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Cited by 132Systemic Lupus Erythematosus ResearchComplement system in diseasesBlood Coagulation and Thrombosis Mechanisms

Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients

Open access
Schmidt‐Tanguy, A., Voswinkel, J., Henrion, D., Subra, J.F., Loufrani, L., Rohmer, V., Ifrah, N., Belizna, C.·2013·Journal of Thrombosis and Haemostasis
DOI 10.1111/jth.12363
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AI snapshot

Written from the paper’s full text.

TL;DR

In this prospective non-randomized study of 40 primary antiphospholipid syndrome (APS) patients with prior venous thrombosis, adding hydroxychloroquine (HCQ) 400 mg daily to oral anticoagulation was associated with no recurrent venous thromboses over 3 years, versus 6 recurrences (30%) in patients on oral anticoagulation alone. The authors conclude these preliminary results require confirmation in a randomized controlled trial.

Key findings

  • Six recurrent venous thromboses (30%) occurred in APS patients receiving oral anticoagulant alone, and none occurred in patients receiving additional HCQ; the time-to-event difference was significant by log-rank test (chi-square 6.901, P = 0.0086) and Gehan-Breslow-Wilcoxon test (chi-square 6.855, P = 0.0088).
  • Recurrences in the anticoagulant-only group included three femoral and three tibial thromboses, appearing after 15–18 months and 12–14 months of follow-up, respectively; the recurrent localization was identical to the previous event in 3 of 6 cases (50%).
  • The percentage of time within therapeutic INR range was 98% in all cases, including during the 30 days before recurrent events (mean INR 2.7 in controls, 2.6 in HCQ-treated patients; range 2.32–2.98).
  • Minor hemorrhages occurred in two patients (10%) in each group; no other complications were reported.

Methods

  • Prospective non-randomized study approved by the institutional review board, analyzing 3 years (October 2009 to January 2013) of incident primary APS patients with previous venous thrombosis and ongoing oral anticoagulant treatment (fluindione; target INR 2–3).
  • Patients were divided into 20 who received HCQ 400 mg daily added to oral anticoagulant and 20 controls treated with oral anticoagulant alone; inclusion and follow-up periods were 6 and 36 months, respectively. Median age was 29.1 years in the anticoagulant group and 28.9 years in the HCQ group.
  • APS diagnosis was confirmed after two tests 12 weeks apart; lupus anticoagulant and anticardiolipin/anti-β2-glycoprotein-1 antibodies were assessed. Statistical analysis used Mann-Whitney U-test, odds ratios with 95% CIs, chi-squared test, Kaplan-Meier curves, log-rank test, and Gehan-Breslow-Wilcoxon test; P < 0.05 was significant.

Limitations

  • The paper states this is a preliminary, non-randomized small cohort; it investigated venous but not arterial thrombosis to obtain an evaluable population; possible explanations for the higher-than-expected relapse rate in the anticoagulant group include enrollment bias at their hospital and complementary diagnostic tests for thrombosis; the authors state results should be confirmed in a randomized controlled trial.
  • Evident from the text: the study is single-center, unblinded, and non-randomized, with only 20 patients per group, so confounding by indication and limited generalizability are possible.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/jth.12363

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 11 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Published evidence indicates a 20% recurrence rate of thrombosis in antiphospholipid syndrome patients on oral anticoagulants after five years.

    “Published data support a 20% prevalence rate of thrombosis recurrence in APS patients treated with OAs after 5 years of follow-up [1].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
  • Premisecitation

    In antiphospholipid syndrome patients, thromboembolic event incidence was significantly higher among those not receiving oral anticoagulants (HR 2.4, 95% CI 1.3-4.1, P<0.003).

    “The incidence was significantly higher in patients not taking OAs (HR 2.4, 95% CI 1.3-4.1,P < 0.003) [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] source

      The ‘Thromboembolic events during the followup period’ section reports significantly higher event incidence without oral anticoagulants and gives the stated HR, confidence interval, and P value. However, the cohort comprised high-risk APS patients positive on all three antiphospholipid antibody tests; the citing sentence does not retain that population restriction. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Findingown data

    In primary antiphospholipid syndrome patients with prior venous thrombosis, six recurrent venous thromboses (30%) occurred in those given oral anticoagulants alone, whereas none occurred in those given oral anticoagulants plus hydroxychloroquine.

