Term
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Definition
| property of the circulation that maintains blood as a fluid within the blood vessels and the system's ability to prevent excessive blood loss upon injury |
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Term
| Three physioloic compartments involved in the hemostatic mechanism |
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Definition
| extrinsic, the intrinsic and the common pathways |
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Term
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Definition
| physiologic action of platelets, blood vessels |
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Term
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Definition
| dynamic equilibrium between thrombosis and fibrinolysis and the stabilization of the platelet plug by fibrin |
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Term
| How is fibrinogen (F-I) evaluated by lab testing? |
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Definition
| Fibrinogen is evaluated quantitatively by the clauss assay |
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Term
| How is prothrombin(F-II) evaluated by lab testing? |
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Definition
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Term
| How is tissue factor (F-III) evaluated by lab testing? |
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Definition
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Term
| How is calcium ion (F-IV) evaluated by lab testing? |
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Definition
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Term
| How is proaccelerin (F-V) evaluated by lab testing? |
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Definition
| PT screening test, or factor V assay |
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Term
| How is proconvertin (F-VII) evaluated by lab testing? |
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Definition
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Term
| How is antihemophillic factor (F-VIII)evaluated by lab testing? |
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Definition
| PT, aPTT, platelet count and factor VIII assay |
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Term
| How is christmas factor (F-IX) evaluated by lab testing? |
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Definition
| PT, aPTT, platelet count and factor IX assay |
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Term
| How is stuart factor (F-X)evaluated by lab testing? |
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Definition
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Term
| How is plasma thromboplastin ant. (F-XI) evaluated by lab testing? |
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Definition
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Term
| How is fibrin stabilizing factor (F-XIII) evaluated by lab testing? |
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Definition
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Term
| Characteristics of the prothrombin group |
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Definition
| they are all produced in the liver and they have a small molecular weight. Their formation is vitamin K dependent. |
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Term
| Characteristics of the fibrinogen group |
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Definition
| they are all upon by Thrombin (IIa), they have a large molecular weight and they are consumed during clotting process so that they are not found in the serum after coagulation. |
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Term
| Which factors are part of the fibrinogen group? |
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Definition
| Factors V, VIII, XIII and Fibrinogen (I) |
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Term
| Which factors are part of the prothrombin group? |
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Definition
| 1972= factor X, IX, VII and II + Protein C and S |
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Term
| Which factors are part of the contact group? |
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Definition
| Factors XI, XII, Prekallikrein and High Molecular Weight Kininogen (HMWK) |
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Term
| Characteristics of the contact group? |
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Definition
| they are involved in the activation of the intrinsic pathway and require contact with a negatively charged surface. They are not essential in in-vivo hemostasis (except XI) but they are integral to other physiologic systems. |
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Term
| Why is vitamin K important in hemostasis? |
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Definition
| Vitamin K is required for g-carboxylation of glutamic acid in GLA domain of coagulation factors. This g-carboxylation is essential for factor binding to platelet phospholipid surface via Calcium bridges |
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Term
| What is the mechanism of action of the coagulation proteins? |
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Definition
| The catalytic domains of the coagulation proteins have active sites which can activate other proteins. These coagulation proteins are usually serine proteases which can selectively hydrolyze arginine or lysine peptide bonds for target zymogens. |
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Term
| Explain the intrinsic pathway |
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Definition
| Contact with negative surfaces activates Factor XII XIIa. XIIa activates XI XIa, XIa activates IX in the presence of calcium to IXa which complexes with VIII, platelet phospholipids and Calcium to form the intrinsic Xase complex. |
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Term
| Explain the extrinsic pathway |
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Definition
| Tissue factor on surface of nonvascular cells are exposed to blood, Tissue factor binds to factor VII creating a Tissue Factor VIIa Calcium complex (extrinsic Xase complex). |
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Term
| Explain the common pathway |
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Definition
| : Factor X is activated by Extrinsic Xase Complex (TF + VIIa + Ca2+) and/or Intrinsic Xase Complex (IXa + VII + PL + Ca2+) to Xa. Xa complexes with V, platelets and Ca2+ to form the Prothrombinase complex. Prothrombinase complex activates Prothrombin (II) to thrombin (I). Thrombin can activate both (1) fibrinogen to fibrin and (2) XIII to XIIIa which cross-links the activated fibrin. |
