Tisseel Mechanism of Action

Pharmacotherapeutic group: Local hemostatics. ATC code: B02BC. Tissue adhesives. ATC code: V03AK.
Pharmacology: Pharmacodynamics: The fibrin adhesion system imitates the last phase of physiological blood coagulation.
Conversion of fibrinogen into fibrin occurs by the splitting of fibrinogen into fibrin monomers and fibrinopeptides. The fibrin monomers aggregate and form a fibrin clot. Factor XIIIa, which is generated from Factor XIII by the concerted action of thrombin and calcium ions, stabilizes the clot by the cross-linking of fibrin fibres.
As wound healing progresses, increased fibrinolytic activity is induced by plasmin, and decomposition of fibrin to fibrin degradation products is initiated. Proteolytic degradation of fibrin is inhibited by anti-fibrinolytics. Aprotinin is present in TISSEEL Fibrin Sealant with Synthetic Aprotinin as an antifibrinolytic to prevent premature degradation of the clot.
To prove the efficacy, in vivo studies with four animal models which imitated the patient situation as closely as possible, were carried out. TISSEEL Fibrin Sealant with Synthetic Aprotinin was effective with regard to primary and secondary hemostasis as well as wound healing.
Clinical studies demonstrating hemostasis and suture support were conducted in a total of 213 patients (120 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 93 with control) undergoing vascular surgery with ePTFE conduits, in a total of 70 patients (35 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 35 with control) undergoing partial hepatic resection and in a total of 317 patients (157 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 160 with a predecessor single virus inactivated form of the product as control) undergoing cardiac surgery with a cardiopulmonary bypass and median sternotomy.
Efficacy of TISSEEL Fibrin Sealant with Synthetic Aprotinin as an adjunct to conventional surgical methods in sealing colonic anastomoses in trauma patients undergoing closure of temporary colostomies has been demonstrated in a randomized, controlled, prospective, single-center study conducted in 1986 in a total of 120 patients (61 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 59 with control).
Pharmacokinetics: TISSEEL Fibrin Sealant with Synthetic Aprotinin is intended for epilesional use only. Intravascular administration is contraindicated. As a consequence, intravascular pharmacokinetic studies were not performed in man.
Pharmacokinetic studies in different species of laboratory animals were not conducted.
Fibrin sealants/hemostatics are metabolized in the same way as endogenous fibrin by fibrinolysis and phagocytosis.
Toxicology: Preclinical safety data: Due to its nature as well as its special method of application (usually single, only in exceptional cases repeated application of a few mL) and mechanism of action (local efficacy without systemic effect or distribution to other organs and tissues), no preclinical safety data are available for TISSEEL Fibrin Sealant with Synthetic Aprotinin on chronic toxicity, carcinogenicity, reproductive and developmental toxicity or immune stimulation.
Single-dose toxicity studies in rats and rabbits indicated no acute toxicity of TISSEEL Fibrin Sealant with Synthetic Aprotinin. Furthermore, no evidence for mutagenicity could be seen inappropriate in vitro tests. The sealer protein solution was also well tolerated in vitro, in human fibroblast cultures, demonstrating excellent cellular compatibility and non-cytotoxicity. Based on a detailed literature review, any negative influence or toxicity due to residual S/D reagents on TISSEEL Fibrin Sealant with Synthetic Aprotinin can be excluded.