Coagulation

Question 1

Dibigatran 
Class- 
Type-  prodrug name?
Target -
Action- 
Physiology- 1,2,3
Clinical- 2

Answer 1

Class- NOAC - Novel Oral Anti- Coagulant
Type- small mol Dibigatran etexilate
Target - Thrombin (Factor IIa)
Action- Competitive Inhibitor
Physiology-
1) Dec. Cleavage of a and b fibrinopeptides
2) Dec. In fibrinogen -> fibrin which cross-linkage of platelets/ platelet aggregation
3) ALSO dec. in thrombin dependant platelet activation
Clinical- PE, DVT, also prophylaxis

Question 2

Rivaroxaban

Class- 
Type- 
Target -
Action- 
Physiology- 1,2,3,4
Clinical- 2

Answer 2

Class- NOAC - Novel Oral Anti- Coagulant 
Type- small mol 
Target - Factor Xa
Action- competitive Inhibitor 
Physiology-
1) Dec. Factor Xa
2) Dec. Prothrombinase complex 
3) Dec. Prothrombin -> thrombin 
4) Dec. In fibrin formation AND thrombin dependant platelet activation 
Clinical- DVT and PE + prophylaxis

Question 3

Heparins
What do they form a complex with?
What’s the gene for this protein?
Function: inhibits (4) AND….

Heparin ->
LMWH ->
Fondaparinux ->

Answer 3

AT III (Antithrombin 3)
SERPIN C1 -> Serine Protease Inhibitor
Functions: Inhibit FIIa, FXa, FIXa and FXIa AND very potent!

Heparin + ATIII -> inhibit FIIa and FXa
LMWH + ATIII -> inhibit FXa only
Fondaparinux + ATIII -> inhibit FXa only

Question 4

Alteplase

Class- 
Type- 
Target -
Action- 
Physiology- 1,2,3
Clinical- 3!

Answer 4

Class- fibrinolytic 
Type- small mol.
Target- fibrinolysin 
Action- activator 
Physiology- 
1) promotes endogenous fibrinolysin/ fibrinolytic system
2) activates plasmin! 
3) dissolves thrombus 
Clinical- ACUTE! PE, DVT, Ischaemic stroke

Question 5

Prothrombinase complex made of?

What does fibrin do?

Tissue Factor:
What is it? (2)
What if there’s vessel damage?

Haemophilia A and B difference?

Answer 5

FXa, FVa, Ca2+, phospholipids

Fibrin spontaneously polymerises -> fibrin clot -> coagulation

Co- factor and also a transmembrane glycoprotein (not circulating!)
Vessel damage -> blood intersects with FIII -> coagulation!

A - F VIII deficient
B - F IX deficient (INTRINSIC!)

Question 6

Intrinsic pathway 
Factor? 
How is it activated? 
Extra (2)
Function:

Extrinsic
Factors aka
Function

Answer 6

Intrinsic
FIXa CHRISTMAS FACTOR
Activated via FXII and FXI
Vit K dependant also linked to Haemophilia B
Function: cleaves and activates FX -> FXa

Extrinsic
FVII and FIII (Tissue Factor) = Tenase Complex
Function: cleaves and activates FX -> FXa

Question 7

Thrombin functions 1,2,3,4,5 (big on!) what does it need?

Plasmin
Causes?
From?
Via (2)

Answer 7

1) Activates and cleaves Fibrinogin -> fibrin
2) FV activation (for prothrombinase complex)
3) FVII activation
4) FVIII activation
5) FXIII -> FXIIIa which crosslinks glutamine to lysine in fibrin -> SOLIDIFIES CLOT! (needs Ca2+)

Plasmin
Causes fibrinolysin/ dissolves clot or thrombus
From plasminogen
Via tPA (tissue plasminogen activator) or Urokinase