4.6 Article

Increased reactive oxygen species lead to overactivation of platelets in essential thrombocythemia

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THROMBOSIS RESEARCH
卷 226, 期 -, 页码 18-29

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2023.04.001

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Essential thrombocytopenia; N-acetylcysteine; Platelets; Reactive oxygen species; Thrombosis

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This study investigated the causes of abnormal platelet function and potential therapeutic strategies in patients with essential thrombocythemia (ET). It was found that platelet aggregation, activation, apoptosis, ROS, and clot retraction were all elevated in ET patients. Inhibiting ROS reduced platelet dysfunction and lowered platelet count.
Introduction: Platelet function, rather than platelet count, plays a crucial role in thrombosis in essential thrombocythemia (ET). However, little is known about the abnormal function of platelets in ET. Here, we investigated the functional characteristics of platelets in ET hemostasis to explore the causes of ET platelet dysfunction and new therapeutic strategies for ET.Materials and methods: We analyzed platelet aggregation, activation, apoptosis, and reactive oxygen species (ROS) in ET patients and JAK2V617F-positive ET-like mice. The effects of ROS on platelet function and the underlying mechanism were investigated by inhibiting ROS using N-acetylcysteine (NAC).Results: Platelet aggregation, activation, apoptosis, ROS, and clot retraction were elevated in ET. No significant differences were observed between ET patients with JAK2V617F or CALR mutations. Increased ROS activated the JAK-STAT pathway, which may further influence platelet function. Inhibition of platelet ROS by NAC reduced platelet aggregation, activation, and apoptosis, and prolonged bleeding time. Furthermore, NAC treatment reduced platelet count in ET-like mice by inhibiting platelet production from megakaryocytes.Conclusions: Elevated ROS in ET platelets resulted in enhanced platelet activation, function and increased risk of thrombosis. NAC offers a potential therapeutic strategy for reducing platelet count.

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