Identification
- Summary
Thrombin alfa is a platelet activating factor used to treat minor bleeding.
- Brand Names
- Recothrom
- Generic Name
- Thrombin alfa
- DrugBank Accession Number
- DB11572
- Background
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 2.
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 2.
- 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
- Human Thrombin (recombinant, glycosylated)
- Thrombin (synthetic human)
- Thrombin alfa
Pharmacology
- Indication
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 Label.
Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP Label.
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- Contraindications & Blackbox Warnings
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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 2.
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 1. 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 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
Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding 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 Label,2. 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 Label,2.
Target Actions Organism ACoagulation factor V activatorHumans ACoagulation factor VIII activatorHumans AFibrinogen alpha chain activatorHumans AFibrinogen beta chain activatorHumans AFibrinogen gamma chain activatorHumans - Absorption
Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa 2.
Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys 2.
- Volume of distribution
Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa 2. Volume of distribution data is subsequently not readily available.
- Protein binding
Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa 2. Protein binding data is subsequently not readily available, although thrombin alfa functions predominantly to interact with a very specific set of clotting factors - a function that endogenous thrombin (of which thrombin alfa is a recombinant replica of) is naturally designed to perform.
- Metabolism
Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long Label. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) Label,2. 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 Label,2.
- Route of elimination
Thrombin alfa, like endogenous 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 2. Specific thrombin inhibitors include ATIII, alpha-2M and heparin cofactor II 2.
- Half-life
Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) 2. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours 2. This data follows administration of thrombin alfa to cynomolgus monkeys.
- Clearance
Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa 2. 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 2.
- Adverse Effects
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Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa 2. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring 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 Recothrom Kit 1000 [iU]/1mL Topical Zymo Genetics 2008-01-29 2016-11-30 US 
Recothrom Powder, for solution 24000 unit / vial Topical Baxter Laboratories Not applicable Not applicable Canada 
Recothrom Kit; Powder, for solution 1000 [iU]/1mL Topical Baxter Healthcare Corporation 2008-06-09 Not applicable US Recothrom Kit 1000 [iU]/1mL Topical The Medicines Company 2008-06-09 Not applicable US Recothrom Kit 1000 [iU]/1mL Topical Mallinckrodt Hospital Products Inc. 2008-06-09 2019-09-21 US Recothrom Kit; Powder, for solution 1000 [iU]/1mL Topical Baxter Healthcare Corporation 2008-06-09 Not applicable US Recothrom Kit 1000 [iU]/1mL Topical Zymo Genetics 2008-06-09 2015-08-30 US Recothrom Powder, for solution 6000 unit / vial Topical Baxter Laboratories 2010-03-24 Not applicable Canada Recothrom Kit 1000 [iU]/1mL Topical Mallinckrodt Hospital Products Inc. 2008-01-29 2019-09-21 US Recothrom Kit 1000 [iU]/1mL Topical The Medicines Company 2008-01-29 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
- SCK81AMR7R
- CAS number
- 869858-13-9
References
- General References
- External Links
- FDA label
- Download (201 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit Topical 1000 [iU]/1mL Kit; powder, for solution Topical 1000 [iU]/1mL Powder, for solution Topical 24000 unit / vial Powder, for solution Topical 6000 unit / vial - 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
- 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
- Ustinov NB, Zav'yalova EG, Kopylov AM: Effect of Thrombin Inhibitors on Positive Feedback in the Coagulation Cascade. Biochemistry (Mosc). 2016 Mar;81(3):242-8. doi: 10.1134/S0006297916030068. [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
References
- Ustinov NB, Zav'yalova EG, Kopylov AM: Effect of Thrombin Inhibitors on Positive Feedback in the Coagulation Cascade. Biochemistry (Mosc). 2016 Mar;81(3):242-8. doi: 10.1134/S0006297916030068. [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
References
- Ustinov NB, Zav'yalova EG, Kopylov AM: Effect of Thrombin Inhibitors on Positive Feedback in the Coagulation Cascade. Biochemistry (Mosc). 2016 Mar;81(3):242-8. doi: 10.1134/S0006297916030068. [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 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
References
- Ustinov NB, Zav'yalova EG, Kopylov AM: Effect of Thrombin Inhibitors on Positive Feedback in the Coagulation Cascade. Biochemistry (Mosc). 2016 Mar;81(3):242-8. doi: 10.1134/S0006297916030068. [Article]
- 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
References
- Ustinov NB, Zav'yalova EG, Kopylov AM: Effect of Thrombin Inhibitors on Positive Feedback in the Coagulation Cascade. Biochemistry (Mosc). 2016 Mar;81(3):242-8. doi: 10.1134/S0006297916030068. [Article]
Drug created at April 06, 2016 22:25 / Updated at March 24, 2023 20:20