Hydroxychloroquine Reduces Platelet Activity, Improves Vascular Health in Systemic Lupus Erythematosus

Hydroxychloroquine treatment may reduce platelet aggregation and improve vascular health in patients with systemic lupus erythematosus (SLE), according to study results published in Lupus Science & Medicine. In addition, study results also suggest that RNA expression of platelet function pathway downregulation is inversely related to increased hydroxychloroquine dose.

A team of researchers studied the effects of hydroxychloroquine use and dose on platelet activity, platelet transcriptomics, and vascular health in patients with SLE. Platelet aggregation, messenger RNA (mRNA) expression, vascular health, red blood cell filling, and brachial artery reactivity testing were assessed.

A total of 132 patients with SLE (mean age, 39.7±12.9 years; 97% women) were included in the study; 108 patients received hydroxychloroquine. Patients receiving aspirin and nonsteroidal anti-inflammatory drugs, or with a platelet count less than 100´10⁹/L were not eligible to participate in the study.

At baseline, lupus disease activity was 3.58 (range, 0-20), as assessed by the HYBRID SELENA Systemic Lupus Erythematosus Disease Activity Index. Platelet count and size did not significantly differ between the patient groups.

Platelet aggregation was lower in patients who received treatment with hydroxychloroquine compared with those who did not. There was an inverse relationship between hydroxychloroquine dosing and platelet aggregation, in response to adenosine diphosphate (r=-0.27; P =.008). Aggregation in response to arachidonic acid was similar between both groups; however, when platelets were intubated with 3 mM of aspirin in vitro, platelet aggregation in response to arachidonic acid was lower in the hydroxychloroquine cohort compared with the nontreatment cohort (P =.017).

Expression of the gene encoding P-selectin was negatively correlated with hydroxychloroquine dose and weight (r=-0.41; P =.003). After data validation, results suggested that there was a significantly reduced fold change in P-selectin expression in patients who received treatment with hydroxychloroquine compared with those who did not (P =.037).

Compared with patients in the untreated group, those in the hydroxychloroquine group had improved microvascular function (P =.014) and smaller perfused boundary region (P =.042). Brachial artery reactivity testing also revealed positive results in association with hydroxychloroquine dose and weight(r=0.43; P =.056).

Study limitations included the significant difference in the number of patients in each cohort; lack of information on other medications taken by the participants, which could have affected platelet reactivity; and the fact that long-term cardiovascular outcomes could not implied as the association between hydroxychloroquine and platelet activity was observed in a cross-sectional analysis. 

“[T]hese results reinforce the antithrombotic properties of [hydroxychloroquine] in patients with SLE and potential protective benefit in a disease where premature atherosclerosis is a significant comorbidity,” the researchers concluded.

Reference

Cornwell MG, Luttrell-Williams Es, Golpanian M, et al. Hydroxychloroquine is associated with lower platelet activity and improved vascular health in systemic lupus erythematosus. Lupus Sci Med. 2021;8(1):e000475. doi:10.1136/lupus-2021-000475