The intrinsic pathway is the longer and more intricate pathway:
- Factor XII is activated once it comes into contact with negatively charged collagen on the damaged endothelium, triggering the cascade as detailed in Figure 1.
- Along with clotting factors, platelets form a cellular ‘plug’ at the site of injury. ...
- Factor IX combines with Factor VIII to form an enzyme complex that activates factor X, which along with factor Va, stimulates the production of thrombin.
Which factor initiates the intrinsic clotting mechanism quizlet?
The intrinsic clotting pathway (in blue) is initiated when factor XII (Hageman factor) is activated by contact with exposed collagen at a damaged vessel surface or by contact with a foreign surface.
What triggers the extrinsic pathway of coagulation?
The extrinsic pathway begins when there is injury to the endothelial tissue (i.e., skin tissue), exposing tissue factor (factor III) to the blood. Tissue factor then becomes bound with calcium and factor VIIa to activate factor X. Factor VII is present in the blood and requires vitamin K to be activated.
What event leads to activation of the intrinsic pathway?
The intrinsic pathway is initiated by the activation of factor XII by certain negatively charged surfaces, including glass. High-molecular-weight kininogen and prekallikrein are two proteins that facilitate this activation.
What event initiates the intrinsic or contact pathway of coagulation?
activation of factor XIIThe contact pathway of coagulation is initiated by activation of factor XII (fXII) in a process that also involves high-molecular-weight kininogen (HK) and plasma prekallikrein (PK).
Which of the following triggers the extrinsic pathway of coagulation quizlet?
The extrinsic pathway is triggered by tissue factor.
What initiates the extrinsic mechanism of coagulation quizlet?
What initiate the extrinsic pathway? The extrinsic pathway is initiated in response to damage occurring outside the blood vessel. The coagulation factors of the extrinsic pathway are III (also known as tissue factor or thromboplastin) and VII.
What starts the extrinsic pathway of blood clotting quizlet?
How is each pathway initiated? The faster extrinsic pathway is initiated by the release of a glycoprotein called tissue factor byu damaged endothelial cells or peripheral tissues.
What activates the extrinsic apoptotic pathway?
The extrinsic pathway that initiates apoptosis is triggered by a death ligand binding to a death receptor, such as TNF-α to TNFR1. The TNFR family is a large family consisting of 29 transmembrane receptor proteins, organized in homotrimers and activated by binding of the respective ligand(s).
What receptors are involved in platelet aggregation?
Platelet aggregation begins once platelets have been activated. Once activated, the Gp IIb/IIIa receptors adhere to vWF and fibrinogen. Fibrinogen is found in the circulation and forms a connection between the Gp IIb/IIIa receptors of platelets to interconnect them with each other. This ultimately forms the weak platelet plug.
What is platelet activation?
Platelet activation consists of platelets undergoing two specific events once they have adhered to the exposed vWF (i.e. the damaged vessel site). First, platelets will undergo an irreversible change in shape from smooth discs to multi-pseudopodal plugs, which greatly increases their surface area. Second, platelets secrete their cytoplasmic granules.
What is the process of adhesion of platelets?
Platelet adhesion is the process by which platelets attach to the exposed subendothelial vWF. Post vascular damage, platelets begin to roll along vessel walls and adhere to areas of exposed subendothelial collagen and vWF. Platelet membranes are rich in G protein (Gp) receptors located within the phospholipid bilayer. Specifically, it is Gp Ib-IX receptor on platelets that bind to vWF within the endothelium that creates the initial connection between the two. Once bound, a variety of events can occur in the third phase of primary hemostasis to activate the platelet.
How does thrombin activate platelets?
Thrombin directly activates platelets via proteolytic cleavage by binding the protease-activated receptor. Thrombin also stimulates platelet granule release which includes serotonin, platelet activating factor, and Adenosine Diphosphate (ADP). ADP is an important physiological agonist which is stored specifically in the dense granules of platelets. When ADP is released, it binds to P2Y1 and P2Y12 receptors on platelet membranes. P2Y1 induces the pseudopod shape change and aids in platelet aggregation. P2Y12 plays a major role in inducing the clotting cascade. When ADP binds to its receptors, it induces Gp IIb/IIIa complex expression at the platelet membrane surface. The Gp IIb/IIIa complex is a calcium-dependent collagen receptor which is necessary for platelet-to-endothelial adherence and platelet-to-platelet aggregation. Simultaneously, platelets synthesize Thromboxane A2 (TXA2). TXA2 further intensifies vasoconstriction and platelet aggregation (next step in the primary hemostasis process). The process of platelet activation readies the local environment for platelet aggregation.
How does the body protect itself from blood loss?
