Lira André L, Puy Cristina, Shatzel Joseph J, Lupu Florea, McCarty Owen J T
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR.
Division of Hematology and Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR.
Blood Vessel Thromb Hemost. 2025 Jul 5;2(4):100091. doi: 10.1016/j.bvth.2025.100091. eCollection 2025 Nov.
The excessive inflammatory and prothrombotic response to a bacterial infection creates a life-threatening medical condition in sepsis. The transition from localized to systemic thrombin generation is a hallmark of disseminated intravascular coagulation (DIC), a severe prothrombotic disorder resulting in microvascular thrombosis and subsequent multiorgan failure. The contact pathway of coagulation has been shown to play roles both in the initiation and amplification of thrombin generation in models of sepsis. The contact pathway consists of the coagulation factors XII (FXII) and XI (FXI), prekallikrein, and high- molecular-weight kininogen. Activation of the contact pathway can be triggered by binding to anionic surfaces, such as the ionized phosphoryl and carboxylate groups present on bacterial surface macromolecules. In particular, FXII has been shown to bind to the components of the bacterial envelope, including adhesins, peptidoglycan, lipopolysaccharides from gram-negative bacteria, and lipoteichoic acids from gram-positive bacteria. This review discusses the molecular pathways linking activation of the contact pathway by the envelope structures of bacterial and downstream thrombin generation and inflammation associated with sepsis-induced coagulopathies. We highlight the potential for FXII and FXI as potential therapeutic options for safely preventing DIC in sepsis.
对细菌感染的过度炎症和促血栓形成反应会在脓毒症中引发危及生命的医学状况。从局部凝血酶生成向全身凝血酶生成的转变是弥散性血管内凝血（DIC）的一个标志，DIC是一种严重的促血栓形成疾病，会导致微血管血栓形成及随后的多器官功能衰竭。在脓毒症模型中，凝血接触途径已被证明在凝血酶生成的起始和放大过程中均发挥作用。凝血接触途径由凝血因子XII（FXII）和XI（FXI）、前激肽释放酶和高分子量激肽原组成。接触途径的激活可通过与阴离子表面结合而触发，如细菌表面大分子上存在的离子化磷酰基和羧基。特别是，FXII已被证明可与细菌包膜的成分结合，包括黏附素、肽聚糖、革兰氏阴性菌的脂多糖以及革兰氏阳性菌的脂磷壁酸。本综述讨论了细菌包膜结构激活接触途径与下游凝血酶生成及与脓毒症诱导的凝血病相关的炎症之间的分子途径。我们强调FXII和FXI作为安全预防脓毒症中DIC的潜在治疗选择的可能性。
