/PT) antibodies. Information on the influence of these antibodies on thrombin generation and activated protein C resistance (aPCr) is still sparse and contradictory. Methods Plasma of 16 patients poured into a β2GPI affinity column allowed the perfect separation of aβ2GPI and aPS/PT antibodies. aPS/PT antibodies were further purified through a prothrombin affinity column. Obtained material was spiked into normal pooled plasma (NPP) and tested in the thrombin generation assay in the absence or presence of aPC. Results aPS/PT antibodies showed a marked anticoagulant effect. Affinity purified aPS/PT and aβ2GPI antibodies from five patients were compared. aPS/PT antibodies showed significantly prolonged lag time and time to peak (5.0 minutes [interquartile range (IQR)3.5–6.1] versus 2.7 minutes [IQR2.2–3.5], P = .03 and 8.7 minutes [IQR6.7–10.3] versus 5.7 minutes [IQR4.5–6.2], P = .05, respectively) and significantly lower peak and velocity index (143 nmol/L [IQR131–163] versus 171 nmol/L [IQR157–182], P = .03 and 35 nmol/L/min [IQR32–59] versus 72 nmol/L/min [IQR54–77], P = .03, respectively). When aPC was added to the system, aPCr was significantly increased compared to controls for both aβ2GPI and aPS/PT antibodies. However, it was significantly stronger using aPS/PT antibodies. Median inhibition of endogenous thrombin potential was 22% (IQR16–33) with aPS/PT compared to 52% (IQR46–56) with aβ2GPI antibodies (P = .002). Conclusions Aβ2GPI antibodies show a mild anticoagulant and moderate procoagulant effect in thrombin generation and moderate aPC resistance. Conversely, aPS/PT antibodies show a strong anticoagulant effect and a strong aPCr.

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Section: Discussionmentioning

confidence: 58%

“…17,19 Fluorogenic thrombin generation measurements have shown that the presence of LA is associated with a decreased aPC-induced inhibition of the ETP and peak thrombin. 15,[34][35][36] In this study, we have shown that, in high-risk Which mechanism is behind the aPC resistance is still elusive.…”

Section: Discussionmentioning

confidence: 93%

Insight into the hypercoagulable state of high‐risk thrombotic APS patients: Contribution of aβ2GPI and aPS/PT antibodies

Pontara

Cattini

Cheng

et al. 2021

Journal of Thrombosis and Haemostasis

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“…23 Other studies showed similar results. [24][25][26] Arachchillage et al studied APC-R in APS and non-APS venous thromboembolism (VTE) patients on warfarin and normal controls by thrombin generation. 27 Thrombotic APS showed greater APC-R, using both recombinant APC and the protein C activator Protac.…”

Section: Experiments Confirming a Relation Between Antiphospholipid A...mentioning

confidence: 99%

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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Enhanced thrombin generation detected with ST-Genesia analyzer in patients with newly diagnosed multiple myeloma

Velasco-Rodríguez

Martínez-Alfonzo

Velasco-Valdazo

et al. 2023

J Thromb Thrombolysis

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Thrombin generation in subjects with lupus anticoagulant without prior thrombosis or gestational morbidities

Cited by 5 publications

References 37 publications

Insight into the hypercoagulable state of high‐risk thrombotic APS patients: Contribution of aβ2GPI and aPS/PT antibodies

Insight into the hypercoagulable state of high‐risk thrombotic APS patients: Contribution of aβ2GPI and aPS/PT antibodies

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

Enhanced thrombin generation detected with ST-Genesia analyzer in patients with newly diagnosed multiple myeloma

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