Blood Coagulation Flashcards

Question

Surface receptor expression

Answer 1

* activation of platelets results in expression of PhosphatidylSerine (PS) & Phosphatidylinositol (PI) on platelet surfaces * allow platelets to contribute to secondary hemostasis (coagulation cascade) as they provide binding sites for coagulation factors * ex. VIIIa binds to PS & PI on platelet surfaces -> recruit Ca2+, IXa & X during coagulation cascade

Answer 2

* white thrombus (soft clot) + fibrin (from fibrinogen cleaved by thrombin) = red thrombus (hard clot) * Fibrin enmeshes the platelet aggregates at the sites of injury & converts the unstables primary platelet plugs to firm, definitive & stables hemostatic plugs * soft clot converted to hard clot by Fibrin stabilizing factor (XIII) which needs to be activated by thrombin before it can act on soft clot 2 pathways can lead to the formation of thrombin: * Intrinsic * Extrinsic * after activation, Factor XIII acts as enzyme to cause covalent bonds b/w fibrin monomer molecules and also multiple cross-linkages b/w adjacent fibrin fibres adding to the 3-D strength of fibrin meshwork

Answer 3

required for hepatic synthesis of factors, i.e post-translationaly mod: * II (prothrombin) * VII * IX * X * Protein C & S * serves as co-enzyme in the carboxylation of certain glutamate residues present in these factors leading to formation of mature clotting factors capable of subsequent activation * gamma-carboxylation of these residues allows more efficient Ca2+ binding b/c of 2 adjacent -ve charged carboxylase groups. This clotting factor Ca2+ complex can then bind to phospholipids on platelet membrane *

Answer 4

Inactive plasminogen gets incorporated in the developing clot * Inhibitors: Plasminogen activator inhibitor 1 & 2 * Activator: Tissue-type Plasminogen Activator, Urokinase, Streptokinase, FXIIa Active plasmin (proteolytic) degrades Fibrin * Inhibitor: alpha2-antiplasmin * Plasmin is a Ser protease * Plasminogen has a high affinity for fibrin, promoting its incorporation in the developing clot * Fibrin degradation product levels are icnreased in Pt with DVT. They are used in clinical practice to estimate the extent and rate of fibrinolysis and in follow up of Pt with thrombosis

Answer 5

* circulating protease inhibitor which rapidly inactivates circulating plasmin * when plasmin is NOT bound to fibrin (free in soln). alpha2-AP complexes with plasmin and thereby inactvates plasmin * when plasmin is attached to Lys residues on fibrin, this inhibition is greatly reduced.

Answer 6

* important route for plasminogen activation * released from endothelial cells * Inactive until bound to fibrin * upon binding to fibrin, t-PA cleaves plasminogen to generate plasmin, which in turn digests fibrin to produce fibrin degradation activator inhibitor

Answer 7

* variety of mechanisms exist which act to limit coagulation to the site of injury & prevent its dissemination * normal endothelium is anti-thrombotic * endothelial cells maintain an environment conducive to liquid blood flow by mechanisms that block platelet adhesion and aggregation and also interfere with the coagulation cascade * smoothness of endothelium prevents contact activation of clotting process while a layer of absorbed glycocalyx repels platelets and clotting factors * chemical mediators such as prostacyclin and NO are released by healthy endothelium and prevent platelet aggregation * many required coagulation factors for clotting are concentrated by their selective absorption to activated platelet at injury sites * macrophages have a high affinity for circulating coagulation factors & selectively remove them from the circulation * coagulation automatically initiates fibrinolysis * endothelium and blood also contain very powerful anticoagulant factors, which combine with and inactivate specific clotting factors including antithrombin III, proteins C & S, alpha-1 antiprotease, and alpha1-antitrypsin

Answer 8

* binds to & inhibits factor Xa & thrombin * causes the formation of a complex b/w thrombin and activated Ser protease, inactivating both compounds * activated by binding to heparin like molecules on endothelial cells * antithrombin III also known as heparin co-factor I * Heparin acts by activating this factor & preventing coagulation

Answer 9

* act together to inactive cofactors Va & VIIIa * enhance fibrinolysis * Protein C is activated by binding of thrombomodulin to thrombin * Thrombomodulin-thrombin complex activates protein C which localises to the endothelial surface and is able to destroy activated factors V & VIII * action of protein C is enhanced by protein S, which binds it to platelet surface *

Answer 10

* alpha1-antiprotease/alpha-1 antitrypsin, alpha-2 macroglobulin: inhibit many proteolytic enzymes * PGI2 aka Prostacyclin: synthesised by endothelium; increases cAMP levels within platelets and inhibits platelet activation. TXA2 antagonist * Tissue Factor Pathway Inhibitor (TFPI): limits the action of tissue factor & prevents TF-mediated activation of factor X

Answer 11

* critical fx in generating the hard clot * thrombin directly induces platelet aggregation and secretion Thrombin (proteolytic) acts on many other clotting factors including: * Prothrombin * V * VIII * XI * XIII * Fibrinogen * binding of thrombin to thrombomodulin is essential for activation of protein C, which is important in regulating the coagulation process