Identification
- Summary
Thrombin is a coagulation factor used to stop bleeding during surgery.
- Brand Names
- Thrombin-jmi
- Generic Name
- Thrombin
- DrugBank Accession Number
- DB11300
- Background
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 Label. This thrombosis may result from the development of antibodies against bovine thrombin Label. Bleeding may result from the development of antibodies against bovine factor V Label. These antibodies may subsequently cross-react with endogenous human factor V and lead to its deficiency 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 Label. Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis Label.
A variety of human thrombin and recombinant thrombin (ie. thrombin alfa) products are available as alternatives to using bovine thrombin.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Blood factors - Protein Structure
- Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
>sp|P00735|THRB_BOVIN Prothrombin OS=Bos taurus OX=9913 GN=F2 PE=1 SV=2 MARVRGPRLPGCLALAALFSLVHSQHVFLAHQQASSLLQRARRANKGFLEEVRKGNLERE CLEEPCSREEAFEALESLSATDAFWAKYTACESARNPREKLNECLEGNCAEGVGMNYRGN VSVTRSGIECQLWRSRYPHKPEINSTTHPGADLRENFCRNPDGSITGPWCYTTSPTLRRE ECSVPVCGQDRVTVEVIPRSGGSTTSQSPLLETCVPDRGREYRGRLAVTTSGSRCLAWSS EQAKALSKDQDFNPAVPLAENFCRNPDGDEEGAWCYVADQPGDFEYCDLNYCEEPVDGDL GDRLGEDPDPDAAIEGRTSEDHFQPFFNEKTFGAGEADCGLRPLFEKKQVQDQTEKELFE SYIEGRIVEGQDAEVGLSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNF TVDDLLVRIGKHSRTRYERKVEKISMLDKIYIHPRYNWKENLDRDIALLKLKRPIELSDY IHPVCLPDKQTAAKLLHAGFKGRVTGWGNRRETWTTSVAEVQPSVLQVVNLPLVERPVCK ASTRIRITDNMFCAGYKPGEGKRGDACEGDSGGPFVMKSPYNNRWYQMGIVSWGEGCDRD GKYGFYTHVFRLKKWIQKVIDRLGS
Download FASTA Format- Synonyms
- coagulation factor II
- Thrombin
- Thrombin bovine
- Thrombin, Topical (Bovine)
Pharmacology
- Indication
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 Label. Additionally, topical bovine thrombin can also be used in combination with an absorbable gelatin sponge, USP Label.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Refractory to surgical techniques bleeding •••••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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Little has been reported about the systemic pharmacodynamics and pharmacokinetics of bovine thrombin preparations 2, 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 1. 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 1. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets 1.
- Mechanism of action
Bovine thrombin requires no intermediate physiological agent for its action Label. It activates platelets and catalyzes the conversion of fibrinogen to fibrin, which are essential steps for clot formation Label. Failure to clot blood occurs in the case where the primary clotting defect is the absence of fibrinogen itself Label. The speed with which the bovine thrombin clots blood is dependent upon the concentration of both the bovine thrombin and the fibrinogen present Label.
Target Actions Organism 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 ACoagulation factor V activatorHumans ACoagulation factor VIII activatorHumans UProteinase-activated receptor 1 Not Available Humans UProteinase-activated receptor 4 Not Available Humans - Absorption
Little has been reported about the systemic pharmacokinetics of bovine thrombin preparations 2, but owing to its topical mode of administration, it is expected that any kind of systemic absorption would be minimal.
- Volume of distribution
Little has been reported about the systemic pharmacokinetics of bovine thrombin preparations 2, but owing to its topical mode of application, systemic exposure or distribution to other organs and tissues is not expected.
- Protein binding
Little has been reported about the systemic pharmacokinetics of bovine thrombin preparations 2. Protein binding data is subsequently not readily available, although thrombin functions naturally to interact with a very specific set of clotting factors 1.
- Metabolism
Although little has been reported about the systemic pharmacokinetics of bovine thrombin preparations 2, 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 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
Although little has been reported about the systemic pharmacokinetics of bovine thrombin preparations 2, they 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
Unfortunately, little has been reported about the systemic pharmacokinetics of bovine thrombin preparations 2.
