Factor VIIa
Thromboplastin
Factor VII
Factor X
Factor Xa
Blood Coagulation
Hemophilia A
Off-Label Use
Hemostatics
Factor IX
Antithrombin III
1-Carboxyglutamic Acid
Terbium
Prothrombin Time
Hemostasis
Hemophilia B
Postoperative Hemorrhage
Blood Coagulation Factors
Partial Thromboplastin Time
Benzamidines
Factor XIa
Factor IXa
Lipoproteins
Disseminated Intravascular Coagulation
Prothrombin
Binding Sites
Factor VIII
Factor VII Deficiency
Embolism, Amniotic Fluid
Fibrin
Chromogenic Compounds
Receptor, PAR-2
Protein Binding
Blood Coagulation Disorders
Tumor Necrosis Factor-alpha
Serum Albumin, Bovine
Blood-borne tissue factor: another view of thrombosis. (1/627)
Arterial thrombosis is considered to arise from the interaction of tissue factor (TF) in the vascular wall with platelets and coagulation factors in circulating blood. According to this paradigm, coagulation is initiated after a vessel is damaged and blood is exposed to vessel-wall TF. We have examined thrombus formation on pig arterial media (which contains no stainable TF) and on collagen-coated glass slides (which are devoid of TF) exposed to flowing native human blood. In both systems the thrombi that formed during a 5-min perfusion stained intensely for TF, much of which was not associated with cells. Antibodies against TF caused approximately 70% reduction in the amount of thrombus formed on the pig arterial media and also reduced thrombi on the collagen-coated glass slides. TF deposited on the slides was active, as there was abundant fibrin in the thrombi. Factor VIIai, a potent inhibitor of TF, essentially abolished fibrin production and markedly reduced the mass of the thrombi. Immunoelectron microscopy revealed TF-positive membrane vesicles that we frequently observed in large clusters near the surface of platelets. TF, measured by factor Xa formation, was extracted from whole blood and plasma of healthy subjects. By using immunostaining, TF-containing neutrophils and monocytes were identified in peripheral blood; our data raise the possibility that leukocytes are the main source of blood TF. We suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury. (+info)Thermal effects on an enzymatically latent conformation of coagulation factor VIIa. (2/627)
Activation of the zymogen factor VII yields an enzyme form, factor VIIa, with only modest activity. The thermal effect on this low activity of factor VIIa and its enhancement by the cofactor tissue factor was investigated. Factor VIIa activity measured with a chromogenic peptide substrate is characterized by an unusual temperature dependency which indicates that the activated protease exists in an equilibrium between a latent (enzymatically inactive) and an active conformation. As shown by calorimetry and activity measurements the thermal effects on factor VIIa are fully reversible below the denaturation temperature of 58.1 degrees C. A model for factor VIIa has been proposed [Higashi, S., Nishimura, H., Aita, K. & Iwanaga, S. (1994) J. Biol. Chem. 269, 18891-18898] in which the protease is supposed to exist primarily as a latent enzyme form because of the poor incorporation into the protease structure of the N-terminal Ile153 released by proteolytic cleavage during activation of factor VII. Binding of tissue factor to factor VIIa is assumed to shift the equilibrium towards an active conformation in which the N-terminal Ile153 forms a salt bridge with Asp343. We corroborate the validity of this model by: (a) chemical modification of factor VIIa; this suggests that the thermal effect on the equilibrium between the active and inactive conformation is reflected in the relative accessibility of the active site and the N-terminal Ile153; (b) measurements of factor VIIa binding to tissue factor indicating that complex formation is favoured by stabilization of the active conformation; and (c) activity measurements of a cross-linked factor VIIa-tissue factor complex; this showed that cross-linking stabilized the active conformation of factor VIIa and essentially prevented its thermally-induced transformation into the inactive state. (+info)Activation of the tissue factor pathway occurs during continuous venovenous hemofiltration. (3/627)
BACKGROUND: Activation of the tissue factor pathway occurs during continuous venovenous hemofiltration (CVVH). Despite adequate exogenous anticoagulation, the occlusion of CVVH circuits can occur within minutes to a few hours of use and is associated with evidence of thrombin generation. Having found no evidence of activation of the contact factor (intrinsic coagulation) pathway during CVVH, we sought to examine the effect of the first episode of CVVH on the tissue factor (extrinsic) pathway of coagulation and thrombin generation. METHODS: Twelve critically ill patients were studied prior to the commencement of hemofiltration and at regular intervals thereafter until the filter clotted. RESULTS: Prior to hemofiltration, most patients had increased levels of plasma tissue factor, thrombin-antithrombin (TAT) complexes, and tissue factor pathway inhibitor (TFPI); during hemofiltration, further generation of TAT complexes occurred. Initially, levels of activated factor VII (FVIIa) fell and TFPI increased, but during the course of hemofiltration, the levels of TFPI fell and FVIIa increased. Levels of tissue factor increased during CVVH in some patients, but this was not related to the generation of FVIIa. CONCLUSIONS: These data indicate that activation of FVII occurred during CVVH, which was related to levels of TFPI, but not tissue factor, and was coincidental to thrombin generation. (+info)Two common functional polymorphisms in the promoter region of the coagulation factor VII gene determining plasma factor VII activity and mass concentration. (4/627)
Recent studies have provided evidence for associations between common polymorphic markers in the coagulation factor VII (FVII) gene and plasma FVII levels. Here we describe two common, nonrelated, functional polymorphisms in the promoter region of the FVII gene, a G to T substitution at position -401 and a novel G to A substitution at position -402. Both polymorphisms strongly influence the binding properties of nuclear protein(s). The rare -401T allele is associated with a reduced basal rate of transcription of the FVII gene in human hepatoblastoma cells and with reduced plasma concentrations of total FVII (VIIag) and fully activated FVII molecules (VIIa). In contrast, the rare -402A allele confers increased transcriptional activity and is associated with increased plasma FVII levels. Together, the two polymorphisms explained 18% and 28% of the variation in VIIag and VIIa, respectively, in a group of 183 healthy, middle-aged men. It is concluded that these polymorphisms are important for the regulation of the plasma levels of FVII and that they are likely to be useful genetic markers to resolve the issue of whether a causal relationship exists between FVII levels and risk of coronary heart disease. (+info)Thrombogenic factors and recurrent coronary events. (5/627)
BACKGROUND: Thrombosis is a pivotal event in the pathogenesis of coronary disease. We hypothesized that the presence of blood factors that reflect enhanced thrombogenic activity would be associated with an increased risk of recurrent coronary events during long-term follow-up of patients who have recovered from myocardial infarction. METHODS AND RESULTS: We prospectively enrolled 1045 patients 2 months after an index myocardial infarction. Baseline thrombogenic blood tests included 6 hemostatic variables (D-dimer, fibrinogen, factor VII, factor VIIa, von Willebrand factor, and plasminogen activator inhibitor-1), 7 lipid factors [cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, lipoprotein(a), apolipoprotein (apo)A-I, and apoB], and insulin. Patients were followed up for an average of 26 months, with the primary end point being coronary death or nonfatal myocardial infarction, whichever occurred first. The hemostatic, lipid, and insulin parameters were dichotomized into their top and the lower 3 risk quartiles and evaluated for entry into a Cox survivorship model. High levels of D-dimer (hazard ratio, 2.43; 95% CI, 1.49, 3.97) and apoB (hazard ratio, 1.82; 95% CI, 1.10, 3.00) and low levels of apoA-I (hazard ratio, 1.84; 95% CI, 1.10, 3.08) were independently associated with recurrent coronary events in the Cox model after adjustment for 6 relevant clinical covariates. CONCLUSIONS: Our findings indicate that a procoagulant state, as reflected in elevated levels of D-dimer, and disordered lipid transport, as indicated by low apoA-1 and high apoB levels, contribute independently to recurrent coronary events in postinfarction patients. (+info)Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men. (6/627)
