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Identification
- Summary
Human thrombin is a platelet activating factor used to treat minor bleeding.
- Brand Names
- Artiss, Evarrest, Evicel, Evithrom, Tachosil, Tisseel, Vistaseal
- Generic Name
- Human thrombin
- DrugBank Accession Number
- DB11571
- Background
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 Label. Furthermore, human thrombin is manufactured by chromatographic purification of prothrombin from cryo-poor plasma followed by activation with calcium chloride Label.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Blood factors - Protein Structure
- Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
>sp|P00734|THRB_HUMAN Prothrombin OS=Homo sapiens OX=9606 GN=F2 PE=1 SV=2 MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLEREC VEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHV NITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQE CSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASA QAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETG DGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYI DGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTEN DLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHP VCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDST RIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKY GFYTHVFRLKKWIQKVIDQFGE
Download FASTA Format- Synonyms
- Thrombin (human)
- Thrombin human
- Thrombin Human Plasma-derived
- Trombina humana
Pharmacology
- Indication
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.
In combination with fibrinogen, it is used indicated as an adjunct to hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical.4,5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used as adjunct in combination to manage Bleeding Combination Product in combination with: Fibrinogen human (DB09222) •••••••••••• ••••• •••••••••• •••••••• •• •••••••••••• ••••••• ••••• Used as adjunct in combination to manage Bleeding Combination Product in combination with: Fibrinogen human (DB09222) •••••••••••• •••••••••• •••••••• •• •••••••••••• ••••••• ••••• Used as adjunct in combination to manage Bleeding Combination Product in combination with: Fibrinogen human (DB09222) •••••••••••• •••••••••• •••••••• •• •••••••••••• ••••••• ••••• Adjunct therapy in prevention of Bleeding •••••••••••• Used in combination for prophylaxis of Suture rupture Combination Product in combination with: Aprotinin (DB06692), Calcium chloride (DB01164), Fibrinogen human (DB09222) •••••••••••• ••••••••••••••••••••••• ••••••• •• •••••••• •••• •••••••• •••••••• •••••••••• •••• ••••••• ••••••••• ••• ••••••• •••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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Clinical pharmacodynamic studies with human thrombin have not been performed at this time Label.
Regardless, commercial human thrombin products are expected to demonstrate activity that is identical to thrombin found endogenously in the body. 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 2. 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 2. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets 2.
- Mechanism of action
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 Label. 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 Label. 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 Label.
Human thrombin does not require any intermediate physiological agent because it naturally clots the fibrinogen of the blood directly Label. Any failure to clot blood occurs in the rare case where the primary clotting defect is the absence of fibrinogen itself Label. The speed with which human thrombin clots blood is dependent upon the concentration of both the human thrombin used and fibrinogen present Label.
Target Actions Organism ACoagulation factor V activatorHumans ACoagulation factor VIII activatorHumans ACoagulation factor XI activatorHumans ACoagulation factor XIII A chain activatorHumans ACoagulation factor XIII B chain activatorHumans AFibrinogen alpha chain activatorHumans AFibrinogen beta chain activatorHumans AFibrinogen gamma chain activatorHumans - Absorption
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 Label. Particularly because the agent is topical, systemic absorption is expected to be small 1.
- 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 Label. Precisely because human thrombin is applied only topically, systemic exposure or distribution to other organs and tissues is not expected 1.
- Protein binding
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 Label. Protein binding data is subsequently not readily available, although human thrombin functions naturally to interact with a very specific set of clotting factors.
- Metabolism
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 Label.
Nevertheless, commercial human thrombin 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 3. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) 3. 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 3.
- Route of elimination
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 Label.
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 3. Specific thrombin inhibitors include ATIII, alpha-2M and heparin cofactor II 3.
- Half-life
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 Label.
- 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 Label.
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 3.
