Factor VII
Encyclopedia
Factor VII is one of the protein
s that causes blood to clot in the coagulation cascade
. It is an enzyme
of the serine protease
class. A recombinant
form of human factor VIIa (NovoSeven, eptacog alfa [activated]) has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients. It is often used unlicensed in severe uncontrollable bleeding, although there has been safety concerns.
(TF/factor III). Tissue factor is found on the outside of blood vessels - normally not exposed to the bloodstream. Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII. Once bound to TF, FVII is activated to FVIIa by different proteases, among which are thrombin
(factor IIa), factor Xa, IXa, XIIa, and the FVIIa-TF complex itself. The most important substrates for FVIIa-TF are Factor X
and Factor IX
.
The action of the factor is impeded by tissue factor pathway inhibitor
(TFPI), which is released almost immediately after initiation of coagulation. Factor VII is vitamin K
dependent; it is produced in the liver
. Use of warfarin
or similar anticoagulant
s decreases hepatic synthesis of FVII.
human factor VIIa (NovoSeven, eptacog alfa [activated], ATC code B02BD08) has been introduced for use in uncontrollable bleeding in hemophilia patients (with Factor VIII
or IX
deficiency) who have developed inhibitors against replacement coagulation factor.
It is being increasingly used in uncontrollable hemorrhage. The first report of its use was in an Israel
i soldier with uncontrollable bleeding in 1999. The rationale for its use in hemorrhage is, that it will only induce coagulation in those sites where tissue factor (TF) is also present. Still, O'Connell et al. report an increased risk of deep vein thrombosis
, pulmonary embolism
and myocardial infarction
in association with the use of rhFVIIa. A 2008 meta-analysis
of randomized controlled trials of of rhFVIIa in patients without hemophilia showed no additional risk of deep vein thrombosis
or pulmonary embolism
and the risk of arterial thrombosis to be substantially less than the potential to reduce mortality. In 2010 a larger study combining the results 35 trials showed a definite increase in arterial thrombosis, the risk of which was higher in older patients.
According to a 2005 study, recombinant human factor VII improves outcomes in acute intracerebral hemorrhage., but a more recent, larger 2008 study by the same group to address these initial findings failed to show any mortality benefit. Factor VII is no longer recommended in the treatment of patients with intracerebral hemorrhage.
with Tissue factor
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that causes blood to clot in the coagulation cascade
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
. It is an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
of the serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
class. A recombinant
Recombinant
Recombinant may refer to:* A recombinant organism - an organism that contains a different combination of alleles from either of its parents.* Recombinant DNA - a form of artificial DNA* Recombinant virus - a virus formed by recombining genetic material...
form of human factor VIIa (NovoSeven, eptacog alfa [activated]) has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients. It is often used unlicensed in severe uncontrollable bleeding, although there has been safety concerns.
Physiology
The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with tissue factorTissue factor
Tissue factor, also called platelet tissue factor, factor III, thrombokinase, or CD142 is a protein present in subendothelial tissue, platelets, and leukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. An incorrect synonym is thromboplastin...
(TF/factor III). Tissue factor is found on the outside of blood vessels - normally not exposed to the bloodstream. Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII. Once bound to TF, FVII is activated to FVIIa by different proteases, among which are thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
(factor IIa), factor Xa, IXa, XIIa, and the FVIIa-TF complex itself. The most important substrates for FVIIa-TF are Factor X
Factor X
Factor X, also known by the eponym Stuart-Prower factor or as prothrombinase, is an enzyme of the coagulation cascade. It is a serine endopeptidase .-Physiology:...
and Factor IX
Factor IX
Factor IX 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...
.
The action of the factor is impeded by tissue factor pathway inhibitor
Tissue factor pathway inhibitor
Tissue factor pathway inhibitor is a single-chain polypeptide which can reversibly inhibit Factor Xa and Thrombin...
(TFPI), which is released almost immediately after initiation of coagulation. Factor VII is vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
dependent; it is produced in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Use of warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
or similar anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s decreases hepatic synthesis of FVII.
Role in disease
Deficiency is rare (congenital proconvertin deficiency) and inherits recessively. Factor VII deficiency presents as a hemophilia-like bleeding disorder. It is treated with recombinant factor VIIa (NovoSeven).Therapeutic use
RecombinantRecombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
human factor VIIa (NovoSeven, eptacog alfa [activated], ATC code B02BD08) has been introduced for use in uncontrollable bleeding in hemophilia patients (with Factor VIII
Factor VIII
Factor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene...
or IX
Factor IX
Factor IX 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...
deficiency) who have developed inhibitors against replacement coagulation factor.
It is being increasingly used in uncontrollable hemorrhage. The first report of its use was in an Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
i soldier with uncontrollable bleeding in 1999. The rationale for its use in hemorrhage is, that it will only induce coagulation in those sites where tissue factor (TF) is also present. Still, O'Connell et al. report an increased risk of deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
, pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
and myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
in association with the use of rhFVIIa. A 2008 meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of randomized controlled trials of of rhFVIIa in patients without hemophilia showed no additional risk of deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
or pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
and the risk of arterial thrombosis to be substantially less than the potential to reduce mortality. In 2010 a larger study combining the results 35 trials showed a definite increase in arterial thrombosis, the risk of which was higher in older patients.
According to a 2005 study, recombinant human factor VII improves outcomes in acute intracerebral hemorrhage., but a more recent, larger 2008 study by the same group to address these initial findings failed to show any mortality benefit. Factor VII is no longer recommended in the treatment of patients with intracerebral hemorrhage.
Interactions
Factor VII has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Tissue factor
Tissue factor
Tissue factor, also called platelet tissue factor, factor III, thrombokinase, or CD142 is a protein present in subendothelial tissue, platelets, and leukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. An incorrect synonym is thromboplastin...
.
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: S01.215 - Web site for novoseven-us.com