Hem & Onc - Physiology (Secondary Hemostasis)

Question 1

What is the ultimate goal of the coagulation cascade?

Answer 1

To generate fibrin for the clot

Question 2

What roles do high molecular weight kinin (HMWK) play in the coagulation and kinin cascades?

Answer 2

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)

Question 3

How is bradykinin formed? What effects does it have? How is bradykinin inactivated?

Answer 3

Kallikrein cleaves HMWK to form bradykinin; Bradykinin leads to increases in the following: (1) Vasodilation (2) Permeability (3) Pain; Angiotensin-converting enzyme (ACE)

Question 4

How is kallikrein formed? What roles does it play in the coagulation, kinin, and complement cascades?

Answer 4

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)

Question 5

How is the intrinsic coagulation pathway activated?

Answer 5

Two activators: (1) Collagen, basement membrane, & activated platelets (2) HMWK; Activates factor XII to begin the intrinsic coagulation pathway

Question 6

What factors are involved in the intrinsic coagulation pathway?

Answer 6

XII, XI, IX, VIII, X, V, II –> conversion of fibrinogen (factor I) into fibrin (factor Ia)

Question 7

How is the extrinsic coagulation pathway activated?

Answer 7

Thromboplastin (aka Tissue factor); Both activate factor VII to begin the extrinsic coagulation pathway

Question 8

What factors are involved in the extrinsic coagulation pathway?

Answer 8

VII, X, V, II –> conversion of fibrinogen (factor I) into fibrin (factor Ia)

Question 9

How is plasmin formed? What roles does it play?

Answer 9

Kallikrein converts plasminogen to plasmin; (1) COMPLEMENT CASCADE - activates C3 (2) COAGULATION CASCADE - cleaves fibrin to fibrin degradation products = fibrinolytic system

Question 10

What is the name of factor II? What is the name of activated factor II?

Answer 10

Prothrombin; Thrombin

Question 11

What role does factor XIII play?

Answer 11

Cross links fibrin monomers to form fibrin mesh that acts to stabilize platelet plug

Question 12

What compound ties together the coagulation, kinin, and complement cascades? How so?

Answer 12

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

Question 13

What is Hemophilia A? Hemophilia B?

Answer 13

Deficiency of factor VIII; Deficiency of factor IX

Question 14

In terms of procoagulation, what is the key reaction/process to remember? What coagulation factors are matured as a result of this process?

Answer 14

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)

Question 15

By what mechanism does Warfarin work? What is the ultimate result of Warfarin therapy?

Answer 15

Anti-coagulation = Inhibits epoxide reductase –> decrease synthesis of factors II, VII, IX, X, protein C, protein S

Question 16

What is the result of vitamin K deficiency? Why is it important to consider neonates in this regard?

Answer 16

Decrease synthesis of factors II, VII, IX, X, protein C, protein S; Neonates lack enteric bacteria, which produce vitamin K

Question 17

Which coagulation factor does vWF carry/protect?

Answer 17

VIII

Question 18

In terms of anticoagulation, what are key proteins to remember? What roles do they play?

Answer 18

(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

Question 19

What coagulation factors does activated protein C inactivate?

Answer 19

Va and VIIIa

Question 20

What do kallikrein and tPA have in common?

Answer 20

Both cleave plasminogen to plasmin, allowing cleavage of fibrin mesh

Question 21

What factors does Antithrombin inhibit?

Answer 21

Activated form of factors matured by reduced Vitamin K (II, VII, IX, X) plus XI and XIII

Question 22

By what mechanism does Heparin work? What is the ultimate result of Heparin therapy?

Answer 22

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

Question 23

What is the result of Factor V Leiden?

Answer 23

Produces a factor V resistant to inhibition by activated protein C

Question 24

How is tPA used clinically?

Answer 24

As a thrombolytic

Question 25

What are the principal targets of antithrombin?

Answer 25

Principal targets of antithrombin: thrombin and factor Xa.

Question 26

Draw out the steps of the coagulation cascade. In your diagram, also show how the coagulation cascade relates to the complement, fibrinolytic, and kinin systems.

Answer 26

See p. 377 in First Aid for visual at bottom of page