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Term
| What are the factors involved in contact activation? |
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Definition
| Activation of the contact group of factors involved contact with a negatively charged surface. In vivo it is believed that these negatively charged surfaces are membranes of blood & endothelial cells, possibly collagen. |
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Term
| How is the intrinsic pathway activated? |
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Definition
| The Intrinsic pathway begins by activation of factor XII via exposure to a negatively charged surface, possibly a blood cell membrane. The factors for the intrinsic pathway are circulating in the blood and activate each other via the intrinsic pathway. |
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Term
| How is the extrinsic pathway activated? |
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Definition
| The extrinsic pathway begins by the introduction of Tissue Factor into the blood via vessel injury. The extrinsic works toward the common pathway. |
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Term
| How is the common pathway activated? |
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Definition
| When the two pathways met at the beginning of the common pathway and lead to the formation of a platelet/fibrin plug. |
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Term
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Definition
| final stage of blood vessel repair in which the fibrin clot is degraded. |
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Term
| What are the major components of the fibrinolytic system? |
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Definition
| plasma and cellular components |
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Term
| Why is fibrinolysis a neccessary component of hemostasis? |
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Definition
| maintain the delicate balance of coagulation. The system breaks down the formed clots in order to prevent a life threatening clot forming and moving to the heart or lung. |
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Term
| What are the fragments from fibrinolytic degradation? |
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Definition
| D and E domains (from fibrinogen), D-dimers from cross-linked fibrin. |
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Term
| What are the fragments from fibrinogen degradation? |
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Definition
| D-E-D domain or a D-E and a D domain or even a single D or E domain. |
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Term
| What are the fragments from fibrin degradation? |
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Definition
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Term
| What are the major biochemical inhibitors that regulate secondary hemostasis? |
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Definition
| Plasminogen Activator Inhibitors and Alpha-2-Antiplasmin (fibrinolysis), Anti-thrombin, proteins C and S, and alpha-2-antiplasmin (coagulation). |
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Term
| What are the interactions between the three compartments involved in hemostasis? |
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Definition
| The intrinsic and the extrinsic met at the top of the common pathway to activate factor X which activates thrombin and fibrinogen to form a platelet clot |
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Term
| What are the domains of the coagulation factors? |
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Definition
| cataytic and non-catlytic |
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Term
| How does structure effect the action of serine proteases? |
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Definition
| serine proteases have serine in the active sites which selectively hydrolyze arginine or lysine peptide bonds of target zymogens |
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Term
| What is the signifigance of non-catalytic domains? |
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Definition
| specific structure that contains binding sites |
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Term
| How do complexes form on the phospholipid surface? |
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Definition
| Factor IXa + VIII +calcium form the intrinsic Xase on the phospholipid surface, and Tissue Factor + Calcium and Factor VIIa form the Extrinsic Xase complex |
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Term
| What is the significance of these phospholipid complexes to hemostasis |
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Definition
| They both have the ability to activate factor X to Xa which forms the Prothrombinase complex. |
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Term
| What is the role of contact factors in the fibrinolysis system? |
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Definition
| the contact factors degrade fibrin; Factor XIa, XIIa and kallikrein activate plasminogen to plasmin |
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Term
| What is the role of contact factors in the complement system? |
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Definition
| Plasmin initiates the complement cascade by activating C1 |
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Term
| What is the role of contact factors in the inflammatory system? |
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Definition
| Kallikrein cleaves HMWK to Bradykinin, which causes vasodilatation, increased vascular permeability, and release of t-PA, swelling and pain. Kallikrein also attracts monocytes and neutrophils |
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Term
| What are the 7 roles of thrombin in hemostasis? |
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Definition
Thrombin (1) cleaves fibrinopeptides from fibrinogen to form Fibrin
(2) Activates factor V, VII, VIII, and IX to amplify Thrombin generation
(3) Activates factor XIII to stabilize fibrin clot
(4) Activated platelets stimulating aggregation
(5) Attracts T cells and monocytes
(6) Activates Protein C which inactivates Factor V and VIII
(7) Stimulates endothelial cells to release t-PA and prostacyclin and NO to relax blood vessels to restore normal blood flow |
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Term
| What is the physiologic function of ADAMTS-13 |
