Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia.

Chuanbin Shen, Ming Liu, Daniel Thomas Mackeigan, Zi Yan Chen, Pingguo Chen, Danielle Karakas, June Li, Peter A A Norris, Jiayao Li, Yanling Deng, Chengbo Long, Ren Lai, Heyu Ni

Archives of toxicology 2021 Nov

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Venomous snakebites cause clinical manifestations that range from local to systemic and are considered a significant global health challenge. Persistent or refractory thrombocytopenia has been frequently reported in snakebite patients, especially in cases caused by viperidae snakes. Viper envenomation-induced thrombocytopenia may persist in the absence of significant consumption coagulopathy even after the antivenom treatment, yet the mechanism remains largely unknown. Our study aims to investigate the mechanism and discover novel therapeutic targets for coagulopathy-independent thrombocytopenia caused by viper envenomation. Here we found that patients bitten by Protobothrops mucrosquamatus and Trimeresurus stejnegeri, rather than Naja. atra may develop antivenom-resistant and coagulopathy-independent thrombocytopenia. Crude venoms and the derived C-type lectin-like proteins from these vipers significantly increased platelet surface expression of neuraminidase and platelet desialylation, therefore led to platelet ingestion by both macrophages and hepatocytes in vitro, and drastically decreased peripheral platelet counts in vivo. Our study is the first to demonstrate that desialylation-mediated platelet clearance is a novel mechanism of viper envenomation-induced refractory thrombocytopenia and C-type lectin-like proteins derived from the viper venoms contribute to snake venom-induced thrombocytopenia. The results of this study suggest the inhibition of platelet desialylation as a novel therapeutic strategy against viper venom-induced refractory thrombocytopenia. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Chuanbin Shen, Ming Liu, Daniel Thomas Mackeigan, Zi Yan Chen, Pingguo Chen, Danielle Karakas, June Li, Peter A A Norris, Jiayao Li, Yanling Deng, Chengbo Long, Ren Lai, Heyu Ni. Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia. Archives of toxicology. 2021 Nov;95(11):3589-3599