New Biological Tests in Patients With Antiphospholipid Antibodies (LYON SAPL)

Domain 1 of β2-Glycoprotein 1 Autoantibodies and Thrombin Generation Capacity in Patients With Antiphospholipid Antibodies

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thromboembolic events or pregnancy complications associated with circulating antiphospholipid antibodies (aPL-Abs). APS diagnosis needs the presence of both clinical and serological criteria (SAPORRO criteria, updated with Sydney criteria in 2006). However, no correlation between laboratory assays and the clinical thrombosis risk in patients with aPL-Abs was observed as only few patients with aPL-Abs developed clinical manifestations. Thrombin generation assays (TGA) is a global coagulation test that may represent a certain interest to evaluate thrombosis risk as a high thrombin generation capacity seems to be an independent risk factor for recurrent thromboembolic events. Another point of interest to assess the thrombotic risk is the detection of autoantibodies recognizing domain 1 of β2Gp1 (aβ2GP1-dm1). These autoantibodies are strongly related correlated with thrombotic and pregnancy manifestations. Recently, a commercial chemiluminescence immunoassay (CLIA) for detection of aβ2GP1-dm1 became available on Acustar® analyzer (HemosIL Acustar®, Instrument Laboratory, Bedford, USA) to facilitate aβ2GP1-dm1 research.

The aim of this study is to evaluate two additional laboratory assays to improve the correlation between laboratory assays and the clinical thrombosis risk in patients with antiphospholipid (APL): thrombin generation assay and aβ2GP1-dm1. Each biological result (Antibodies to Domain 1 (Dm1) of β2-Glycoprotein 1 (aβ2GP1-dm1) and Thrombin Generation Test (TGT) parameters: endogen thrombin potential (ETP), lag time and time to peak) will be compared to the history of clinical thrombosis (venous or arterial thrombosis and/or obstetrical complications such as defined by the Saporro criteria updated with Sydney criteria in 2006) for each patient.

Study Overview

• Status: Recruiting
• Conditions: Antiphospholipid Syndrome
• Intervention / Treatment: Biological: blood sample

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Yesim DARGAUD, PH; Phone Number: +33 4.72.11.88.10; Email: gamze.dargaud@chu-lyon.fr
• Study Contact Backup: Name: Stéphanie Désage; Email: stephanie.desage@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69500
    • Recruiting
    • Hôpital cardiologique Louis Pradel
    • Contact: Stéphanie Désage; Email: stephanie.desage@chu-lyon.fr
    • Contact: Yesim DARGAUD, PH; Phone Number: +33 04.72.11.88.10; Email: gamze.dargaud@chu-lyon.fr
    • Principal Investigator: Yesim DARGAUD, PH
  • Clermont-Ferrand, France, 63003
    • Not yet recruiting
    • CHU de Clermont-Ferrand
    • Contact: Aurélien LEBRETON, MD, PhD; Phone Number: +33 0473750200; Email: alebreton@chu-clermontferrand.fr
    • Principal Investigator: Aurélien LEBRETON, MD, PhD
  • Lyon, France, 69421
    • Recruiting
    • Hôpital Edouard Herriot
    • Contact: Arnaud HOT, PH; Phone Number: +33 0472117565; Email: arnaud.hot@chu-lyon.fr
    • Contact: Hélène DESMURS CLAVEL, MD, PhD; Phone Number: +33 0472117565; Email: helene.desmurs-clavel@chu-lyon.fr
    • Principal Investigator: Arnaud HOT, PH
    • Sub-Investigator: Hélène DESMURS CLAVEL, MD, PhD
  • Pierre-Bénite, France, 69310
    • Recruiting
    • Centre Hospitalier Lyon Sud
    • Contact: Claire GRANGE, MD,PhD; Phone Number: +33 0478861463; Email: claire.grange@chu-lyon.fr
    • Principal Investigator: Claire GRANGE, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

150 adult patients with known aPL-Abs (Antiphospholipid antibodies) will be including in the study after collecting their informed consent.

