ArticleBlood2010
Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 247 citations in OpenAlex.
- The Impact of Systemic Lupus Erythematosus on the Clinical Phenotype of Antiphospholipid Antibody-Positive Patients: Results From the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Clinical Database and Repository.Arthritis care & research · 2019Trial
- Trial
- Association of EndometrialBiomedicines · 2026Article
- Antiphospholipid syndrome and pregnancy-a hematologic perspective.Research and practice in thrombosis and haemostasis · 2026Article
- Mapping organ-associated autoantigenic landscapes in systemic lupus erythematosus.Frontiers in immunology · 2026Review
- Mechanism of antiphospholipid antibody-mediated thrombosis in antiphospholipid syndrome.Frontiers in immunology · 2025Review
- Immune-mediated mechanisms and maternal-fetal interface dysfunction in obstetric antiphospholipid syndrome.Frontiers in immunology · 2025Review
- Hydroxychloroquine's diverse targets: a new frontier in precision medicine.Frontiers in immunology · 2025Review
- Differential inflammatory conditioning of the bone marrow by acute myeloid leukemia and its impact on progression.Blood advances · 2024Article
- The effects of hydroxychloroquine and its promising use in refractory obstetric antiphospholipid syndrome.Rheumatology international · 2024Review
- Risk factors of first thrombosis in obstetric antiphospholipid syndrome.Lupus science & medicine · 2024Article
- Interaction of antiphospholipid antibodies with endothelial cells in antiphospholipid syndrome.Frontiers in immunology · 2024Review
- How to diagnose and manage antiphospholipid syndrome.Hematology. American Society of Hematology. Education Program · 2023Review
- The pathogenesis of obstetric APS: a 2023 update.Clinical immunology (Orlando, Fla.) · 2023Review
- Trophoblast Cell Function in the Antiphospholipid Syndrome.Biomedicines · 2023Review
- Association of Hydroxychloroquine Dose With Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus.Arthritis care & research · 2023Article
- Identification of hub genes and therapeutic drugs in osteonecrosis of the femoral head through integrated bioinformatics analysis and literature mining.Scientific reports · 2023Article
- The ABCs of antiphospholipid syndrome.Archives of rheumatology · 2023Review
- Chloroquine reduces neutrophil extracellular trap (NET) formation through inhibition of peptidyl arginine deiminase 4 (PAD4).Clinical and experimental immunology · 2023Article
- Hydroxychloroquine as an Immunomodulatory and Antithrombotic Treatment in Antiphospholipid Syndrome.International journal of molecular sciences · 2023Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Annexin A5 (AnxA5) is a potent anticoagulant protein that crystallizes over phospholipid bilayers (PLBs), blocking their availability for coagulation reactions. Antiphospholipid antibodies disrupt AnxA5 binding, thereby accelerating coagulation reactions. This disruption may contribute to thrombosis and miscarriages in the antiphospholipid syndrome (APS). We investigated whether the antimalarial drug, hydroxychloroquine (HCQ), might affect this prothrombotic mechanism. Binding of AnxA5 to PLBs was measured with labeled AnxA5 and also imaged with atomic force microscopy. Immunoglobulin G levels, AnxA5, and plasma coagulation times were measured on cultured human umbilical vein endothelial cells and a syncytialized trophoblast cell line. AnxA5 anticoagulant activities of APS patient plasmas were also determined. HCQ reversed the effect of antiphospholipid antibodies on AnxA5 and restored AnxA5 binding to PLBs, an effect corroborated by atomic force microscopy. Similar reversals of antiphospholipid-induced abnormalities were measured on the surfaces of human umbilical vein endothelial cells and syncytialized trophoblast cell lines, wherein HCQ reduced the binding of antiphospholipid antibodies, increased cell-surface AnxA5 concentrations, and prolonged plasma coagulation to control levels. In addition, HCQ increased the AnxA5 anticoagulant activities of APS patient plasmas. In conclusion, HCQ reversed antiphospholipid-mediated disruptions of AnxA5 on PLBs and cultured cells, and in APS patient plasmas. These results support the concept of novel therapeutic approaches that address specific APS disease mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.