Haematology 7: Haemostasis Flashcards

1
Q

Explain the mechanisms of normal haemeostasis

A

injury occurs –> vessel constricts –> unstable platelet plug forms –> plus is stabilized with fibrin –> dissolution of clot –> vessel repair

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

List the routinely available lab tests for investigating the coagulation cascade

A
  • platelet count (monitor thrombocytopenia)
  • bleeding time
  • platelet aggregation (measures functional defect of platelets)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

explain the mechanism of warfarin

A
  • warfarin inhibits vitamin K
  • gamma carboxylation = dependent on vitamin K in the liver
  • so since warfarin –> inhibits vitamin K
  • it stops gamma carboxylation (by inhibiting enzyme Vitamin K Epoxide Reductase)
  • so it stops the ability of clotting factors to bind to surface of platelets
  • hence reduces thrombin production
  • warfarin uses = long term anticoagulation (e.g venous thrombosis, atrial fibrillation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

explain the mechanism of heparin

A
  • Heparin potentiates action of anti thrombin
  • antithrombin = main inhibitor of coagulation enzymes
  • heparin = used for immediate anticoagulation (e.g in venous thrombosis / pulmonary embolism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are main antiplatelet agents currently used as anti thrombotic agents?

A
  • COX-1 Inhibitor (e.g aspirin)
  • ADP receptor antagonist (e.g clopidogrel, prasugrel)
  • GDPIIb/IIIa antagonists (e.g abciximab,tirofiban, eptifibatide)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the normal range for platelet count?

A

150-350 x10^9 /L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

If platelet count drops –>

A

If platelet count drops –> abnormal bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the 2 main routes of coagulation?

A
  • extrinsic

- intrinsic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List lab tests for blood coagulation

A
  • APTT (activated partial thromboplastin time)
  • PT (prothrombin time)
  • TCT (thrombin clotting time)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does APTT (activated partial thromboplastin time) measure?

A

APTT

  • detects abnormalities in intrinsic + common pathways
  • test measures clotting time
  • used to monitor heparin therapy for thrombosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does PT (prothrombin time) measure?

A

PT

  • detects abnormalities in the extrinsic + common pathways
  • used to monitor warfarin treatment in thrombosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does TCT (thrombin clotting time) measure?

A

TCT

  • not v important
  • shows abnormality in fibrinogen –> fibrin conversion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

APTT + PT = used together to screen causes of ________

A

APTT + PT = used together to screen causes of bleeding disorders

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

Why doesn’t blood clot completely when the cascade is activated?

A
  • due to antithrombin

- antithrombin = plasma protein that can directly inhibit the clotting factors

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

Haemostasis definition:

A
  • cellular + biochemical processes that enables both specific and regulated cessation of bleeding in response to vascular insult.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is haemeostasis for?

A

to prevent blood loss from intact + injured vessels, and to enable tissue repair.

17
Q

NOTE:
decrease in fibrinolytic factors = causes bleeding
increase in fibrinolytic factors = causes blood clotting

A

-

18
Q

Note: Haemostatic plug formation = mainly important in small vessel

A

-

19
Q

What are platelets derived from?

A

Megakaryocytes

20
Q

What is the normal lifespan of platelets?

A

10 days

21
Q

What is a key characteristic of the nucleus of the platelet?

A
  • it is anuclear
22
Q

Ultrastructure of platelets

A
  • dense granules (containing ADP/ATP/Ca2+ etc.)
23
Q

How is clotting factors recruited by the platelets?

A

through negative charge on the phospholipid membrane

24
Q

What is meant by platelet activation?

A

conversion from a passive to an interactive cell

25
Q

Describe the process of platelet activation

A
  • interaction with collagen + thrombin surface sends singal into platelet
    causing them to become activated –> granule contents are released, phospholipid surface conformation is changed

*platelets bound to collagen/ VWF releases ADP + thromboxane –> which activates platelets

26
Q

describe how the platelet changes shape when activated

A

normally: disc shaped
–> rolling ball shaped platelet
–> hemisphere shaped platelet
(firm but reversible adhesion)
–> spreading platelet
(irreversible adhesion)

27
Q

What do serine protease domain containing proteins do?

A
  • they cleave / catalyze proteolysis of target substrate
28
Q

Serine protease contains what catalytic traid

A

His/Asp/Ser

29
Q

hemophilia A

hemophilia B

A

F8 deficiency

F9 deficiency

30
Q

Describe the process of platelet adhesion

A
  • Vascular injury damages endothelium + exposes sub endothelial collagen
  • exposed sub endothelial collagen binds with globular VWF –> undergoes structural transformation –> into linear polypeptide form –> which exposes its platelet binding side –> platelets bind through platelet GLP1B –> which recruits platelets to site of vessel damage –> platelets become activated –> further recruitment occurs
  • Platelets can also bind directly to collagen via GPVI + a2b1 under low shear forces
31
Q

3 anticoagulant pathways

A
  1. TFPI (Tissue factor pathway inhibiter)
    - targets initiation of coagulation
  2. APC + Protein S
  3. AT (antithrombin)
32
Q

What happens when injury is plugged?

DO THIS

A
  • initiation phase = exposure of TF
  • f7 binds
  • f10 –> f10a
33
Q

What kind of inhibitor is antithrombin?

A

Serine protease inhibitor

34
Q

clinical homeostasis tests

A

PT/ APTT

Platelet function tests

35
Q

Describe the process of platelet aggregation.

A

activated platelets –> present receptors (GPIIb/IIIa) –> recruits platelets –> fibrinogen bridges platelets together –> platelet plug develops

36
Q

Why do you need a platelet plug?

A

helps to slow bleeding
+
provides surface for coagulation