Haemostasis

Question 1

What triggers primary haemostasis?

Answer 1

• Damage to endothelium causing collagen to become exposed.

Question 2

What happens following vascular injury?

Answer 2

Exposes collagen to come into contact with blood components to activate clotting

Question 3

What are the 3 stages of primary haemostasis?

Answer 3

• Adhere
• Activate
• Aggregate (via fibrinogen)

Question 4

What happens during platelet adherence?

Answer 4

• Endothelium continuously releases small amounts of von Willebrand Factor, circulates in blood.
• Endothelial cell also store von Willebrand factor in Weibel- Palade boxes
• When collagen exposed, von Willebrand factor binds to collagen receptors.
• Platelets express receptors for collagen and von Willebrand Factor and become activated when these proteins bind to them.
• Activated platelets express functional fibrinogen receptors, required for aggregation

Question 5

What are Weibel- Palade bodies?

Answer 5

Small storage granules located in endothelial cells, store von Willebrand factor

Question 6

What happens during platelet activation?

Answer 6

• Platelets begin to aggregate by binding to fibrinogen which links them together.
• This is because the fibrinogen receptors on platelets bind together, binding the platelets together.
• Platelets release multiple pro-activation/aggregation signalling molecules.

Question 7

What molecules do platelets release during platelet activation?

Why are these released?

Answer 7

ADP
Thromboxane A2 (TXA2)

Released to encourage further platelet recruitment

Question 8

When platelets become activated, what can they become?

Answer 8

Degranulated, releasing some of their storage granules (including alpha granules, dense granules, lysosomes)

These also include cytokines that can further activate platelets

Question 9

What do alpha granules release?

Answer 9

Fibrinogen and von Willebrand factor

Question 10

What do dense granules release?

Answer 10

Serotonin, which recruits other platelets

Question 11

What do lysosomes do in haemostasis?

Answer 11

Mobilises energy stores

Question 12

What happens during platelet aggregation?

Answer 12

• Platelets bind and collect together with other platelets, creating a mesh.
• Bind with fibrinogen through fibrinogen receptors

Question 13

What happens in secondary haemostasis?

Answer 13

• Deposition of insoluble fibrin generated by coagulation cascade:

Thrombin(protease) - cleaves circulating soluble fibrinogen into an insoluble fibrin mesh

Question 14

What is tissue factor?

Answer 14

• Sub-endothelial trigger for coagulation cascade, mechanism for which fibrinogen is converted to fibrin.
• Initiator of clotting

Question 15

When does tissue factor become exposed?

Answer 15

When the endothelial layer is damaged, so tissue factor is released by damaged tissue

Question 16

How is thrombin production amplified?

Answer 16

• Via the intrinsic or extrinsic pathway

Question 17

What happens during the intrinsic pathway?

Answer 17

• Endothelial tissue damaged
• Primary complex on collagen by high-molecular-weight kininogen (HMWK) formed
• Factor 12 released
• Prekallikrein is converted to kvllikrein and factor 12 becomes activated
• Factor 12 activates Factor 11
• Factor 11 activates Factor 9, which with its co-factor 8A, forms the tense complex which activates factor 10.

Question 18

What does factor 10 do?

Answer 18

Factor 10 cleaves its natural substrate (meaning dissolution of peptide bonds in a polypeptide chain) to convert prothrombin to thrombin

Question 19

What happens during the extrinsic pathway?

Answer 19

• Tissue factor is released by damaged tissue
• Factor 7 binds to tissue factor
• This complex activates Factor 9
• Activated Factor 9 works with Factor 8 to activate Factor 10
• Factor 10 converts prothrombin to thrombin

Question 20

Describe the test done for the intrinsic pathway

Answer 20

APTT test- measures time needed to generate fibrin from imitation of intrinsic pathway after addition of a contact agent that fully activates Factor XII (12) along with calcium and phospholipids

Question 21

Describe the test done for the extrinsic pathway

Answer 21

PT test measures time in seconds for plasma to clot after addition of phospholipid tissue factor 3 and calcium to the specimen

Question 22

Describe fibrinolysis

Answer 22

-This is wound healing
- Means breaking down the fibrin mesh
- Plasminogen is converted into plasmin
- tPA (tissue plasminogen activator) released, activates plasminogen which is converted into plasmin, which digests fibrin into fibrin fragments (including D-dimer) and also degrades factor V (5) and factor VII (7)

Question 23

What factor converts fibrinogen to fibrin

Answer 23

Factor IIa (2a) as it is responsible for making thrombin, which converts fibrinogen into fibrin

Factor 2 is the same as prothrombin

Question 24

What is haemophilia?

Answer 24

Failure of blood to successfully clot

Question 25

Why does haemophilia occur?

Answer 25

Due to mutations in coagulation factor

Question 26

What are the 2 types of haemophilia and their subsequent mutations?

Answer 26

- Haemophilia A- mutations in factor 8 - Haemophilia B- mutations in factor 9

Question 27

What is thrombophilia?

Answer 27

- When the blood has an increased tendency to clot

Question 28

What is the role of the clotting system in defence?

Answer 28

- Coagulation proteins are necessary for eradication of invading pathogens. - Coagulation factors such as thrombin can activate immune cells and increase the release of pro-inflammatory cytokines. - Tissue factor also triggers coagulation independent signalling pathways mediated by protease activated receptors (PARs) on immune cells - PAR- dependent signals evoke pro- and anti- inflammatory pathways that regulate migration and proliferation of immune cells - Containment 'hypothesis'- coagulation activation contributes to pathogen clearance by forming a physical barrier facilitating pathogen clearance by immune cells

Question 29

Describe the structure of platelets

Answer 29

- Granulocytes

Question 30

What causes endothelium in skin to maintain an anticoagulant surface?

Answer 30

Expression of anticoagulant proteins