Hydroxychloroquine inhibits hemolysis-induced arterial thrombosis ex vivo and improves lung perfusion in hemin-treated mice

Joshua H. Bourne, Gina Perrella, Juma El-Awaisi, Lauren V. Terry, Veronika Tinkova, Rebecca L. Hogg, Poppy Gant, Beata Grygielska, Neena Kalia, Dean Kavanagh, Alexander Brill, Jordan D. Dimitrov, Steve P. Watson, Julie Rayes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Free labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis and muscle injury supporting platelet activation and thrombosis.

Aim: We investigated the anti-thrombotic potential of hydroxychloroquine on hemolysis-induced arterial thrombosis ex vivo, hemin-induced platelet activation, ferric-chloride (FeCl3)-induced arterial thrombosis and lung perfusion following hemin injection in mice.

Results: Erythrocyte lysis and endothelial cell activation cooperatively supported platelet aggregation and thrombosis at arterial shear stress. This thrombotic effect was reversed by hydroxychloroquine. In a purified system, hydroxychloroquine inhibited platelet build-up on immobilized von Willebrand factor in hemolyzed blood without altering initial platelet recruitment. Hydroxychloroquine inhibited hemin-induced platelet activation and phosphatidylserine exposure independently of reactive oxygen species generation. In the presence of hemin, hydroxychloroquine did not alter glycoprotein VI shedding but reduced C-type-lectin-like-2 expression on platelets. In vivo, hydroxychloroquine reversed pulmonary perfusion decline induced by exogenous administration of hemin. In arterial thrombosis models, hydroxychloroquine inhibited FeCl3-induced thrombosis in the carotid artery and reduced von Willebrand factor accumulation in the thrombi.

Conclusion: Hydroxychloroquine inhibited hemolysis-induced arterial thrombosis ex-vivo and improved pulmonary perfusion in hemin-treated mice, supporting a potential benefit of its use as an adjuvant therapy in hemolytic diseases to limit arterial thrombosis and to improve organ perfusion.
Original languageEnglish
JournalJournal of Thrombosis and Haemostasis
Early online date24 Apr 2024
Publication statusE-pub ahead of print - 24 Apr 2024


  • Hydroxychloroquine
  • platelets
  • thrombosis
  • hemin
  • hemolysis


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