Proteins clotting factors

Hypersensitivity reactions (fever, hypotension, rash, dyspnea in 25%), much lower risk with polyethylene gycol form low emetogenic potential pancreatitis decreased synthesis of proteins, clotting factors CNS lethargy... 

Figure 8.2 A developing blood clot is shown in this picture. A blood clot is made of platelets, membrane fragments of a bone marrow cell, and a network of insoluble proteins, particularly fibrin generated from a precursor protein, fibrinogen, through the work of a cascade of protein clotting factors. Several bleeding disorders result from inherited deficiencies in clotting proteins.

Q4 Vitamin K is a fat-soluble vitamin which is composed of a number of related compounds known as quinones. Most of the protein clotting factors in blood are produced in the liver and depend on the presence of adequate vitamin K for their synthesis. Some of the necessary vitamin K is present in the diet (in green, leafy vegetables), but most is synthesized by bacteria in the intestine. Vitamin K is particularly important in maintaining blood levels of coagulation factors II, VII, IX and X. 

Plasma electrolytes C-reactive protein Clotting factors... 

The protein-C pathway is one of the most important anticoagulant mechanisms. It is activated by thrombin. Thrombin binds to a cofactor in the membrane of endothelial cells, thrombomodulin (TM). TM bound thrombin no longer activates clotting factors or platelets but becomes an effective protein C (PC) activator. Activated PC (APC) forms a complex with Protein S, which inactivates FVIIIa and FVa. Hereby generation of Flla by the prothrombinase complex is inhibited (Fig. 9). Thus, the PC-pathway controls thrombin generation in a negative feedback manner. 

Blood plasma is the liquid part of blood, containing water, sugar, electrolytes, fats, gases, proteins, bile pigment, and clotting factors. Human plasma, also called... 

In the case of prothrombin and related clotting factors, interruption of the vitamin K cycle leads to the production of nonfunctional, undercarboxylated proteins, which are duly exported from hepatocytes into blood (Thijssen 1995). They are nonfunctional because there is a requirement for the additional carboxyl residues in the clotting process. Ionized carboxyl groups can establish links with negatively charged sites on neighboring phospholipid molecules of cell surfaces via calcium bridges. 

Vitamin E (tocopherol) is the most important antioxidant in the body, acting in the lipid phase of membranes and protecting against the effects of free radicals. Vitamin K functions as cofactor to a carboxylase that acts on glutamate residues of clotting factor precursor proteins to enable them to chelate calcium. 

Clotting factor Plasma proteins found in the blood that are essential to the formation of blood clots clotting factors circulate in inactive forms, but are activated by their predecessor in the clotting cascade or a thrombogenic substance. Each clotting factor is designated by a Roman numeral (e.g., factor VII) and by the letter a when activated (e.g., factor Vila). 

All together, 12 clotting factors are in the plasma. These factors, which are proteins synthesized in the liver, are normally found circulating in plasma... 

Rapid-acting dermally hazardous cytotoxin that inhibits protein synthesis and affects clotting factors in the blood. It is capable of producing incapacitating or lethal effects. T2 is obtained from various molds and fungi (Fusarium sp.). It is a colorless crystalline solid of white powder that melts at 304°F. Impure samples may be a colorless to slightly yellow oil. It is slightly soluble in water, but soluble in ethyl acetate, acetone, ethanol, chloroform, methylene chloride, diethyl ether, and dimethyl sulfoxide (DMSO). It is heat stable and can be stored at room temperature for years. 

The initial steps of the intrinsic pathway are somewhat more complicated. This system requires the presence of clotting factors VIII, IX, XI and XII, all of which, except for factor VIII, are endo-acting proteases. As in the case of the extrinsic pathway, the intrinsic pathway is triggered upon exposure of the clotting factors to proteins present on the surface of body tissue exposed by vascular injury. These protein binding/activation sites probably include collagen. 

Heparin is a carbohydrate-based (glycosaminoglycan) anticoagulant associated with many tissues, but mainly found stored intracellularly as granules in mast cells that line the endothelium of blood vessels. Upon release into the bloodstream, heparin binds to and thereby activates an additional plasma protein, namely antithrombin. The heparin-antithrombin complex then binds a number of activated clotting factors (including Ha, IXa, Xa, XIa and Xlla), thereby inactivating them. The heparin now disassociates from the complex and combines with another antithrombin molecule, thereby initiating another turn of this inhibitory cycle. 

Hypercoagulable states include malignancy activated protein C resistance deficiency of protein C, protein S, or antithrombin factor VIII or XI excess antiphospholipid antibodies and other situations. Estrogens and selective estrogen receptor modulators have been linked to venous thrombosis, perhaps due in part to increased serum clotting factor concentrations. Although a thrombus can form in any part of the venous circulation, the majority of thrombi begin in the lower extremities. Once formed, a venous... 

Haemostasis is achieved by the interplay between platelets, proteins within the plasma (the clotting factors) and endothelial cells. The endothelial cells lining the... 

The protein-based clotting process is a classic example of an enzyme cascade (see Figure 5.23). The clotting factors (which are designated with a Roman numeral, I to XIII) are synthesized in the liver and circulate in the blood as inactive precursors, strictiy, proenzymes. Most of the clotting factors are serine protease enzymes, that is they are enzymes which cleave other proteins (substrates) by a mechanism which involves a serine residue at the active site. 

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