Category: F

Factor IX (or Christmas factor) (EC 3.4.21.22) is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes hemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to hemophilia.

Factor V (pronounced factor five) is a protein of the coagulation system, rarely referred to as proaccelerin orlabile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Deficiency leads to predisposition for hemorrhage, while some mutations (most notably factor V Leiden) predispose for thrombosis.

Factor V Leiden thrombophilia is a genetically inherited disorder of blood clotting. Factor V Leiden is a variant (mutated form) of human factor V that causes an increase in blood clotting (hypercoagulability). In this disorder, the Leiden variant (form) of factor V cannot be inactivated (switched off) by activated protein C, and so clotting is encouraged. Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst European Caucasians.

Factor VII (EC 3.4.21.21, blood-coagulation factor VIIa, activated blood coagulation factor VII, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class.

Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the F8 gene. Defects in this gene results in hemophilia A, a recessive X-linked coagulation disorder. Factor VIII is produced in liver sinusoidal cells and endothelial cells outside of the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein (sometimes written as coagulation factor VIIIa) interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.

Factor VIII participates in blood coagulation; it is a cofactor for factor IXa which, in the presence of Ca²⁺ andphospholipids forms a complex that converts factor X to the activated form Xa. The factor VIII gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity.

People with high levels of factor VIII are at increased risk for deep vein thrombosis and pulmonary embolism. Copper is a required cofactor for factor VIII and copper deficiency is known to increase levels of factor VIII.

Factor X, also known by the eponym Stuart–Prower factor or as prothrombinase, thrombokinase orthromboplastin, is an enzyme (EC 3.4.21.6) of the coagulation cascade. It is a serine endopeptidase (protease group S1).

The active site of factor Xa is divided into four sub pockets as S1, S2, S3 and S4. The S1 subpocket determines the major component of selectivity and binding. The S2 sub-pocket is small, shallow and not well defined. It merges with the S4 subpocket. The S3 sub-pocket is located on the rim of the S1 pocket and is quite exposed to solvent. The S4 sub-pocket has three ligand binding domains: the “hydrophobic box”, the “cationic hole” and the water site. Factor Xa inhibitors generally bind in an L-shaped conformation, where one group of the ligand occupies the anionic S1 pocket lined by residues Asp189, Ser195, and Tyr228, and another group of the ligand occupies the aromatic S4 pocket lined by residues Tyr99, Phe174, and Trp215. Typically, a fairly rigid linker group bridges these two interaction sites.

Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of thecoagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene.

 

Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme (EC 3.4.21.38) of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the F12 gene.

Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen which causes the latter to polymerize. The polymerized fibrin together with platelets forms ahemostatic plug or clot over a wound site.

When the lining of a blood vessel is broken, platelets are attracted forming a platelet plug. These platelets express thrombin receptors on their surfaces that bind serum thrombin molecules which in turn convert soluble fibrinogen in the serum into fibrin at the wound site. Fibrin forms long strands of tough insoluble protein that are laid down and are bound to the platelets.Factor XIII completes the cross-linking of fibrin so that it hardens and contracts. The cross-linked fibrin forms a mesh overlying the platelet plug that completes the clot.

Fibrin degradation product (FDPs), also known as fibrin split products, are components of the blood produced by clot degeneration. Clotting, also called coagulation, at the wound site produces a mass of fibrin threads called a net that remains in place until the cut is healed. As a cut heals, the clotting slows down. Eventually the clot is broken down and dissolved by plasmin. When the clot and fibrin net dissolve, fragments of protein are released into the body. These fragments are fibrin degradation products or FDPs. If your body is unable to dissolve a clot, you may have abnormal levels of FDPs. The most notable subtype of fibrin degradation products is D-dimer.

The levels of these FDPs rise after any thrombotic event.

Fibrin and fibrinogen degradation product (FDP) testing is commonly used to diagnose disseminated intravascular coagulation.

