Article Text

other Versions

Download PDFPDF
Thrombin generation assay and lupus anticoagulant synergically distinguish populations of patients with antiphospholipid antibodies
  1. Massimo Radin1,2,
  2. Alice Barinotti1,2,
  3. Irene Cecchi1,2,
  4. Silvia Grazietta Foddai1,2,
  5. Elena Rubini1,2,
  6. Dario Roccatello1,2,
  7. Elisa Menegatti1,3,
  8. Savino Sciascia1,2
  1. 1Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
  2. 2University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
  3. 3School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
  1. Correspondence to Dr Savino Sciascia, Department of Clinical and Biological Sciences, University of Turin, Torino 10124 TO, Italy; savino.sciascia{at}


Aim To apply thrombin generation assay (TGA) in a large cohort of antiphospholipid antibodies (aPL)-positive patients.

Material and methods 108 patients were tested with TGA and lupus anticoagulant (LA) testing and divided according to their aPL profile. Briefly, 21 patients were positive for anti-phosphatidylserine (aPS)/prothrombin (PT) IgG/IgM (group1), 29 for anti-ß2-glycoprotein-I (aβ2GPI) and anti-cardiolipin (aCL) IgG/IgM (group2), 31 for aPS/PT, aβ2GPI and aCL IgG/IgM (group3), 27 for aPS/PT and/or aβ2GPI+aCL IgM at low-titres (group4). 31 healthy donors (HDs) and 24 controls treated with vitamin K antagonists (VKA) were included.

Results The most deranged TGA and LA profiles were observed in tetra-positive patients (group3) that differed significantly to the other groups, thus those with isolated, double or triple aPL-positivity. Moreover, when comparing the TGA profile of all antiphospholipid syndrome (APS) patients, aPL-carriers, HDs and VKA controls, we observed that the aPL+ patients (especially APS) showed a distinctive profile that allowed to distinguish them from the other groups with significantly higher tLag and tPeak, and lower Peak and area under the curve.

When focusing on APS clinical manifestations, patients with a high-risk profile (group3) showed significant differences from those presenting low-titres aPL (group 4) regarding the number of venous events (p=0.04), recurrence of any thrombotic event (p=0.01), of arterial events (5 vs 0, p=0.02), the occurrence of TIA (p=0.04), DVT (p=0.02) and, when analysing extracriteria manifestations, of peripheral artery disease (p=0.04).

Conclusions TGA seems a valuable approach to stratify aPL+ patients according to their risk profile. The differences among different populations of autoantibodies specificities could be considered a translational validation of the increased thrombotic risk of patients with triple or tetra aPL-positivity.

  • Antibodies, Antiphospholipid

Data availability statement

Data are available on reasonable request.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available on reasonable request.

View Full Text


  • Handling editor Tahir S Pillay.

  • MR and AB contributed equally.

  • EM and SS contributed equally.

  • Contributors MR, AB, SGF, IC and ER: significantly contributed to laboratory testing, patients recruitment, drafting of the manuscript and of figures and tables, critical analysis of the final draft of the manuscript. DR, EM and SS: significantly contributed to the manuscript preparation, critical analysis of the figures and tables and final drafting of the manuscript. SS is the guarantor for this paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.