2. Academic Validation
  3. Leukadherin-1 mitigates disseminated intravascular coagulation in acute pancreatitis by suppressing necroptosis

Leukadherin-1 mitigates disseminated intravascular coagulation in acute pancreatitis by suppressing necroptosis

  • Thromb Res. 2025 Aug:252:109363. doi: 10.1016/j.thromres.2025.109363.
Zhongjie Yi 1,  Xueming Xu 2,  Xingyu Xiang 1,  Jinyuan Chang 1,  Jie Shi 3,  Yongjun Wang 4
Affiliations

Affiliations

  • 1 Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2 Department of Intensive Care Unit, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 3 Department of Blood Transfusion, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: shijie@csu.edu.cn.
  • 4 Department of Blood Transfusion, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
PMID: 40494132 DOI: 10.1016/j.thromres.2025.109363
Abstract

Disseminated intravascular coagulation (DIC) is a fatal complication of acute pancreatitis (AP), leading to multiple organ dysfunction syndrome (MODS), but its pathogenic mechanism is poorly understood. Here, we identify Leukadherin-1 (LA-1) as a potential therapeutic agent against AP-associated DIC. LA-1 effectively attenuated DIC progression by suppressing tissue factor (TF) release from necroptotic macrophages, achieved through inhibition of RIPK1 phosphorylation at Ser166-a critical step in Necroptosis signaling pathways. Additionally, LA-1 inhibited Necroptosis in pancreatic acinar cells, potentially disrupting macrophage Necroptosis. These findings propose a novel approach to targeting the interplay between Necroptosis and coagulation and provides valuable insights into potential therapeutic strategies for managing coagulation disorders associated with AP, thus alleviates the burden of this debilitating condition.

Keywords

DIC; Leukadherin-1; Necroptosis; Pancreatitis.

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