Haemostasis

Question 1

what are the 5 main components of haemostatic system?

Answer 1

1: formation of platelet plug (primary haemostasis)
2: formation of fibrin clot (secondary haemostasis)
3: fibrinolysis (clots are broken down as bleeding stops
4: anticoagulant defences (body switches off the clotting system)

Question 2

Which haemostasis mechanisms are important for a minor vs major haemorrhage?

Answer 2

Minor bleeding - platelet plug is enough
Major - fibrin clot forms over the platelet plug = more stable clot

Question 3

Platelets:

• lifespan
• describe the activation and formation of a platelet plug

Answer 3

Lifespan: 7-10 days

• endothelial wall damage exposes collagen and releases von willebrand factor and other proteins to which platelets have receptors = platelet adhesion
• platelets then secrete various chemicals and this leads to aggregation of platelets at site of injury (they release calcium and express a positive charge to allow factors to be attracted towards it)

(von willebrand factor acts as a glue for platelets to stick to exposed collagen and to eachother)

Question 4

What are three causes for failure of the platelet plug?

Answer 4

1: von willebrand factor problems
- decrease in VWF seen mostly in inherited disorders

2: vascular problems
- vessel wall collagen is lost with age/steroids/vit C deficiency

3: Platelet factors
- thrombocytopenia or reduced platelet function (drugs)

Question 5

What are 4 potential consequences of failure of platelet plug?

Answer 5

1: mucosal bleeding
- epistaxis/GI/conjunctiva/menorrhagia

2: spontaneous bruising and purpura
- mostly seen in lower limbs due to gravity
- if someone has a cough may see this on their chest

3: intracranial haemorrhage
4: retinal haemorrhage

Question 6

What screening tests are available to screen for failure of formation of platelet plug?

Answer 6

• platelet count

- no simple screening tests

Question 7

Describe the formation of a fibrin clot (draw the diagram to help you)?

Answer 7

Secondary haemostasis:
Extrinsic pathway
1. Damaged endothelial cells release tissue factor, which activates factor VII = VIIa and forms a TF:VIIa complex
2. TF:VIIa activates factor X (X→Xa)

Intrinsic pathway

3: factor IX is activated by pathways that are initiated by exposed collagen = IXa
4: Thrombin liberates factor VIII from vWF and activates it = VIIIa
5: factor VIIIa forms complex with factor IXa = VIIIa:IXa AKA tenase which powerfully activates factor X

Common pathway

6: Factor Xa (activated via TF:VIIa or tenase) converts prothrombin (factor II) to thrombin (factor IIa).
7: thrombin activates factor V =Va. Va increases the rate of prothrombin conversion to thrombin
8: Thrombin cleaves fibronogen to fibrin = fibrin polymerises = clot (this is helped by factor VIIIa)

Question 8

What is the intrinsic pathway, extrinsic pathway? What coagulation tests are used for each pathway?

Answer 8

Extrinsic - this begins at the vessel wall and is the formation of the TF:VIIa complex. Prothrombin time tests this pathway.

Intrinsic - this begins in the blood stream when cells are exposed to collagen and is the formation of tenase (VIIIa:IXa). Activated partial thromboplastin time tests this pathway

Question 9

Which part of the clotting cascade is initiation/propagation/amplification

Answer 9

Initiation: extrinsic pathway
Propagation: prothrombin to thrombin
Amplification: thrombin - this activates factor V and factor VIII directly

Question 10

What are the three general reasons for failure of a fibrin clot formation?

Answer 10

1: increased fibrinolysis (usually as part of a complex coagulopathy)
2: single clotting factor deficiency (e.g. haemophilia)
3: multiple clotting factor deficiencies (e.g. DIC/liver failure/vit K deficiencies/warfarin therapy)

Question 11

Describe the pathway of fibrinolysis?

Answer 11

This is the breakdown of the fibrin clot

1: tissue plasminogen activator (tPA) converts plasminogen to plasmin
2: plasmin causes fibrin to break down to fibrin degeneration products (D-dimers)

Question 12

How is the failure of fibrin clotting (secondary haemostasis) screened for?

Answer 12

Prolonged prothrombin time: this would show problems in the extrinsic pathway (factor VIIa or TF problem)

Prolonged APTT: would show intrinsic pathway problems (VIII or XI problems)

If there is a problem in the common pathway - both prolonged

Question 13

What clotting factor deficiency would result in a vWF deficiency?

Answer 13

Factor VIII as vWF carries this

Question 14

What is the role of naturally occurring anticoagulants? what naturally occurring anticoagulants exist?

Answer 14

These are regulating systems for once bleeding has stopped

Antithrombin:

• breaks down thrombin or factor Xa
• heparin is a co-factor
• isn’t vit K dependant

Proteins C and S (thrombin binds to thrombomodulin and activates these):

• Protein C breaks down factor V and VIII
• Protein S acts as a cofactor for protein C by changing it’s conformation to be more effective
• vit K dependant

Question 15

Where are coagulation factors synthesised? Which components of haemostasis are vit K dependant

Answer 15

-Hepatocytes

Vit K dependant:

• Factors II, VII, IX, X
• protein C and S

Question 16

what is a thrombophilia? what is this caused by?

Answer 16

increased tendency to develop venous thrombosis

-deficiency of naturally occurring anticoag: may be hereditary