The human body protects against loss of blood through the clotting mechanism. Vascular mechanisms, platelets, coagulation factors, prostaglandins, enzymes, and proteins are the contributors to the clotting mechanism which act together to form clots and stop a loss of blood. Through vasoconstriction, adhesion, activation, and aggregation, the contributors form a transient plug to act as the cork to the leaking blood flow. Soon after, fibrin, the functioning form of fibrinogen, stabilizes this weak platelet plug. The scope of this article will highlight the physiological aspects of the clotting mechanism .[1][2][3]
What is the initial response to vessel injury?
Vasoconstriction is the initial response whenever there is vessel injury. Vasospasm of the blood vessels occurs first in response to injury of the vasculature. This vasospasm, in turn, stimulates vasoconstriction. Vasoconstriction is primarily mediated by endothelin-1, a potent vasoconstrictor, which is synthesized by the damaged endothelium. Damaged endothelium exposes sub-endothelial collagen, von Willebrand factor (vWF), releases ATP, and inflammatory mediators. vWF is synthesized by megakaryocytes which later gets stored in a-granules of platelets. Weibel-Palade bodies of the endothelium also synthesize vWF. It is the combination of exposure of vWF, subendothelial collagen, ATP, and inflammatory mediators which provide the gateway into the second phase of primary hemostasis, platelet adhesion.
What is primary hemostasis?
Primary hemostasis: Formation of a weak platelet plug
How does TFPI regulate coagulation?
TFPI regulates coagulation via direct inhibition of fXa, and via fXa -dependent feedback-inhibition of TF:VIIa. The TFPIβ isoform is a weaker inhibitor of fXa than is TFPIα (Chang et al., 1999). Protein S substantially enhances the inhibition of fXa by TFPIα (Hackeng et al., 2006). Heparin and other polyanions accelerate fXa inhibition by TFPIα in a template-dependent manner (Huang et al., 1993; Wesselschmidt et al., 1993). FXa-dependent inhibition of TF:VIIa by TFPI involves the formation of a quaternary complex consisting of TFPI, fVIIa, TF, and fXa. TFPI-mediated regulation of coagulation is critically important, as evidenced by the effects of disruption of this protein in mouse models, where TFPI-deficient mice die in uterofrom a consumptive coagulopathy (Huang et al., 1997), but can be rescued by concomitant fVII or TF deficiency (Chan et al., 1997; Pedersen et al., 2005). Antithrombin, in the presence of heparin, is also able to inhibit the TF:VIIa complex (Rao et al., 1993; Lawson et al., 1993).
Where is zymogen fVII synthesized?
FVII is synthesized in the liver and circulates in plasma at a concentration of about 10 nM (Fair, 1983). When initially synthesized inside the endoplasmic reticulum of hepatocytes, fVII contains a signal peptide and a propeptide (removed intracellularly) that mediate, respectively, secretion and a specific type of post-translational modification (γ-carboxylation) of all the glutamate residues within about 45 amino acids of the N-terminus of the mature protein. Like other related vitamin-K dependent coagulation proteins, fVII contains an N-terminal γ-carboxyglutamate–rich domain (GLA domain). The fVII GLA domain contains ten γ-carboxyglutamate (Gla) residues that are essential for the clotting activity of this protein. The GLA domain confers reversible, Ca2+-dependent binding of fVII to membranes containing negatively charged phospholipids such as phosphatidylserine or phosphatidic acid (Neuenschwander & Morrissey, 1994; Tavoosi et al., 2013).
What is the term for a blood clot that can impede the flow of blood within a vessel?
Thrombosis is a group of pathologic conditions in which the clotting cascade is triggered inside the lumen of a blood vessel, leading to the formation of a blood clot (known, in this case, as a “thrombus ”) that can impede the flow of blood within a vessel.
How many amino acids are in the heavy chain?
The heavy chain, approximately 30 kDa, has 254 amino acids and contains the trypsin-like serine protease domain. The active forms of most coagulation serine proteases have extremely short plasma half-lives (measured in seconds to minutes) because plasma contains high concentrations of protease inhibitors.
What is the plasma portion of blood?
The plasma portion of blood contains a collection of soluble proteins that act together in a cascade of enzyme activation events, culminating in the formation of a fibrin clot. This review addresses the mechanisms by which the blood clotting cascade is initiated in both hemostasis and pathologic thrombosis.
Is fVIIa a weak enzyme?
Free fVIIa is a very weak enzyme, but the TF:VIIa complex is an extremely potent activator of coagulation. Once formed, the TF:VIIa complex activates two downstream substrates in the coagulation cascade via limited proteolysis: factor IX (fIX) is converted to fIXa, and fX is converted to fXa (Figure 1).
