Antiplatelet effects of hydroxychloroquine in patients with systemic lupus erythematosus evaluated by the total thrombus-formation analysis system (T-TAS)

Lupus Sci Med. 2024 Jul 8;11(2):e001223. doi: 10.1136/lupus-2024-001223.

Abstract

Objectives: Hydroxychloroquine (HCQ) has been shown to reduce thrombotic events in patients with SLE. However, the antiplatelet effects of HCQ are only supported by the platelet aggregation assay, which is a non-physiological test. The total thrombus-formation analysis system (T-TAS) is a microchip-based flow chamber system that mimics physiological conditions and allows for the quantitative analysis of thrombogenicity. The present study investigated the antiplatelet effects of HCQ using T-TAS.

Methods: This was a single-centre cross-sectional study on 57 patients with SLE. We measured the area under the pressure curve for 10 min (PL-AUC10) and the time to 10 kPa (T10) in patients with SLE using T-TAS and examined their relationships with the use of HCQ. PL-AUC10 and platelet aggregation were also measured at several HCQ concentrations using blood samples from healthy donors.

Results: PL-AUC10 was significantly lower in the HCQ/real body weight (RBW) ≥5 mg/kg group than in the <5 mg/kg group, while T10 was similar, indicating that HCQ inhibited overall thrombus formation rather than the initiation of thrombus formation. The antiplatelet effects of HCQ were initially detected at HCQ/RBW of approximately 4 mg/kg and reached a plateau at around 5.5 mg/kg. The administration of HCQ/RBW >4.6 mg/kg clearly exerted antiplatelet effects. Additionally, HCQ inhibited thrombus formation in T-TAS and the platelet aggregation response to epinephrine in a dose-dependent manner.

Conclusions: We demonstrated the antiplatelet effects of HCQ under conditions simulating the physiological environment by using T-TAS and identified the range of doses at which HCQ exerted antiplatelet effects.

Keywords: Cardiovascular Diseases; Lupus Erythematosus, Systemic; Myocardial infarction.

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use
  • Cross-Sectional Studies
  • Female
  • Humans
  • Hydroxychloroquine* / therapeutic use
  • Lupus Erythematosus, Systemic* / blood
  • Lupus Erythematosus, Systemic* / complications
  • Lupus Erythematosus, Systemic* / drug therapy
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Platelet Aggregation* / drug effects
  • Platelet Function Tests / methods
  • Thrombosis* / drug therapy
  • Thrombosis* / etiology
  • Thrombosis* / prevention & control
  • Young Adult

Substances

  • Hydroxychloroquine
  • Platelet Aggregation Inhibitors
  • Antirheumatic Agents