Prof. Dr Gerhard Dickneite, Preclinical R&D, CSL Behring, PO Box 1230, 35002 Marburg, Germany, Tel.: +49 6421 392306, Fax: +49 6421 394663, E-mail:
Thromb Haemost. 2015 Apr;113(4):686-97. doi: 10.1160/TH14-07-0625. Epub 2015 Feb 5.
Coagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of α2-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and αvβ3 integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and neovascularisation. Under infectious disease conditions, FXIII cross-links bacterial surface proteins to fibrinogen, resulting in immobilisation and killing, while during wound healing, FXIII induces cross-linking of the provisional matrix. The latter process has been shown to influence the interaction of leukocytes with the provisional extracellular matrix and promote wound healing. Through these actions, there are good rationales for evaluating the therapeutic potential of FXIII in diseases in which tissue repair is dysregulated or perturbed, including systemic sclerosis (scleroderma), invasive bacterial infections, and tissue repair, for instance healing of venous leg ulcers or myocardial injuries. Adequate levels of FXIII are also required in patients undergoing surgery to prevent or treat perioperative bleeding, and its augmentation in patients with/at risk for perioperative bleeding may also have potential clinical benefit. While there are preclinical and/or clinical data to support the use of FXIII in a range of settings, further clinical evaluation in these underexplored applications is warranted.
凝血因子 XIII（FXIII），一种血浆转谷氨酰胺酶，最广为人知的是作为凝血级联反应的最后一种酶，在该反应中它负责纤维蛋白的交联。然而，越来越多的证据表明，FXIII 靶向广泛的其他底物，这些底物在健康和疾病中具有重要作用。这些底物包括抗纤维蛋白溶酶蛋白，α2-抗纤溶酶与纤维蛋白交联，以及潜在的纤维蛋白原，是纤溶酶介导的血凝块降解最小化的主要机制。FXIII 还作用于血管内皮细胞 VEGFR-2 和 αvβ3 整合素，最终导致抗血管生成蛋白血栓调节蛋白-1 的下调，促进血管生成和新生血管形成。在传染病条件下，FXIII 将细菌表面蛋白交联到纤维蛋白原上，导致细菌被固定和杀死，而在伤口愈合过程中，FXIII 诱导临时基质的交联。已经表明，这一过程会影响白细胞与临时细胞外基质的相互作用，并促进伤口愈合。通过这些作用，在组织修复失调或受损的疾病中评估 FXIII 的治疗潜力是有充分理由的，包括系统性硬化症（硬皮病）、侵袭性细菌感染和组织修复，例如静脉性腿部溃疡或心肌损伤的愈合。在接受手术的患者中，需要足够水平的 FXIII 以预防或治疗围手术期出血，并且在围手术期出血的患者或有出血风险的患者中增加 FXIII 也可能具有潜在的临床益处。虽然有临床前和/或临床数据支持 FXIII 在多种情况下的应用，但在这些探索不足的应用中进一步的临床评估是必要的。
