Hemodynamics II Flashcards
What are the three general components that contribute to hemostasis?
- Endothelium/vascular wall
- Platelets
- Coagulation cascade
What are the “bricks” of the clotting system?
Platelets
What is the “cement” of hemostasis?
Coagulation cascade and fibrin
What is the very first thing to happen in an initial injury?
Vasoconstriction
What happens in the hemostasis after the initial vasoconstriction?
Endothelial damage exposes subendothelium causing platelets to become activated and adhere
What is the cytokine that activates the coagulation cascade?
Tissue factor (factor III)
What happens after tissue factor is released?
Platelets activation further coagulates
What are the two main components of a clot?
Platelets and fibrin
What is the function of vWF?
Causes platelets to adhere to the region of a clot
What does vWF bind to?
Collagen IV
What is in alpha granules in clotting? What does this do?
TXA2, recruits more platelets
What are the two cytokines that endothelial cells release to keep the clot in check?
tPA
Thrombomodulin
What are the four things mentioned in lecture that are procoagulative?
Infectious agents
Hemodynamic forces
Cytokines
Plasma mediators
What are the two cytokines that endothelium releases that are anti thrombotic?
PGI2
NO
What is the enzyme that endothelium produces that prevents platelet aggregation? What does this do?
Adenosine diphosphatase which degrades ADP
What is heparin?
Polysaccharide that are cofactors to antithrombin
What is the function of thrombomodulin?
Converts thrombin to an anticoagulant
What is the function of vWF?
Firmly adhere platelets to the endothelium via GPIb
What is the substance that the endothelium secretes to inhibit tPA?
Plasminogen activator inhibitor
What causes the release of tissue factor?
Endotoxin, trauma, cytokines
What activates protein C, and what does it in turn inactivate?
Activated by protein S
Factors V and VIII
What activates protein C?
Thrombin/antithrombin complex
In general, under normal conditions, what do endothelial cells do?
Inhibit platelet adherence
What produces platelets?
Megakaryocytes
What exactly are platelets?
Anuclear cell fragments
What are the contents of platelets?
Alpha granules and dense granules
What are the three steps that ensure to platelets after vWF binds to collagen IV?
Adhesion
Secretion and activation
Aggregation
Is the initial platelet adhesion to the ECM firm?
No
What does vWF bind on platelets?
Glycoprotein Ib receptors
Adhesion of platelets causes what?
Release of platelet granules
What ion is needed in the coagulation cascade?
Ca
What is the function of the ADP release by platelets?
Mediates platelet aggregation which drives increasing platelet aggregation at the site
What is the function of platelet factor 4 released by platlets?
Inactives heparin
What is the function of serotonin that platelets release?
Induces vasoconstriction
What is the function of ADP and TXA2 that platelets release?
Further stimulates platelet aggregation
What is the protein found on the surface of platelets that link fibrin together?
GpIIb-IIIa
Where does thrombin bind to?
Platelet surface
Platelet activation causes expression of what on the surface to bind coag factors? What do these do?
Phospholipid complexes, which act as surfaces to bind coagulation factors.
What are the three major platelet secretions that further activates platelets?
ADP
TXA2
Thrombin
What is the end product of the coagulation cascade?
Fibrin
What are clotting factors?
Inactive enzymes (S proteases)
What is the ion needed for the assembly of the complex of coagulation factors?
Ca
What is serum?
Liquid part - clot factors
What is plasma?
Liquid + clotting factors
What is added to plasma to prevent clotting? How?
EDTA containing solution to get rid of Ca
What converts fibrinogen to fibrin?
Thrombin
What is the order of factor activation in the extrinsic pathway?
3, 7, 10
What is the order of factor activation in the intrinsic pathway?
12, 11, 9, 8, 10
What two factors make up the prothrombinase complex?
factor V and factor X
Where do both the intrinsic and extrinsic pathway converge?
Factors 9 and 10
What does prothrombin time (PT) measure?
The extrinsic arm
What does PTT measure?
Intrinsic arm
What is PT prolonged by? PTT?
PT = Warfarin PTT = Heparin
What happens in the clotting cascade is not kept in check?
Thrombus can form
What are the three main anticoagulants produced by the body?
Antithrombin III
Protein C
Plasmin
What is the function of antithrombin III? What is it potentiated by?
Inactivates serine proteases (factors 9, 10, 11, and 12)
Potentiated by Heparin
What is the function of Protein C?
Inhibits V and VIII
What is the function of plasmin?
breaks down fibrin
What is the function of protein S?
Enhances protein C
What is thrombomodulin activated by? What does it do?
Thrombin
Activates protein C
What is the function of thrombomoduin?
Binds to thrombin and alters its conformation
What is the function of tissue pathway factor inhibitor?
Inhibits III and VII (tissue factor = factor III, thus “tissue factor pathway inhibitor)
Free plasmin is inactivated by what?
Circulating alpha2 antiplasmin
tPA is inactivated by what?
plasminogen activator inhibitor (PAI)
What do endothelial cells secrete to balance coagulation/anticoagulation?
plasminogen activator inhibitor (PAI)
What are the three substances that can activate plasminogen?
Urokinase
tPA
Streptokinase
What activates antithrombin III? What does that inactivate?
Activated by heparin
Inactivates Factors 10 and 9
What prevents plasmin from circulating freely and dissolving clots?
alpha2-antiplasmin
What are anticoagulants?
Prevents clot formation and extension
What are antiplatelets?
Drugs that interfere with platelet activity
What are thrombolytic agents?
Dissolve existing thrombi
What are the two traditional anticoagulants?
Heparin and warfarin
What cells produce heparin?
Basophils and mast cells
Does heparin disintergrate clots that have already formed?
No
What are the two routes Heparin is given?
IV and SQ
How does heparin work? What are the three main clotting factors it inhibits?
Binds and activated antithrombin III
Inhibits thrombin, factors 9 and 10
What is the MOA of coumadin?
Interfering with vitamin K metabolism
What are the vitamin K dependent factors? What drug interferes with their synthesis?
10, 9, 7, 2 (vitamin K was born in 1972)
Coumadin
What is the MOA of dabigatran?
Direct thrombin inhibitor
What is the MOA of rivaroxaban and apixaban?
Inhibit factor X
What is the MOA of Tissue factor pathway inhibitor (TFPI)?
Inhibits factors 3 and 7
Hageman factor = what number?
12
What activates plasminogen activator inhibitor?
Thrombin
various cytokines
What cells produce tPA?
Endothelial cells
What is streptokinase?
A bacterial product used clinically to activated plasminogen