How does blood clotting work?
Following vascular injury, any escaping blood must rapidly be converted into a gel (“clot”) to plug the hole and minimize further blood loss. The plasma portion of blood contains a collection of soluble proteins that act together in a cascade of enzyme activation events, culminating in the formation of a fibrin clot. This review addresses the mechanisms by which the blood clotting cascade is initiated in both hemostasis and pathologic thrombosis. Hemostasis is the normal process by which the clotting cascade seals up vascular damage to limit blood loss following injury. Thrombosis is a group of pathologic conditions in which the clotting cascade is triggered inside the lumen of a blood vessel, leading to the formation of a blood clot (known, in this case, as a “thrombus”) that can impede the flow of blood within a vessel. Severe thrombosis can block the flow of blood to a tissue, leading to ischemia and tissue death.
What is the intrinsic pathway of blood coagulation?
Intrinsic pathway of blood coagulation. All the components necessary for the clotting process to proceed are found in the blood. As such, the proteins required for such clotting to take place are part of the intrinsic pathway of blood coagulation. This pathway involves a series of proteins, protein cofactors, and enzymes, ...
Why is clotting delayed?
Delayed clotting, measured as a prolonged partial thromboplastin time, may be due to a deficiency in the activity of one or more of the blood-clotting factors or to a chemical inhibitor of blood coagulation. Load Next Page.
What is the intrinsic pathway?
The intrinsic pathway is initiated by the activation of factor XII by certain negatively charged surfaces, including glass. High-molecular-weight kininogen and prekallikrein are two proteins that facilitate this activation. The enzyme form of factor XII (factor XIIa) catalyzes the conversion of factor XI to its enzyme form (factor XIa).
What is the function of factor IXA?
Factor IXa assembles on the surface of membranes in complex with factor VIII; the factor IXa–factor VIII complex requires calcium to stabilize certain structures on these proteins associated with their membrane-binding properties. Factor X binds to the factor IXa–factor VIII complex and is activated to factor Xa.
What is the XA factor that binds to thrombin?
Prothrombin binds to the factor Xa–factor V complex and is converted to thrombin, a potent enzyme that cleaves fibrinogen to fibrin, a monomer. The monomer fibrin molecules then link together (polymerize) to form long fibres.
What are inactive surfaces?
Inactive surfaces include some oils, waxes, resins, silicones, a few plastics, and endothelial cells, the most inert surface of all. The physicochemical properties that determine activity are not known. The problem is important, for modern surgery requires a perfectly inactive material to make substitutes ...
What is the enzyme form of factor XII?
The enzyme form of factor XII (factor XIIa) catalyzes the conversion of factor XI to its enzyme form (factor XIa). Factor XIa catalyzes the conversion of factor IX to the activated form, factor IXa, in a reaction that requires calcium ions.
What is the activation of factor X?
This cascade results in the activation of factor X. Activated factor X is an enzyme that converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin monomers, which then polymerize in fibrin fibers. Fibirin fibers form a losse meshwork that is stabilized by crosslinks created by factor XIII.
What is the fiber that traps red blood cells and platelets?
Fibirin fibers form a losse meshwork that is stabilized by crosslinks created by factor XIII. The stabilized meshwork of fibrin fibers ins now a clot that traps red blood cells and platelets and thus stops the flow of blood.
What is the role of platelets in clotting?
Small tears of the capillaries and arterioles are happening all the time Platelets are responsible for quickly sealing these tears before the slower process of clotting completes the job .
What is the process of forming a platelet plug?
(The key stages of this process are called platelet adhe sion, platelet release reaction , and platelet aggregation )
How much does streptokinase cost?
Streptokinase cost $2 dollars per does while TPA costs $2000 dollars per dose. Based on economic concerns, streptokinase is the drug of choice. However, streptokinase is not a human enzyme, therefore the immune system sees it as a foreign molecule that should be distorted.
What is the intrinsic pathway?
The intrinsic pathway, which is triggered by elements that lie within the blood inself (intrinsic to the blood), occurs in the flowing way. Damage to the vessel wall stimulates the activation of a cascade of clotting factors (for the sake of simplicity we will not consider the individual factors).
How many clotting factors are in the blood?
The blood contains about a dozen clotting factors. These factors are proteins that exist in the blood in an inactive state, but can be called into action when tissues or blood vessels are damaged.
How long does it take for a blood clot to form?
The extrinsic pathway usually produces a clot in as little as 15 sec, while the intrinsic pathway requires 2 to 6 min.
What happens to platelets during hemostasis?
