Process of Coagulation
The intrinsic pathway affects all of the factors of the extrinsic pathway PLUS Factors ___and ___
The intrinsic pathway affects all of the factors of the extrinsic pathway PLUS Factors XII and XI
Anticoagulant effects of endothelial cells are mediated by membrane-bound h________ and thrombo______, both of which inactivate thrombin
Anticoagulant effects of endothelial cells are mediated by membrane-bound heparin and thrombomodulin, both of which inactivate thrombin
Endothelium -maintain an environment that promotes blood ____ by blocking platelet ________ and activation, by inhibiting the _________ process and _______ blood clots -_____ endothelial surface prevents platelets and plasma coagulation factors from interacting with underlying thrombogenic ____________ extracellular matrix -if platelets are activated, they are ________ from adhering to surrounding uninjured endothelium by endothelial p______________ I2 and ______ oxide (potent vaso_______ and ________ of platelet aggregation)
Endothelium -maintain an environment that promotes blood flow by blocking platelet adhesion and activation, by inhibiting the coagulation process and lysing blood clots -intact endothelial surface prevents platelets and plasma coagulation factors from interacting with underlying thrombogenic subendothelial extracellular matrix -if platelets are activated, they are inhibited from adhering to surrounding uninjured endothelium by endothelial prostaglandin I2 and nitric oxide (potent vasodilators and inhibitors of platelet aggregation)
PT is part of which pathway?
Extrinsic
Extrinsic Pathway: much _______ and begins with ______ to the blood vessel or surrounding tissues and release of adhesive lipoprotein, ______ ______,from subendothelial cells -this pathway is activated when blood is exposed to ______ extracts
Extrinsic Pathway: much faster and begins with trauma to the blood vessel or surrounding tissues and release of adhesive lipoprotein, tissue factor from subendothelial cells -this pathway is activated when blood is exposed to tissue extracts
Hemostasis 1) Vessel Spasm -Injury to blood vessel causes vascular ________ muscle in the vessel wall to _______.. This reduces ______ flow from the vessel rupture. Both local nervous reflexes and local humoral factors, such as ___________ A2 (TXA2 ), which is released from platelets, contribute to vaso_____________ (major player for vessel spasm)
Hemostasis 1) Vessel Spasm -Injury to blood vessel causes vascular smooth muscle in the vessel wall to contract. This reduces blood flow from the vessel rupture. Both local nervous reflexes and local humoral factors such as thromboxane A2 (TXA2 ), which is released from platelets, and contributes to vasoconstriction (major player for vessel spasm)
Hemostasis 2) Formation of Platelet Plug -seconds after injury, ____ __________ factor (released from endothelium) binds to _______ receptors causing adhesion of platelets to exposed _________. As platelets adhere to collage on the damaged vessel wall, they become ________ and release ADP and T______. These attract more platelets, leading to platelet a__________
Hemostasis 2) Formation of Platelet Plug -seconds after injury, von Willebrand factor (released from endothelium) binds to platelet receptors causing adhesion of platets to exposed collagen. As platelets adhere to collage on the damaged vessel wall, they become activated and release ADP and TXA2. These attract more platelets, leading to platelet aggregation
Hemostasis 3) Blood Coagulation 2 pathways: 1) Intrinsic pathway: begins in circulation and initiated by circulating factor ____ and 2) extrinsic pathway: activated by a cellular lipoprotein, _______ factor, that becomes exposed when tissues are ________ -Both pathways lead to activation of factor ___, conversion of prothrombin to _______, and conversion of fibrinogen to insoluble ______ threads that hold the clot together.
Hemostasis 3) Blood Coagulation 2 pathways: 1) Intrinsic pathway: begins in circulation and initiated by circulating factor XII and 2) extrinsic pathway: activated by a cellular lipoprotein, tissue factor, that becomes exposed when tissues are injured -Both pathways lead to activation of factor X, conversion of prothrombin to thrombin, and conversion of fibrinogen to insoluble fibrin threads that hold the clot together.
Hemostasis 4) Clot Retraction -A few minutes after clot is formed, actin and myosin in platelets that are trapped in clot begin to ________ in a manner similar to that in muscles. As a result, ______ strands of clot are pulled toward platelets, thereby squeezing _______ (plasma without fibrinogen) from clot and causing it to _______.
Hemostasis 4) Clot Retraction -A few minutes after clot is formed, actin and myosin in platelets that are traped in clot begin to contract in a manner similar to that in muscles. As a result, fibrin strands of clot are pulled toward platelets, thereby squeezing serum (plasma without fibrinogen) from clot and causing it to shrink.