Patients with diabetes have an increased prevalence of premature atherosclerotic vascular disease, and alterations in plasma coagulation proteins have been incriminated as a possible cause. The roles of hyperglycemia and hyperinsulinemia in the pathogenesis of these changes are unknown. To examine the effects of prolonged hyperglycemia and of selective hyperinsulinemia on the tissue factor pathway of blood coagulation, nine healthy young men were infused with glucose to maintain levels at 11.1 mmol/l (approximately 200 mg/dl) for 18-72 h (hyperglycemia-hyperinsulinemia group). Five normal men were infused with regular insulin to maintain levels comparable to that in the previous group (900 pmol/l, approximately 150 microU/ml) and with glucose to maintain levels at 5.6 mmol/l (approximately 100 mg/dl) (euglycemia-hyperinsulinemia group). Measured were plasma activated factor VII activity (FVIIa), FVII coagulant (FVIIC) activity, FVIII coagulant (FVIIIC) activity, tissue factor pathway inhibitor (TFPI) antigen, and thrombin markers; and serum glucose, insulin, and electrolytes. Plasma FVIIa, FVIIC, FVIIIC, and TFPI rose during hyperglycemic-hyperinsulinemia but not during euglycemic-hyperinsulinemia. Markers of thrombin generation rose transiently and inconsistently during hyperglycemia-hyperinsulinemia. We concluded that in normal subjects, hyperglycemia-hyperinsulinemia induced activation of the tissue factor pathway, reflected by increases in plasma FVIIa, FVIIC, and TFPI. This activation was independent of hyperinsulinemia, hypertriglyceridemia, and hyperosmolality. The elevations in plasma coagulation factors during hyperglycemia-hyperinsulinemia, characteristic of type 2 diabetes, may constitute a potential for enhanced thrombin generation and thrombosis when triggered by exposure of tissue factor, such as during arterial plaque rupture. (+info)An Arg/Ser substitution in the second epidermal growth factor-like module of factor IX introduces an O-linked carbohydrate and markedly impairs activation by factor XIa and factor VIIa/Tissue factor and catalytic efficiency of factor IXa. (7/627)
Factor IXR94S is a naturally occurring hemophilia B defect, which results from an Arg 94 to Ser mutation in the second epidermal growth factor (EGF)-like module of factor IX. Recombinant factor IXR94S was activated by factor XIa/calcium with an approximately 50-fold reduced rate and by factor VIIa/tissue factor/phospholipid/calcium with an approximately 20-fold reduced rate compared with wild-type factor IX. The apparent molecular mass of the light chain of factor IXaR94S was approximately 6 kD higher than that of plasma or wild-type factor IX, which was not corrected by N-glycosidase F digestion. This result indicated the presence of additional O-linked carbohydrate in the mutant light chain, probably at new Ser 94. The initial rate of activation of factor X by factor IXaR94S in the presence of polylysine was 7% +/- 1% of the initial rate of activation of factor X by plasma factor IXa, and the kc/Km for activation of factor X by factor IXaR94S/factor VIIIa/phospholipid/calcium was 4% +/- 1% of the kc/Km for activation of factor X by plasma factor IXa/factor VIIIa/phospholipid/calcium. The reduced efficiency of activation of factor X by factor IXaR94S in the tenase enzyme complex was due to a 58-fold +/- 12-fold decrease in kcat with little effect on Km. In conclusion, the R94S mutation had introduced an O-linked carbohydrate, which markedly impaired both activation by factor XIa and turnover of factor X in the tenase enzyme complex. (+info)Probing the structural changes in the light chain of human coagulation factor VIIa due to tissue factor association. (8/627)
The crystallographic structure of human coagulation factor VIIa/tissue factor complex bound with calcium ions was used to model the solution structure of the light chain of factor VIIa (residues 1-142) in the absence of tissue factor. The Amber force field in conjunction with the particle mesh Ewald summation method to accommodate long-range electrostatic interactions was used in the trajectory calculations. The estimated TF-free solution structure was then compared with the crystal structure of factor VIIa/tissue factor complex to estimate the restructuring of factor VIIa due to tissue factor binding. The solution structure of the light chain of factor VIIa in the absence of tissue factor is predicted to be an extended domain structure similar to that of the tissue factor-bound crystal. Removal of the EGF1-bound calcium ion is shown by simulation to lead to minor structural changes within the EGF1 domain, but also leads to substantial relative reorientation of the Gla and EGF1 domains. (+info)Factor VIIa is a protein involved in the coagulation cascade, which is a series of chemical reactions that leads to the formation of a blood clot. Factor VIIa is the activated form of factor VII, which is normally activated by tissue factor (TF) when there is damage to the blood vessels. Together, TF and Factor VIIa convert Factor X to its active form, Factor Xa, which then converts prothrombin to thrombin, leading to the formation of a fibrin clot.
In summary, Factor VIIa is an important protein in the coagulation cascade that helps to initiate the formation of a blood clot in response to injury.
Thromboplastin is a substance that activates the coagulation cascade, leading to the formation of a clot (thrombus). It's primarily found in damaged or injured tissues and blood vessels, as well as in platelets (thrombocytes). There are two types of thromboplastin:
1. Extrinsic thromboplastin (also known as tissue factor): This is a transmembrane glycoprotein that is primarily found in subendothelial cells and released upon injury to the blood vessels. It initiates the extrinsic pathway of coagulation by binding to and activating Factor VII, ultimately leading to the formation of thrombin and fibrin clots.
2. Intrinsic thromboplastin (also known as plasma thromboplastin or factor III): This term is used less frequently and refers to a labile phospholipid component present in platelet membranes, which plays a role in the intrinsic pathway of coagulation.
In clinical settings, the term "thromboplastin" often refers to reagents used in laboratory tests like the prothrombin time (PT) and activated partial thromboplastin time (aPTT). These reagents contain a source of tissue factor and calcium ions to initiate and monitor the coagulation process.
Factor VII, also known as proconvertin, is a protein involved in the coagulation cascade, which is a series of chemical reactions that leads to the formation of a blood clot. Factor VII is synthesized in the liver and is activated when it comes into contact with tissue factor, which is exposed when blood vessels are damaged. Activated Factor VII then activates Factor X, leading to the formation of thrombin and ultimately a fibrin clot.
Inherited deficiencies or dysfunctions of Factor VII can lead to an increased risk of bleeding, while elevated levels of Factor VII have been associated with an increased risk of thrombosis (blood clots).
Factor X is a protein that is essential for blood clotting, also known as coagulation. It is an enzyme that plays a crucial role in the coagulation cascade, which is a series of chemical reactions that lead to the formation of a blood clot. Factor X is activated by one of two pathways: the intrinsic pathway, which is initiated by damage to the blood vessels, or the extrinsic pathway, which is triggered by the release of tissue factor from damaged cells. Once activated, Factor X converts prothrombin to thrombin, which then converts fibrinogen to fibrin to form a stable clot.
Inherited deficiencies in Factor X can lead to bleeding disorders, while increased levels of Factor X have been associated with an increased risk of thrombosis or blood clots. Therefore, maintaining appropriate levels of Factor X is important for the proper balance between bleeding and clotting in the body.
Factor Xa is a serine protease that plays a crucial role in the coagulation cascade, which is a series of reactions that lead to the formation of a blood clot. It is one of the activated forms of Factor X, a pro-protein that is converted to Factor Xa through the action of other enzymes in the coagulation cascade.
Factor Xa functions as a key component of the prothrombinase complex, which also includes calcium ions, phospholipids, and activated Factor V (also known as Activated Protein C or APC). This complex is responsible for converting prothrombin to thrombin, which then converts fibrinogen to fibrin, forming a stable clot.
Inhibitors of Factor Xa are used as anticoagulants in the prevention and treatment of thromboembolic disorders such as deep vein thrombosis and pulmonary embolism. These drugs work by selectively inhibiting Factor Xa, thereby preventing the formation of the prothrombinase complex and reducing the risk of clot formation.
Blood coagulation, also known as blood clotting, is a complex process that occurs in the body to prevent excessive bleeding when a blood vessel is damaged. This process involves several different proteins and chemical reactions that ultimately lead to the formation of a clot.
The coagulation cascade is initiated when blood comes into contact with tissue factor, which is exposed after damage to the blood vessel wall. This triggers a series of enzymatic reactions that activate clotting factors, leading to the formation of a fibrin clot. Fibrin is a protein that forms a mesh-like structure that traps platelets and red blood cells to form a stable clot.
Once the bleeding has stopped, the coagulation process is regulated and inhibited to prevent excessive clotting. The fibrinolytic system degrades the clot over time, allowing for the restoration of normal blood flow.
Abnormalities in the blood coagulation process can lead to bleeding disorders or thrombotic disorders such as deep vein thrombosis and pulmonary embolism.
Coagulants are substances that promote the process of coagulation or clotting. They are often used in medical settings to help control bleeding and promote healing. Coagulants work by encouraging the formation of a clot, which helps to stop the flow of blood from a wound or cut.