The next event in hemostasis is the escape from blood vessels of platelets, which swell and adhere to the collagen in adjacent connective tissues. This attachment stimulates vasoconstriction. By now, the platelets have become very sticky, so that as more and more of them move into the injured are they stick together.
How do blood vessels help prevent clotting?
Most of the body’s anticoagulant substances circulate within the blood, and the blood vessels themselves help prevent clotting. The blood vessels contribute in two ways. First, the smoothness of the inner walls normally prevents activation of the intrinsic clotting mechanism.
How many compounds are needed for coagulation?
As many as 35 compounds may be required for blood coagulation. Such a complex system of checks and balances is necessary to prevent clotting when there is no bleeding. An unwanted clot in a blood vessel that cuts off the blood supply to a vital organ is one of the body’s worst enemies.
What is the basic mechanism of blood clotting?
Coagulation phase: Basic mechanism of blood clotting. If the blood vessel damage is so extensive that the platelet plug cannot stop the bleeding, the complicated process of blood clotting- the coagulation phase- begins. The basic clotting mechanism involves the following events:
Why is platelet aggregation important?
The process is called platelet aggregation. It is important partly because it successfully stops hundreds of small hemorrhages every day and partly because it triggers the blood-clotting mechanism. 3. Coagulation phase: Basic mechanism of blood clotting.
What is the enzyme that disintegrates blood platelets?
Supported by a plasma globulin called antihemophilic factor (AHF), blood platelets disintegrate and release the enzyme thromboplastinogenase and platelet factor 3. Thromboplastinogenase combines with AHF to convert the plasma globulin thromboplastinogen into the enzyme thromboplastin.
What is Blood Clotting?
A blood clot consists of fibrin, platelets and blood cells. The formation of a stable blood clot is facilitated by an enzyme called thrombin. Thrombin enzyme catalyzes the polymerization of insoluble fibrin from fibrinogen. Thrombin is formed from prothrombin. The conversion of prothrombin to thrombin is done by prothrombin activator or the factor X. Prothrombin activator is activated by the two blood clotting pathways: intrinsic and extrinsic pathways. Intrinsic and extrinsic pathways in blood clotting initiate and progress towards activating prothrombin activator when there is an injury in the blood vessel. As mentioned above the difference between intrinsic and extrinsic pathways in blood clotting is their initiation factors.
What is Extrinsic Pathway in Blood Clotting?
Extrinsic pathway is another way of blood coagulation. This system is activated by vascular tissue trauma or surrounding extra-vascular tissue trauma. These external factors release a complex of several factors which is collectively known as tissue factor or tissue thromboplastin or factor III. Tissue factor is a protein found in many tissues of the body, including brain, lungs, and placenta. Tissue factor is the main component which activates the extrinsic pathway of blood clotting. Under normal conditions, blood is not contacted or exposed to these tissue factors. But when there is an injury, tissue factor exposes to blood and activates factor VII into factor VIIa. Factor VIIa activates factor IX into IXa. Factor IXa activates factor X into factor Xa. Factor Xa is the prothrombin activator which is responsible for the conversion of prothrombin into thrombin. Once prothrombin activator is formed, the common pathway starts and blood coagulation proceeds. Extrinsic pathway is quicker than intrinsic pathway. Within about 15 seconds, it completes blood coagulation.
What are the Similarities Between Intrinsic and Extrinsic Pathways in Blood Clotting?
Intrinsic and extrinsic pathways are two processes of blood coagulation.
What happens when a prothrombin activator is activated?
When prothrombin activator is activated, it facilitates the conversion of prothrombin into thrombin. Thrombin catalyzes the polymerization of fibrinogen into fibrin, which is the basic component of the blood clot. Intrinsic pathway of blood clotting is a slow process which completes within several minutes.
What is intrinsic pathway?
Intrinsic pathway is a type of blood clotting pathway which is activated by a trauma in blood or when blood is exposed to a subendothelial collagen. Components required for intrinsic pathway are entirely contained within the blood or the vasculature. Hence this process is named as ‘intrinsic pathway.’.
What is the process of converting prothrombin to thrombin?
The conversion of prothrombin to thrombin is done by prothrombin activator or the factor X. Prothrombin activator is activated by the two blood clotting pathways: intrinsic and extrinsic pathways. Intrinsic and extrinsic pathways in blood clotting initiate and progress towards activating prothrombin activator when there is an injury in ...
What is the process of forming a blood clot?
Blood coagulation refers to the process of forming a clot to stop bleeding. A blood clot is mainly formed from fibrin and platelets. Formation of fibrin is catalyzed by the enzyme called thrombin. Thrombin formation is facilitated by prothrombin activator made from two pathways named intrinsic and extrinsic pathways.
