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

Abstract

ObjectivesHydroxychloroquine (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.MethodsThis 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-AUC10and platelet aggregation were also measured at several HCQ concentrations using blood samples from healthy donors.ResultsPL-AUC10was significantly lower in the HCQ/real body weight (RBW) ≥5 mg/kg group than in the <5 mg/kg group, while T10was 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.ConclusionsWe 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.