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Platelet-bound C4d, low C3 and lupus anticoagulant associate with thrombosis in SLE
  1. Michelle A Petri1,
  2. John Conklin2,
  3. Tyler O'Malley2 and
  4. Thierry Dervieux2
  1. 1Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  2. 2Research and Development, Exagen, Vista, California, USA
  1. Correspondence to Dr Thierry Dervieux; tdervieux{at}exagen.com; Dr Michelle A Petri; mpetri{at}jhmi.edu

Abstract

Background Low C3 and lupus anticoagulant (LAC) are known risk factors for thrombosis in SLE. We evaluated the association between C4d products deposited on platelets (PC4d) and thrombosis in SLE. Antiphosphatidyl serine/prothrombin (PS/PT) complex antibody was also evaluated as an alternative to LAC.

Methods This was a cross-sectional analysis of 149 consented patients with SLE (mean age: 47±1 years, 86% female) classified with (n=16) or without (n=133) thrombotic events in the past 5 years. Abnormal PC4d (≥20 units) was measured using flow cytometry. LAC and C3 were measured using dilute Russell’s viper venom time (>37 s) and immunoturbidimetry, respectively. Anti-PS/PT antibody status (IgG) was measured by immunoassay. Statistical analysis consisted of logistic regression and calculation of OR estimates with 95% CI.

Results Abnormal PC4d (OR=8.4, 95% CI 2.8 to 24.8), low C3 (OR=9.5, 95% CI 3.0 to 30.3), LAC (OR=5.4, 95% CI 1.3 to 22.3) and anti-PS/PT IgG (OR=3.4, 95% CI 1.2 to 9.7) status associated with thrombosis (p<0.05). Cumulatively, the presence of PC4d, low C3 and LAC abnormalities as a composite risk score was higher in the presence of thrombosis (1.93±0.25) than in its absence (0.81±0.06) (p<0.01). Each unit of this composite risk score yielded an OR of 5.2 (95% CI 2.5 to 10.7) to have thrombosis (p<0.01). The composite risk score with anti-PS/PT antibody status instead of LAC also associated with thrombosis (p<0.01).

Conclusion A composite risk score including PC4d, low C3 and LAC was associated with recent thrombosis and acknowledges the multifactorial nature of thrombosis in SLE.

  • systemic lupus erythematosus
  • thrombosis
  • complement
  • lupus anti-coagulant

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors MAP and TD designed the study. TD performed the analysis and wrote the first draft of the manuscript. JC performed flow cytometry and clinical data management. TO'M participated in flow cytometry data acquisition. All authors approved the final manuscript.

  • Funding The study is funded by Exagen. The Hopkins Lupus cohort is supported by NIH grants R01 AR43727 and AR69572.

  • Competing interests MAP has received research grants from Exagen. TD JC and TO’M are employed by Exagen Diagnostics.

  • Patient consent for publication Obtained.

  • Ethics approval The Johns Hopkins University School of Medicine internal review board approved the study and informed consent was collected from all subjects.

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

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