- Clearance
Although little has been reported about the systemic pharmacokinetics of bovine thrombin preparations 2, 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 3.
- Adverse Effects
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With regards to bovine thrombin, no cases of overdose have been reported so far 2. Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis Label. This thrombosis may result from the development of antibodies against bovine thrombin Label. Bleeding may result from the development of antibodies against bovine factor V Label. These antibodies may subsequently cross-react with endogenous human factor V and lead to its deficiency 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 Label. Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis 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 Label.
- 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 Thrombin-jmi Kit; Solution 5000 [iU]/5mL Topical Pfizer Laboratories Div Pfizer Inc 1995-02-24 Not applicable US 
Thrombin-jmi Kit; Solution 20000 [iU]/20mL Topical Pfizer Laboratories Div Pfizer Inc 1995-02-24 Not applicable US Thrombin-jmi Kit; Solution 5000 [iU]/5mL Topical Pfizer Laboratories Div Pfizer Inc 1995-02-24 Not applicable US Thrombin-jmi Kit; Solution 5000 [iU]/5mL Topical Pfizer Laboratories Div Pfizer Inc 1995-02-24 Not applicable US Thrombinar Pws 5000unit/vial Powder, for solution 5000 unit / vial Topical Armour Pharmaceutical Co. 1984-12-31 1999-12-15 Canada 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ARTISS - Lösungen für einen Gewebekleber Thrombin (2 IU/ml) + Aprotinin (1500 KIE/ml) + Calcium chloride (20 μmol/ml) + Fibrinogen human (45.5 mg/ml) Solution Topical Baxter Medical Products Gmb H 2009-03-19 Not applicable Austria 
ARTISS 10 ML ÇÖZELTİ İÇEREN KULLANIMA HAZIR ENJEKTOR, 1 ADET Thrombin (4 IU/ml) + Aprotinin (3000 KIU/ml) + Calcium chloride dihydrate (40 mcmol/ml) + Fibrinogen human (91 mg/ml) Solution Topical BAXTER TURKEY RENAL HİZMETLER A.Ş. 2020-08-14 Not applicable Turkey 
ARTISS 2 ML ÇÖZELTİ İÇEREN KULLANIMA HAZIR ENJEKTOR, 1 ADET Thrombin (4 IU/ml) + Aprotinin (3000 KIU/ml) + Calcium chloride dihydrate (40 mcmol/ml) + Fibrinogen human (91 mg/ml) Solution Topical BAXTER TURKEY RENAL HİZMETLER A.Ş. 2020-08-14 Not applicable Turkey ARTISS 4 ML ÇÖZELTİ İÇEREN KULLANIMA HAZIR ENJEKTOR, 1 ADET Thrombin (4 IU/ml) + Aprotinin (3000 KIU/ml) + Calcium chloride dihydrate (40 mcmol/ml) + Fibrinogen human (91 mg/ml) Solution Topical BAXTER TURKEY RENAL HİZMETLER A.Ş. 2020-08-14 Not applicable Turkey BERIPLAST-P COMBI SET 1 ML TROMBİN ÇÖZELTİSİ VE 1 ML FİBRİNOJEN ÇÖZELTİSİ İÇEREN FİBRİN YAPIŞTIRICI Thrombin (500 IU/ml) + Antihemophilic factor human (60 IU/ml) + Aprotinin (1000 KIU/ml) + Calcium chloride dihydrate (5.9 mg/ml) + Fibrinogen human (90 mg/ml) Solution CSL BEHRİNG BİYOTERAPİ İLAÇ DIŞ TİC. A.Ş. 2015-08-31 2022-04-15 Turkey
Categories
- ATC Codes
- B02BC06 — Thrombin
- B02BC — Local hemostatics
- B02B — VITAMIN K AND OTHER HEMOSTATICS
- B02 — ANTIHEMORRHAGICS
- B — BLOOD AND BLOOD FORMING ORGANS
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Biological Factors
- Blood and Blood Forming Organs
- Blood Coagulation Factors
- Blood Proteins
- Coagulants
- Endopeptidases
- Enzyme Precursors
- Enzymes
- Enzymes and Coenzymes
- Hematologic Agents
- Hemostatics
- Hydrolases
- Increased Coagulation Factor Activity
- Local Hemostatics
- Peptide Hydrolases
- Protein Precursors
- Proteins
- Prothrombin, agonists
- Serine Endopeptidases
- Serine Proteases
- 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
- 25ADE2236L
- CAS number
- Not Available
References
- General 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]
