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| Primary information |
|---|
| ID | 13362 |
| Therapeutic ID | Th1398 |
| Protein Name | Thrombin alfa |
| Sequence | >Th1398_Thrombin_alfa
MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE
|
| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. |
| Description | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. |
| Indication/Disease | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. |
| Pharmacodynamics | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. |
| Mechanism of Action | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. |
| Toxicity | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. |
| Metabolism | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. |
| Absorption | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. |
| Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. |
| Clearance | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. |
| Categories | Biological Factors |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain |
| Brand Name | Recothrom |
| Company | Zymo Genetics |
| Brand Description | Zymo Genetics |
| Prescribed For | Topical |
| Chemical Name | 1000 [iU]/1mL |
| Formulation | Do not inject directly into the circulatory system. Do not use for the treatment of massive or brisk arterial bleeding. Do not administer to patients with a history of hypersensitivity to RECOTHROM or any components of RECOTHROM. Do not use in patients with known hypersensitivity to hamster proteins. |
| Physical Appearance | blood clots detaching from their point of origin and moving through the bloodstream (thromboembolic events), and antibody formation. |
| Route of Administration | RECOTHROM, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. |
| Recommended Dosage | RECOTHROM®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |