Term
| the purpose of the coagulation cascade is to catalyze rapid formation of a fibrin clot through generation of the potent enzyme called: |
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Definition
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Term
| blood coagulation is under tight control so that the area of clot formation is limited to the |
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Definition
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Term
| the 6 main components of the coagulation system are: |
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Definition
1) the ultimate substrate, fibrinogen
2) cofactors
3) vitamin K dependent proteins (VKDPs)
4) initiators
5) calcium
6) phospholipids |
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Term
| formation of a fibrin blood clot results when the enzyme _____ is generated |
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Definition
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Term
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Definition
| this enzyme is able to cleave 2 small peptides from the fibrinogen molecule forming fibrin monomer which can then dimerize and mutimerize to form a large lattic like protein. |
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Term
| how does the generation of thrombin occur |
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Definition
| it occurs after a series of enzyme linked, phospholipid dependent reactions iccur on cell surfaces (PLT's, monocytes, endothelial cells, etc) |
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Term
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Definition
| immediately after injury, this is exposed at the site, and then this rapidly binds to factor 7a present in the blood |
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Term
| When tissue factor is bound to 7a, the complex is able to convert the zymogens ____1____ or ____2____ to their respective ezymes factor ___3____ or ____4_____ |
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Definition
1) factor 10
2) factor 9
3) factor 10a
4) factor 9a |
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Term
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Definition
| this is a cofactor that when added to factor 10a, is able to convert the substrate prothrombin to the enzyme thrombin |
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Term
| what is the alternate pathway that factor 10a can be generated? |
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Definition
| if factor 9a acts with its cofactor factor 8a (with inactive factor 10) |
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Term
| What are the 2 ways that you can make active factor 9a? |
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Definition
1) add factor 11a to inactive 9
2) add tissue factor/7a complex to inactive factor 9 |
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Term
| what are the two ways to make factor 11a? |
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Definition
1) thrombin acting on factor 11
2) IN VITRO- add factor 12a, prekallikrein, and HMW kininogen |
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Term
| Properties of Tissue factor |
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Definition
-a 47 kD integral membrane lipoprotein
-expressed under basal circumstances by a number of cells including vascular smooth muscle cells, pericytes, fibroblasts, brain astrocytes, epithelial cells in lungs, cardiomyocytes in heart, placental trophoblasts, etc) |
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Term
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Definition
-there is a TINY amount of circulating TF in blood
-may be in form that's not functionally active (encrypted) and may be associated with membrane microparticles derived from endothelial cells, vascular SM cells, leukocytes, and monocytes. this may be important in thrombosis developing with mittle endothelial damage |
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Term
| Decryption of microparticle TF |
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Definition
| circulating microparticle TF (encrypted) binds to/is transferring to activated platelets by interaction between PSGL1 (p-selectin glycoprotein ligand 1) on microparticle and P selectin on platelet. This 'decrypts' TF activity. |
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Term
| what are the vitamin K dependent proteins? |
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Definition
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Term
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Definition
| is an uncommon amino acid introduced into proteins by a post-translational carboxylation of glutamic acid residues. This modification is found, for example, in clotting factors and other proteins of the coagulation cascade. This modification introduces an affinity for calcium ions. In the blood coagulation cascade, Vitamin K is required to introduce gamma-carboxylation of clotting factors II, VII, IX, and X. |
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Term
| gamma-glutamyl carboxylase |
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Definition
| this reduces vitamin K, and allows for carboxylation on gamma carbon of glutamic acid when dealing with vitamin K dependent proteins function |
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Term
| what factor is needed to go from prothrombin to thrombin? |
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Definition
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Term
| Amplification occurs mainly as result of this enzyme's ability to 'activate' a number of other coagulation factors and stimulate platelets |
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Definition
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Term
| what are the negative controls of coagulation? |
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Definition
-serine protease inhibition
-degradation of cofactors
-inhibition of TF
-inhibition of platelet activation
-vWF proteolysis
-phospholipid surface sequestration |
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Term
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Definition
| clot dissolution that ensures that vessel patency is reestablished (a fibrin clot, the product of coagulation, is broken down.Its main enzyme plasmin cuts the fibrin mesh at various places, leading to the production of circulating fragments that are cleared by other proteases or by the kidney and liver.) |
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Term
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Definition
| plays a critical role in inhibiting clot formation under 'resting' conditions |
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Term
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Definition
| this cofactor is able to activate the cofactors, 5 and 8, to factors 5a and 8a through limited proteolysis, significantly enhancing the two cofactors' ability to act on proteolytic activity of factors 10a and 9a respectively. |
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Term
| activation of factor 11 to 11a can occur by 2 pathways: |
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Definition
1) thrombin can convert factor 11 to lla by limited proteolysis (most important of the 2 pathways)
2) IN VITRO (NOT IN VIVO): activation by contact factors (factor X11a, prekallikrein, and high molecular weight kininogen) |
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Term
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Definition
| thrombin is able to convert this factor to its active form which can then chemically cros link fibrin to form an insoluble clot |
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Term
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Definition
| most potent platelet activator known |
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Term
| name the several naturally occuring anticoagulants: |
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Definition
1) antithrombin (aka antithrombin-III)
2) protein C
3) protein S
4) tissue factor pathway inhibitor
all these molcules inhibit serine proteases, cofactors, and the initiator (TF) |
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Term
| does an anticoagulant do? |
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Definition
| these inhibit serine proteases, cofactors, and the initiator TF |
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Term
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Definition
| occurs when plasminogen activators convert plasminogen to active enzyme plasmin |
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Term
| Endothelial cells express/secrete these 5 things which all inhibit coagulation, inhibit platelet function, and/or cause vasodilation |
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Definition
1) thrombomodulin
2) prostacyclin
3) heparin like molecules
4) protein C receptor
5) NO |
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Term
| ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin like domains) |
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Definition
| cleaves the highest molecular weight forms of vWF into smaller forms that circulate (decreasing vWF activity) |
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Term
| Bleeding Time Test and Platelet function studies |
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Definition
| used to assess primary hemostasis |
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Term
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Definition
| this is infrequently used due to test result variability and poor correlation with bleeding |
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Term
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Definition
| The partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT or APTT) is a performance indicator measuring the efficacy of both the "intrinsic" (now referred to as the contact activation pathway) and the common coagulation pathways. Apart from detecting abnormalities in blood clotting, it is also used to monitor the treatment effects with heparin, a major anticoagulant. It is used in conjunction with the prothrombin time (PT) which measures the extrinsic pathway. These are useful, however, the reactions in the test tube do not reflect how events occur in vivo. |
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Term
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Definition
| measures the conversion of fibrinogen to fibrin |
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