    “Six recurrent venous thromboses (30%) were detected in APS patients receiving OA and none in patients receiving additional HCQ.”
    • Also stated in: § Abstract · hedged
      “Within the limits of this non-randomized small cohort, we documented the absence of recurrent thrombotic events in APS patients receiving OA plus HCQ, although six recurrent thromboses (30%) were observed in APS patients receiving OA despite an INR in the therapeutic range.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Hydroxychloroquine may be beneficial as an antithrombotic in the general population.

    “HCQ could be useful as an antithrombotic both in the general population [9] and in systemic lupus erythematosus and/or APS patients [10]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] source
  • Interpretationnone given

    This is the first prospective study in primary antiphospholipid syndrome to examine hydroxychloroquine for secondary venous thrombosis prophylaxis.

    “To the best of our knowledge, this is the first prospective study in primary APS investigating HCQ for secondary venous thrombosis prophylaxis.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 2
  • May combine two claims. 10

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    According to the literature, most relapses in antiphospholipid syndrome occur early during follow-up and at the same site as the previous event.

    “According to the literature, most of these relapses were observed early during the study, at the same site as the previous event [2].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [2] source

      The Addendum (Table 2; page unavailable) reports recurrent thrombosis by event type and treatment group, but not when events occurred or whether they were at the site of a previous event. Searches for early recurrences and the site of previous events found no passage establishing either part of the claim. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In a retrospective antiphospholipid syndrome study, cumulative thromboembolic event incidence was 12.2% at one year and 44.2% at ten years.

    “At 1 year, the cumulative incidence of thromboembolic events was 12.2%, and at 10 years it was 44.2%, in a retrospective study in APS patients [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Findingown data

    The time-to-event difference between groups was statistically significant by log-rank (P=0.0086) and Gehan-Breslow-Wilcoxon (P=0.0088), with a hazard ratio of 2.4 (95% CI 1.3-4.1).

    “For the time to event difference between the two groups, the log-rank (Mantel-Cox) test showed a chi-square value of 6.901, and a statistically significant P-value of 0.0086, and the Gehan-Breslow-Wilcoxon test showed a chi-square value of 6.855, and a statistically significant P-value of 0.0088 (OR, 95% CI 1.735-44.28;hazard ratio [HR] 2.4, 95% CI 1.3-4.1;P < 0.005).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Minor hemorrhages occurred in two patients (10%) in each group, and no other complications were observed.

    “Complications exclusively consisted of minor hemorrhages in two patients (10%) in each group.”
    • Also stated in: § Abstract · plain
      “A prevalence of 10% of complications, consisting of minor bleeding, was observed in each group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In three of six recurrent thromboses (50%), the location matched the previous event.

    “The localization of the recurrent thromboses was identical to that of the previous event in three of six cases (50%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The two groups were comparable in antiphospholipid antibody profile, isotype, simple or double positivity, and antibody evolution, and no test became negative.

    “The two groups were comparable in terms of aPL profile and isotype, simple or double aPL positivity, aPL evolution in both groups.No test became negative.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The two groups had similar clinical histories, with prior venous thrombosis (one or two episodes) and no obstetric or arterial events except stroke in two patients.

    “Patients in the two groups had similar clinical histories: previous venous thrombosis (one or two episodes), but no obstetric/arterial event (except for stroke in two patients).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    No additional thrombosis risk factors were identified in the cohort, and smoking did not differ between groups.

    “Additional risk factors for thrombosis were not identified in our cohort, and no differences were found concerning smoking.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The series was characterized by homogeneity of the studied population, thrombosis type, and treatment type.

    “Hence, our series was characterized by homogeneity of the studied population, the type of thrombosis, and the type of treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The proportion of time within the therapeutic INR range was 98% overall and in the 30 days before recurrent events, with mean INR 2.7 in controls and 2.6 in hydroxychloroquine-treated patients.

    “The percentage of time within therapeutic range was 98% in all cases and specifically during the previous 30 days before the recurrent event (mean INR in controls 2.7; mean INR in patients treated with HCQ 2.6; range 2.32-2.98).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    No differences were found between the two groups in demographic factors or additional thrombosis risk factors.

    “Furthermore, no differences were found between the two groups of APS patients, in terms of either demographic factors or additional risk factors for thrombosis.”
    Quote in the paperNot a substantial claim
11 of 11

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The majority of patients had experienced venous thromboembolism as the index event, while arterial thrombosis accounted for a smaller but clinically relevant proportion of cases.

    “The majority of patients had experienced venous thromboembolism as the index event, while arterial thrombosis accounted for a smaller but clinically relevant proportion of cases.”

