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Cited by 250Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsPlatelet Disorders and Treatments

Hydroxychloroquine Reverses Thrombogenic Properties of Antiphospholipid Antibodies in Mice

Edwards, Michael H., Pierangeli, Silvia, Liu, XiaoWei, Barker, John H., Anderson, Gary, Harris, E. Nigel·1997·Circulation
DOI 10.1161/01.cir.96.12.4380
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Abstract

Background Previous studies have demonstrated that human monoclonal and polyclonal anticardiolipin antibodies have thrombogenic properties in vivo. Using such a model in which these antibodies have been shown to increase both the size of an induced thrombus and the duration of time in which such a clot lasts, we investigated whether hydroxychloroquine alters the dynamics of such thrombus formation. Methods and Results Three groups of nine mice were injected with purified immunoglobulin G (IgG) from a patient with the antiphospholipid syndrome (IgG-APS) and then fed with hydroxychloroquine at various doses (100, 6, and 3 mg/kg body wt). Three control groups of mice were also studied, including mice injected with IgG-APS and then fed with placebo, as well as two other groups injected with IgG from normal human serum and fed either hydroxychloroquine or placebo. A standardized thrombogenic injury was subsequently induced in the femoral vein of each mouse and the area (size) of thrombus measured as well as the total period of time that thrombus was present. Mice treated with hydroxychloroquine and IgG-APS showed significantly smaller thrombi that persisted for a shorter period of time compared with animals treated with IgG-APS and placebo. Conclusions Hydroxychloroquine significantly diminished both thrombus size and total time of thrombus formation in mice previously injected with IgG-APS.

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  • Experimental studies show that hydroxychloroquine interferes with the binding of antiphospholipid antibody-β2-glycoprotein I complexes to phospholipid surfaces, reverses antiphospholipid antibody-induced thrombogenicity, reduces platelet activation, downregulates endothelial tissue factor expression, modulates complement activation and improves endothelial function.

    “Experimental studies have shown that HCQ interferes with the binding of aPL–β2-glycoprotein I complexes to phospholipid surfaces, reverses aPL-induced thrombogenicity, reduces platelet activation, downregulates endothelial tissue factor expression, modulates complement activation and improves endothelial function [3–5].”

    From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [5]

  • Hydroxychloroquine reduces platelet activation, downregulates endothelial tissue factor expression, modulates complement activation and improves endothelial function, collectively targeting multiple thrombo-inflammatory pathways central to APS pathophysiology.

    “In addition, HCQ reduces platelet activation, downregulates endothelial tissue factor expression, modulates complement activation and improves endothelial function, collectively targeting multiple thrombo-inflammatory pathways central to APS pathophysiology [3, 5].”

    From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [5]

  • Hydroxychloroquine administration significantly decreased thrombus size and duration.

    “Its administration significantly reduced thrombus size and duration [8].”

    From Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients (2013) · cites this paper as [8]

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Authors
Edwards, M. H., Pierangeli, S., Liu, X., Barker, J. H., Anderson, G., & Harris, E. N.
Affiliations
University of Louisville (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1997-12-16
Volume
96
Issue
12
Pages
4380-4384
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.96.12.4380
OpenAlex
W2001976130
Cited by
250
References
30
Citations by year
2026: 3 · 2025: 1 · 2024: 10 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 17 · 2019: 9 · 2018: 7 · 2017: 13 · 2016: 14 · 2015: 10 · 2014: 16 · 2013: 11 · 2012: 10
FWCI
2.01
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
Keywords
hydroxychloroquine, antiphospholipid syndrome, anticardiolipin antibodies, antiphospholipid antibodies, thrombosis, thrombus size, thrombogenicity, IgG, thromboprophylaxis
MeSH terms
Animals, Dose-Response Relationship, Drug, Humans, Hydroxychloroquine, Immunoglobulin G, Male, Mice, Inbred Strains, Reference Values, Thrombosis, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Mice

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