There are several different types of coagulants that may be used in medical treatments. Some coagulants are naturally occurring substances, such as vitamin K, which is essential for the production of certain clotting factors in the body. Other coagulants may be synthetic or semi-synthetic compounds, such as recombinant activated factor VII (rFVIIa), which is used to treat bleeding disorders and prevent excessive bleeding during surgery.
Coagulants are often administered through injection or infusion, but they can also be applied topically to wounds or cuts. In some cases, coagulants may be used in combination with other treatments, such as compression or cauterization, to help control bleeding and promote healing.
It is important to note that while coagulants can be helpful in controlling bleeding and promoting healing, they can also increase the risk of blood clots and other complications. As a result, they should only be used under the guidance and supervision of a qualified healthcare professional.
Hemophilia A is a genetic bleeding disorder caused by a deficiency in clotting factor VIII. This results in impaired blood clotting and prolonged bleeding, particularly after injuries or surgeries. Symptoms can range from mild to severe, with the most severe form resulting in spontaneous bleeding into joints and muscles, leading to pain, swelling, and potential joint damage over time. Hemophilia A primarily affects males, as it is an X-linked recessive disorder, and is usually inherited from a carrier mother. However, about one third of cases result from a spontaneous mutation in the gene for factor VIII. Treatment typically involves replacement therapy with infusions of factor VIII concentrates to prevent or control bleeding episodes.
Off-label use refers to the practice of prescribing or using pharmaceutical drugs for purposes, dosages, patient populations, or routes of administration that are not included in the approved labeling of the drug by the regulatory authority, such as the U.S. Food and Drug Administration (FDA). It is not illegal or unethical for physicians to prescribe medications off-label when they judge that it is medically appropriate for their patients. However, manufacturers are prohibited from promoting their drugs for off-label uses.
Hemostatics are substances or agents that promote bleeding cessation or prevent the spread of bleeding. They can act in various ways, such as by stimulating the body's natural clotting mechanisms, constricting blood vessels to reduce blood flow, or forming a physical barrier to block the bleeding site.
Hemostatics are often used in medical settings to manage wounds, injuries, and surgical procedures. They can be applied directly to the wound as a powder, paste, or gauze, or they can be administered systemically through intravenous injection. Examples of hemostatic agents include fibrin sealants, collagen-based products, thrombin, and oxidized regenerated cellulose.
It's important to note that while hemostatics can be effective in controlling bleeding, they should be used with caution and only under the guidance of a healthcare professional. Inappropriate use or overuse of hemostatic agents can lead to complications such as excessive clotting, thrombosis, or tissue damage.
Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.
Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.
The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.
Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.
Factor IX is also known as Christmas factor, which is a protein that plays a crucial role in the coagulation cascade, a series of chemical reactions that leads to the formation of a blood clot. It is one of the essential components required for the proper functioning of the body's natural blood-clotting mechanism.
Factor IX is synthesized in the liver and activated when it comes into contact with an injured blood vessel. Once activated, it collaborates with other factors to convert factor X to its active form, which then converts prothrombin to thrombin. Thrombin is responsible for converting fibrinogen to fibrin, forming a stable fibrin clot that helps stop bleeding and promote healing.
Deficiencies in Factor IX can lead to hemophilia B, a genetic disorder characterized by prolonged bleeding and an increased risk of spontaneous bleeding. Hemophilia B is inherited in an X-linked recessive pattern, meaning it primarily affects males, while females serve as carriers of the disease. Treatment for hemophilia B typically involves replacing the missing or deficient Factor IX through infusions to prevent or manage bleeding episodes.
Antithrombin III is a protein that inhibits the formation of blood clots (thrombi) in the body. It does this by inactivating several enzymes involved in coagulation, including thrombin and factor Xa. Antithrombin III is produced naturally by the liver and is also available as a medication for the prevention and treatment of thromboembolic disorders, such as deep vein thrombosis and pulmonary embolism. It works by binding to and neutralizing excess clotting factors in the bloodstream, thereby reducing the risk of clot formation.
1-Carboxyglutamic acid, also known as γ-carboxyglutamic acid, is a post-translational modification found on certain blood clotting factors and other calcium-binding proteins. It is formed by the carboxylation of glutamic acid residues in these proteins, which enhances their ability to bind to calcium ions. This modification is essential for the proper functioning of many physiological processes, including blood coagulation, bone metabolism, and wound healing.
Terbium is not a medical term, but a chemical element. It is a rare earth element with the symbol Tb and atomic number 65. It is soft, silvery-white, and has a metallic shine. Terbium is not used in medicine to treat or diagnose diseases directly. However, it does have some applications in medical technology such as in doping materials for magnetic resonance imaging (MRI) machines and in the creation of high-intensity gas discharge lamps that are used in medical lighting.
Prothrombin time (PT) is a medical laboratory test that measures the time it takes for blood to clot. It's often used to evaluate the functioning of the extrinsic and common pathways of the coagulation system, which is responsible for blood clotting. Specifically, PT measures how long it takes for prothrombin (a protein produced by the liver) to be converted into thrombin, an enzyme that converts fibrinogen into fibrin and helps form a clot.
Prolonged PT may indicate a bleeding disorder or a deficiency in coagulation factors, such as vitamin K deficiency or the use of anticoagulant medications like warfarin. It's important to note that PT is often reported with an international normalized ratio (INR), which allows for standardization and comparison of results across different laboratories and reagent types.
Hemostasis is the physiological process that occurs to stop bleeding (bleeding control) when a blood vessel is damaged. This involves the interaction of platelets, vasoconstriction, and blood clotting factors leading to the formation of a clot. The ultimate goal of hemostasis is to maintain the integrity of the vascular system while preventing excessive blood loss.
Hemophilia B is a genetic disorder that affects the body's ability to control blood clotting, also known as coagulation. This condition is caused by a deficiency or dysfunction in Factor IX, one of the proteins essential for normal blood clotting. As a result, people with Hemophilia B experience prolonged bleeding and bruising after injuries, surgeries, or spontaneously, particularly in joints and muscles.
There are different degrees of severity, depending on how much Factor IX is missing or not functioning properly. Mild cases may only become apparent after significant trauma, surgery, or tooth extraction, while severe cases can lead to spontaneous bleeding into joints and muscles, causing pain, swelling, and potential long-term damage. Hemophilia B primarily affects males, as it is an X-linked recessive disorder, but females can be carriers of the condition and may experience mild symptoms.
Thrombin is a serine protease enzyme that plays a crucial role in the coagulation cascade, which is a complex series of biochemical reactions that leads to the formation of a blood clot (thrombus) to prevent excessive bleeding during an injury. Thrombin is formed from its precursor protein, prothrombin, through a process called activation, which involves cleavage by another enzyme called factor Xa.
Once activated, thrombin converts fibrinogen, a soluble plasma protein, into fibrin, an insoluble protein that forms the structural framework of a blood clot. Thrombin also activates other components of the coagulation cascade, such as factor XIII, which crosslinks and stabilizes the fibrin network, and platelets, which contribute to the formation and growth of the clot.
Thrombin has several regulatory mechanisms that control its activity, including feedback inhibition by antithrombin III, a plasma protein that inactivates thrombin and other serine proteases, and tissue factor pathway inhibitor (TFPI), which inhibits the activation of factor Xa, thereby preventing further thrombin formation.
Overall, thrombin is an essential enzyme in hemostasis, the process that maintains the balance between bleeding and clotting in the body. However, excessive or uncontrolled thrombin activity can lead to pathological conditions such as thrombosis, atherosclerosis, and disseminated intravascular coagulation (DIC).
Postoperative hemorrhage is a medical term that refers to bleeding that occurs after a surgical procedure. This condition can range from minor oozing to severe, life-threatening bleeding. Postoperative hemorrhage can occur soon after surgery or even several days later, as the surgical site begins to heal.
The causes of postoperative hemorrhage can vary, but some common factors include:
1. Inadequate hemostasis during surgery: This means that all bleeding was not properly controlled during the procedure, leading to bleeding after surgery.
2. Blood vessel injury: During surgery, blood vessels may be accidentally cut or damaged, causing bleeding after the procedure.
3. Coagulopathy: This is a condition in which the body has difficulty forming blood clots, increasing the risk of postoperative hemorrhage.
4. Use of anticoagulant medications: Medications that prevent blood clots can increase the risk of bleeding after surgery.
5. Infection: An infection at the surgical site can cause inflammation and bleeding.
Symptoms of postoperative hemorrhage may include swelling, pain, warmth, or discoloration around the surgical site, as well as signs of shock such as rapid heartbeat, low blood pressure, and confusion. Treatment for postoperative hemorrhage depends on the severity of the bleeding and may include medications to control bleeding, transfusions of blood products, or additional surgery to stop the bleeding.
