Normal Coagulation

Question 1

What are the requirements for normal coagulation? (4)

Answer 1

Functioning platelets
Functioning endothelium
Functioning clotting factors
Balance between coagulation and anti-coagulant factors

Question 2

Describe the steps involved in coagulation. (4)

Answer 2

1. Blood vessel damage
2. Primary haemostasis
3. Secondary haemostasis
4. Fibrinolysis

Question 3

How does blood vessel damage stimulate haemostasis? (2)

Answer 3

Disrupts endothelium

Exposes collagen, tissue factor and Von Willebrand factor

Question 4

Describe the process of primary haemostasis. (3)

Answer 4

1. Platelets bind to Von Willebrand factor via GPIb-V-IX (on platelet surface)
2. VWF causes platelet activation, causing:
   a. Platelet degranulation (attracts more platelets & causes platelet aggregation)
   b. Expression of phospholipid on the platelet surface
3. This forms the platelet plug

Question 5

List the 2 ways of activating secondary haemostasis.

What is required for secondary haemostasis? (2)

Answer 5

Extrinsic pathway
Intrinsic pathway

Requirements:

• Phospholipids
• Calcium

Question 6

What stimulates the extrinsic pathway of secondary haemostasis?

What stimulates the intrinsic pathway of secondary haemostasis?

Answer 6

Extrinsic pathway - tissue factor

Intrinsic pathway - factor IIa (thrombin)

Question 7

Describe the extrinsic pathway of secondary haemostasis. (7 steps)

Answer 7

1. Tissue factor activates factor 7
2. 7a activates factor 10
3. 10a combines with 5a to form the prothrombinase complex
4. Prothrombinase complex activates factor 2 (prothrombin) into 2a (thrombin)
5. Thrombin converts fibrinogen into fibrin
6. Thrombin coverts factor 13 into 13a
7. 13a causes cross-linking of fibrin to form the fibrin mesh

Question 8

Describe the intrinsic pathway of secondary haemostasis. (2 steps)

Answer 8

1. Thrombin (2a) converts factor 11 into 11a
   a. 11a converts factor 9 into 9a
   b. Factor 9a stimulates more thrombin (2a) production
2. Thrombin (2a) converts factor 8 into 8a
   a. 8a stimulates more thrombin (2a) production

Question 9

What are the 3 methods of regulating coagulation?

Answer 9

Antithrombin
Activated protein C
Tissue factor pathway inhibitor

Question 10

How does antithrombin regulate coagulation?

Answer 10

Downregulates production of factors 7a, 11a, 9a, 10a and 2a (thrombin)

Question 11

How does tissue factor pathway inhibitor regulate coagulation? (2)

Answer 11

Inhibits factor 7a

Inhibits factor 10a

Question 12

How does activated protein C (APC) regulate coagulation? (2)

Answer 12

1. Thrombomodulin causes activation of protein C (forming APC)
2. Protein S combines with APC and causes:
   a. Inhibition of intrinsic pathway
   b. Inhibition of prothrombinase complex formation

Question 13

Describe the process of fibrinolysis. (3)

Answer 13

1. Fibrin stimulates formation of tissue plasminogen activator (tPA) and urinary plasminogen activator (uPA)
2. tPA and uPA convert plasminogen into plasmin
3. Plasmin breaks down fibrin into fibrin degradation products (FDPs, including D-dimer)

Question 14

What are the 3 methods of regulation of fibrinolysis?

Answer 14

Plasminogen activator inhibitors (PAI 1 and 2)
Thrombin activated fibrinolysis inhibitor (TAFI)
Alpha 2 antiplasmin

Question 15

How do plasminogen activator inhibitors (PAI 1 and 2) regulate fibrinolysis? (1)

Answer 15

Inhibit uPA and tPA

Question 16

How does alpha 2 antiplasmin regulate fibrinolysis? (1)

Answer 16

Inactivates plasmin

Question 17

How does thrombin activated fibrinolysis inhibitor (TAFI) regulate fibrinolysis? (1)

Answer 17

Inhibits uPA