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Definition
| ADAMTS-13 reduces Ultra Large vWF to normal size which is important to prevent spontaneous thrombosis. |
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Term
| What is physiological fibrinolysis? |
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Definition
| proteolytic enzymes released from leukocytes to breakdown platelets |
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Term
| What is systemic fibrinolysis? |
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Definition
| fibrin degradation by plasmin |
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Term
| What are the physiologic controls of hemostasis related to blood flow? |
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Definition
| blood flow restoration (after vasoconstriction) |
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Term
| What are the physiologic controls of hemostasis related to feedback inhibition? |
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Definition
| can be negative or positive |
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Term
| What are the physiologic controls of hemostasis related to liver clearance? |
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Definition
| removes activated coagulation factors complexed with their inhibitors, plasmin-anti-plasmin complexes, and fibrin degradation products from the circulation via LRP receptors on hepatocytes and liver macrophages. |
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Term
| What are the physiologic controls of hemostasis related to inhibitors? |
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Definition
| soluble plasma proteins that regulate enzymatic reaction of serine proteases by preventing the initiation or amplification of the coagulation cascade |
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Term
| What does thrombin do in positive feedback? |
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Definition
| : (1)thrombin promotes the release of platelet F-Va and the exposure of negatively charged phospholipid surface used for assembly of coagulation proteins complexes (2) thrombin activates F-Va and F-VIIIa |
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Term
| What does F-Xa do in positive feedback? |
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Definition
| (3) F-Xa activates F-VII and (4) F-Xa can limitedly activate F-VIII before thrombin is produced |
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Term
| What does negative feedback cause? |
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Definition
| limits further production of the enzymes and dampens the coagulation cascade |
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Term
| What does thrombin do in negative feedback? |
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Definition
| thrombin can inactivate F-Va and F-VIIIa via APC. Fibrin has a high affininty for thrombin, clot absorbs thrombin and releases it slowly limiting the amount of thrombin to cleave fibrinogen to fibrin |
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Term
| What does FDP do in negative feedback? |
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Definition
| FDPs from plasmin digestion can inhibit fibrin formation by interfering with the conversion of fibrinogen to fibrin and the polymerization of fibrin monomers. |
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Term
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Definition
| Primary hemostasis test, elevated = disorder of secondary hemostasis (extrinsic) |
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Term
| Extrinsic pathway factors? |
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Definition
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Term
| Intrinsic pathway factors? |
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Definition
| XII, XI, IX, and VIII (+ Prekallikrein and HMWK) |
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Term
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Definition
| X, V and Prothrombin (II) and Fibrinogen (I) |
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Term
| What should you consider if the patient has an abnormal PT and a normal aPTT? |
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Definition
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Term
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Definition
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Term
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Definition
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Term
| What is involved in hemostasis? |
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Definition
| clot formation, clot dissolution and vessel repair |
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Term
| What describes the events involved in secondary hemostasis? |
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Definition
| lead to the formation of a chemically stable fibrin clot |
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Term
| What is known as the antihemophilic factor? |
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Definition
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Term
| Which coagulatuon proteins are included in the prothrombin group? |
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Definition
| Factors II, VII, IX, and X |
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Term
| What are the cofactors in hemostasis? |
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Definition
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Term
| Hemostasis depends on the balance of.. |
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Definition
| the interaction between blood vessels platelets and coagulation proteins |
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Term
| What most accuratley describes the domains of coagulation proteins? |
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Definition
| the domains impart specificity and recognition to control hemostasis |
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Term
| What is true concerning the formation of protein complexes that occur during coagulation? |
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Definition
| localizes the reaction to the site of injury |
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Term
| what activates the extrinsic pathway? |
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Definition
| contact with tissue factor |
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Term
| what factors are involved in the inital activation of the coagulation system and require contact with a negatively charged surface for their activation? |
