Tisseel Fibrin Sealant

Uses

Fibrinogen human is a hemostatic agent used for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.

For the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.

Human thrombin is a platelet activating factor used to treat minor bleeding.

Human thrombin is indicated as an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules are accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical .

Tisseel Fibrin Sealant is also used to associated treatment for these conditions: Bleeding, Dura Mater Nick Cut or Tear, Surgical Bleeding, Acute bleeding episodes, Mild Bleeding, Moderate Bleeding, Tissue Adhesions, Maintenance of surgical hemostasis therapyBleeding, Suture rupture, Myringoplasty

How Tisseel Fibrin Sealant works

Fibrinogen (factor I) is a soluble plasma glycoprotein with a molecular weight of about 340 kDa. The native molecule is a dimer and consists of three pairs of polypeptide chains (Aα, Bβ and γ). Fibrinogen is a physiological substrate of three enzymes: thrombin, factor XIIIa, and plasmin. During the coagulation process, thrombin cleaves the Aα and Bβ chains releasing fibrinopeptides A and B (FPA and FPB, respectively). FPA is separated rapidly and the remaining molecule is a soluble fibrin monomer (fibrin I). The slower removal of FPB results in formation of fibrin II that is capable of polymerization that occurs by aggregation of fibrin monomers. The resulting fibrin is stabilized in the presence of calcium ions and by activated factor XIII, which acts as a transglutaminase. Factor XIIIa-induced cross-linking of fibrin polymers renders the fibrin clot more elastic and more resistant to fibrinolysis. Cross-linked fibrin is the end result of the coagulation cascade, and provides tensile strength to a primary hemostatic platelet plug and structure to the vessel wall.

Human thrombin (coagulation factor IIa) is a highly specific protease that transforms plasma fibrinogen into fibrin which, in the presence of clotting factor XIII in the patient's plasma, is cross-linked to form a stable clot . When applied to a surgical wound where bleeding is present, thrombin activates fibrinogen in the patient's plasma to form fibrin, which results in clot formation and hemostasis . The fibrin clot is stabilized by cross-linking occurring as a result of activation of the patient's endogenous factor XIII, which requires the presence of calcium .

Human thrombin does not require any intermediate physiological agent because it naturally clots the fibrinogen of the blood directly . Any failure to clot blood occurs in the rare case where the primary clotting defect is the absence of fibrinogen itself . The speed with which human thrombin clots blood is dependent upon the concentration of both the human thrombin used and fibrinogen present .

Toxicity

No cases of overdose have been reported at this time . The LD50 value for the mouse model is calculated to be approximately 3 gm/kg .

Volume of Distribution

Mean volume of distribution is 52.7 mL/kg.

Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Precisely because human thrombin is applied only topically, systemic exposure or distribution to other organs and tissues is not expected .

Elimination Route

Cmax is 140 mg/dL

Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Particularly because the agent is topical, systemic absorption is expected to be small .

Half Life

78.7 hours

Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted .

Clearance

0.59 mL/h/kg

Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted .

Regardless, commercial human thrombin, like endogenous thrombin, is generally rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation .

Elimination Route

Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted .

Nevertheless, commercial human thrombin products are expected to act in much the same way as endogenous thrombin does. Natural bodily thrombin is cleared by two primary separate pathways: (1) through rapid formation of thrombin inhibitor complexes, which are recognized by hepatic receptors and degraded, and (2) via direct binding to thrombomodulin on the endothelium, followed by internalization and degradation . Specific thrombin inhibitors include ATIII, alpha-2M and heparin cofactor II .

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