Centeno Alberto, Rojas Santiago, Arias Belén, Miquel Ignasi, Sánchez Pilar, Ureta Claudia, Rincón Esther, López Ramón, Murat Jesús
Unit of Experimental Surgery, Institute of Biomedical Investigation of A Coruña, Xubias de Arriba, 84, A Coruña 15006, Spain.
Thombotargets Europe S.L. Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels 08860, Spain.
J Invest Surg. 2020 Apr;33(4):339-349. doi: 10.1080/08941939.2018.1517840. Epub 2018 Oct 31.
: Excessive blood loss is a relevant complication of partial liver resection. Topical hemostatic agents have proven useful to improve the control of the bleeding in this among other surgical indications. Until now all of these products have been based on the action of thrombin. In contrast TT-173 is a new topical hemostatic agent based on recombinant tissue factor naturally incorporated into membrane vesicles. This work sought to assess the efficacy and toxicity of TT-173 in an animal model of liver resection.: Procoagulant activity of 0.15, 0.41, and 1 mg of TT-173 was evaluated in pigs subjected the resection of hepatic lobe margins. The most effective of these doses was also compared against thrombin. In addition, the toxicity, local tolerance, systemic absorption, and immunogenicity of the product were investigated in rats subjected to liver biopsy lesion.: The three doses of TT-173 evaluated significantly reduced the bleeding time in liver lesions. The highest dose of product was significantly more effective than the others and thrombin. Application of high doses of TT-173 in rats did not cause any local or systemic alterations. Absorption into blood stream was negligible and no immunogenic reaction against the product was detected.: TT-173 shows favorable pharmacodynamic properties for improving hemostasis in partial liver resection which support further investigation of the product in this surgical indication.
大量失血是部分肝切除术的一种相关并发症。局部止血剂已被证明在改善此类及其他手术指征中的出血控制方面是有用的。到目前为止,所有这些产品都基于凝血酶的作用。相比之下,TT - 173是一种新型局部止血剂,基于天然掺入膜泡中的重组组织因子。这项研究旨在评估TT - 173在肝切除动物模型中的疗效和毒性。
在接受肝叶边缘切除的猪中评估了0.15、0.41和1毫克TT - 173的促凝血活性。还将这些剂量中最有效的剂量与凝血酶进行了比较。此外,在接受肝活检损伤的大鼠中研究了该产品的毒性、局部耐受性、全身吸收和免疫原性。
评估的三种剂量的TT - 173均显著缩短了肝损伤的出血时间。最高剂量的产品比其他剂量和凝血酶显著更有效。在大鼠中应用高剂量的TT - 173未引起任何局部或全身改变。进入血流的吸收可忽略不计,且未检测到针对该产品的免疫反应。
TT - 173在改善部分肝切除术中的止血方面显示出良好的药效学特性,这支持在该手术指征中对该产品进行进一步研究。