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Definition
| Factors XII, XI, PK, and HK |
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Term
| What is not involved in the fibrinolytic system |
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Definition
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Term
| What is involved in the fibrinolytic system |
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Definition
| PAI, plasmin, F-XII and kallikrein |
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Term
| what is (are) the end products in the breakdown of fibrin? |
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Definition
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Term
| What is a pair of protein with its inhibitor? |
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Definition
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Term
| what describes the contact factors? |
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Definition
| contribute to fibrinolysis, inflammation and complement activation |
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Term
| What is the role of ADAMTS-13 in hemostasis? |
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Definition
| cleave ULVWF to multimers normally found in the circulation |
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Term
| What is the hepatic cell receptor which binds and clears tPA-PAI-1, plasmin/AP, and uPA/PAI-1 complexes from the circulation? |
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Definition
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Term
| What is the procoagulant function of thrombin? |
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Definition
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Term
| What is needed for fibrinolysis to occur at a physiologically significant rate? |
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Definition
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Term
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Definition
| unique because two different proteases are inhibited at the same time |
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Term
| 10 year old male, with a history of bleeding problems, PT prolonged, aPTT normal, what does this indicate? |
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Definition
| F-VII defect or deficieny exists |
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Term
| The "fibrinogen group" of coagulation proteins includes |
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Definition
| factors I, V, VIII, and XIII |
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Term
| Which of the following coagulation factors is NOT a serine protease |
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Definition
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Term
| Which of the following coaulation factors are serine proteases? |
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Definition
| factor IIa, factor XIIa, factor XIa |
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Term
| Which of the following coagulation factors are involved in the "common pathway" of coagulation? |
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Definition
| factors X, V, II, and XIII |
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Term
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Definition
| inactive precursors of proteases |
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Term
| Deficiency of which of the following proteins is associated with a prolonged aPTT, but no evidence of defective hemostasis in vivo? |
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Definition
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Term
| Which of the following coagulation factors serves as a cofactor in the "contact activation" phase of coagulation? |
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Definition
| high molecular weight kininogen |
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Term
| Which of the following coagulation factors constitute the "intrinsic Xase" complex? |
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Definition
| factors IXa, VIIIa, phospholipid, and Ca2+ |
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Term
| The main function of PAI-1 is to |
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Definition
| inhibit plasminogen activators |
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Term
| The activity of which of the following protease inhibitors is accelerated by heparin? |
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Definition
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Term
| Protein C and protein S function as: |
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Definition
| inhibitors of coagulation |
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Term
| Formation of procoagulant complexes on phospholipid surfaces functions to: |
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Definition
| localize the reaction to the site of injury |
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Term
| Which of the following proteases are capable of reciprocal activation? |
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Definition
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Term
| Bradykinin is a small peptide with a profound effect on vascular permeability that is produced as a result of proteolytic cleavage of what protein? |
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Definition
| high molecular weight kininogen |
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Term
| Which of the following coagulation proteins are capable of "autoactivation?" |
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Definition
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Term
| What is the physiologic significance of the formation of γ-carboxy-glutamic acid residues by the action of vitamin K? |
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Definition
| creates a docking site for Ca2+ (for bridging to phospholipids) |
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Term
| Which of the following is NOT a physiologic function of thrombin? |
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Definition
| activation of fibrinolysis by inhibiting TAFI |
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Term
| The assembly of fibrin polymers from fibrin monomers |
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Definition
| is a spontaneous polymerization process |
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Term
| All of the following serve to localize fibrinolysis to the area of clot formation EXCEPT: |
