Could Isoquercetin Solve Thromboinflammation in Sickle Cell Disease?

Therapy with short-term, fixed-dose isoquercetin exhibited no off-target bleeding and induced positive reductions in several biomarkers for thromboinflammation in patients with sickle cell disease (SCD), according to a randomized controlled trial published in Blood Advances.

The data “confirm the utility of a relatively inexpensive and safe oral flavonoid with demonstrable efficacy in reducing several thromboinflammatory biomarkers in SCD,” wrote the study’s authors, led by Maria Lizarralde-Iragorri, PhD, from the National Heart Lung and Blood Institute at the National Institutes of Health in Bethesda, Maryland.

Between November 2019 and July 2022, researchers enrolled 46 adults with a mean age of 40 ± 11 years with steady-state SCD variants. The cohort was 56% female and 75% were receiving hydroxyurea treatment. After randomization, 23 patients received isoquercetin and 23 received placebo.

Treatment Reduces Inflammation in Sickle Cell Disease

Isoquercertin was well tolerated, and the authors stated that the 21 adverse events (AEs) and 14 serious AEs were not related to treatment. After treatment, the mean change from baseline in plasma soluble P-selectin (the primary outcome) was not significantly different between the groups at 0.10 ± 6.53 with isoquercetin versus 0.74 ± 4.54 with placebo (P=.64); however, isoquercetin did significantly reduce or inhibit the following:

• Whole-blood coagulation (P=.03)
• Collagen-induced platelet aggregation (P=.03)
• Inducible mononuclear cell tissue factor gene expression (P=.003)
• Plasma protein disulfide isomerase reductase activity (P=.02)

Considering these data together, “findings suggest that trials of higher dose [isoquercetin] for more extended treatment durations are required for patients with SCD,” Dr. Lizarralde-Iragorri and colleagues wrote.

Reference

Lizarralde-Iragorri MA, Gopalan BP, Merriweather B, et al. Isoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial. Blood Adv. 2024;8(1):172-182. doi:10.1182/bloodadvances.2023011542hemeto

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