Hemostasis 5) Clot Dissolution or Lysis -Begins shortly after clot is formed -begins with activation of __________, an inactive precursor of the proteolytic enzyme, plasmin -When a clot is formed, large amounts of plasminogen are trapped in the clot. The slow release of a very powerful activator, tissue plasminogen ________ (t-Pa) from injured tissues and vascular endothelium, converts pasminogen to _______, which digests the fibrin strands (Fibrinolysis), causing the clot to __________
Hemostasis 5) Clot Dissolution or Lysis -Begins shortly after clot is formed -begins with activation of plasminogen, an inactive precursor of the proteolytic enzyme, plasmin -When a clot is formed, large amounts of plasminogen are trapped in the clot. The slow release of a very powerful activator, tissue plasminogen activator (t-Pa) from injured tissues and vascular endothelium, converts pasminogen to plasmin, which digests the fibrin strands (Fibrinolysis), causing the clot to dissolve
Hemostasis refers to stoppage of blood flow and is divided into 5 stages: 1) Vessel S_______ 2) Formation of the _________ Plug 3) Blood C_________ 4) Clot R_________ 5) Clot D__________ or Lysis
Hemostasis refers to stoppage of blood flow and is divided into 5 stages: 1) Vessel Spasm 2) Formation of the Platelet Plug 3) Blood Coagulation 4) Clot Retraction 5) Clot Dissolution or Lysis
Heparin is _______ formed and released in small amounts by _____ cells in ________ tissue surrounding capillaries -it binds to __________ III, causing a conformational change that increases the ability of antithrombin III to inactivate _______, factor __a, and other clotting factors -heparin ultimately suppresses the formation of ______ -Heparin is unable to cross the membranes of the ____ tract and must be given by ___ infusion
Heparin is naturally formed and released in small amounts by mast cells in connective tissue surrounding capillaries -it binds to Antithrobmin III, causing a conformational change that increases the ability of antithrombin III to inactivate thrombin, factor Xa, and other clotting factors -heparin ultimately suppresses the formation of fibrin -Heparin is unable to cross the membranes of the GI tract and must be given by IV infusion
PTT is part of which pathway?
Intrinsic
Low-molecuelr weight heparins (LMWH) inhibit activation of factor ___, but have little effect on ________ and other coagulation factors -they are given by ________ injection and require less frequent a__________ and m_________ compared to unfractioned heparin
Low-molecuelr weight heparins (LMWH) inhibit activation of factor X, but have little effect on thrombin and other coagulation factors -they are given by subcutaneous injection and require less frequent administration and monitoring compared to unfractioned heparin
Partial thromboplastin time assesses the function of the _________ pathway (Factors ____, ___, ___, ____, ___, ___, ___, and f________)
Partial thromboplastin time assesses the function of the intrinsic pathway (Factors XII, XI, IX, VII, X, II,V, and fibrinogen)
Platelet Plug Formation -_______ line of defense -involves a_______, granule _______, and a__________ of platelets
Platelet Plug Formation -second line of defense -involves adhesion, granule release, and aggregation of platelets
Platelet aggregation inhibitors, such as A______, P______ and Ticlid, can be used to ______ platelet aggregation and clot formation in people at risk for M_________ i________, S______ or p_________ a______ disease. -_____ dose aspirin therapy inhibits prostaglandin synthesis, including TXA2 -Plavix and Ticlid inhibit the ______ pathway in platelets and, unlike aspirin, have no effect on the _____________ synthesis
Platelet aggregation inhibitors, such as Asprin, Plavix and Ticlid, can be used to prevent platelet aggregation and clot formation in people at risk for MI, Stroke or periphery artery disease. -Low dose aspirin therapy inhibits prostaglandin synthesis, including TXA2 -Plavix and Ticlid inhibit the ADP pathway in platelets and, unlike aspirin, have no effect on the prostaglandin synthesis
Platelets -1/3 stored in blood-filled spaces of _______ and can be released into circulation as needed -platelet production controlled by thrombo_______ -platelets lack a _______ -___/____ is a glycoprotein located on platelets that binds to fibrinogen and acts to connect many platelets together to form a________ -central part of platelet contains ATP and the prostglandin TXA2 and granules that release mediators for _________ (fibrinogen, coagulation factors, plasminogen, Plasminogen activator inhibitor (PAI), and platelet-derived growth factors
Platelets -1/3 stored in blood-filled spaces of spleen and can be released into circulation as needed -platelet production controlled by thrombopoieten -platelets lack a nucleus -IIb/IIIa is a glycoprotein located on platelets that binds to fibrinogen and acts to connect many platelets together to form aggregates -central part of platelet contains ATP and the prostglandin TXA2 and granules that release mediators for hemostasis (fibrinogen, coagulation factors, plasminogen, Plasminogen activator inhibitor (PAI), and platelet-derived growth factors
Proteins __ and ___ are two vitamin K-dependent plasma proteins that inactive the cofactors __a and ____a
Proteins C and S are two vitamin K-dependent plasma proteins that inactive the cofactors Va and VIIIa
Prothrombin Time assess the function of the ________ pathway (factors ____, __, ___, ___, and f________)
