Thrombosis proteins

Two types of Protein S deficiency have been described. In type I deficiency there is tittle to no free Protein S but normal amounts of bound Protein S are present. In type II Protein S deficiency both free and bound Protein S are very low to absent. Deficiency of free Protein S is associated with venous and arterial thrombosis. 

Hemostasis is the cessation of bleeding from a cut or severed vessel, whereas thrombosis occurs when the endothelium lining blood vessels is damaged or removed (eg, upon rupmre of an atherosclerotic plaque). These processes encompass blood clotting (coagulation) and involve blood vessels, platelet aggregation, and plasma proteins that cause formation or dissolution of platelet aggregates. 

An important namral inhibitor of coagulation is antithrombin III genetic deficiency of this protein can result in thrombosis. 

The chapter on plasma proteins, immunoglobulins, and blood coagulation in the previous edition has been split into two new chapters on plasma proteins and immunoglobuhns and on hemostasis and thrombosis. 

Section VI consists of discussions of eleven special topics nutrition, digestion, and absorption vitamins and minerals intracellular traffic and sorting of proteins glycoproteins the extracellular matrix muscle and the cy-toskeleton plasma proteins and immunoglobulins hemostasis and thrombosis red and white blood cells the metabolism of xenobiotics and the Human Genome Project. 

Describe the processes of hemostasis and thrombosis, including the role of the vascular endothelium, platelets, coagulation cascade, and thrombolytic proteins. 

Mutations in the antithrombin (AT) gene have been the basis of AT deficiency. In type I AT deficiency the level of circulating protein molecule and activity are reduced to nearly 50% of normal. Molecular defects in the AT gene resulting in gene deletions at specific DNA sequences may be the basis for type I AT deficiency predisposing such patients to thrombosis (82). 

Individuals with heterozygous protein C deficiency are seven times more likely to be afflicted with venous thrombosis than normal individuals. A combination of protein C deficiency with a mutation in the factor V gene (factor V Leiden) carries a much greater risk for venous thrombosis than the presence of only one of these conditions (89). 

By far the most widely measured marker of hemostatic activation is D-dimer, which is a product formed by the action of plasmin on cross-linked fibrin (95). D-dimer levels in plasma are generally elevated in DIC. The consumption of platelets and coagulation proteins as a result of thrombin generation leads to the deposition of fibrin thrombi at multiple organ sites. This triggers fibrinolysis with an increase in the formation of fibrin degradation products, which can cause bleeding at multiple sites. Because DIC can have a variety of causes and may coexist with systemic fibrinolysis, such as in pulmonary embolism or deep vein thrombosis, the d-Dimer test is not specific for DIC (95). 

Dahlback B. Resistance to activated protein C, the Arg506 to Gin mutation in the factor V gene and venous thrombosis. Functional tests and DNA based assays, pros and cons. Thromb Haemost, 1995 73,739-42. 

EHEC all ages/primarily in US, Canada, Europe, South America and Japan 12-60h acute bloody (hemorrhagic colitis in 31— 61%) occasionally nonbloody diarrhea SLT-I and -II - bloodstream - inhibition of protein synthesis - endothelial cell damage - microvascular thrombosis - hemolytic-uremic syndrome... 

POEMS is an eponym applied to patients with a variety of plasma cell dyscrasias who present with polyneuropathy, organomegaly, endocrinopathy, an M protein and skin changes this disorder is also referred to as Crow-Fukase syndrome. Additional manifestations of this disorder are pulmonary hypertension, renal failure, a predisposition to thrombosis and congestive heart failure some of these features are likely to be attributable to vascular endothelial growth factor (VEGF) and matrix metalloproteinases, which are often elevated in the plasma of these patients [43]. 

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... 

Protein S The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors Villa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH]... 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

Like coumarin derivatives, phenindione, a compound of the indandione class, acts by altering biosynthesis of coagulant proteins in the liver. It is used for preventing and treating thrombosis, thrombophlebitis, and thromboembolism. However, because of a number of side effects such as poly urea, polydipsia, tachycardia, and others, it is rarely used in practical medicine. Synonyms of this drug are pindone, bindan, gevuUn, indan, phenyhne, and rectadione. 

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