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Introduction to medicine (Year 1) > Haemostasis > Flashcards

Haemostasis Flashcards

1- Describe the haemostatic pathway and explain why cells and their surfaces are crucial to the pathway 2) Explain how clots participate in wound healing 3) Describe a mechanism by which the vascular endothelial cell regulates haemostasis and how It may be altered by physical damage or infection 4) Describe the difference between haemophilia and thrombophilia 5) Describe the role of the clotting system in defence

1
Q

What triggers primary haemostasis?

A
  • Damage to endothelium causing collagen to become exposed.
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2
Q

What happens following vascular injury?

A

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

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3
Q

What are the 3 stages of primary haemostasis?

A
  • Adhere
  • Activate
  • Aggregate (via fibrinogen)
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4
Q

What happens during platelet adherence?

A
  • 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
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5
Q

What are Weibel- Palade bodes?

A

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

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6
Q

What happens during platelet activation?

A
  • 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.
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7
Q

What molecules do platelets release during platelet activation?

Why are these released?

A

ADP
Thromboxane A2 (TXA2)

Released to encourage further platelet recruitment

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8
Q

When platelets become activated, what can they become?

A

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

These also include cytokines that can further activate platelets

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9
Q

What do alpha granules release?

A

Fibrinogen and von Willebrand factor

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10
Q

What do dense granules release?

A

Serotonin, which recruits other platelets

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11
Q

What do lysosomes do in haemostasis?

A

Mobilises energy stores

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12
Q

What happens during platelet aggregation?

A
  • Platelets bind and collect together with other platelets, creating a mesh.
  • Bind with fibrinogen through fibrinogen receptors
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13
Q

What happens in secondary haemostasis?

A
  • Deposition of insoluble fibrin generated by coagulation cascade:

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

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14
Q

What is tissue factor?

A
  • Sub-endothelial trigger for coagulation cascade, mechanism for which fibrinogen is converted to fibrin.
  • Initiator of clotting
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15
Q

When does tissue factor become exposed?

A

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

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16
Q

How is thrombin production amplified?

A
  • Via the intrinsic or extrinsic pathway
17
Q

What happens during the intrinsic pathway?

A
  • 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.
18
Q

What does factor 10 do?

A

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

19
Q

What happens during the extrinsic pathway?

A
  • 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
20
Q

Describe the test done for the intrinsic pathway

A

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

21
Q

Describe the test done for the extrinsic pathway

A

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

22
Q

Describe fibrinolysis

A

-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 plasminogen, which digests fibrin into fibrin fragments (including D-dimer) and also degrades factor V (5) and factor VII (7)

23
Q

What factor converts fibrinogen to fibrin

A

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

Factor 2 is the same as prothrombin

24
Q

What is haemophilia?

A

Failure of blood to successfully clot

25
Q

Why does haemophilia occur?

A

Due to mutations in coagulation factor

26
Q

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

A
  • Haemophilia A- mutations in factor 8
  • Haemophilia B- mutations in factor 9
27
Q

What is thrombophilia?

A
  • When the blood has an increased tendency to clot
28
Q

What is the role of the clotting system in defence?

A
  • 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
29
Q

Describe the structure of platelets

A
  • Granulocytes
30
Q

What causes endothelium in skin to maintain an anticoagulant surface?

A

Expression of anticoagulant proteins

Introduction to medicine (Year 1) (56 decks)

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