Haemostasis Flashcards

1
Q

What is Haemostasis?

A

the specific, regulated cessastion of bleeding in response to a vascular injury to stop bleeding and allow vessel repair to occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Explain the vascular response to bleeding

A

Vasoconstriction to reduce blood flow and therefore bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is primary haemostasis?
What is its funciton?

A
  • platelet adhesion
  • platelet aggregation that forms an
  • unstable white plug

–> limits blood loss + provides surface for coagulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is secondary haemostasis?

What is its function?

A

To stabalise cloth formed in primary haemostasis

  • activated coagulation factors
  • fibrin mesh
  • —> stops blood loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is involved in Blood coagulation

A

Vessel wall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Explain the structure and function of the vasculature wall in haemostasis

A

Vascular wall endothelium is anti-coagulant

  • e.g. thrombomodulin etc.

The sub-endothelium is pro thrombotic and procuagulant basement membrane

  • Elastin, Collagen, TF (on vascular SM cell, fibroblasts)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Explain the role of the vascular response to injury

A
  1. st step in Haemostasis–> vasoconstriction
    • most important in small vessels
    • local response to injury
    • to reduce blood flow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where are platelets derived from?

A

Derived from Megacaryocytes (one cell around 4000 platelets)

  • released as pro platelets into blood stream
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are platelets?

What is a normal platelet count?

A
  • small
  • anuclear cells
  • lifespan about 10 days
  • very responsive because of many receptors that can interact with outside stiummuli
  • normal count: 150-350 x 109/L
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is a alpha-granule in a platelet?

A

granule in platelet containing

  • growth factor
  • fibrinogen
  • VWF

–> released when activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is a dense granule in a platelet?

A

contains

  • ADP
  • ATP
  • Serotonin
  • Ca2+ and get released when activated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the role of the platelet membrane in haemostasis

A

In inactivated state: normal membrane

When Activated: negatve charge from phospholipids turns outside and makes surface very attractive for anti-coagulants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does the platelet shape changes in platelet activation?

A

Cytoskeleton changes:

conversion from a passive to an interactive cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Explain the Recruitement of platelets to the site of injury

A

Vessel Injury exposes collagen

VWF binds to collagen–> changes conformation that exposes binding sites on VWF for platelets

Platelets adhere to now exposed VWF via Gp1b

platelets can also adhere to collagen but only when low blood flow, it is VWF dependant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How do platelets get activated

A

Different stimmuli lad to activation

  • Collagen
  • Thrombin
  • ADP
  • Thromboxane
  • each other via alpah2bß3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens when platelets get activated ?

A

Relase granule

  • change of membrane –> negative charge
  • release of thromboxane
  • release of ADP
    • more
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the Thrombocytopaenia levels when do certain characteristics occur?

A

Normal range 10-300 109 /l

<10 spontaneous bleeding common

<40 spontaneous bleeding

<100 no spontaneous bleeding but bleeding in trauma

18
Q

Where are coagulation factors synthesised?

A
  1. The liver – most plasma haemostatic proteins
  2. Endothelial cells – VWF, TM, TFPI
  3. Megakaryocytes – VWF, FV
19
Q

What are zymogen hormones in haemostasis?

A

Precursors to serine proteases

20
Q

What is the role of serine proteases in haemostasis?

A

Cleaving someting and activating it by this

–> factors have a serine protease domain at activated site

21
Q

What is a Gla domain?

Where is it present

A

Domain that give clotting factors the ability to interact with phospholipid surfaces

on

  • VII
  • X
  • Prothrombin
  • IX
  • Protein C
  • Protein S
22
Q

Where is Tissue factor present?

What is its role in haemostasis ?

A

Factor III–> binds complex with VII to set of extrinsic pathway–>

  • normally located at extravascular sites
    • i.e not usually exposed to the blood (VSMC, fibroblasts etc…)
  • TF expressed higher in certain organs
    • (i.e. lungs, brain, heart, testis, uterus, and placenta)
      • TF in these locations provide further haemostatic protection in these organs.
23
Q

Where is Coagulation factor VII synthesised?

What is its funciton?

A

Circulates inactively in plasma –> Has to get activated

  • has Gla domain
  • Serine protease domain

very small amount of active factor VII citculates 1%

24
Q

What is the role of vitamine K in blood coagulation?

A

Important in Gla domain formation:

It does post-translational modification of proteins that give rise to calcium binding site

–> calcium changes conformation, can now interact with negative phospholipid membranes

25
Q

What is the mechanism of action of Warfarin?

A

Vit.K carboxylase antagonist

–> deminishes function of a number of clotting facotrs by impairing interaction with phospholipid membrane with Gla domain

26
Q

Explain the coagulation cascase

A
27
Q

What is Haemophilia A?

A

Lack of clotting factor VIII

28
Q

What is Haemophilia B?

A

Lack of clotting factor IX

29
Q

How is Haemophilia inherited?

A

X-chromosomal recessive

30
Q

What is the role of TFPI in haemostasis?

A

Inhibits coagulation at site of activation

–> binds to factor Xa which then binds to complex III+VII –> inactivation of all 3 proteins

31
Q

Explain the role of protein C in haemostasisi

A

Cleave factor V and VIII –> inhibits them

32
Q

Explain the formation of protein C in haemostasis

A

Thrombin binds to Thrombomodulin on tissues

–> Thrombomodulin modulates thrombrin to cleave Protein C to activate it –> shots down coagulation at edges of blood coagulation (because thrombomodulin is present at intact endothelial surface

33
Q

What is the role of Antithrombin

A

serine protease inhibitor (not just inactivated thrombine)

• AT inactivates many activated coagulation serine proteases (FXa, thrombin, FIXa, FXIa)

34
Q

What is the site of action of heparine

A

Enhances the activity of Antithrombin to make it more effective to inhibit Thrombin + FX

35
Q

Explain the process of fibrinolysis

A

Done by Plasmin –> degrades fibrin fibres

Plasmin is activated from precursor form plasminogen by tissue plasminogen activator (tpa)

36
Q

Explain the clinical use and mechanism of action of tPA

A

tissue Plasminogen activator

–> turns plaminogen into plasmin

Plasmin degrades fibrin and lyses blood cloths

This can be used in thrombotic infarctions e.g. stroke, MI etc.

37
Q

What is the drug group and of heparin and warfarin.

When would you give it to a patient?

A

Thea are anticoagulatns

Manily used for someone at risk of venous thrombosis

38
Q

Which type of drugs would you perscribe to someone at risk of venous thrombosis?

A

Hepatin, warfarin, directly acting anticoagulatns

–> Anticoagulants (over anti-platelet agents)

39
Q

Explain the mechanism of action of Asperin and its clinical use

A

It is an anti-platelet agent –> irreversibly blocks COX1+2 leading to

  1. reduced production of TxA2 –> less thrombocyte aggregation (Cox1)
  2. reduced prostacyclin –> anti fever+analgesic effect

Used in arterial thrombosis

40
Q

Which type of drug (and which specific drug) would you perscribe someone at risk of arterial thrombosis?

A

Anti-platelet agent (Thrombozytenaggregationshemmer)

–> Asperin

41
Q

What are the tests available to test coagulation?

A
  1. Coagulation
    • PT time ( measures the number of seconds it takes for a clot to form in your sample of blood after reagents are added
    • APPT test
  2. Platelet funciton test
  3. d-dimer test –> fibrin degradation product (how much clotting is happening in individual in the past)
42
Q

What is the role of Protein S in Coagulation?

A

It is a co-factor of Protein C –> anti-thrombotic effects