Activated Protein C–protein C Inhibitor
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Activated Protein C–protein C Inhibitor
Activated protein C–protein C inhibitor (APC-PCI) is a complex of activated protein C (APC) and protein C inhibitor (PCI). It has been measured in coagulation testing to evaluate coagulation, thrombosis, and other cardiovascular complications. It is a marker of thrombin generation and indicates hypercoagulability. The half-life of APC-PCI is either 40 minutes or 140minutes. Ethinylestradiol-containing birth control pills have been found to increase levels of APC-PCI to a similar degree as thrombin–antithrombin complex (TAT) and to a greater extent than D-dimer D-dimer (or D dimer) is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein joined by a cross .... However, only APC-PCI was able to differentiate between a second- and third-generation birth control pill. Another complex related to APC-PCI is the activated protein Câ ...
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Activated Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintaining the permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolytically inactivating proteins Factor Va and Factor VIIIa. APC is classified as a serine protease since it contains a residue of serine in its active site. In humans, protein C is encoded by the ''PROC'' gene, which is found on chromosome 2. The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond. The protein C zymogen is activated when it binds to thrombin, another protein heavily involved in coagulation, and protein C's a ...
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Protein C Inhibitor
Protein C inhibitor (PCI, SERPINA5) is a serine protease inhibitor (serpin) that limits the activity of protein C (an anticoagulant). An N-terminal fragment of PCI is a possible serum biomarker for prostate cancer. Protein C inhibitor is activated by heparin against thrombin. Protein C inhibitor (PCI) is serine protease inhibitor of serpin type that is found in most tissues and fluids, including blood plasma, seminal plasma and urine of human. It is a 52kD glycoprotein and belongs to serine protease inhibitor ( Serpin) super family of protein. In the beginning protein C Inhibitor (PCI) was identified as an inhibitor of activated protein C (APC), it is currently clear that this inhibitor has an expansive specificity, inhibiting several blood coagulation enzymes counting thrombin and factor Xa. Isolation In the beginning, protein C inhibitor(PCI) was originally identified in human plasma by Griffin and Marlar and first isolation was performed by Suzuki et al. Protein C inhibitor ...
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Coagulation Testing
Blood clotting tests are the tests used for diagnostics of the hemostasis system. Coagulometer is the medical laboratory analyzer used for testing of the hemostasis system. Modern coagulometers realize different methods of activation and observation of development of blood clots in blood or in blood plasma. Classification of blood clotting tests Substantially all coagulometers used in laboratory diagnostics are based on the methods of testing of the hemostasis system created more than fifty years ago. The majority of these methods are good to detect defects in one of the hemostasis components, without diagnosing other possible defects. Another problem of the actual hemostasis system diagnostics is the thrombosis prediction, i.e. sensitivity to the patient's prethrombotic state. All the diversity of clinical tests of the blood coagulation system can be divided into 2 groups: global (integral, general) tests, and «local» (specific) tests. Global tests Global tests, also known as gl ...
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Coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin. Coagulation begins almost instantly after an injury to the endothelium lining a blood vessel. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial tissue factor to plasma factor VII, which ultimately leads to cross-linked fibrin formation. Platelets immediately form a plug at the site of injury; this is called ''primary hemostasis. Secondary hemostasis'' occurs simultaneously: additional coagulation (clotting) factors beyond factor VII ( listed below) respond in a cascade to form fibrin strands, which strengthen the platelet plug. Disorders of ...
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Thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus. Thrombosis may occur in veins (venous thrombosis) or in arteries (arterial thrombosis). Venous thrombosis (sometimes called DVT, deep vein thrombosis) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery (ischemia and necrosis). A piece of either an arterial or a venous thrombus can break off as an embolus, which could ...
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Cardiovascular Complication
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina pectoris, angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, arrhythmia, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, Thrombosis, thromboembolic disease, and venous thrombosis. The underlying mechanisms vary depending on the disease. It is estimated that dietary risk factors are associated with 53% of CVD deaths. Coronary artery disease, stroke, and peripheral artery disease involve atherosclerosis. This may be caused by hypertension, high blood pressure, tobacco smoking, smoking, diabetes mellitus, lack of physical exercise, exercise, obesity, hypercholesterolaemia, high blood cholesterol, poor diet, excessive alcoholi ...
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Biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. as cited in Biomarkers are used in many scientific fields. Medicine Biomarkers used in the medical field, are a part of a relatively new clinical toolset categorized by their clinical applications. The three main classes are molecular biomarkers, cellular biomarkers or imaging biomarkers. All three types of biomarkers have a clinical role in narrowing or guiding treatment decisions and follow a sub-categorization of being either predictive, prognostic, or diagnostic. Predictive Predictive molecular, cellular, or imaging biomarkers that pass validation can serve as a method of predicting clinical outcomes. Predictive biomarkers are used to help optimize id ...
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Thrombin Generation
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma-thrombin'') is a serine protease, an enzyme that, in humans, is encoded by the ''F2'' gene. Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions. History After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872. Prothrombin was discovered by Pekelharing in 1894. Physiology Synthesis Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly ...
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Hypercoagulability
Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who have an episode of thrombosis (such as deep vein thrombosis in the leg) that was not provoked by other causes. A significant proportion of the population has a detectable thrombophilic abnormality, but most of these develop thrombosis only in the presence of an additional risk factor. There is no specific treatment for most thrombophilias, but recurrent episodes of thrombosis may be an indication for long-term preventive anticoagulation. The first major form of thrombophilia to be identified by medical science, antithrombin deficiency, was identified in 1965, while the most common abnormalities (including factor V Leiden) were described in the 1990s. Signs and symptoms The most common conditions associated with thrombophilia are deep v ...
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Elimination Half-life
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma, and is denoted by the abbreviation t_. This is used to measure the removal of things such as metabolites, drugs, and signalling molecules from the body. Typically, the biological half-life refers to the body's natural cleansing through the function of the liver and through the excretion of the measured substance through the kidneys and intestines. This concept is used when the rate of removal is roughly exponential. In a medical context, half-life explicitly describes the time it takes for the blood plasma concentration of a substance to halve (''plasma half-life'') its steady-state when circulating in the full blood of an organism. This measurement is useful in medicine, pharmacology and pharmacokinetics because it helps det ...
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Ethinylestradiol
Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring. The general side effects of EE include breast tenderness and enlargement, headache, fluid retention, and nausea among others. In men, EE can additionally cause breast development, feminization in general, hypogonadism, and sexual dysfunction. Rare but serious side effects include blood clots, liver damage, and cancer of the uterus. EE is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol. It is a synthetic derivative of estradiol, a natural estrogen, and differs from it in various ways. Compared to estradiol, EE has greatly improved bioavailability when taken by m ...
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Birth Control Pill
The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progestin (a synthetic form of the hormone progestogen/progesterone) and estrogen (usually ethinylestradiol and 17β estradiol). When taken correctly, it alters the menstrual cycle to eliminate ovulation and prevent pregnancy. COCPs were first approved for contraceptive use in the United States in 1960, and are a very popular form of birth control. They are used by more than 100 million women worldwide and by about 9 million women in the United States. From 2015 to 2017, 12.6% of women aged 15–49 in the US reported using COCPs, making it the second most common method of contraception in this age range (female sterilization is the most common method). Use of COCPs, however, varies widely by country, age, education, and marital status. For exam ...
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