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Definition
| binding of plasmin to thrombomodulin |
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Term
| The role of the protein TAFI in coagulation is to |
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Definition
| suppress fibrinolysis by eliminating the fibrin-binding sites for plasminogen |
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Term
| The protein C-protein S system is characterized by all of the following EXCEPT: |
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Definition
| Protein S associated with C4b-binding protein (C4b-BP) serves as the functional cofactor for APC inhibitory actions |
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Term
| Physiologic functions of thrombin |
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Definition
| proteolytic cleavage of fibrinogen to form fibrin monomers, activation of platelets, activation of protein C and degradation of factors Va and VIIIa |
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Term
| What serves to localize fibrinolysis to the area of clot formation |
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Definition
| binding of plasminogen and plasmin to fibrin, binding of plasminogen activators to fibrin, and binding free plasmin by α2antiplasmin |
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Term
| The protein C-protein S system is characterized by |
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Definition
| Protein C/S serves as an anticoagulant system, by degrading factors Va and VIIIa. The protein C/S system is activated by thrombomodulin-bound thrombin. The precursor proteins, factors V and VIII, are resistant to the action of APC. |
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Term
| What is the major distinction between the so-called extrinsic and intrinsic pathways? |
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Definition
extrinsic requires an activator (tissue factor) that is not found in the blood under normal circumstances
both require enzymes and protein cofactors originally present in plasma |
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Term
| Will a patient who is vitamin K-deficient produce any of the vitamin K-dependent factors? |
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Definition
| Still synthesize the proteins but fails to attach extra carboxyl group to the gamma carbon of glutamic acid residues in the GLA domains of the protein |
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Term
| Why is vitamin K so vital to the formation of coagulation complexes? |
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Definition
| the gamma carboxy form of the proteins is required for Ca2+ mediated interaction with phospholipid surfaces, which is required for forming the coagulation activation complexes |
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Term
| Why are the domains of the serine proteases involved in blood clotting so important in the hemostatic mechanism? |
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Definition
| The catalytic domain of the protease cleaves the substrate(s) of this protease. The noncatlytic domains of the serine proteases contain the reulatory elements of the proteins and are responsible for conferring the specificity of activation and activity of each enzyme. They bind calcium and promote interaction with phospholipids, cofactors, receptors and substrates |
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Term
| Which components of the intrinsic pathway are believed to be essential for in vivo hemostasis? |
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Definition
| Factors IX, VIII, and possibly factor XI are componets. Factor XII, prekallikrein, and HMW kininogen are not essential for normal in vivo hemostasis |
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Term
| What are some observations that suggest that they classic concepts for initiation of coagulation were not accurate? |
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Definition
| Thrombin can activate factor XI, bypassing the need for contact activation by factor XII/kallikrein/HK. Factor IX can be activated by factor VIIa as well as factor XIa. Initiaion of coagulation by tissue factor/factor VII is sufficient to initiate activation of both pathways. Full escalation of the coagulation system requires proteins of both pathways. |
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Term
| What are the three steps in the formation of an insoluble fibrin clot? |
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Definition
| (1) proteolytic cleavage of fibrinopepides A and B by thrombin forming the fibrin monomer (2) spontaneous polymerization of fibrin monomers to form fibrin polymers and (3) stabilization of the fibrin polymers of F-XIIIa |
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Term
| Why is the process of fibrinolysis a vital part of the hemostatic mechanism? |
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Definition
| Fibrinolysis is needed to restore the blood vessel structure and function to normal when the fibrin clot if no longer needed. It is essential to balance the activity of the procoagulant activity |
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Term
| Why must fibrinolysis be closely regulated and controlled? |
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Definition
| If activity of fibrinolysis is deficient, the result is thrombosis; if fibrinolysis is excessive, the result is hemorrhage |
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Term
| Why are the PLN degradation products of fibrinogen and fibrin different? |
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Definition
| Plamin cleaves at the same place on molecules of either fibrin or fibrinogen. In fibrinoen this produces seperate D and E fragments. Fibrin monomers have been covalently crosslinked by F-XIIIa, complees of various combinations (d-dimers) are formed. The presence of D-dimer confirms that both the procoagulant system (thrombin) and the fibrinolytic system (plasmin) have been activated |
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Term
| Why are naturally occuring inhibitors important in the hemostatic mechanism? |
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Definition
| They help to ctronol the activity of the coagulation and fibrinolytic proteases. They are inactive when distant from a site of vessel damage, helpin to limit clot formation to areas of vessel injury. They are essential in preventing unwarrented initiation of excessive amplification of the coagulation cascade. |
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