- Richard C. Dart (2004). Medical Toxicology Third Edition (3rd ed.). Lippincott Williams & Wilkins. [ISBN:0781728452]
- EMEA European Medicines Agency Withdrawal Assessment Report for Recothrom (thrombin alpha) [Link]
- External Links
- FDA label
- Download (51.2 KB)
- MSDS
- Download (36.6 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Prevention Osteoarthritis of the Knee 1 4 Completed Treatment Bloodloss 1 4 Completed Treatment Control of Local Bleeding in Patients Undergoing Prostatectomy 1 4 Unknown Status Prevention Osteoarthritis of the Knee 1 4 Unknown Status Prevention Pancreatic Bordeline Tumor / Pancreatic Neoplasms / Pancreatic Periampullary Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Topical Solution Patch Topical Powder, for solution Topical Sponge Topical Kit; solution Topical 20000 [iU]/20mL Kit; solution Topical 5000 [iU]/5mL Powder Topical 10000 unit / vial Powder Topical 1000 unit / vial Powder, for solution Topical 5000 unit / vial Powder Topical Kit; solution Solution Topical 3000 KIU/ml Powder Soft tissue - 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
- Serine-type endopeptidase activity
- Specific Function
- Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Protein-glutamine gamma-glutamyltransferase activity
- Specific 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 fibr...
- Gene Name
- F13A1
- Uniprot ID
- P00488
- Uniprot Name
- Coagulation factor XIII A chain
- Molecular Weight
- 83266.805 Da
- 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
- Structural molecule activity
- Specific 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 ...
- Gene Name
- FGA
- Uniprot ID
- P02671
- Uniprot Name
- Fibrinogen alpha chain
- Molecular Weight
- 94972.455 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Structural molecule activity
- Specific 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...
- Gene Name
- FGB
- Uniprot ID
- P02675
- Uniprot Name
- Fibrinogen beta chain
- Molecular Weight
- 55927.9 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Structural molecule activity
- Specific 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. I...
- Gene Name
- FGG
- Uniprot ID
- P02679
- Uniprot Name
- Fibrinogen gamma chain
- Molecular Weight
- 51511.29 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Copper ion binding
- Specific 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.
- 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
- Oxidoreductase activity
- Specific Function
- Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
- Gene Name
- F8
- Uniprot ID
- P00451
- Uniprot Name
- Coagulation factor VIII
- Molecular Weight
- 267007.42 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thrombin receptor activity
- Specific Function
- High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation and in vascular development.
- Gene Name
- F2R
- Uniprot ID
- P25116
- Uniprot Name
- Proteinase-activated receptor 1
- Molecular Weight
- 47439.83 Da
References
- Leger AJ, Jacques SL, Badar J, Kaneider NC, Derian CK, Andrade-Gordon P, Covic L, Kuliopulos A: Blocking the protease-activated receptor 1-4 heterodimer in platelet-mediated thrombosis. Circulation. 2006 Mar 7;113(9):1244-54. Epub 2006 Feb 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.
- Specific Function
- G-protein coupled receptor activity
- Gene Name
- F2RL3
- Uniprot ID
- Q96RI0
- Uniprot Name
- Proteinase-activated receptor 4
- Molecular Weight
- 41132.43 Da
References
- Leger AJ, Jacques SL, Badar J, Kaneider NC, Derian CK, Andrade-Gordon P, Covic L, Kuliopulos A: Blocking the protease-activated receptor 1-4 heterodimer in platelet-mediated thrombosis. Circulation. 2006 Mar 7;113(9):1244-54. Epub 2006 Feb 27. [Article]
Drug created at December 03, 2015 16:52 / Updated at May 21, 2021 10:21