Johansson Pär I, Jacobsen Niels, Viuff Dorthe, Olsen Eva H N, Rojkjaer Rasmus, Andersen Søren, Petersen Lars C, Kjalke Marianne
Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Br J Haematol. 2008 Nov;143(4):559-69. doi: 10.1111/j.1365-2141.2008.07379.x.
The haemostatic effect of recombinant activated factor VII (rFVIIa;NovoSeven) in thrombocytopenic patients has been a matter of controversy. Haemostasis by rFVIIa occurs via FVIIa-mediated thrombin generation in a platelet-dependent manner and may therefore be suboptimal in patients without functional platelets. Under such conditions, a clot-stabilizing agent, such as factor XIII (FXIII), may supplement the effect ofrFVIIa and improve haemostasis. Recombinant factor XIII (rFXIII-A2) is produced as an A2 homodimer of the FXIII A subunit and is equivalent to cellular FXIII normally found in platelets. The combined effects of rFVIIa andrFXIII-A2 were evaluated in clot lysis assays using factor XIII-deficient plasma and by whole blood thrombelastography (TEG) analysis from normal donors and thrombocytopenic stem cell transplantation patients. Clotting time was shortened by rFVIIa (0.6-10 microg/ml). rFVIIa only modestly improved anti-fibrinolysis,whereas rFXIII-A2 (0-20 microg/ml) enhanced anti-fibrinolysis without effect on clotting time. TEG analysis showed rFVIIa shortened the clotting time, and enhanced clot development, maximal mechanical strength and resistance to fibrinolysis, whereas, rFXIII-A2 enhanced clot development,maximal mechanical strength and markedly enhanced resistance to fibrinolysis. These data illustrate that rFVIIa and rFXIII-A2 contribute to clot formation and stability by different mechanisms suggesting enhanced haemostatic efficacy by combining these agents.
重组活化凝血因子 VII（rFVIIa；诺其）在血小板减少患者中的止血作用一直存在争议。rFVIIa 通过 FVIIa 介导的凝血酶生成以依赖血小板的方式实现止血，因此在没有功能性血小板的患者中可能效果欠佳。在这种情况下，一种凝块稳定剂，如凝血因子 XIII（FXIII），可能会补充 rFVIIa 的作用并改善止血效果。重组凝血因子 XIII（rFXIII-A2）作为 FXIII A 亚基的 A2 同二聚体产生，等同于通常在血小板中发现的细胞 FXIII。使用缺乏凝血因子 XIII 的血浆进行凝块溶解试验，并通过对正常供体和血小板减少的干细胞移植患者进行全血血栓弹力图（TEG）分析，评估了 rFVIIa 和 rFXIII-A2 的联合作用。rFVIIa（0.6 - 10 微克/毫升）可缩短凝血时间。rFVIIa 仅适度改善抗纤维蛋白溶解作用，而 rFXIII-A2（0 - 20 微克/毫升）增强抗纤维蛋白溶解作用且对凝血时间无影响。TEG 分析显示，rFVIIa 缩短了凝血时间，并增强了凝块形成、最大机械强度和抗纤维蛋白溶解能力，而 rFXIII-A2 增强了凝块形成、最大机械强度，并显著增强了抗纤维蛋白溶解能力。这些数据表明，rFVIIa 和 rFXIII-A2 通过不同机制促进凝块形成和稳定，提示联合使用这些药物可增强止血效果。
