Thrombin Alfa, Recombinant Human Thrombin

Specification

• Cat#: THP-0096
• Product Name: Thrombin Alfa, Recombinant Human Thrombin
• Cas No: 869858-13-9
• Description: Recombinant Human Thrombin is a human coagulation protein expressed in CHO cell line. The product is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. The product 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 the product has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of the product employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The product product ultimate comes from recombinant human prethrombin-1.
• Sequences: MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE
• Species: Human
• Molecular Weight: Not Available
• Source: CHO
• Purity: >99% by SDS-Page and HPLC analysis
• Formula: Not Available
• Endotoxin: <0.001 EU per 1 μg by the LAL method
• Biological Activity: 1000U/ml
• Application: 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. Additionally, the product can be used in conjunction with an absorbable gelatin sponge, USP.

Pharmaceutical Information

• Pharmaceutical Application: Thrombin Alfa
• Targets: Target 1. Coagulation factor XI; Target 2. Coagulation factor VIII; Target 3. Coagulation factor V; Target 4. Coagulation factor XIII A chain; Target 5. Coagulation factor XIII B chain; Target 6. Fibrinogen alpha chain; Target 7. Fibrinogen beta chain; Target 8. Fibrinogen gamma chain

Related Reading

Thrombin Alfa, also known as Factor II or Prothrombin, is a globally-recognized protein that has significant roles in the coagulation of blood and diverse cellular processes.

Background of Thrombin Alfa

The initial discovery of thrombin took place in the late 19th century, with the credit often attributed to Rudolf Virchow. His discovery paved the way for comprehensive pioneering studies on the complexities of blood coagulation. Decades of continuous research led to identifying its gene locus which is on chromosome 11 in humans.
Thrombin Alfa, also represented as F2 in gene databases, encodes a glycoprotein that has 622 amino acids. This protein undergoes a series of processing during its journey from the liver, its site of synthesis, to the bloodstream where it acts as a chief player in the coagulation cascade. Its structure is unique with two chains linked by a disulfide bridge, with a highly negatively charged region that is crucial for its activity.

Thrombin Alfa Function

As a serine protease, Thrombin Alfa plays a central role in the coagulation process, promoting hemostasis through clot formation. It does so by converting soluble fibrinogen into insoluble fibrin strands. Further, it activates Factors V, VIII, and XI, and stimulates platelet aggregation, thereby contributing to blood clotting.
In addition, Thrombin Alfa has pleiotropic effects on cells. It modulates cellular processes such as proliferation, protection from apoptosis, and migration by activating Protease-Activated Receptors (PARs).

Thrombin Alfa-related Signaling Pathways

Thrombin Alfa influences multiple signaling pathways. One significant pathway is the activation of Protein C, a regulatory pathway that hinders the thrombin generation and suppresses inflammation. Once activated, Protein C operates by inactivating Factors Va and VIIIa, thus down-regulating the coagulation cascade.
Another crucial pathway involves the cleavage and activation of PARs by Thrombin Alfa. This has a plethora of effects, including inducing platelet aggregation, mediating inflammation, and triggering cellular proliferation and migration, contributing to diverse physiological processes.

Related Diseases and Role of Thrombin Alfa in Diseases

Numerous diseases are correlated with abnormal thrombin levels or function. Overactivity or excessive thrombin generation could lead to thrombotic disorders, such as deep vein thrombosis, pulmonary embolism, and stroke. Conversely, reduced thrombin activity can lead to a broad range of hemorrhagic disorders.
Moreover, the broad cellular effects of Thrombin Alfa mean it's linked to other conditions beyond blood coagulation. It was implicated in pathological processes like sepsis, due to its potent role in the inflammatory response, and cancer, where it can promote tumor growth and metastasis.

Application of Thrombin Alfa in Medicine

Thrombin Alfa found different uses in the medical world. It's often applied in surgeries to promote local hemostasis. Moreover, recombinant Thrombin Alfa is used in formulation with fibrinogen to form a fibrin sealant to control bleeding.

List of Drug Candidates Related to Thrombin Alfa

Numerous drugs revolve around Thrombin Alfa, either as inhibitors or as substitutes for its natural form. Direct thrombin inhibitors, such as Dabigatran, Argatroban, and Bivalirudin, are important anticoagulant drugs. Moreover, products like Recothrom and Evithrom, which are recombinant or human thrombin, are used as hemostatic agents in surgery.