Description

Inclusion Criteria:

• Adult patients with confirmed aPL-Abs (at least two positive determinations at least 12 week apart)
• Subject non opposition

Exclusion Criteria:

• Age < 18 years
• Patient under the protection of justice, under guardianship or under curatorship
• Patient with anticoagulant treatment, except heparin
• Clinically symptomatic liver disease, supported by e.g. diagnosis of cirrhosis, portal hypertension, ascites, PT superior or egal to 5 seconds above upper normal limit
• Platelet count < 100 G/L (giga/liter)
• Poor venous access
• Non confirmed suspicion of APS

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Biological APS; 50 Asymptomatic patients with aPL antibodies and prolonged APTT	Biological: blood sample; A single 15 mL blood draw is planned for this study, as follow: 10 mL citrated tube (2 tubes) for APTT, PT, D-Dimers, LA, aCL, aβ2GP1, aβ2GP1-dm1 and TGA; 5 mL EDTA tube for blood count During a follow up visit, a 5 ml citrated tube and a 5 mL EDTA tube are collected from each patient for their routine laboratory evaluation. One additional citrated tube will be required to measure thrombin generation and aβ2GP1-dm1.
Obstetrical APS; 50 patients with Obstetrical aPL syndrome	Biological: blood sample; A single 15 mL blood draw is planned for this study, as follow: 10 mL citrated tube (2 tubes) for APTT, PT, D-Dimers, LA, aCL, aβ2GP1, aβ2GP1-dm1 and TGA; 5 mL EDTA tube for blood count During a follow up visit, a 5 ml citrated tube and a 5 mL EDTA tube are collected from each patient for their routine laboratory evaluation. One additional citrated tube will be required to measure thrombin generation and aβ2GP1-dm1.
Thrombosis APS; APS with a personal history of venous or arterial thrombosis (50 patients)	Biological: blood sample; A single 15 mL blood draw is planned for this study, as follow: 10 mL citrated tube (2 tubes) for APTT, PT, D-Dimers, LA, aCL, aβ2GP1, aβ2GP1-dm1 and TGA; 5 mL EDTA tube for blood count During a follow up visit, a 5 ml citrated tube and a 5 mL EDTA tube are collected from each patient for their routine laboratory evaluation. One additional citrated tube will be required to measure thrombin generation and aβ2GP1-dm1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
aβ2GP1-dm	The hypercoagulability status will be compared in each group. Each biological result of aβ2GP1-dm1 will be compared to a gold standard: the history of clinical thrombosis (venous or arterial thrombosis and/or obstetrical complications such as defined by the Saporro criteria updated with Sydney criteria in 2006) for each patient.	One day
Endogenous Thrombin Potential (ETP)	The hypercoagulability status will be compared in each group. Each biological result of ETP will be compared to a gold standard: the history of clinical thrombosis (venous or arterial thrombosis and/or obstetrical complications such as defined by the Saporro criteria updated with Sydney criteria in 2006) for each patient.	One day
peak of thrombin	The hypercoagulability status will be compared in each group. Each biological result of peak of thrombin will be compared to a gold standard: the history of clinical thrombosis (venous or arterial thrombosis and/or obstetrical complications such as defined by the Saporro criteria updated with Sydney criteria in 2006) for each patient.	One day
lag time	The hypercoagulability status will be compared in each group. Each biological result of lag time will be compared to a gold standard: the history of clinical thrombosis (venous or arterial thrombosis and/or obstetrical complications such as defined by the Saporro criteria updated with Sydney criteria in 2006) for each patient.	One day
time to peak	The hypercoagulability status will be compared in each group. Each biological result of time to peak will be compared to a gold standard: the history of clinical thrombosis (venous or arterial thrombosis and/or obstetrical complications such as defined by the Saporro criteria updated with Sydney criteria in 2006) for each patient.	One day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Estimated): March 13, 2027
• Study Completion (Estimated): March 13, 2027

Study Registration Dates

• First Submitted: February 28, 2019
• First Submitted That Met QC Criteria: March 22, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Antiphospholipid Syndrome
• Other Study ID Numbers: 69HCL18_0522; 2018-A03020-55 (Other Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No