靶向止血酶：从机制洞察到治疗前沿
Targeting hemostatic enzymes: from mechanistic insights to therapeutic frontiers.
作者信息
Zakar Rida, Neal Matthew D, Shea Susan M
机构信息
Trauma and Transfusion Medicine Research Center, Department of Surgery.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
出版信息
Curr Opin Hematol. 2025 Jul 15. doi: 10.1097/MOH.0000000000000884.
PURPOSE OF REVIEW
This review examines the enzymatic regulation of coagulation and fibrinolysis, focusing on key players such as thrombin, plasmin, and ADAMTS13. We highlight how dysregulation of these enzymes contributes to thrombotic and hemorrhagic disorders and review emerging diagnostic biomarkers and therapeutic strategies.
RECENT FINDINGS
Recent studies demonstrate the prognostic utility of biomarkers such as thrombin-antithrombin (TAT) and plasmin-α2-antiplasmin (PAP) complexes across critical illnesses including trauma, sepsis, and stroke. Advances in plasmin and thrombin generation assays, enzyme-specific assays, and enzyme-modulating therapies (e.g., factor XI inhibitors and recombinant ADAMTS13) are reshaping approaches to hemostatic balance.
SUMMARY
Understanding hemostatic enzymatic regulation offers new avenues for risk stratification, diagnosis, and treatment of coagulation disorders. Although significant progress has been made, challenges remain in translating laboratory findings to clinical practice, necessitating further large-scale validation. Precision-guided enzymatic therapies hold promise for improving outcomes in acute care settings.
综述目的
本综述探讨凝血和纤维蛋白溶解的酶促调节，重点关注凝血酶、纤溶酶和ADAMTS13等关键因子。我们强调这些酶的失调如何导致血栓形成和出血性疾病，并综述新兴的诊断生物标志物和治疗策略。
最新发现
最近的研究表明，凝血酶 - 抗凝血酶（TAT）和纤溶酶 - α2 - 抗纤溶酶（PAP）复合物等生物标志物在包括创伤、脓毒症和中风在内的危重症中具有预后价值。纤溶酶和凝血酶生成检测、酶特异性检测以及酶调节疗法（如因子XI抑制剂和重组ADAMTS13）的进展正在重塑止血平衡的方法。
总结
了解止血酶促调节为凝血障碍的风险分层、诊断和治疗提供了新途径。尽管已取得重大进展，但将实验室研究结果转化为临床实践仍面临挑战，需要进一步大规模验证。精准导向的酶促疗法有望改善急性护理环境中的治疗效果。
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