The effect of hydroxychloroquine on haemostasis, complement, inflammation and angiogenesis in patients with antiphospholipid antibodies

Rheumatology (Oxford). 2018 Jan 1;57(1):120-124. doi: 10.1093/rheumatology/kex378.

Abstract

Objectives: HCQ has been described as having a beneficial effect in patients with APS but its mechanism of action is unclear. We hypothesized that HCQ may have effects on subnormal angiogenesis, inflammation and haemostatic biomarkers seen in APS. The aim of our study was to assess laboratory markers [annexin A5 (AnxA5) anticoagulant activity, tissue factor (TF) levels, thromboelastography (TEG), CRP, Bb, C3a and VEGF] in HCQ-naïve patients with aPL at baseline and after commencing HCQ.

Methods: Twenty-two patients with aPL [20 female, 2 male, median age 55 (range 18-70) years] had blood taken pre- and 3 months after starting HCQ 200 mg daily.

Results: Soluble TF levels were significantly reduced comparing baseline and 3 months after HCQ commencement [401.8 (152.8) vs 300.9 (108) pg/ml (P = 0.010)]. No significant changes were found in the following [reported as pre- and post-HCQ commencement, mean (s.d.)]: AnxA5 anticoagulant ratio [187.1 (29.5) vs 193 (31) (P = 0.157)], anti-domain1 β2 glycoprotein1 IgG activity [1.8 (2) vs 1.2 (1.4) μg/ml (P = 0.105)], complement C3a-des-Arg [147.8 (84.5) vs 154.4 (88.1) ng/ml (P = 0.905)], complement Bb [1.3 (0.7) vs 1.1 (0.7) μg/ml (P = 0.422)], VEGF [68.8 (40) vs 59.4 (19.6) pg/ml (P = 0.454)] and CRP [7 (3.5) vs 7 (3.9) μg/ml (P = 0.917)]. TEG results including TEG reaction time, achievement of clot firmness, TEG maximum amplitude and TEG percentage lysis 30 and 60 min after maximum amplitude showed no significant difference.

Conclusion: HCQ significantly reduced soluble TF levels in patients with aPL. No significant change was observed in AnxA5 activity, anti-domain 1 IgG activity, TEG, CRP, complement Bb and C3a-des-Arg, and VEGF. Further studies of a larger patient cohort are needed.

Keywords: APS; Tissue factor; antiphospholipid syndrome; hydroxychloroquine; synthetic DMARD.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Annexin A5 / metabolism
  • Antibodies, Antinuclear / immunology
  • Antibodies, Antiphospholipid / immunology
  • Antiphospholipid Syndrome / drug therapy*
  • Antiphospholipid Syndrome / immunology
  • Antiphospholipid Syndrome / metabolism
  • Antirheumatic Agents / therapeutic use*
  • C-Reactive Protein / metabolism
  • Complement C3a / immunology
  • Complement System Proteins / immunology
  • Hemostasis
  • Humans
  • Hydroxychloroquine / therapeutic use*
  • Immunoglobulin G / immunology
  • Middle Aged
  • Neovascularization, Physiologic
  • Prospective Studies
  • Thrombelastography
  • Thromboplastin / metabolism
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult
  • beta 2-Glycoprotein I / immunology

Substances

  • Annexin A5
  • Antibodies, Antinuclear
  • Antibodies, Antiphospholipid
  • Antirheumatic Agents
  • Immunoglobulin G
  • SS-B antibodies
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • beta 2-Glycoprotein I
  • Hydroxychloroquine
  • Complement C3a
  • Complement System Proteins
  • C-Reactive Protein
  • Thromboplastin