Haemostasis

Question 1

What is haemostasis?

Answer 1

The stopping of the flow of blood
Insufficient haemostasis = Too much bleeding
Excessive haemostasis = Not enough blood flow

Question 2

What are the components of haemostasis?

Answer 2

1. Vascular constriction
2. Formation of platlet plug
3. Formation of blood clot
4. Fibrous tissue repair and clot lysis

Question 3

What is Vascular Constriction?

Answer 3

Smooth muscle wall of the vasculature constricts (vasoconstriction) as a result of damage
* Local myogenic spasm
* Vasoconstricotry factors from tissue, endothelium and platelets
* Reflex responses as a result of pain/sensory impulses (causing even more vasoconstriction)

Question 4

How does formation of the Platlet Plug occur?

Answer 4

1. Damage/hole/puncture in endothelium that exposes collagen (exposes Von Willebrand Factor excreted by endothelial cells) and activates platelets
2. Activated platelets activate cyclo-oxygenase activity which lets the platelet express membrane receptors and adhesion molecules - platelet adheres to the vessel wall, VWF and other platelets
3. Secrete ADP, platelet activating factor, serotonin and thromboxane A2 (vasoconstrictor) - Activation of other platlets by PAF and ADP also vasoconstriction occurs

Question 5

How does a blood clot form?

Answer 5

1. Sequential activation of proenzymes to activate enzymes/coagulation factors
2. This is triggered by exposed collagen (intrinsic pathway) and tissue factor release from endothelial cells (extrinisic pathway)
3. Both pathways produce thrombin which activates fibrin for secondary haemostasis
4. Fibrin binds to platelets activating them as well as activating coagulation factors
5. Platelets cross-link fibrin to produce a stable clot

Question 6

What is fibrous tissue repair and clot lysis?

Answer 6

• Fibroblasts invade the clot to initiate repair (fibrosis)
• Injured tissue will slowly release tissue plasminogen activator
• Plasminogen (trapped in clot during formation) activated to plasmin (as tissue releases plasminogen activator) which digests fibrin and other clotting factors

Question 7

What mechanisms do anti-platlet drugs use?

Answer 7

1. Inhibit TxA2 synthesis
2. Block TxA2 receptor
3. Increase cAMP or cGMP
4. Block ADP receptor
5. Block glycoprotein IIb/IIIa receptors

Question 8

In regards to pharmacology of anticoagulants what drugs will affect vascular constriction and formation of the platelet plug?

Answer 8

Drugs which affect platelets

Question 9

In regards to pharmacology of anticoagulants what drugs will affect formation of a blood clot?

Answer 9

Drugs that affect the clotting factors

Question 10

In regards to pharmacology of anticoagulants what drugs will affect fibrous tissue repair and clot lysis?

Answer 10

Drugs which affect clot lysis

Question 11

How do we treat bleeding disorder?

Answer 11

• Replace deficient clotting factors - fresh blood or fresh frozen plasma
• Stimulate production of new clotting factors - Vitamin K, ADH (stimulated VWF production), Delayed action = new factors need to be synthesized
• Provide antidote to anticoagulant
• Reduce fibrinolysis