    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 [10]

    The Abstract says all 40 patients had previous venous thrombosis and no arterial event, except for strokes in two patients. It also says the study investigated venous, not arterial, thrombosis. The paper therefore does not describe a subgroup whose index thrombosis was arterial. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • High-risk antiphospholipid antibody profiles (lupus anticoagulant positivity and/or double antiphospholipid antibody positivity) were frequent, although reporting of triple positivity was heterogeneous.

    “High-risk antiphospholipid antibody profiles (lupus anticoagulant positivity and/or double aPL positivity) were frequent, although reporting of triple positivity was heterogeneous [8–10].”

    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 [10]

    The Results passage in our copy (labeled Abstract; page unavailable) reports lupus anticoagulant positivity in four of six patients with recurrent thrombosis and double aPL positivity in two, with no triple positivity among those patients. This supports frequent high-risk profiles among patients with recurrences, but does not establish their frequency across the full cohort or show heterogeneous reporting of triple positivity. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The three included studies were a randomized prospective trial in Greece, a retrospective multicenter propensity score-matched cohort in Italy, and a prospective non-randomized controlled study in France.

    “One study was a randomized prospective trial conducted in Greece [8], one a retrospective multicenter propensity score-matched cohort from Italy [9], and one a prospective non-randomized controlled study from France [10].”

    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 [10]

    The Abstract (page unavailable) identifies this as a prospective, non-randomized study and describes a control group, supporting the study-design description attached to [10]. The passages in our copy do not identify France as the study location, so that part is unverified. The Greece and Italy descriptions are attached to other citations, not this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Across included studies, patients were predominantly female (approximately 70-80% when reported) and all had a documented history of objectively confirmed thrombosis fulfilling APS classification criteria.

    “Across studies, patients were predominantly female (approximately 70–80% women, when reported), and all had a documented history of objectively confirmed thrombosis fulfilling APS classification criteria.”

    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 [10]

    The paper’s Abstract (page unavailable) says its 40 patients met primary APS criteria and had a history of venous thrombosis. It does not report that approximately 70–80% were women, and a single study cannot establish the statement about patients across studies. The passage describing imaging confirmation concerns thrombosis diagnosis but does not explicitly say every prior event was objectively confirmed. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Three clinical studies met inclusion criteria, comprising 164 adult patients with thrombotic primary antiphospholipid syndrome, of whom 82 received hydroxychloroquine and 82 received standard therapy alone.

    “Three clinical studies met the inclusion criteria, comprising a total of 164 adult patients with thrombotic primary antiphospholipid syndrome (PAPS), of whom 82 received hydroxychloroquine (HCQ) in addition to standard antithrombotic therapy and 82 received standard therapy alone [8–10].”

    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 [10]

    The study description (Abstract) reports 40 adults with primary APS: 20 received hydroxychloroquine plus oral anticoagulation, and 20 received anticoagulation alone. This supports the paper’s contribution to the cited group of studies, but the paper does not establish the pooled totals of three studies, 164 patients, or 82 patients per treatment group. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Previous-thrombosis site counts fall short of the patient count

    Minor

    The listed sites total 39, although all 40 patients had a previous venous thrombosis. The statement that two initial thromboses involved multiple localizations would require more, not fewer, site entries if the list is exhaustive.

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Authors
Schmidt‐Tanguy, A., Voswinkel, J., Henrion, D., Subra, J. F., Loufrani, L., Rohmer, V., Ifrah, N., & Belizna, C.
Affiliations
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Inserm (FR)
  • Centre Hospitalier Universitaire d'Angers (FR)
Corresponding author
Belizna, C.
ORCID
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2013-10
Volume
11
Issue
10
Pages
1927-1929
ISSN
1538-7836 (ISSN-L)
DOI
10.1111/jth.12363
OpenAlex
W2032097852
Semantic Scholar
04b04d79bf3203a2980f6a64cf0c8a8f43c2198d
Cited by
132
References
12
Citations by year
2026: 4 · 2025: 4 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 12 · 2019: 18 · 2018: 17 · 2017: 8 · 2016: 10 · 2015: 10 · 2014: 10 · 2013: 2
FWCI
7.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (Le Centre pour la Communication Scientifique Directe) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
hydroxychloroquine, antithrombotic activity, primary antiphospholipid syndrome, complement activation
MeSH terms
Adult, Humans, Hydroxychloroquine, Thrombosis, Antiphospholipid Syndrome

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

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Statistics and arithmetic are recomputed, not judged.

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