3.3. Haemostasis

Question 1

What are the four components of haemostasis?

Answer 1

Vascular constriction

Formation of platelet plug

Formation of blood clot

Fibrous tissue repair and clot lysis

Question 2

Describe vascular constriction

Answer 2

• Local myogenic spasm
• Vasoconstrictory factors from tissue, endothelium, platelets
• Reflex response from pain/sensory impulses

Question 3

Describe the formation of the platelet plug

Answer 3

• exposed collagen = activates platelets (exposes VWF in vessel wall)
• Activated platelets express membrane receptors and adhesion molecules (adhere to vessel wall, VWF, other platelets)
• Activated platelets secrete ADP, platelet activating factor, serotonin, thromboxane A2 (activates other platelets, vasoconstriction)
• Absences of platelets = petechiae

Question 4

Describe the formation of a bloodclot

Answer 4

• Sequential activation of proenzymes > active enzymes (Ca2+ and Vit K needed)
• Triggered by exposed collagen (intrinsic pathway) and tissue factor release (extrinsic pathway)
• Fibrin binds platelets = activation of platelets and coagulation factors
• Platelets cross-link fibrin = stable clot
• Platelets contract = clot retraction = smaller injury

Question 5

Describe fibrous tissue repair and clot lysis

Answer 5

Fibroblasts invade clot to initoate repair (make tissue)

Injured tissue slowly releases tissue plasminogen activator (tPA)

Plasminogen (trapped in clot) > plasmin
(digests fibrin and clotting factors)

Question 6

What are anticoagulants

Answer 6

Slow down blood clotting process

Question 7

How is endothelium a natural anticoagulants?

Answer 7

• Smooth surface
• Glycocalyx repels clotting factors and platelets
• Thrombomodulin (binds thrombin, protein C inactivates clotting factors)
• Prostacyclin and nitric oxide (vasodilators, inhibit platelet aggregation)

Question 8

How is blood a natural anticoagulant?

Answer 8

• Clotting factors circulate in inactive form
• Fibrin in clot binds thrombin (prevents growth clot)
• Antithrombin III inactivates clotting factors
• Heparin from mast cells ↑ binding of antithrombin III to clotting factors

Question 9

Outline the pharmacology of anticoagulants for each of the four stages of haemostasis

Answer 9

Vascular constriction - drug affecting platelets
Platelet plug - drug affecting platelets
Blood clot - drug affecting clotting factors
Fibrous repair/clot lysis - drug affecting clot lysis

Question 10

How do anti-platelet drugs work?

Answer 10

• inhibit TxA2 synthesis
• Block TxA2 receptors
• ↑cAMP
• Block AP receptor
• Block glycoprotein IIb/IIIa receptors

Question 11

Give examples of anti-platelet drugs

Answer 11

ASPIRIN
- irriversible COX inhibitor
- inhibits thromboxane synthesis

EPOPROSTENOL
- ↑platelet cAMP

DIPYRIDAMOLE
- inhibits phosphodiester
- ↑ platelet cAMP

ADP RECEPTOR ANTAGONIST
- blocks ADP potentiation of platelet activation

GLYCOPROTEIN INHIBITORS
- block platelet binding to fibrinogen

Question 12

How do coagulation inhibitors work?

Answer 12

• Calcium chelation
• Activation of antithrombin III
• Prevents Vit K- dependant activation
• Thrombin inhibition

Question 13

Explain how activation of antithrombin III acts as an anticoagulant

Answer 13

Heparin (produced by mast cells)
- Binds to ATIII = ↑ inactivation of clotting factors
- Binds thrombin = antiplatelet action

Question 14

How do drugs promoting clot lysis work?

Answer 14

TISSUE PLASMINOGEN ACTIVATOR (TPA)
- acts on fibrin-bound plasminogen in clot
- low affinity for circulating plasminogen
- clot selective

STREPTOKINASE
- streptococcal enzymes activte plasminogen

UROKINASE
- natural TPA extracted from human urine
- unblocks catheters