Flashcards in Hem & Onc - Physiology (Secondary Hemostasis) Deck (26):
What is the ultimate goal of the coagulation cascade?
To generate fibrin for the clot
What roles do high molecular weight kinin (HMWK) play in the coagulation and kinin cascades?
COAGULATION - HMWK activates the intrinsic coagulation pathway by activating factor XII; KININ - HMWK is cleaved to bradykinin by kallikrein (which is created from prekallikrein, activated by XIIa)
How is bradykinin formed? What effects does it have? How is bradykinin inactivated?
Kallikrein cleaves HMWK to form bradykinin; Bradykinin leads to increases in the following: (1) Vasodilation (2) Permeability (3) Pain; Angiotensin-converting enzyme (ACE)
How is kallikrein formed? What roles does it play in the coagulation, kinin, and complement cascades?
Activated factor XII (which is activated by HMWK) converts prekallikrein to kallikrein; Kallikrein goes on to (1) Cleave HMWK into bradykinin (allowing bradykinin to increase vasodilation, permeability, & pain) (2) Converts plasminogen to plasmin (allowing plasmin to cleave fibrin and activate C3)
How is the intrinsic coagulation pathway activated?
Two activators: (1) Collagen, basement membrane, & activated platelets (2) HMWK; Activates factor XII to begin the intrinsic coagulation pathway
What factors are involved in the intrinsic coagulation pathway?
XII, XI, IX, VIII, X, V, II --> conversion of fibrinogen (factor I) into fibrin (factor Ia)
How is the extrinsic coagulation pathway activated?
Thromboplastin (aka Tissue factor); Both activate factor VII to begin the extrinsic coagulation pathway
What factors are involved in the extrinsic coagulation pathway?
VII, X, V, II --> conversion of fibrinogen (factor I) into fibrin (factor Ia)
How is plasmin formed? What roles does it play?
Kallikrein converts plasminogen to plasmin; (1) COMPLEMENT CASCADE - activates C3 (2) COAGULATION CASCADE - cleaves fibrin to fibrin degradation products = fibrinolytic system
What is the name of factor II? What is the name of activated factor II?
What role does factor XIII play?
Cross links fibrin monomers to form fibrin mesh that acts to stabilize platelet plug
What compound ties together the coagulation, kinin, and complement cascades? How so?
Kallikrein; (1) COAGULATION - (a) is formed when activated factor XII converts prekallikrein (b) Converts plasminogen to plasmin (2) KININ - (a) Cleaves bradykin from HMWK (3) CASCADE - (a) After converting plasminogen to plasmin, plasmin goes on to activate C3
What is Hemophilia A? Hemophilia B?
Deficiency of factor VIII; Deficiency of factor IX
In terms of procoagulation, what is the key reaction/process to remember? What coagulation factors are matured as a result of this process?
Oxidized vitamin K is acted on by epoxide reductase to produce Reduced vitamin K, which acts a cofactor to convert precursors of the following factors into their mature forms: II, VII, IX, X (also proteins C and S)
By what mechanism does Warfarin work? What is the ultimate result of Warfarin therapy?
Anti-coagulation = Inhibits epoxide reductase --> decrease synthesis of factors II, VII, IX, X, protein C, protein S
What is the result of vitamin K deficiency? Why is it important to consider neonates in this regard?
Decrease synthesis of factors II, VII, IX, X, protein C, protein S; Neonates lack enteric bacteria, which produce vitamin K
Which coagulation factor does vWF carry/protect?
In terms of anticoagulation, what are key proteins to remember? What roles do they play?
(1) Protein C - after activation by thrombin-thrombomodulin complex (endothelial cells), activated protein C (using protein S as a cofactor) cleaves and inactivates factors Va and VIIIa (2) Tissue plasminogen activator - (like kallikrein) converts plasminogen to plasmin, allowing cleavage of fibrin mesh AND destruction of coagulation factors (3) Antithrombin - Inhibits activated form of factors matured by reduced Vitamin K (II, VII, IX, X) plus XI and XIII
What coagulation factors does activated protein C inactivate?
Va and VIIIa
What do kallikrein and tPA have in common?
Both cleave plasminogen to plasmin, allowing cleavage of fibrin mesh
What factors does Antithrombin inhibit?
Activated form of factors matured by reduced Vitamin K (II, VII, IX, X) plus XI and XIII
By what mechanism does Heparin work? What is the ultimate result of Heparin therapy?
Anti-coagulation = enhances the activity of Antithrombin; Inhibition of activated forms of factors matured by reduced Vitamin K (II, VII, IX, X) plus XI and XIII
What is the result of Factor V Leiden?
Produces a factor V resistant to inhibition by activated protein C
How is tPA used clinically?
As a thrombolytic
What are the principal targets of antithrombin?
Principal targets of antithrombin: thrombin and factor Xa.