Hemorrhage is defined in the medical context as an excessive loss of blood from the circulatory system, which can occur due to various reasons such as injury, surgery, or underlying health conditions that affect blood clotting or the integrity of blood vessels. The bleeding may be internal, external, visible, or concealed, and it can vary in severity from minor to life-threatening, depending on the location and extent of the bleeding. Hemorrhage is a serious medical emergency that requires immediate attention and treatment to prevent further blood loss, organ damage, and potential death.
Blood coagulation factors, also known as clotting factors, are a group of proteins that play a crucial role in the blood coagulation process. They are essential for maintaining hemostasis, which is the body's ability to stop bleeding after injury.
There are 13 known blood coagulation factors, and they are designated by Roman numerals I through XIII. These factors are produced in the liver and are normally present in an inactive form in the blood. When there is an injury to a blood vessel, the coagulation process is initiated, leading to the activation of these factors in a specific order.
The coagulation cascade involves two pathways: the intrinsic and extrinsic pathways. The intrinsic pathway is activated when there is damage to the blood vessel itself, while the extrinsic pathway is activated by tissue factor released from damaged tissues. Both pathways converge at the common pathway, leading to the formation of a fibrin clot.
Blood coagulation factors work together in a complex series of reactions that involve activation, binding, and proteolysis. When one factor is activated, it activates the next factor in the cascade, and so on. This process continues until a stable fibrin clot is formed.
Deficiencies or abnormalities in blood coagulation factors can lead to bleeding disorders such as hemophilia or thrombosis. Hemophilia is a genetic disorder that affects one or more of the coagulation factors, leading to excessive bleeding and difficulty forming clots. Thrombosis, on the other hand, occurs when there is an abnormal formation of blood clots in the blood vessels, which can lead to serious complications such as stroke or pulmonary embolism.
Partial Thromboplastin Time (PTT) is a medical laboratory test that measures the time it takes for blood to clot. It's more specifically a measure of the intrinsic and common pathways of the coagulation cascade, which are the series of chemical reactions that lead to the formation of a clot.
The test involves adding a partial thromboplastin reagent (an activator of the intrinsic pathway) and calcium to plasma, and then measuring the time it takes for a fibrin clot to form. This is compared to a control sample, and the ratio of the two times is calculated.
The PTT test is often used to help diagnose bleeding disorders or abnormal blood clotting, such as hemophilia or disseminated intravascular coagulation (DIC). It can also be used to monitor the effectiveness of anticoagulant therapy, such as heparin. Prolonged PTT results may indicate a bleeding disorder or an increased risk of bleeding, while shortened PTT results may indicate a hypercoagulable state and an increased risk of thrombosis.
Benzamidines are a group of organic compounds that contain a benzene ring linked to an amidine functional group. They are commonly used as antimicrobial agents, particularly in the treatment of various gram-negative bacterial infections. Benzamidines work by inhibiting the enzyme bacterial dehydrogenases, which are essential for the bacteria's survival.
Some examples of benzamidine derivatives include:
* Tempanamine hydrochloride (Tembaglanil): used to treat urinary tract infections caused by susceptible strains of Escherichia coli and Klebsiella pneumoniae.
* Chlorhexidine: a broad-spectrum antimicrobial agent used as a disinfectant and preservative in various medical and dental applications.
* Prothiobenzamide: an anti-inflammatory and analgesic drug used to treat gout and rheumatoid arthritis.
It is important to note that benzamidines have a narrow therapeutic index, which means that the difference between an effective dose and a toxic dose is small. Therefore, they should be used with caution and under the supervision of a healthcare professional.
Factor XIa is a serine protease enzyme that plays a crucial role in blood coagulation. It is formed through the activation of Factor XI, which is one of the key components in the intrinsic pathway of the coagulation cascade. The activation of Factor XI to Factor XIa occurs via either autoactivation or through the action of thrombin. Once activated, Factor XIa can cleave and activate Factor IX, leading to the formation of Factor IXa, which further amplifies the coagulation cascade.
In summary, Factor XIa is a vital enzyme in the blood coagulation process, contributing to the formation of a stable fibrin clot that helps prevent excessive bleeding during injury or trauma.
Factor IXa is a protein that plays a crucial role in the coagulation cascade, which is a series of biochemical reactions involved in blood clotting. It is an activated form of Factor IX, which is one of the coagulation factors that help convert prothrombin to thrombin, leading to the formation of a fibrin clot and stopping bleeding at the site of injury.
Factor IXa works by activating Factor X in the presence of calcium ions, phospholipids, and Factor VIIIa, which is another activated coagulation factor. This complex is called the tenase complex. The activation of Factor X leads to the formation of thrombin, which then converts fibrinogen to fibrin, forming a stable clot.
Deficiencies or dysfunctions in Factor IXa can lead to bleeding disorders such as hemophilia B, also known as Christmas disease, which is characterized by prolonged bleeding times and spontaneous bleeding episodes.
In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."
1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.
2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.
3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.
4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).
Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.
Lipoproteins are complex particles composed of multiple proteins and lipids (fats) that play a crucial role in the transport and metabolism of fat molecules in the body. They consist of an outer shell of phospholipids, free cholesterols, and apolipoproteins, enclosing a core of triglycerides and cholesteryl esters.
There are several types of lipoproteins, including:
1. Chylomicrons: These are the largest lipoproteins and are responsible for transporting dietary lipids from the intestines to other parts of the body.
2. Very-low-density lipoproteins (VLDL): Produced by the liver, VLDL particles carry triglycerides to peripheral tissues for energy storage or use.
3. Low-density lipoproteins (LDL): Often referred to as "bad cholesterol," LDL particles transport cholesterol from the liver to cells throughout the body. High levels of LDL in the blood can lead to plaque buildup in artery walls and increase the risk of heart disease.
4. High-density lipoproteins (HDL): Known as "good cholesterol," HDL particles help remove excess cholesterol from cells and transport it back to the liver for excretion or recycling. Higher levels of HDL are associated with a lower risk of heart disease.
Understanding lipoproteins and their roles in the body is essential for assessing cardiovascular health and managing risks related to heart disease and stroke.
Disseminated Intravascular Coagulation (DIC) is a complex medical condition characterized by the abnormal activation of the coagulation cascade, leading to the formation of blood clots in small blood vessels throughout the body. This process can result in the consumption of clotting factors and platelets, which can then lead to bleeding complications. DIC can be caused by a variety of underlying conditions, including sepsis, trauma, cancer, and obstetric emergencies.
The term "disseminated" refers to the widespread nature of the clotting activation, while "intravascular" indicates that the clotting is occurring within the blood vessels. The condition can manifest as both bleeding and clotting complications, which can make it challenging to diagnose and manage.
The diagnosis of DIC typically involves laboratory tests that evaluate coagulation factors, platelet count, fibrin degradation products, and other markers of coagulation activation. Treatment is focused on addressing the underlying cause of the condition while also managing any bleeding or clotting complications that may arise.
Prothrombin is a protein present in blood plasma, and it's also known as coagulation factor II. It plays a crucial role in the coagulation cascade, which is a complex series of reactions that leads to the formation of a blood clot.
When an injury occurs, the coagulation cascade is initiated to prevent excessive blood loss. Prothrombin is converted into its active form, thrombin, by another factor called factor Xa in the presence of calcium ions, phospholipids, and factor Va. Thrombin then catalyzes the conversion of fibrinogen into fibrin, forming a stable clot.
Prothrombin levels can be measured through a blood test, which is often used to diagnose or monitor conditions related to bleeding or coagulation disorders, such as liver disease or vitamin K deficiency.
In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.
The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.
In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.
Factor VIII is a protein in the blood that is essential for normal blood clotting. It is also known as antihemophilic factor (AHF). Deficiency or dysfunction of this protein results in hemophilia A, a genetic disorder characterized by prolonged bleeding and easy bruising. Factor VIII works together with other proteins to help form a clot and stop bleeding at the site of an injury. It acts as a cofactor for another clotting factor, IX, in the so-called intrinsic pathway of blood coagulation. Intravenous infusions of Factor VIII concentrate are used to treat and prevent bleeding episodes in people with hemophilia A.
