Physiological Coagulation

Question 1

Arterial and venous clots

Answer 1

Arterial: Platelets, occlusive
Venous: red cells and fibrin

Question 2

Basic Principle of clotting

Answer 2

Vessel injury and platelet plug formation ->
Activates clotting factors ( via tissue factor) ->
Thrombin (IIa) ->
fibrinogen to fibrin

Question 3

How do coagulation factors change in plasma at a basic level?

Importance of cofactors

Answer 3

Are in plasma doing nothing. Then protein cleavage (by an activated protease) activates the coagulation factor at site of injury

Reinforce cleavage, as without is a slow inefficient process

Question 4

How does physiological coagulation begin?

Answer 4

Starts at the tissue factor pathway first at the vessel wall (extrinsic pathway)

Intrinsic pathway not required for repair/physiological coagulation

Question 5

Physiological coagulation

-___ ____ on injured vessel endothelium and combines with factor ___ (activates it)
-Factor VIIa activates factor _ to __, and some factor __ to ___. __ causes _____ to thrombin (small amount)
-Thrombin activates factor ____ to ____, factor _ to __ and factor __ to ___. Factors VIII and V are _____.
- Now on the _____ _____, factors ____ and __ activate _ to __.
(NB factor ___ makes factor ___)
- On platelet, __ and __ form a complex that convert prothrombin to ____. This connects fibrinogen to make ___. Thrombin can ______ more components!

Answer 5

-Tissue factor on injured vessel endothelium and combines with factor VIIa
-Factor VIIa activates factor X to Xa, IX to IXa. Xa Causes prothrombin to thrombin. (small amount)
- Thrombin activates factor VIII to VIIIa, factor V to Va and factor XI to XIa. Factors VIII and V are cofactors.
- Now on the activated platelet, factors VIIIa and IXa activate X to Xa.
(NB factor XIa makes factor IXa)
- On platelet, Xa and Va form a complex that convert prothrombin to thrombin. This connects fibrinogen to make fibrin. Thrombin can activate more components!

Question 6

What is in the initiation complex?

Answer 6

Tissue factor, VIIa which then activates IX and X on disrupted endothelial cell

Question 7

What cofactors does thrombin activate needed for further complexes?

Answer 7

V and VIII.

Some XI?

Question 8

Source and role of factor IX

Answer 8

Some from tissue factor complex
Some from Factor XIa

Role: Second complex on activated platelet

Question 9

Second complex, tenase complex

Answer 9

VIIIa and IXa. VIII is cofactor
Factor X is converted to Xa

Need calcium + phospholipid

Question 10

Amplification loop recap

Answer 10

Thrombin activates factor XIa to make more IXa

Question 11

Complex 3 on platelet surface, prothrombinase complex

Answer 11

Va, Xa and prothrombin, being converted to thrombin.
Xa is protease, and Va is cofactor
Huge burst of thrombin made, which can further make more cofactors and Xa, more than extrinsic pathway (tissue factor)
Calcium + phospholipid needed

Question 12

What shuts down the first complex?

Answer 12

Occurs quickly by Tissue factor pathway inhibitor TFPI.

Question 13

What inhibits the activated cofactors?

Answer 13

Protein C, but needs Protein S to function

Question 14

What is the most important inhibitor?

Answer 14

Antithrombin, which inactivates IXa, Xa, thrombin, XIa. less so IXa and XIa

Question 15

Summary of thrombins actions

Answer 15

Fibrinogen to fibrin
Activates: V-Va; VIII-VIIIa; XI-XIa (feedback loop for IXa); XIII (cross links fibrin); protein C
Inflammation roles

Question 16

Common pathway

Answer 16

Xa, Va, thrombin (IIa), firbrinogen (I)

Question 17

Vitamin K dependent proteins

Answer 17

VII, IX, X, prothrombin, protein C, protein S

Question 18

Action of vitamin K

• _______ _____ residues in the ____ domain of vit K dependent proteins
• Absence of _____ results in failure to bind to _____
• Cyclical process in the _____

Deficiency results in ____, NB newborns have low Vit _ and need ______

Answer 18

• Carboxylates glutamate residues in the GLA domain of vit K dependent proteins
• Absence of carboxylation results in failure to bind to membrane
• Cyclical process in the liver

Deficiency results in bleeding, NB newborns have low Vit K and need supplementation

Question 19

Contact activation/intrinsic pathway

is it important?

Answer 19

Occurred on glass
Factor VII activates XI to XIa then IX to IXa

Factor XII not needed for physiological coagulation, factor XI deficiency is mild.
Shows abnormal result if deficient in factor XII! APTT

Question 20

Fibrinolysis

Answer 20

Plasminogen to plasmin by TPA

Breaks down fibrinogen to FDP, and insoluble fibrin clot to D-dimers. D dimers measured in tests?