Prothrombin Time assess the function of the extrinsic pathway (factors VII, X, II, V, and fibrinogen)
The Coagulation Cascade Intrinsic Pathway: relatively ____ and begins in circulation with activation of Factor ____ (Hageman factor) -this pathway is activated as blood comes in contact with _________ in injured vessel wall
The Coagulation Cascade Intrinsic Pathway: relatively slow and begins in circulation with activation of Factor XII (Hageman factor) -this pathway is activated as blood comes in contact with collagen in injured vessel wall
The Coagulation System -most of the coagulation factors are synthesized in the ______ and circulate around the blood in an ________ state until needed -Vitamin __ is necessary for the synthesis of factors VII, IX and X, prothrombin and protein C -_________ (factor IV) is required in all but the first two steps of the clotting process -Inactivation of Calcium ion prevents blood from ________ when it is removed from the body
The Coagulation System -most of the coagulation factors are synthesized in the liver and circulate around the blood in an inactive state until needed -Vitamin K is necessary for the synthesis of factors VII, IX and X, prothrombin and protein C -Calcium (factor IV) is required in all but the first two steps of the clotting process -Inactivation of Calcium ion prevents blood from clotting when it is removed from the body
The Coagulation system -a clot is not meant to be a _________ solution to vessel injury -therefore, blood clotting is accompanied by processes designed to control ___________ process and _______ the clot once bleeding is controlled -blood coagulation is regulated by several natural anticoagulants such as Antithrombin III and proteins __ and __, which ________ some of the clotting factors -plasma containts plasminogen that, when activated, converts into _______, an enzyme capable of digesting _____ strands of the clot
The Coagulation system -a clot is not meant to be a permanent solution to vessel injury -therefore, blood clotting is accompanied by processes designed to control coagulation process and dissolve the clot once bleeding is controlled -blood coagulation is regulated by several natural anticoagulants such as Antithrombin III and proteins C and S, which inactivate some of the clotting factors -plasma containts plasminogen that, when activated, converts into plasmin, an enzyme capable of digesting fibrin strands of the clot
The primary hemostatic plug involves the combined actions of A___ and ____2, which lead to the _________ of the platelet aggregate,
The primary hemostatic plug involves the combined actions of ADP and TXA2, which lead to the expansion of the platelet aggregate,
The secondary hemostatic plug involves the conversion of the primary platelet plug into a definitive ____, which occurs as the coagulation pathway is activated and fibrinogen is converted to ______, creating a fibrin m__________ that cements platelets and other blood components.
The secondary hemostatic plug involves the conversion of the primary platelet plug into a definitive clot, which occurs as the coagulation pathway is activated and fibrinogen is converted to fibrin, creating a fibrin meshwork that cements platelets and other blood components.
The terminal in both intrinsic and extrinsic pathways is the same: activation of Factor ___ and conversion of prothrombin to _________ -Thrombin acts as an enzyme to convert fibrinogen to ______ the material that stabilizes a clot
The terminal in both intrinsic and extrinsic pathways is the same: activation of Factor X and conversion of prothrombin to thrombin -Thrombin acts as an enzyme to convert fibrinogen to fibrin the material that stabilizes a clot
What begins the clotting cascade?
Tissue Factor
______ factor pathway inhibitor is a protein secreted by the endothelium that inactivates factor __a and tissue factor VIIa complexes
Tissue factor pathway inhibitor is a protein secreted by the endothelium that inactivates foactor Xa and tissue factor VIIa complexes
Warfarin and heparin are __________ drugs used to prevent thrombo______ disorders, such as deep vein ________ and pulmonary ________ -Warfarin acts by decreasing _________ and other procoagulation factors -it alters Vitamin __, reducing its ability to synthesize Vitamin K-dependent coagulation factors in the ______ -readily absorbed after ______ administraion and its maximum effect occurs in ___ to ___ hours
Warfarin and heparin are anticoagulant drugs used to prevent thromboembolic disorders, such as deep vein thrombosis and pulmonary embolism -Warfarin acts by decreasing prothrombin and other procoagulation factors -it alters Vitamin K, reducing its ability to synthesize Vitamin K-dependent coagulation factors in the liver -readily absorbed after oral administraion and its maximum effect occurs in 36 to 72 hours
von Willebrand factor (vWF) is a protein molecule produced by m______________ and endothelial cells and circulates in the blood as a carrier protein for coagulation factor ____ -Adhesion to the vessel subendothelial layer occurs when the platelet membrane receptor binds to _____ at the injury site, linking the platelet to exposed ________ fibers
von Willebrand factor (vWF) is a protein molecule produced by megakaryoctyes and endothelial cells and circulates in the blood as a carrier protein for coagulation factor VIII -Adhesion to the vessel subendothelial layer occurs when the platelet membrane receptor binds to vWF at the injury site, linking the platelet to exposed collagen fibers