Factor VII deficiency is a bleeding disorder that is caused by a deficiency or dysfunction of coagulation factor VII, which is a protein involved in the coagulation cascade and is necessary for the initiation of blood clotting. This condition can lead to prolonged bleeding after injury or surgery, easy bruising, and spontaneous bleeding. The severity of the disorder varies widely, depending on the level of factor VII activity. In severe cases, factor VII activity may be less than 1% of normal, leading to a high risk of bleeding. In milder cases, factor VII activity may be between 5-40% of normal, leading to a lower risk of bleeding. Treatment typically involves replacement therapy with fresh frozen plasma or recombinant factor VIIa to control bleeding episodes and prevent complications.
An amniotic fluid embolism (AFE) is a rare but serious condition that can occur during pregnancy, labor, or shortly after delivery. It occurs when amniotic fluid, fetal cells, hair, or other debris enter the mother's bloodstream and block the flow of blood to the lungs or other parts of the body. This can cause a range of symptoms including sudden shortness of breath, rapid heartbeat, low blood pressure, chills, and in severe cases, cardiac arrest or seizures. AFE is a medical emergency that requires immediate treatment.
The exact causes of amniotic fluid embolism are not well understood, but it is thought to occur when there is a disruption in the placental barrier that allows amniotic fluid and fetal debris to enter the mother's bloodstream. Risk factors for AFE include advanced maternal age, cesarean delivery, placenta previa, and other pregnancy complications.
Treatment for AFE typically involves supportive care, such as oxygen therapy, medications to support blood pressure and heart function, and in some cases, surgery to remove the blockage from the blood vessels. Despite treatment, AFE can be a life-threatening condition with significant morbidity and mortality rates.
Blood coagulation tests, also known as coagulation studies or clotting tests, are a series of medical tests used to evaluate the blood's ability to clot. These tests measure the functioning of various clotting factors and regulatory proteins involved in the coagulation cascade, which is a complex process that leads to the formation of a blood clot to prevent excessive bleeding.
The most commonly performed coagulation tests include:
1. Prothrombin Time (PT): Measures the time it takes for a sample of plasma to clot after the addition of calcium and tissue factor, which activates the extrinsic pathway of coagulation. The PT is reported in seconds and can be converted to an International Normalized Ratio (INR) to monitor anticoagulant therapy.
2. Activated Partial Thromboplastin Time (aPTT): Measures the time it takes for a sample of plasma to clot after the addition of calcium, phospholipid, and a contact activator, which activates the intrinsic pathway of coagulation. The aPTT is reported in seconds and is used to monitor heparin therapy.
3. Thrombin Time (TT): Measures the time it takes for a sample of plasma to clot after the addition of thrombin, which directly converts fibrinogen to fibrin. The TT is reported in seconds and can be used to detect the presence of fibrin degradation products or abnormalities in fibrinogen function.
4. Fibrinogen Level: Measures the amount of fibrinogen, a protein involved in clot formation, present in the blood. The level is reported in grams per liter (g/L) and can be used to assess bleeding risk or the effectiveness of fibrinogen replacement therapy.
5. D-dimer Level: Measures the amount of D-dimer, a protein fragment produced during the breakdown of a blood clot, present in the blood. The level is reported in micrograms per milliliter (µg/mL) and can be used to diagnose or exclude venous thromboembolism (VTE), such as deep vein thrombosis (DVT) or pulmonary embolism (PE).
These tests are important for the diagnosis, management, and monitoring of various bleeding and clotting disorders. They can help identify the underlying cause of abnormal bleeding or clotting, guide appropriate treatment decisions, and monitor the effectiveness of therapy. It is essential to interpret these test results in conjunction with a patient's clinical presentation and medical history.
Fibrin is defined as a protein that is formed from fibrinogen during the clotting of blood. It plays an essential role in the formation of blood clots, also known as a clotting or coagulation cascade. When an injury occurs and bleeding starts, fibrin threads form a net-like structure that entraps platelets and red blood cells to create a stable clot, preventing further loss of blood.
The process of forming fibrin from fibrinogen is initiated by thrombin, another protein involved in the coagulation cascade. Thrombin cleaves fibrinogen into fibrin monomers, which then polymerize to form long strands of fibrin. These strands cross-link with each other through a process catalyzed by factor XIIIa, forming a stable clot that protects the wound and promotes healing.
It is important to note that abnormalities in fibrin formation or breakdown can lead to bleeding disorders or thrombotic conditions, respectively. Proper regulation of fibrin production and degradation is crucial for maintaining healthy hemostasis and preventing excessive clotting or bleeding.
Chromogenic compounds are substances that can be converted into a colored product through a chemical reaction. These compounds are often used in various diagnostic tests, including microbiological assays and immunoassays, to detect the presence or absence of a specific analyte (such as a particular bacterium, enzyme, or antigen).
In these tests, a chromogenic substrate is added to the sample, and if the target analyte is present, it will react with the substrate and produce a colored product. The intensity of the color can often be correlated with the amount of analyte present in the sample, allowing for quantitative analysis.
Chromogenic compounds are widely used in clinical laboratories because they offer several advantages over other types of diagnostic tests. They are typically easy to use and interpret, and they can provide rapid results with high sensitivity and specificity. Additionally, chromogenic assays can be automated, which can help increase throughput and reduce the potential for human error.
Proteinase-activated receptor 2 (PAR-2) is a type of G protein-coupled receptor that is widely expressed in various tissues, including the respiratory and gastrointestinal tracts, skin, and nervous system. PAR-2 can be activated by serine proteases such as trypsin, mast cell tryptase, and thrombin, which cleave the N-terminal extracellular domain of the receptor to expose a tethered ligand that binds to and activates the receptor.
Once activated, PAR-2 signaling can lead to a variety of cellular responses, including inflammation, pain, and altered ion channel activity. PAR-2 has been implicated in several physiological and pathophysiological processes, such as airway hyperresponsiveness, asthma, cough, gastrointestinal motility disorders, and skin disorders.
In summary, PAR-2 is a type of receptor that can be activated by serine proteases, leading to various cellular responses and involvement in several disease processes.
Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.
In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.
Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.
HEPES (4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid) is not a medical term itself, but it is a chemical compound that is often used in biology and medicine. It is a type of buffer solution that is commonly used in cell culture and laboratory experiments to maintain a stable pH level. This is important for the survival and growth of cells and organisms in artificial environments. HEPES is a weak organic acid that can donate protons (H+) and accept them back, thus maintaining a stable pH. It has a pKa of 7.5, making it suitable for use in biological systems with a physiological pH range.
Blood coagulation disorders, also known as bleeding disorders or clotting disorders, refer to a group of medical conditions that affect the body's ability to form blood clots properly. Normally, when a blood vessel is injured, the body's coagulation system works to form a clot to stop the bleeding and promote healing.
In blood coagulation disorders, there can be either an increased tendency to bleed due to problems with the formation of clots (hemorrhagic disorder), or an increased tendency for clots to form inappropriately even without injury, leading to blockages in the blood vessels (thrombotic disorder).
Examples of hemorrhagic disorders include:
1. Hemophilia - a genetic disorder that affects the ability to form clots due to deficiencies in clotting factors VIII or IX.
2. Von Willebrand disease - another genetic disorder caused by a deficiency or abnormality of the von Willebrand factor, which helps platelets stick together to form a clot.
3. Liver diseases - can lead to decreased production of coagulation factors, increasing the risk of bleeding.
4. Disseminated intravascular coagulation (DIC) - a serious condition where clotting and bleeding occur simultaneously due to widespread activation of the coagulation system.
Examples of thrombotic disorders include:
1. Factor V Leiden mutation - a genetic disorder that increases the risk of inappropriate blood clot formation.
2. Antithrombin III deficiency - a genetic disorder that impairs the body's ability to break down clots, increasing the risk of thrombosis.
3. Protein C or S deficiencies - genetic disorders that lead to an increased risk of thrombosis due to impaired regulation of the coagulation system.
4. Antiphospholipid syndrome (APS) - an autoimmune disorder where the body produces antibodies against its own clotting factors, increasing the risk of thrombosis.
Treatment for blood coagulation disorders depends on the specific diagnosis and may include medications to manage bleeding or prevent clots, as well as lifestyle changes and monitoring to reduce the risk of complications.
Tumor Necrosis Factor-alpha (TNF-α) is a cytokine, a type of small signaling protein involved in immune response and inflammation. It is primarily produced by activated macrophages, although other cell types such as T-cells, natural killer cells, and mast cells can also produce it.
TNF-α plays a crucial role in the body's defense against infection and tissue injury by mediating inflammatory responses, activating immune cells, and inducing apoptosis (programmed cell death) in certain types of cells. It does this by binding to its receptors, TNFR1 and TNFR2, which are found on the surface of many cell types.
