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| Primary information |
|---|
| ID | 13269 |
| Therapeutic ID | Th1392 |
| Protein Name | Thrombin |
| Sequence | >Th1392_Thrombin
MARVRGPRLPGCLALAALFSLVHSQHVFLAHQQASSLLQRARRANKGFLEEVRKGNLERECLEEPCSREEAFEALESLSATDAFWAKYTACESARNPREKLNECLEGNCAEGVGMNYRGNVSVTRSGIECQLWRSRYPHKPEINSTTHPGADLRENFCRNPDGSITGPWCYTTSPTLRREECSVPVCGQDRVTVEVIPRSGGSTTSQSPLLETCVPDRGREYRGRLAVTTSGSRCLAWSSEQAKALSKDQDFNPAVPLAENFCRNPDGDEEGAWCYVADQPGDFEYCDLNYCEEPVDGDLGDRLGEDPDPDAAIEGRTSEDHFQPFFNEKTFGAGEADCGLRPLFEKKQVQDQTEKELFESYIEGRIVEGQDAEVGLSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTVDDLLVRIGKHSRTRYERKVEKISMLDKIYIHPRYNWKENLDRDIALLKLKRPIELSDYIHPVCLPDKQTAAKLLHAGFKGRVTGWGNRRETWTTSVAEVQPSVLQVVNLPLVERPVCKASTRIRITDNMFCAGYKPGEGKRGDACEGDSGGPFVMKSPYNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDRLGS
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| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Unfortunately, little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155]. |
| Description | Also known as coagulation factor II, thrombin is a serine protease that plays a physiological role in regulating hemostasis and maintaining blood coagulation. Once converted from prothrombin, thrombin converts fibrinogen to fibrin, which, in combination with platelets from the blood, forms a clot. Medical thrombin is a protein substance produced through a conversion reaction in which prothrombin of bovine origin is activated by tissue thromboplastin in the presence of calcium chloride. Thrombin requires no intermediate physiological agent for its action. It clots the fibrinogen of the blood directly. Failure to clot blood occurs in the rare case where the primary clotting defect is the absence of fibrinogen itself. Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis [FDA Label]. This thrombosis may result from the development of antibodies against bovine thrombin [FDA Label]. Bleeding may result from the development of antibodies against bovine factor V [FDA Label]. These antibodies may subsequently cross-react with endogenous human factor V and lead to its deficiency [FDA Label]. Patients who are know or suspected to have antibodies to bovine thrombin and/or bovine factor V should not be re-exposed to the product [FDA Label]. Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis [FDA Label]. A variety of human thrombin and recombinant thrombin (ie. thrombin alfa) products are available as alternatives to using bovine thrombin. |
| Indication/Disease | Bovine thrombin 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 (like suture, ligature, or cautery) is ineffective or impractical [FDA Label]. Additionally, topical bovine thrombin can also be used in combination with an absorbable gelatin sponge, USP [FDA Label]. |
| Pharmacodynamics | Little has been reported about the systemic pharmacodynamics and pharmacokinetics of bovine thrombin preparations [T155], but it is expected that bovine thrombin elicits similar activities as endogenous thrombin. Subsequently, it is believed that bovine thrombin, like endogenous 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, factor XIIIa catalyzes covalent bonds between lysine and glutamine residues that are 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 | Bovine thrombin requires no intermediate physiological agent for its action [FDA Label]. It activates platelets and catalyzes the conversion of fibrinogen to fibrin, which are essential steps for clot formation [FDA Label]. Failure to clot blood occurs in the case where the primary clotting defect is the absence of fibrinogen itself [FDA Label]. The speed with which the bovine thrombin clots blood is dependent upon the concentration of both the bovine thrombin and the fibrinogen present [FDA Label]. |
| Toxicity | With regards to bovine thrombin, no cases of overdose have been reported so far [T155]. Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis [FDA Label]. This thrombosis may result from the development of antibodies against bovine thrombin [FDA Label]. Bleeding may result from the development of antibodies against bovine factor V [FDA Label]. These antibodies may subsequently cross-react with endogenous human factor V and lead to its deficiency [FDA Label]. Patients who are know or suspected to have antibodies to bovine thrombin and/or bovine factor V should not be re-exposed to the product [FDA Label]. Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis [FDA Label]. LD50 values are available for rat and mouse models where rat subcutaneous LD50 > 40mg/kg, rat IP LD50 > 40mg/kg, and mouse subcutaneous LD50 > 50 mg/kg (in which the greater than symbol indicates that the toxicity endpoint being tested was not achievable at the highest dose used in the test) [MSDS]. Regardless, the most common adverse reactions following administration of bovine thrombin include hypersensitivity, bleeding, anemia, post-operative wound infection, thromboembolic events, hypotension, pyrexia, tachycardia, and/or thrombocytopenia [FDA Label]. |
| Metabolism | Although little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], such products are expected to be metabolized in the same way as endogenous thrombin is. Endogenous thrombin does not circulate in the blood as a free, active molecule for very long [L2079]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [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 [L2079]. |
| Absorption | Little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], but owing to its topical mode of administration, it is expected that any kind of systemic absorption would be minimal. |
| Little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], but owing to its topical mode of application, systemic exposure or distribution to other organs and tissues is not expected. |
| Clearance | Although little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], it is expected that they are generally 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 | Enzymes and Coenzymes |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Proteinase-activated receptor 1,Proteinase-activated receptor 4,Coagulation factor XI,Coagulation factor XIII A chain,Coagulation factor XIII B chain,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain,Coagulation factor V,Coagulation factor VIII |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | 7-iminophenothiazin-3-amine;hydrochloride |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |