TISSEEL Ready to use sSealant
TISSEEL Ready to use sSealant Uses, Dosage, Side Effects, Food Interaction and all others data.
Aprotinin is a protein-based drug that is also known as bovine pancreatic trypsin inhibitor (BPTI). Since it demonstrates the capacity to slow fibrinolysis, it has been employed to reduce bleeding during complex surgery such as heart and liver surgery. For this use, it is typically administered by injection. The goal of using of aprotinin was subsequently to minimize end-organ damage resulting from hypotension due to blood loss in surgery and to reduce the necessity for blood transfusions during surgery. Nevertheless, the drug was formally withdrawn worldwide in May of 2008 after studies confirmed that its use enhanced the risk of complications or death. The substance is consequently made available only for very restricted research use.
Aprotinin is a broad spectrum protease inhibitor which modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery. SIR results in the interrelated activation of the hemostatic, fibrinolytic, cellular and humoral inflammatory systems. Aprotinin, through its inhibition of multiple mediators [e.g., kallikrein, plasmin] results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa), while in granulocytes it prevents the expression of pro-inflammatory adhesive glycoproteins (e.g., CD11b). The effects of aprotinin use in CPB involves a reduction in inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding.
Calcium chloride is an ionic compound of calcium and chlorine. It is highly soluble in water and it is deliquescent. It is a salt that is solid at room temperature, and it behaves as a typical ionic halide. It has several common applications such as brine for refrigeration plants, ice and dust control on roads, and in cement. It can be produced directly from limestone, but large amounts are also produced as a by-product of the Solvay process. Because of its hygroscopic nature, it must be kept in tightly-sealed containers.
Calcium is the fifth most abundant element in the body and the major fraction is in the bony structure. Calcium plays important physiological roles, many of which are poorly understood. It is essential for the functional integrity of the nervous and muscular systems. It is necessary for normal cardiac function and is one of the factors that operates in the mechanisms involved in the coagulation of blood.
Human thrombin is a sterile solution, pH 6.8-7.2, containing highly purified human thrombin for the activation of clotting. Thrombin is a highly specific serine protease encoded by the F2 gene that transforms soluble fibrinogen into insoluble fibrin. This transformation mimics the final coagulation cascade step which involves the clotting mass that adheres to the wound surface and achieves hemostasis and sealing of open tissues.
In particular, while human thrombin products are made from pooled human source plasma, recombinant thrombin is a human coagulation protein produced via recombinant DNA technology from a genetically modified Chinese hamster ovary cell line . Furthermore, human thrombin is manufactured by chromatographic purification of prothrombin from cryo-poor plasma followed by activation with calcium chloride .
Clinical pharmacodynamic studies with human thrombin have not been performed at this time .
| Trade Name | TISSEEL Ready to use sSealant |
| Generic | human fibrinogen + human thrombin + aprotinin + calcium chloride |
| Type | |
| Therapeutic Class | |
| Manufacturer | Baxter Healthcare Ltd |
| Available Country | United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Aprotinin is a serine protease inhibitor used to reduce the risk for perioperative blood loss and the need for blood transfusion in high-risk patients during cardiopulmonary bypass for coronary artery bypass graft surgery.
For prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion.
Calcium chloride is an ionic compound used for the treatment of hypocalcemia and hyperkalemia, and as an antidote to magnesium intoxication due to overdosage of magnesium sulfate.
For the treatment of hypocalcemia in those conditions requiring a prompt increase in blood plasma calcium levels, for the treatment of magnesium intoxication due to overdosage of magnesium sulfate, and used to combat the deleterious effects of hyperkalemia as measured by electrocardiographic (ECG), pending correction of the increased potassium level in the extracellular fluid.
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 Ready to use sSealant is also used to associated treatment for these conditions: Wound Healing, Maintenance of surgical hemostasis therapyAcute Renal Failure (ARF), Chronic Renal Failure (CRF), Dehydration, Dehydration Hypertonic, Dry Mouth, Electrolyte depletion, End-stage Chronic Kidney Failure, Fluid Loss, Hyperkalemia, Hypocalcemia, Hypocalcemic tetany, Hypovolaemia, Isotonic Dehydration, Shock, Hypovolemic, Beta blocker overdose, Calcium channel blocker overdose, Continuous Renal Replacement Therapy, Electrolyte replacement, Haemodiafiltration, Hemodialysis Treatment, Hemofiltration, Irrigation therapy, Parenteral Nutrition, Peritoneal dialysis therapy, Plasma Volume Replacement, Urine alkalinization therapy, Distension of the joints, Extraocular irrigation, Fluid and electrolyte maintenance therapy, Induction of cardiac arrest, Irrigation of the jointsBleeding, Suture rupture, Myringoplasty
How TISSEEL Ready to use sSealant works
Aprotinin inhibits serine proteases including trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/mL, and kallikrein at 300,000 IU/mL. The inhibition of kallikrein inhibits formation of factor XIIa. This inhibits the intrinsic pathway of coagulation and fibrinolysis. Inhibition of plasmin also slows fibrinolysis.
Calcium chloride in water dissociates to provide calcium (Ca2+) and chloride (Cl-) ions. They are normal constituents of the body fluids and are dependent on various physiological mechanisms for maintenance of balance between intake and output. For hyperkalemia, the influx of calcium helps restore the normal gradient between threshold potential and resting membrane potential.
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
Too rapid injection may produce lowering of blood pressure and cardiac syncope. Persistent hypercalcemia from overdosage of calcium is unlikely because of rapid excretion.
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
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
100% (IV)
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
Following this distribution phase, a plasma half-life of about 150 minutes is observed. At later time points, (i.e., beyond 5 hours after dosing) there is a terminal elimination phase with a half-life of about 10 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
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
Following a single IV dose of radiolabelled aprotinin, approximately 25-40% of the radioactivity is excreted in the urine over 48 hours. After a 30 minute infusion of 1 million KIU, about 2% is excreted as unchanged drug. After a larger dose of 2 million KIU infused over 30 minutes, urinary excretion of unchanged aprotinin accounts for approximately 9% of the dose.
Approximately 80% of body calcium is excreted in the feces as insoluble salts; urinary excretion accounts for the remaining 20%.
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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