In addition to its role in the immune response, TNF-α has been implicated in the pathogenesis of several diseases, including autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, as well as cancer, where it can promote tumor growth and metastasis.
Therapeutic agents that target TNF-α, such as infliximab, adalimumab, and etanercept, have been developed to treat these conditions. However, these drugs can also increase the risk of infections and other side effects, so their use must be carefully monitored.
Bovine Serum Albumin (BSA) is not a medical term per se, but a biochemical term. It is widely used in medical and biological research. Here's the definition:
Bovine Serum Albumin is a serum albumin protein derived from cows. It is often used as a stabilizer, an emulsifier, or a protein source in various laboratory and industrial applications, including biochemical experiments, cell culture media, and diagnostic kits. BSA has a high solubility in water and can bind to many different types of molecules, making it useful for preventing unwanted interactions between components in a solution. It also has a consistent composition and is relatively inexpensive compared to human serum albumin, which are factors that contribute to its widespread use.
Gelatin is not strictly a medical term, but it is often used in medical contexts. Medically, gelatin is recognized as a protein-rich substance that is derived from collagen, which is found in the skin, bones, and connective tissue of animals. It is commonly used in the production of various medical and pharmaceutical products such as capsules, wound dressings, and drug delivery systems due to its biocompatibility and ability to form gels.
In a broader sense, gelatin is a translucent, colorless, flavorless food ingredient that is derived from collagen through a process called hydrolysis. It is widely used in the food industry as a gelling agent, thickener, stabilizer, and texturizer in various foods such as candies, desserts, marshmallows, and yogurts.
It's worth noting that while gelatin has many uses, it may not be suitable for vegetarians or those with dietary restrictions since it is derived from animal products.
Recombinant factor VIIa
Thromboelastometry
Acute liver failure
Coagulation factor VII
Tissue factor
Intracerebral hemorrhage
Antithrombin
Major trauma
Emergency bleeding control
Acquired haemophilia
Peptic ulcer disease
Jeanne Lusher
Coen Hemker
Factor X
Jehovah's Witnesses
Maxygen
Discovery and development of direct Xa inhibitors
PAPOLA
Glanzmann's thrombasthenia
Wendy Young
Disseminated intravascular coagulation
Prothrombinase
Platelet
Cangene
Abdominal pregnancy
Plateletpheresis
Stephan A. Mayer
List of MeSH codes (D12.776.124)
LRP1
Factor IX
Recombinant factor VIIa - Wikipedia
coagulation factor VIIa (injection) | Cigna
JCI - Binding of human factor VII and VIIa to monocytes.
Brain/Neurological Diseases UCLA Clinical Trial | Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial | UCLA Health...
Alteration of the Substrate and Inhibitor Specificities of Blood Coagulation Factor VIIa: Importance of Amino Acid Residue K192...
Coagulation Factor VIIa Market Opportunity - Article Pedia
Recombinant Factor VIIA in the Treatment of Bleeding
Postpartum Hemorrhage in Emergency Medicine Medication: Uterotonics
Thrombasthenia Medication: Antifibrinolytic agents, Vasopressin analogs, Clotting factors, Hemostatic agents, topical
Coagulation Factor VIIa (F7a) (Recombinant) in: Extended Stability for Parenteral Drugs
Coagulation Factor VIIa (F7a) (Recombinant) in: Extended Stability for Parenteral Drugs
Factor VIIa for correction of traumatic coagulopathy.<...
Protein C inhibitor inhibits factor VIIa when bound to tissue factor - Fingerprint - Johns Hopkins University
Vol. 141 No. 2728 (2011) | Swiss Medical Weekly
Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. - Radcliffe Department of...
Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: An individual patient based meta-analysis of two...
Therapy with Recombinant Factor VIIa for Uncontrollable Hemorrhage in a Patient with a Qualitative or Quantitative Platelet...
Structural model of tissue factor (TF) and TF-factor VIIa complex in a lipid membrane : A combined experimental and...
NovoSeven (recombinant factor VIIa) for the treatment of bleeding episodes and perioperative management in patients with...
NovoSeven® RT 1.0mg, 2.0mg, 5.0mg and 8.0mg - MyDr.com.au
Transfusion and Autotransfusion: Overview, Indications, Component Transfusion
JCI - A coagulation defect arising from heterozygous premature termination of tissue factor
Factor Va human ≥1500 units/mg protein | Sigma-Aldrich
SciELO - Brazil - Procoagulant properties of human MV3 melanoma cells Procoagulant properties of human MV3 melanoma cells
First potential treatment for intracerebral hemorrhage
Drugs - Drug and supplement information - MayoClinic.org
Drugs - Drug and supplement information - MayoClinic.org
SCOP 1.73: Species: Human (Homo sapiens) [TaxId: 9606]
Karafoulidou A[au] - Search Results - PubMed
Novoseven6
- Recombinant factor VIIa also known as eptacog alfa (INN), and sold under the brand name Novoseven among others, is a form of blood factor VII that has been manufactured via recombinant technology. (wikipedia.org)
- Novoseven RT is indicated for the treatment of bleeding episodes and peri-operative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann's thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets and for the treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia. (wikipedia.org)
- Do not use NovoSeven® RT and blood clotting factor concentrates at the same time. (mydr.com.au)
- She hopes NovoSeven®, or recombinant activated factor VIIa, will. (news-medical.net)
- Factor VIIa, recombinant (NovoSeven® RT) and coagulation factor VIIa (recombinant)-jncw (SevenFact®) are coagulation factors. (wellcare.com)
- Saxon, B.R., Shanks, D., Jory, C.B. and Williams, V. (2001) Effective prophylaxis with daily recombinant factor VIIa (rFVIIa.Novoseven) in child with high titre inhibitors and target joint. (scirp.org)
RFVIIa10
- Recombinant factor VIIa (rFVIIa) has become available for treating people with hemophilia with inhibitors who experience bleeding or require surgery. (medscape.com)
- This has become the case for treatment of hemorrhage with recombinant factor VIIa (rFVIIa). (medscape.com)
- Originally, rFVIIa was developed for the treatment of bleeding complications in patients with hemophilia with alloantibodies (inhibitors) against exogenous factor VIII or IX. (medscape.com)
- We describe the uses of rFVIIa in conditions unrelated to hemophilia and the treatment of acquired inhibitors of factors VIII and IX. (medscape.com)
- This increase in the thrombin burst occurs after direct rFVIIa activation of factors IX and X on the surface of activated platelets (even in the absence of factor VIII or IX). (medscape.com)
- The rFVIIa seems to work in a TF-independent manner directly on factors IX and X on the phospholipid surface of activated platelets. (medscape.com)
- rFVIIa is able to activate factor X on phospholipid vesicles, activated platelets, or monocytes independent of TF, although the TF-independent generation of thrombin is much less efficient than the TF-dependent thrombin generation by rFVIIa. (medscape.com)
- BACKGROUND: Recombinant factor VIIa (rFVIIa) is licensed for use in patients with haemophilia and inhibitory allo-antibodies and for prophylaxis and treatment of patients with congenital factor VII deficiency. (ox.ac.uk)
- Infusion of recombinant Factor VIIa (rFVIIa) may help control the bleeding. (medicalalgorithms.com)
- To assess the role of early prophylaxis with recombinant activated factor VII (rFVIIa) in young haemophiliacs with inhibitors and to determine whether it can reduce bleeding episodes and prevent joint damage. (scirp.org)
Tissue8
- Thus the monocyte binding sites appear to represent tissue factor. (jci.org)
- At the site of injury, tissue factor (TF) and factor VIIa activate factors X and IX. (medscape.com)
- It was observed that tumor cells strongly accelerate plasma coagulation as a result of: i) expression of the blood clotting initiator protein, a tissue factor, as shown by flow cytometry and functional assays (factor Xa formation in the presence of cells and factor VIIa), and ii) direct activation of prothrombin to thrombin by cells, as evidenced by hydrolysis of the synthetic substrate, S-2238, and the natural substrate, fibrinogen. (scielo.br)
- Tissue factor (TF) is a 47-kDa membrane-bound protein that serves as a receptor and co-factor for the enzyme factor VIIa (FVIIa), with subsequent formation of the extrinsic tenase complex that converts factor X (FX) to FXa (2). (scielo.br)
- It looks promising for intracerebral hemorrhage patients as well because it works at sites where there is tissue factor, which is exposed at sites of blood vessel injury. (news-medical.net)
- Much like tissue plasminogen activator, or tPA, the first drug FDA approved to treat clot-based or ischemic strokes, activated factor VIIa for hemorrhage needs to be given as soon as possible after the onset of symptoms to minimize damage and maximize recovery, Dr. Hall says. (news-medical.net)
