Haemostasis 2

Question 1

What is another name for procoagulant?

Answer 1

Thrombogenic

Question 2

What is another name for anticoagulant?

Answer 2

Antithrombogenic

Question 3

Which factors are referred to by their common name?

Answer 3

Factors 1 to 4
Fibrinogen
Prothrombin
Tissue factor
Calcium

Question 4

Which factor no longer exists

Answer 4

Factor 6 -> it was named incorrectly

Question 5

Which factors have not yet been assigned Roman numerals?
(2)

Answer 5

Prekallikrein

Kininogen

Question 6

Which factors have more than one factor

Answer 6

Factors V and VIII are also referred to as the labile factors

This is because their coagulant activity is not durable in stored blood

Question 7

What are the vitamin K dependent factors

Answer 7

II
VII
IX
X

Question 8

Why are factors II, VII. IX and X referred to as vitamin K Dependent Factor?
(2)

Answer 8

During their biosynthesis in the liver, a series of post translational enzymatic reaction include a step that required vitamin K to function as a cofactor to a carboxylase enzyme

Vitamin K serves as an essential cofactor for a carboxylase that catalyses carboxylation of glutamic acid (Gla) residues on vitamin K-dependent proteins

Question 9

What is haemophilia C?

Answer 9

Complete lack of factor XI

Question 10

What are the symptoms of haemophilia C

Answer 10

exhibit mild haemorrhagic disorder

Question 11

What happens if a patient has trace quantities of factor XI?

Answer 11

They can have withstand major trauma without unusual bleeding

Question 12

What is Haemophilia A

Answer 12

Complete lack of factor 8

Question 13

What is Haemophilia B

Answer 13

Complete lack of factor 9

Question 14

What is the main pitfall of the the coagulation cascade theory of the intrinsic and extrinsic pathways?
(4)

Answer 14

Doesn’t explain why Haemophilia A or B results in an inability to clot blood

Loss of factor 8 or 9 are from the intrinsic pathway

Therefore clotting should form from the extrinsic pathway

This means the theory may only provide a reasonable model of in vitro coagulation test e.g. aPTT and PT

Question 15

Current evidence proposes what theory
(2)

Answer 15

The intrinsic pathways is not a parallel pathway to the extrinsic

Instead the intrinsic pathway augments thrombin generated primarily by the extrinsic pathway

Question 16

What factors are involved in the extrinsic pathway
(4)

Answer 16

Tissue factor
VII
X
Calcium

Question 17

Where is tissue factor produced

Answer 17

Released by damaged endothelial cells

Question 18

What is the role of tissue factor?
(2)

Answer 18

It is a co-factor with factor VII

It helps convert X to Xa

Question 19

What factors are involved in the intrinsic pathway?
(9)

Answer 19

XII
XI
IX
VIII
X
Prekallikrein (PK)
Kininogens (HK)
Calcium
Platelet phospholipids

Question 20

How is PK converted to kallikrein

Answer 20

Activated platelets present a negatively charged surface which activates PK to kallikrein

Question 21

What does kallikrein do?

Answer 21

This protease activates Factors XII to XIIa

Question 22

What does factor XIIa do?

Answer 22

Converts XI to XIa which converts IX to IXa which converts X to Xa = cascade

This needs Ca++ as a co-factor

Question 23

What is calcium needed for?

Answer 23

It mediates the binding of the coagulation factors to the negatively-charged phospholipids surfaces expressed by platelets via the negatively charged residues on Factor Xa and Factor IXa

It is also required at other points in the coagulation cascade

Question 24

Where are negatively-charged phospholipids found

Answer 24

Found on the surface of activate platelets

Question 25

Who proposed the cell based model of coagulation

Answer 25

D. Monroe M. Hoffman

Question 26

What is notable about the cell based model of coagulation?

Answer 26

The cascade is a biochemical model Not a true reflection of what happens in the body

Question 27

What are the three differences between the cascade and cell based model of coagulation? Give three characteristics of the cascade

Answer 27

Cascade - extrinsic and intrinsic pathways work independently, meet at common end-point - Both can generate large amount of thrombin to form clot - Coag factors control the rate of coagulation, cells are only phospho-lipid surface

Question 28

What are the differences between the coagulation cascade and the cell based model? (Give five characteristics of the cell based model)

Answer 28

Cell Based - Extrinsic pathway initiates the process - Generates small amount of the Thrombin Spark - Followed by Intrinsic Pathway, works on platelets to produce the Thrombin Burst - No role of factor XII - Cells (platelets and endothelium) control the coagulation

Question 29

What are the five steps to the cell based model of coagulation?

Answer 29

Initiation (TF Cell) Amplification (platelet) Propagation (active platelet) Stabilisation of clot Inhibition of further coagulation

Question 30

How is the cell based model initiated? (5)

Answer 30

It occurs by expression of Tissue Factor Tissue binds factor VIIa to activate factor IX and factor X This activation of factor IX by TF-VIIa complex serves as the bridge between classical extrinsic and intrinsic pathways. Factor Xa then binds to factor II to form thrombin (factor IIa) Thrombin generation through the reaction is not robust and can be effectively terminated by TF pathway inhibitor.

Question 31

How is the cell based model amplified (amplification step)? (2)

Answer 31

Since the amount of thrombin generated is not sufficient, therefore numerous positive feedback loops are present that bind thrombin with platelets Thrombin that is generated in the initiation phase further activates factor V and factor VIII, which serves as a cofactor in prothrombinase complex and accelerates the activation of FII by FXa by FIXa, respectively

Question 32

What is the propagation step in the cell based model? (2)

Answer 32

The accumulated enzyme complexes (tenase complex and prothrombinase complex) on platelet surface support robust amount of thrombin generation and platelet activation This ensures continuous generation of thrombin and subsequently fibrin to form a sufficiently large clot

Question 33

What is the stabilisation step of the cell based model? (2)

Answer 33

Thrombin generation leads to activation of factor XIII (fibrin stabilising factor) which covalently links fibrin polymers and provides strength and stability to fibrin incorporated in platelet plug In addition, thrombin activates thrombin activatable fibrinolysis activatable fibrinolysis inhibitor (TAF) that protects the clot from fibrinolysis

Question 34

What is anticoagulation

Answer 34

The inactivation of the pro-coagulant pathway