1.1.2 Haemostasis

Front 1

Phases of haemostasis

Back 1

1. Vascular
2. Platelet
3. Coagulation

Front 2

Vascular phase: vasospasm

Back 2

Cutting the wall of a blood vessels, triggers smooth muscle contraction.
- Vasospasm, lasting around 30 mins to slow or even stop the flow of blood

Front 3

Vascular phase: endothelium

Back 3

- Endothelial cells contract and expose underlying BM to blood stream
- Endothelial cells release local factors and hormones e.g. ADP, tissue factor, prostacyclin, endothelins
- Endothelial plasma membranes become "sticky", facilitating the attachment of platelets and even sticking to the opposite endothelial wall

Front 4

Endothelins

Back 4

Peptide hormones that:
- stimulate smooth muscle contraction and promote vascular spasm
- stimulate the division of endothelial cells, smooth muscle cells and fibroblasts to accelerate the repair process

Front 5

Platelet phase

Back 5

Begins with the attachment of platelets to endothelial surfaces, BM and exposed collagen fibres
Platelet adhesion > platetlet aggregation > platelet plug

Front 6

Activation of platelets

Back 6

First sign of activation: become more spherical, develop cytoplasmic processes to link with other platelets. Release a variety of compounds:
1. ADP stimulates platelet aggregation and secretion
2. Thromoxane A2 and serotonin stimulate vascular spasm
3. Clotting factors are proteins
4. PDGF is a peptide that promotes vessel repair
5. Calcium ions are required for platelet aggregation and in the clotting process

Front 7

Progression of platelet phase

Back 7

ADP, thomboxane and calcium are released from each arriving platelet, stimulating further aggregation
- this is a positive feedback loop

Front 8

Role of prostacyclin

Back 8

A prostaglandin that inhibits platelet aggregation and is released by endothelial cells. Controls and restricts platelet aggregation to the injury site.
- This is reinforced by inhibitory compounds released by WBCs

Front 9

Role of plasma enzyme

Back 9

Circulating plasma enzymes break down ADP near the plug, restricting the response

Front 10

Inhibition of plug formation

Back 10

- Serotonin blocks the action of ADP at high concentrations
- Circulating plasma enzymes
- Inhibitory WBC compounds
- Prostacyclin inhibits platelet aggregation
- development of a blood clot isolates the plug

Front 11

Coagulation phase

Back 11

A complex sequence of steps leading to the conversion of circulating fibrinogen into the insoluble protein fibrin.
- As the fibrin network grows, blood cells and additional platelets are trapped in the fibrous tangle, forming a blood clot.

Front 12

TImings of phases

Back 12

Vascular and platelet phases begin with a few seconds of injury
Coagulation does not start until 30 seconds later

Front 13

Clotting factors

Back 13

- Normal clotting depends on procoagulants in the blood: Ca2+ and 11 proteins
- Many of the proteins are proenzymes, which are converted to active enzymes and direct essential reactions in the clotting response

Front 14

Pathways initiating clotting cascade

Back 14

Extrinsic: begins outside the blood stream in the vessel wall (appropriate activation)
Intrinsic: begins in the blood vessel with the activation of a circulating proenzyme
These two pathways converge at the common pathway

Front 15

Draw clottting cascade

Back 15

Front 16

Extrinsic pathway

Back 16

Appropriate activation:
- TF/FIII is released by damaged endothelial cells or peripheral tissues
- The more damage, the more TF released

Front 17

Intrinsic pathway

Back 17

Inappropriate activation:
- activation of proenzymes exposed to collagen at the site of insult

Front 18

The common pathway

Back 18

Enzymes from either pathway activate FX, forming the enzyme prothrombinase.
- Prothrombinase converts prothrombin into thrombin
- Thrombin completes the clotting cascade by converting fibrinogen to insoluble fibrin

Front 19

Clot retraction

Back 19

One the fibrin mesh-work has formed, platelets and RBCs stick to the fibrin strands.
- The platelets then contract, and the entire clot undergoes clot retraction
- This process continues over 30-60mins

Front 20

Feedback control of coagulation

Back 20

Thrombin generated in the common pathway stimulates clotting by:
- Stimulating the formation of TF
2. Stimulating the release od PF-3 by platelets
This is a positive feedback loop, stimulating intrinsic and extrinsic pathways

Front 21

Restriction of coagulation: antithrombin-III

Back 21

- Normal plasma includes several anticoagulants e.g. antithrombin-III inhibits several factors, including thrombin
- Heparin is released by basophils and mast cells, and accelerates the activation of antithrombin-III

Front 22

Restriction of coagulation: aspirin

Back 22

- Aspirin inhibits the production of thombozane-A2 and prostaglandins.
- Prevents platelet aggregation and so clot formation
- Prolongs bleeding time

Front 23

Restriction of coagulation: thrombomodulin

Back 23

- Thombomodulin is released by endothelial cells and binds to thrombin
- Activated thrombin then activates protein C
- Protein C is a plasma protein that inactivates several clotting factors and stimulates the formation of plasmin
- Plasmin gradually breaks down fibrin strands

Front 24

Restriction of coagulation: prostacyclin

Back 24

Prostacyclin released during the platelet phase inhibits platelet aggregation and opposes the stimulatory action of thrombin and ADP

Front 25

Restriction of coagulation: Vitamin K

Back 25

Sufficient vitamin K is needed in the liver to synthesise 4 of the clotting factors
- long term lack of Vit K causes breakdown of the common pathway and eventual destruction of the clotting cascade

Front 26

Fibrinolysis

Back 26

Activation of proenzyme plasminogen by thrombin and tissue plasminogen activator (t-PA) released by damaged tissues
- produces the enzyme plasmin which begins digesting the clot