Fibrinogen (factor I) is a glycoprotein in vertebrates that helps in the formation of blood clots. It consists of a linear array of three nodules held together by a very thin thread which is estimated to have a diameter between 8 and 15 A. The two end nodules are alike but the center one is slightly smaller. Measurements of shadow lengths indicate that nodule diameters are in the range 50 to 70 A. The length of the dried molecule is 475 ± 25 A.

The fibrinogen molecule is a soluble, large, and complex glycoprotein, 340 kDa plasma glycoprotein, that is converted bythrombin into fibrin during blood clot formation. It has a rod-like shape with dimensions of 9 × 47.5 × 6 nm and it shows a negative net charge at physiological pH (IP at pH 5.2). Fibrinogen is synthesized in the liver by the hepatocytes. The concentration of fibrinogen in the blood plasma is 200–400 mg/dL (normally measured using the Clauss method).

During normal blood coagulation, a coagulation cascade activates the zymogen prothrombin by converting it into theserine protease thrombin. Thrombin then converts the soluble fibrinogen into insoluble fibrin strands. These strands are then cross-linked by factor XIII to form a blood clot. FXIIa stabilizes fibrin further by incorporation of the fibrinolysisinhibitors alpha-2-antiplasmin and TAFI (thrombin activatable fibrinolysis inhibitor, procarboxypeptidase B), and binding to several adhesive proteins of various cells. Both the activation of factor XIII by thrombin and plasminogen activator (t-PA) are catalyzed by fibrin. Fibrin specifically binds the activated coagulation factors factor Xa and thrombin and entraps them in the network of fibers, thus functioning as a temporary inhibitor of these enzymes, which stay active and can be released during fibrinolysis. Research from 2011 has shown that fibrin plays a key role in the inflammatory response and development of rheumatoid arthritis.

Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis. The primary type is a normal body process, whereas secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause.

In fibrinolysis, a fibrin clot, the product of coagulation, is broken down. Its main enzyme plasmin cuts the fibrin mesh at various places, leading to the production of circulating fragments that are cleared by other proteases or by the kidney and liver.

Fibronectin is a high-molecular weight (~440kDa) glycoprotein of the extracellular matrix that binds tomembrane-spanning receptor proteins called integrins. Similar to integrins, fibronectin binds extracellular matrix components such as collagen, fibrin, and heparan sulfate proteoglycans (e.g. syndecans).

Fibronectin exists as a protein dimer, consisting of two nearly identical monomers linked by a pair of disulfide bonds. The fibronectin protein is produced from a single gene, but alternative splicing of its pre-mRNA leads to the creation of several isoforms.

Two types of fibronectin are present in vertebrates:

• soluble plasma fibronectin (formerly called “cold-insoluble globulin”, or CIg) is a major protein component ofblood plasma (300 μg/ml) and is produced in the liver by hepatocytes.
• insoluble cellular fibronectin is a major component of the extracellular matrix. It is secreted by various cells, primarily fibroblasts, as a soluble protein dimer and is then assembled into an insoluble matrix in a complex cell-mediated process.

Fibronectin plays a major role in cell adhesion, growth, migration, and differentiation, and it is important for processes such as wound healing and embryonic development. Altered fibronectin expression, degradation, and organization has been associated with a number of pathologies, including cancer and fibrosis.

In biotechnology, flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second.

Flow cytometry is routinely used in the diagnosis of health disorders, especially blood cancers, but has many other applications in basic research, clinical practice and clinical trials. A common variation is to physically sort particles based on their properties, so as to purify populations of interest.

Fondaparinux is an anticoagulant medication chemically related to low molecular weight heparins. Fondaparinux is given subcutaneously daily for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism.

Fondaparinux is a synthetic pentasaccharide factor Xa inhibitor. Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymericglycosaminoglycans heparin and heparin sulfate (HS). Within heparin and heparin sulfate this monomeric sequence is thought to form the high-affinity binding site for the anti-coagulant factor antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.