Dickneite Gerhard, Metzner Hubert, Pfeifer Thomas, Kroez Monika, Witzke Günther
Pharmacology and Toxicology, Aventis Behring, P.O. Box 1230, D-35002 Marburg, Germany.
Thromb Res. 2003;112(1-2):73-82. doi: 10.1016/j.thromres.2003.10.010.
Fibrin sealants (FS) have been used for many years to facilitate hemostasis and to provide suture support and sealing/adhesion of tissues after surgery. While their composition is similar, different formulations, application devices, and varying concentrations of key components mean that the properties of clots formed by individual FS can be diverse.
We performed several studies, including animal models, to compare the properties of 12 different commercially available FS/application device combinations using partial liver and kidney resection models to assess hemostatic efficacy and a novel pig skin model to measure adhesive clot strength. The quality of mixing was determined using colored spray images.
Although the FS tested shared the principle of combining fibrinogen and thrombin, major differences were found between the individual preparations with regard to hemostatic efficacy. Two pre-requisites for successful early hemostasis were identified--adequate clottable protein content and the ability of the application device to effectively mix the fibrinogen and thrombin components of the FS. Factor XIII activity was a key determinant in prevention of re-bleeding and premature clot lysis. Furthermore, FS lacking measurable factor XIII activity formed the weakest, softest clots.
Clearly, all FS are not the same, and their different characteristics may potentially translate into different clinical outcomes. In our studies, while all FS tested performed well on individual parameters, Beriplast P (Aventis Behring) was the foremost FS in consistently providing early hemostasis, minimizing the risk of re-bleeding, and providing strong adhesive clots capable of resisting mechanical forces.
纤维蛋白密封剂(FS)已使用多年,用于促进止血,并在手术后为组织提供缝合支持以及密封/粘连作用。尽管它们的成分相似,但不同的配方、应用装置以及关键成分的不同浓度意味着各个FS形成的凝块特性可能各不相同。
我们进行了多项研究,包括动物模型研究,以比较12种不同市售FS/应用装置组合的特性,使用部分肝切除和肾切除模型评估止血效果,并使用一种新型猪皮模型测量粘连凝块强度。通过彩色喷雾图像确定混合质量。
尽管所测试的FS都具有将纤维蛋白原和凝血酶混合的原理,但在各个制剂之间,在止血效果方面发现了重大差异。确定了成功早期止血的两个先决条件——足够的可凝蛋白含量以及应用装置有效混合FS中纤维蛋白原和凝血酶成分的能力。因子XIII活性是预防再出血和凝块过早溶解的关键决定因素。此外,缺乏可测量因子XIII活性的FS形成的凝块最弱、最软。
显然,并非所有FS都是相同(等效)的,它们的不同特性可能会转化为不同的临床结果。在我们的研究中,虽然所有测试的FS在各个参数上表现良好,但百林(Beriplast P,安万特贝林公司生产)是始终能提供早期止血、将再出血风险降至最低并提供能够抵抗机械力的强粘连凝块的最佳FS。