- Binding of Factor VIIa to tissue factor on keratinocyte induces gene expression.J. Biol. (thermofisher.com)
- Factor VII/tissue factor complex activates factor IX and factor X. Factor IXa along with factor VIIIa results in formation of more factor Xa. (medscape.com)
Hemorrhage5
- Recombinant human factor VII, while initially looking promising in intracerebral hemorrhage, failed to show benefit following further study and is no longer recommended. (wikipedia.org)
- Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. (medscape.com)
- Mayer SA, Brun NC, Begtrup K. Recombinant activated factor VII for acute intracerebral hemorrhage. (medscape.com)
- Recombinant factor VIIa may be the first proven treatment for intracerebral hemorrhage. (ccjm.org)
- Factor IX is the treatment of choice for acute hemorrhage or presumed acute hemorrhage in patients with hemophilia B. Recombinant factor IX is the preferred source for replacement therapy. (medscape.com)
Inhibitors12
- Sevenfact [coagulation factor VIIa (recombinant)-jncw] is approved for use in the United States and is indicated for the treatment and control of bleeding episodes occurring in adults and adolescents twelve years of age and older with hemophilia A or B with inhibitors (neutralizing antibodies). (wikipedia.org)
- The safety and efficacy of coagulation factor VIIa (recombinant)-jncw were determined using data from a clinical study that evaluated 27 patients with hemophilia A or B with inhibitors, which included treatment of 465 mild or moderate, and three severe bleeding episodes. (wikipedia.org)
- Another study evaluated the safety and pharmacokinetics of three escalating doses of coagulation factor VIIa (recombinant)-jncw in 15 subjects with severe hemophilia A or B with or without inhibitors. (wikipedia.org)
- Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report. (nih.gov)
- However, one-third of patients with hemophilia A and up to 5 percent with hemophilia B develop inhibitors from this factor replacement therapy that render the treatment ineffective. (chop.edu)
- A long-term technique called immune tolerance induction uses repeated injections of factor to eliminate inhibitors, but more than 40 percent of patients fail this therapy. (chop.edu)
- He added, "Because factor VIIa bypasses the need for factor VIII or IX, it should work in both hemophilia A and hemophilia B. Furthermore, it works whether or not inhibitors are present in the blood. (chop.edu)
- Abshire, T. and Kenet, G. (2004) Recombinant factor VIIa: Review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. (scirp.org)
- Obergfell, A., Auven, M.K. and Mathew, P. (2008) Recombinant activated factor VII for hemophilia patients with inhibitors undergoing orthopedic surgery: A review of literature. (scirp.org)
- Young, G., McDaniel, M. and Nugent, D.J. (2005) Prophylactic recombinant factor VIIa in haemophiliac patients with inhibitors. (scirp.org)
- Blatny, J. and Smith, O. (2008) Prophylaxis with recombinant factor VIIa during immune tolerance treatment in a boy with severe haemophilia A and high-response inhibitors. (scirp.org)
- Feiba is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation factor VIII or coagulation factor IX. (medicinenet.com)
Protein4
- Coagulation factor VIIa is a man-made protein similar to a natural protein in the body that helps the blood to clot. (cigna.com)
- Blood coagulation involves a series of zymogen acti-vation reactions that are mainly performed by enzyma- tic complexes consisting of a serine protease, a protein co-factor and membranes containing anionic phospholipids (1). (scielo.br)
- The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions. (embl.de)
- This product contains a man-made form of factor VIIa, which is a protein (clotting factor) in the blood that works with other clotting factors to help the blood clot and stop bleeding. (kaiserpermanente.org)
Prophylaxis4
- In people with hemophilia type A and B who have a deficiency of factors VIII and IX, these two factors are administered for controlling bleeding or as prophylaxis medication before starting surgeries. (wikipedia.org)
- The gene expressed factor VIIa with a dose-dependent effect, simulating prophylaxis. (chop.edu)
- Used for control and prevention of hemorrhagic episodes and surgical prophylaxis in patients with factor VII (FVII) deficiency. (medscape.com)
- Todd T, J Perry D. A review of long-term prophylaxis in the rare inherited coagulation factor deficiencies. (medscape.com)
Deficiency11
- There is a significant risk of arterial thrombosis with its use and thus, other than in those with factor VII deficiency, it should only be given in clinical trials. (wikipedia.org)
- Other indications include use for patients with acquired hemophilia, people born with a deficiency of factor VII, and people with Glanzmann's thrombasthenia. (wikipedia.org)
- Coagulation factor VIIa is used to treat or prevent bleeding in people with hemophilia A or hemophilia B, or factor VII deficiency. (cigna.com)
- Hemophilia B, or Christmas disease, is an inherited, recessive disorder that involves deficiency of functional coagulation factor IX (FIX) in plasma. (medscape.com)
- Mandhyan R, Tiwari A, Cherian G. Congenital factor VII deficiency. (medscape.com)
- Inherited factor VII deficiency: genetics and molecular pathology. (medscape.com)
- Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. (medscape.com)
- Mariani G, Bernardi F. Factor VII Deficiency. (medscape.com)
- Surgery in patients with congenital factor VII deficiency: A single center experience. (medscape.com)
- Mariani G, Dolce A, Marchetti G, Bernardi F. Clinical picture and management of congenital factor VII deficiency. (medscape.com)
- Mariani G, Lapecorella M, Dolce A. Steps towards an effective treatment strategy in congenital factor VII deficiency. (medscape.com)
Sevenfact1
- Coagulation factor VIIa (recombinant)-jncw (Sevenfact) is expressed in the mammary gland of genetically engineered rabbits and secreted into the rabbits' milk. (wikipedia.org)
Prophylactic3
- While factor VIIa continues to be widely used, we still don't know what the level of circulating factor VIIa needs to be in order to use it safely on a prophylactic basis in humans," said Margaritis. (chop.edu)
- For the first time, we have threshold levels of factor VIIa for prophylactic use," said Margaritis. (chop.edu)
- 2007) Prophylactic treatment of haemophilia patients with inhibittors: Clinical experience with recombinant factor VIIa in European Haemophilia Centers. (scirp.org)
Haemophilia2
- Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. (ox.ac.uk)
- This is the third version of the 2007 Cochrane review on the use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia, and has been updated to incorporate recent trial data. (ox.ac.uk)
Prothrombin to thrombin1
- Factor Xa along with factor Va converts prothrombin to thrombin. (medscape.com)
Bound2
- The rate of conversion of Factor X to Xa in mixtures containing Factor VIIa and monocytes was directly related to the quantity of Factor VIIa bound to the monocyte surface. (jci.org)
- Factor VIIa bound to TF on the cell surface activates Factor IX to Factor IXa and Factor X to Factor Xa. (merckvetmanual.com)
Thrombin2
- The decrease in fibrinolysis might be due to an increase in thrombin-activatable fibrinolysis inhibitor and an increase in factor XIIIa. (medscape.com)
- Factor V is a key component in blood coagulation systems, where deficiencies can inhibit thrombin generation and affect hemostasis. (sigmaaldrich.com)
Bypasses1
- Recombinant factor VIIa, which is an activated form of factor VII, bypasses factors VIII and IX and causes coagulation without the need for factors VIII and IX. (wikipedia.org)
Hemophilia patients1
- Activated factor VIIa is a substance certain hemophilia patients may not have enough of. (news-medical.net)
VIII or IX1
- Recombinant factor VIIa is a potent prohaemostatic agent that is licensed for the treatment of patients with inhibiting antibodies towards factor VIII or IX. (nataonline.com)
Aprotinin2
- Aprotinin, tranexamic acid, recombinant factor VIIa, low central venous pressure, and thromboelastography may lower blood loss and transfusion requirements. (cochrane.org)
- Aprotinin, recombinant factor VIIa, and thromboelastography groups may potentially reduce blood loss and transfusion requirements. (cochrane.org)
Monocytes3
- Binding of human factor VII and VIIa to monocytes. (jci.org)
- Human coagulation Factors VII and VIIa bind with equal affinity to monocytes stimulated with endotoxin. (jci.org)
- Ca++ was required for Factor VII and VIIa interaction with monocytes (optimal CaC12 concentration greater than or equal to 2.5 mM) and binding was reversed by the addition of EDTA. (jci.org)
Clinical3
- Because you will receive coagulation factor VIIa in a clinical setting, you are not likely to miss a dose. (cigna.com)
- Margaritis explained that the thresholds of circulating factor VIIa that prevented bleeding episodes in animals can be incorporated into future clinical trials in patients. (chop.edu)
- Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. (medscape.com)
Medication2
- Coagulation factor VIIa may also be used for purposes not listed in this medication guide. (cigna.com)
- This medication is used to treat and prevent bleeding in people with certain conditions (such as hemophilia type A or B, low levels of factor VII, Glanzmann's thrombasthenia). (kaiserpermanente.org)
Glycoprotein2
- Factor V, a glycoprotein is usually seen in the alpha granules of platelets and in plasma. (sigmaaldrich.com)
- Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. (lu.se)
Serves as a receptor1
- Factor Va serves as a receptor and positive effector of factor Xa. (sigmaaldrich.com)
Platelet2
- The evidence for the use of recombinant human activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders. (medscape.com)
- Fresh whole blood has long been thought of as the criterion standard for transfusion, but the advent of whole blood fractionation techniques subsequent to World War II provided a means of more efficient use of the various components (i.e., packed red blood cells [PRBCs], fresh frozen plasma [FFP], individual factor concentrates, platelet concentrates, cryoprecipitate). (medscape.com)
Concentrates2
- Older patients who received unpurified plasma‐derived clotting factor concentrates may have signs and symptoms of infectious disease (eg, hepatitis, HIV infection). (medscape.com)
- Clotting factor concentrates promote hemostasis by providing the deficient clotting factor to the coagulation cascade. (medscape.com)
Infusion2
- The most common side effects of coagulation factor VIIa (recombinant)-jncw are headache, dizziness, infusion site discomfort, infusion related reaction, infusion site hematoma and fever. (wikipedia.org)
- Thromboembolic events have been reported during post-marketing surveillance following infusion of Feiba, particularly following the administration of high doses and/or in patients with thrombotic risk factors. (medicinenet.com)
Coagulation cascade1
- Injury and factors released by platelets initiate the coagulation cascade, which is mediated by blood clotting factors. (medscape.com)
Antibodies1
- Patients who develop antibodies to the coagulation factors usually prescribed for hemophilia have a complicated treatment," said study leader Paris Margaritis, DPhil , a hematology researcher in the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at Children's Hospital of Philadelphia (CHOP). (chop.edu)
Dose1
- Also previous studies showed that the use of high dose recombinant factor VIIa in particularly an elderly population was associated with an increased risk of thromboembolic complications. (nataonline.com)
Exogenous factor1
- This ability was highly potentiated by the addition of exogenous factor Va, which functions as a co-factor for the enzyme factor Xa. (scielo.br)
Allergic1
- You should not receive coagulation factor VIIa if you are allergic to it. (cigna.com)
Acute1
- Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: An individual patient based meta-analysis of two controlled trials. (nataonline.com)
Proteins6
- Coagulation factor VIIa (recombinant)-jncw is contraindicated in those with known allergy or hypersensitivity to rabbits or rabbit proteins. (wikipedia.org)
- Competition experiments showed that Factor VII and VIIa bind to the same monocyte sites and further, that unlabeled Factor VII and VIIa have the same affinity for the binding sites as the 125I-labeled proteins. (jci.org)
- A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF) has been shown [ ( PUBMED:2288911 ) ( PUBMED:6334307 ) ( PUBMED:6607417 ) ( PUBMED:3282918 ) ] to be present, in a more or less conserved form, in a large number of other, mostly animal proteins. (embl.de)
- Various diverse extracellular proteins possess Ca(2+)-binding epidermal growth factor (EGF)-like domains, the function of which remains uncertain. (embl.de)
- Several complementary DNA clones encoding related HRGs were identified, all of which are similar to proteins in the epidermal growth factor family. (embl.de)
- Several ECM proteins such as laminin, tenascin and thrombospondin contain domains with homology to epidermal growth factor (EGF) and exhibit growth promoting activity. (embl.de)
Bleeding6
- As of 2012, recombinant factor VIIa is not supported by the evidence for treating most cases of major bleeding. (wikipedia.org)
- Likewise, two previous studies in patients with variceal bleeding in liver cirrhosis did not find a significant effect of the administration of recombinant factor VIIa on the number of 5-day treatment failures. (nataonline.com)
- The authors conclude that their analysis showed a beneficial effect of recombinant factor VIIa on the control of variceal bleeding in cirrhosis, in particular in case of active bleeding and more severe liver cirrhosis. (nataonline.com)
- Taken together, it is really premature to advocate the use of recombinant factor VIIa for variceal bleeding in cirrhosis. (nataonline.com)
- In these experiments, they deliver corrective DNA carrying the coded instructions to produce factor VIIa and reduce bleeding episodes. (chop.edu)
- Factor that reached a specific level in the bloodstream reduced bleeding in the hemophilia A rats, and at a higher level, eliminated those bleeds altogether. (chop.edu)
Binding2
- Equilibrium binding studies performed at 0 degrees C using 125I-labeled Factor VII and VIIa showed the dissociation constant (Kd) to be congruent to 82 pM with congruent to 3,600 binding sites/monocyte. (jci.org)
- Factor VII binding to TF results in activation to Factor VIIa. (merckvetmanual.com)
Gene2
- The study team used adeno-associated virus (AAV) as a vector to deliver a rat factor VIIa gene. (chop.edu)
- In addition we will address important areas of modern epidemiology such as the influence of early life factors on adult health and disease, but also the importance of the gene-diet-microbiota interaction for body function and health. (lu.se)
Complex3
- For those relapsed patients, the only alternative is to implement a bypass strategy, infusing other compounds that enable the blood to coagulate: activated recombinant clotting factor VIIa, activated prothrombin complex, or more recently, an antibody that has just been approved by the FDA for all hemophilia A patients. (chop.edu)
- FVIII and von Willebrand factor (vWF) circulate in plasma as a noncovalent bimolecular complex. (merckvetmanual.com)
- We have determined, at high resolution (1.5 A), the crystal structure of such a domain, from human clotting factor IX, as a complex with Ca2+. (embl.de)
Cofactor1
- Factor Va is the activated form of factor V and the cofactor of Xa. (sigmaaldrich.com)
Blood4
- citation needed] It is important for some patients to shift to proper blood factors according to their inhibitor titer. (wikipedia.org)
- It is similar to the activated factor VII (7) in human blood. (mydr.com.au)
- A different factor, called coagulation factor VIIa, restores blood clotting when given after a bleed occurs, but we don't know the target level of circulating factor VIIa that would prevent bleeds before they start. (chop.edu)
- Managing hemophilia may involve a series of measures and countermeasures, in which clinicians make use of blood factors. (chop.edu)
Patients2
- MCG is one of about 100 sites worldwide looking at whether patients with this type of stroke - often resulting from the rupture of fragile arteries branching off the main arteries of the brain - can benefit from rapid delivery of a factor that is part of the body's natural clotting process. (news-medical.net)
- Novo Nordisk A/S, the pharmaceutical company that is the main source of the bypass agent VIIa for patients, provided the rats. (chop.edu)
Inhibitor1
- Each vial of Feiba contains the labeled amount of factor VIII inhibitor bypassing activity in units. (medicinenet.com)
Therapy1
- Di Paola J, Nugent D, Young G. Current therapy for rare factor deficiencies. (medscape.com)
Human1
- One unit is equivalent to the Factor V activity in 1.0 mL of normal human plasma at pH 7.4 at 37 °C. (sigmaaldrich.com)
Activation1
- In contrast, prothrombin activation was not observed when cells were previously incubated with DEGR-factor Xa, an inactive derivative of the enzyme. (scielo.br)
Risk factors3
- Traditional CVD Risk Factors and Socio-Economic Deprivation in Roma Minority Population of Croatia (str. (srce.hr)
- Amniotic fluid embolism incidence, risk factors and outcomes: a review and recommendations. (msdmanuals.com)
- As with exposure to fetal antigens, many of the risk factors are commonplace or at least much more likely than amniotic fluid embolism, and there is no good pathophysiologic understanding of why only a few women with risk factors develop the syndrome. (msdmanuals.com)
Tell your doctor1
- If possible before you receive coagulation factor VIIa, tell your doctor about all your medical conditions and allergies. (cigna.com)
Form1
- Prekallikrein is cleaved by Factor XII to form kallikrein, which then cleaves Factor XII first to alpha-factor XIIa and then to beta-factor XIIa. (lu.se)