Lecture 9 – Haemostasis

Question 1

Haemostasis (8)

Answer 1

Protective process evolved in order to maintain a stable physiology
- “An explosive reaction designed to curtail blood loss, restore vascular integrity and ultimately preserve life”
• Life preserving processes designed to maintain blood flow
o Respond to tissue injury
o Curtail blood loss
o Restore vascular integrity & promote healing
o Limit infection
• Four Key Components:
 Endothelium
 Coagulation
 Platelets
 Fibrinolysis

Question 2

What makes a blood clot? (3)

Answer 2

• Fibrin mesh
• Platelets
• Red blood cells

Question 3

What happens if you cut yourself? (6)

Answer 3

Vessel cut + blood loss.
Endothelial cells become agitated + release components.
SM contracts becomes agitated + release compounds.
Platelets plug forms.
Platelets at site of injury, turn into a more active shape - release further mechanics (attract more platelets), set up environment for coagulation factors to interact.
Platelet plug consists of platelets + fibrin (forms a mesh over platelets).

Question 4

The haemostatic system: 3 phases (4,3,3)

Answer 4

1) Primary haemostasis:
• Vasoconstriction (immediate)
• Platelet adhesion (within seconds)
• Platelet aggregation and contraction (within minutes)
2) Secondary haemostasis:
• Activation of coagulation factors (within seconds)
• Formation of fibrin (within minutes)
3) Fibrinolysis:
• Activation of fibrinolysis (within minutes)
• Lysis of the plug (within hours)

Question 5

Vessel wall (6)

Answer 5

•	Normal Endothelium:
o	Inhibits coagulation
o	Prevents platelet aggregation
•	Provides a barrier to reactive elements in the subendothelium
o	Collagen fibronectin
o	Tissue factor

Question 6

Von Willebrand Factor - Use in the haemostatic system (5)

Answer 6

Lack of VWF leads to a bleeding disorder.
In injury, VWF spreads out (exposes sticky portion which binds to collagen on cell wall), it sticks over the site of injury.
VWF binds platelets.
When platelets reach site of injury they are activated –> Get flatter and SA increases.
Coagulation occurs.

Question 7

Von Willebrand Factor - Functions (2)

Answer 7

• Forms a bridge between damaged vessel wall (collagen) and platelets (primary haemostasis).
• Stabilises and protects Factor VIII from rapid clearance.

Question 8

VWF Synthesis (3)

Answer 8

•	Endothelial cells
Weibel Palade bodies
•	Megakaryocytes
Platelet a granules
•	Plasma VWF entirely derived from endothelial cells.

Question 9

VWF Distribution (1)

Answer 9

Endothelial cells - Weibel Palade bodies.

Question 10

Coagulation factors (3)

Answer 10

Fibronogen (I) - Forms clot (fibrin)
Prothrombin (II) - Active form (IIa) activated 1,5,7,13 Protein C, Platelets.
VWF - Binds to VIII, mediates platelet adhesion.

Question 11

Coagulation cascade (6)
Tissue factors

Answer 11

Fibronogen –> Fibrin [Thrombin]
Tissue damage:
Tissue factors found in subendothelium, bind to small amount of Factor VIIa. This activates X and V, leads to small amount of thrombin production which leads to fibrin formation.

Surface contact:
Start of clotting process when exposed to non-physiological surfaces.

VII deficiency causes bleeding.
XII not associated with bleeding.

Question 12

Revised waterfall hypothesis (3)

Answer 12

Each reaction requires:
Ca2+.
Phospholipid.
Specific co-factors.

Question 13

Tissue factor drives coagulation (3)

Answer 13

TF is outside the lumen.
Formation of TF-FVIIa complex.
Recruitment of FX and formation of thrombin.

Question 14

Fibrolysis (9)

Answer 14

Clot dissolution.
Main function
- Clot limiting mechanism
- Repair and healing mechanism
Tightly regulated enzymatic steps - feedback potentiation and inhibition.

Main key players:
Plasminogen
Tissue plasminogen activator (t-PA) and urokinase (u-PA).
Plasminogen activator inhibitor -1 and -2.
a2 plasmin inhibitor.

Plasminogen –> Plasmin [tPA] –> Fibrin clot –> FDP (Fibrin degradation products).

Question 15

Haemostasis and Thrombosis: A balance:

Answer 15

Fibrinolytic factors and anticoagulant proteins.

Coagulation factors and platelets.

Question 16

Thrombosis (6)

Answer 16

DECREASE - Fibrinolytic factors and anticoagulant proteins.
INCREASE - Coagulation factors and platelets.

Chronic venous insufficiency

• Atrophic changes
• Hyperpigmentation
• Ulceration
• Infection

Question 17

Bleeding (3)

Answer 17

INCREASE - Fibrinolyticfactors and anticoagulant proteins.
DECREASE - Coagulation factors and platelets.

Easy bruising (ecchymosis).

Question 18

Laboratory Evaluation of Bleeding (12)

Answer 18

ON TABLE

Question 19

COMPLETE STEPS (10)

Answer 19

1. Smooth muscle contracts/vasodilation and become agitated and release compounds.
2. Initiation of coagulation occurs when sub-endothelial tissue is exposed to the circulation at a site of injury. The cells aggregate and express tissue factor at their surface, which binds to endogenous activated FVIIa.
3. This complex binds small amounts of FX and FV to the exposed endothelial surface, which produce small quantities of thrombin. VWF (Von Willebrand Factor) spreads out (exposes sticky portion which binds to collagen on cell wall), it sticks over the site of injury – its binds to platelets.
4. The thrombin activates platelets that are attracted to the site by the process, as well as other plasma-borne clotting factors.
5. The activated factors (among them FVIII and FIX) enable the binding of activated FX and FV to the surface of previously adhered platelets (called aggregation) whose activation has produce conformational changes (Increase SA/get flatter) in their surface membranes to expose the ‘reaction sites’ necessary for continuation of the process.
6. Platelet plug consists of platelets + fibrin (forms a mesh over platelets). It contracts to form a dense, adherent plug – process is called contraction.
7. This leads to the ‘thrombin burst’ that is necessary for the large-scale production of fibrin and so the development of an effective clot.
8. These three stages are called the initiation, amplification and propagation phases of coagulation.
9. Activation of fibrolysis (clot dissolution).
10. Lysis of plug.