- Adverse Effects
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No cases of overdose have been reported at this time Label. The LD50 value for the mouse model is calculated to be approximately 3 gm/kg MSDS.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Evithrom Liquid 1000 [iU]/1mL Topical Ethicon Inc 2007-10-27 Not applicable US 
Thrombin Human Powder, for solution 2000 [iU]/2mL Topical Ethicon, Inc 2009-09-19 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Artiss Human thrombin (4 unit / mL) + Aprotinin (3000 kiu / mL) + Calcium chloride (40 mcmol / mL) + Fibrinogen human (125 mg / mL) Solution Topical Baxter Laboratories 2011-12-18 Not applicable Canada 
Artiss Human thrombin (4 [iU]/1mL) + Fibrinogen human (90 mg/1mL) Kit Topical Baxalta US Inc. 2008-03-21 2008-03-21 US ARTISS Fibrin Sealant Human thrombin (4 [iU]/1mL) + Fibrinogen human (86.5 mg/1mL) Solution Topical Baxter Healthcare Corporation 2008-03-19 Not applicable US ARTISS Fibrin Sealant Human thrombin (4 [iU]/1mL) + Fibrinogen human (86.5 mg/1mL) Solution Topical Baxter Healthcare Corporation 2008-03-19 Not applicable US ARTISS Fibrin Sealant Human thrombin (4 [iU]/1mL) + Fibrinogen human (86.5 mg/1mL) Solution Topical Baxter Healthcare Corporation 2008-03-19 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6K15ABL77G
- CAS number
- 9002-04-4
References
- General References
- Mandell SP, Gibran NS: Fibrin sealants: surgical hemostat, sealant and adhesive. Expert Opin Biol Ther. 2014 Jun;14(6):821-30. doi: 10.1517/14712598.2014.897323. Epub 2014 Mar 13. [Article]
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- EMEA European Medicines Agency Withdrawal Assessment Report for Recothrom (thrombin alpha) [Link]
- DailyMed Label: VISTASEAL (human fibrinogen, human thrombin) kit, for topical use [Link]
- FDA Approved Drug Products: EVITHROM (Human Thrombin), for topical use [Link]
- External Links
- FDA label
- Download (1.38 MB)
- MSDS
- Download (25.9 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Prevention Osteoarthritis (OA) 1 somestatus stop reason just information to hide 4 Completed Prevention Osteoarthritis of the Knee 1 somestatus stop reason just information to hide 4 Completed Prevention Prostate or Bladder Cancer 1 somestatus stop reason just information to hide 4 Completed Treatment Aspiration / Breast Cancer / Seroma 1 somestatus stop reason just information to hide 4 Completed Treatment Bloodloss 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Topical Solution Topical 360 - Solution Other 70 mg/ml Solution Intralesional; Irrigation Liquid Topical 1000 [iU]/1mL Injection, powder, lyophilized, for solution Intralesional 2500 IU Powder Topical Patch Topical Sponge Topical Powder, for solution Topical 2000 [iU]/2mL Injection, powder, lyophilized, for solution Topical 1000 IU Kit Topical Kit; powder, for solution Topical Kit; solution Topical - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin
- Specific Function
- Copper ion binding
- Gene Name
- F5
- Uniprot ID
- P12259
- Uniprot Name
- Coagulation factor V
- Molecular Weight
- 251701.245 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa
- Specific Function
- Copper ion binding
- Gene Name
- F8
- Uniprot ID
- P00451
- Uniprot Name
- Coagulation factor VIII
- Molecular Weight
- 267007.42 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX
- Specific Function
- Heparin binding
- Gene Name
- F11
- Uniprot ID
- P03951
- Uniprot Name
- Coagulation factor XI
- Molecular Weight
- 70108.56 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- Oliver JA, Monroe DM, Roberts HR, Hoffman M: Thrombin activates factor XI on activated platelets in the absence of factor XII. Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):170-7. doi: 10.1161/01.atv.19.1.170. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin
- Specific Function
- Metal ion binding
- Gene Name
- F13A1
- Uniprot ID
- P00488
- Uniprot Name
- Coagulation factor XIII A chain
- Molecular Weight
- 83267.785 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- The B chain of factor XIII is not catalytically active, but is thought to stabilize the A subunits and regulate the rate of transglutaminase formation by thrombin
- Specific Function
- Not Available
- Gene Name
- F13B
- Uniprot ID
- P05160
- Uniprot Name
- Coagulation factor XIII B chain
- Molecular Weight
- 75510.1 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways
- Specific Function
- Extracellular matrix structural constituent
- Gene Name
- FGA
- Uniprot ID
- P02671
- Uniprot Name
- Fibrinogen alpha chain
- Molecular Weight
- 94972.455 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the antibacterial immune response via both innate and T-cell mediated pathways
- Specific Function
- Extracellular matrix structural constituent
- Gene Name
- FGB
- Uniprot ID
- P02675
- Uniprot Name
- Fibrinogen beta chain
- Molecular Weight
- 55927.9 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the antibacterial immune response via both innate and T-cell mediated pathways
- Specific Function
- Cell adhesion molecule binding
- Gene Name
- FGG
- Uniprot ID
- P02679
- Uniprot Name
- Fibrinogen gamma chain
- Molecular Weight
- 51511.29 Da
References
- Crawley JT, Zanardelli S, Chion CK, Lane DA: The central role of thrombin in hemostasis. J Thromb Haemost. 2007 Jul;5 Suppl 1:95-101. doi: 10.1111/j.1538-7836.2007.02500.x. [Article]
Drug created at April 06, 2016 21:53 / Updated at March 17, 2022 22:25