Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medsci305 > Lecture 21: Hemostasis > Flashcards

Lecture 21: Hemostasis Flashcards

1
Q

What are the two main cascade systems that are activated in response to tissue injury?

A
  1. adhesion and activation of platelets
  2. thrombotic system

these lead to the activation of fibrin and thrombus resulting in blood clots.

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

What is thrombosis?

A
  • presence of a blood clot

- this can break off and go to smaller vessels such as the brain and lungs resulting in stroke, MI, etc

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

What are the two main pathways of the coagulation cascade?

A

-extrinsic and intrinsic.

these both meet in the final common pathway which starts at factor 10.

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

What is the intrinsic pathway of the coagulation cascade?

A
  • usually initiated by contact with a foreign substance

- clotting factors 9, 11 and 12 are invovled

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

What is the extrinsic pathway of the coagulation cascade?

A
  • the most commonly activated pathway

- clotting factor 6 is activated, leading down to factor 10

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

What does the final common pathway of the coagulation cascade involve?

A
  • factor 10, 5 and factor 2 (thrombin)
  • this pathway has two mechanisms which convert soluble fibrnogen to insoluble fibrin
  • insoluble fibrin makes up the thrombus/blood clot
  • also activates factor 13 which stabilises fibrin
  • the two systems talk to each other predominantly through thrombin as this will further activate the platelet aggregation system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the main factor involved in the coagulation inhibition network?

A

-antithrombin 3. This can inhibit the activation of a large number of factors, particularly those in the intrinsic pathway like factor 9, 11, 12, 10 and

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

What does tissue factor pathway inhibitor in the coagulation inhibition network do?

A

-this inhibits factor 7 in the extrinsic pathway of the coagulation cascade

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

What do protein C and cofactor protein S do?

A

-these are activated by thrombin and inhibit factor 8 and factor 5.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What kind of gene deficiencies disrupt the the hemostasis balace?

A
  • deficiency of protein C and cofactor protein S

- when these don’t get activated, they form unwanted blood clots so their blood has a higher risk of forming a thrombus

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

How are most pathologies with the hemostasis system caused?

A
  • either spontaneously or through disease or injury like DVT.
  • as we age, our vasculature loses its tone resulting in pooling of blood in the veins
  • this can clot and cause DVT which can move and break off to cause embolism.
  • a major concern/risk of OC is unwanted blood clots
  • surgery is also a risk, particularly if you want a prosthetic device fitted
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How can the risk of thrombo embolitic diseases be modified?

A
  • modify blood coagulation
  • platelet adhesion and activation
  • move blood clot (not as effective, but there are agents which can break this bloodclot down.)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the mainline anticoagulant agents?

A
  • warfarin, heparin
  • they have wide uses e.g. in arterial thrombosis, embolism, surgery, esp if followed by long bed rest, and cardiomyopathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is the first line anti-coagulant?

A

Heparin

  • binds to antithrombin 3 and increases its ability to inhibit the coagulation factors (9, 11, 12, 10, 2)
  • Heparin mainly enhances AT3 to inhibit factor 10 and 2 which are the two main factors in the common pathway
  • prevents thrombin from being able to produce fibrinogen to fibrin which will prevent blood clot.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the effect of heparin being more sensitive to factor 2?

A
  • it has to bind and form a complex with AT3 and also bind to thrombin to form a tightly bound complex
  • this complex is quite strong and irreversible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the effect of heparin being less sensitive to factor 10?

A

-factor 10 only needs to bind to AT3 to be inhibited. It has no binding site to heparin resulting in heparin being less sensitive.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What can thrombin do?

A

-activate platelets in the platelet activation cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why do some patients not respond to full length heparin?

A
  • it can result in thrombycytopenia, which is the reduction in platelet numbers
  • in some cases they may form an immune response to the inhibition of thrombin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is low molecular weight heparin?

A
  • developed for patients who were intolerant to full length heparin
  • has the binding site for factor 2 removed, resulting in little or no effect on thrombin due to loss of binding site,
  • however it still retains the same inhibitory ability to factor 10 as it does not need to bind to heparin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

When is wafarin used?

A
  • often reserved for patients intolerant to heparin, or may be for temporary or long term use
  • it is our main oral anticoagulant
21
Q

Which blood coagulation factors are synthesised in the liver?

A

factors 2 and 19

  • they need to undergo gamma carboxylation which requires a reduced form of vitamin K
  • uses the enzyme vitamin K reductase.
  • This synthesis is a circulation process
22
Q

what is the mechanism of action of warfarin?

A
  • inhibits vitamin K reductase and prevents vitamin K being reduced
  • also prevents the synthesis of vitamin K from its oxidised form.
  • gamma carboxylation cannot occur so we don’t synthesise factors 2 and 19
23
Q

Which factors does wafarin not have an effect on?

A

factors 2, 7, 9 and 10 as warfarin does not affect any of the blood coagulation factors that are already synthesised.

  • warfarin takes 5 days to have therapeutic effect.
  • patients are often started on heparin therapy first, and then change over to oral warfarin when the two systems overlap
24
Q

What are the problems with anticoagulant factors?

A
  • there is a high degree of bleeding. This is often seen by bruises
  • newer agents like antithrombin 3 independent agents have been developed to reduce this bruising
  • the main groups are the direct thrombin inhibitors
25
Q

What are the direct thrombin inhibitors?

A
  • predominantly generated from hirudin which is an anticoagulant substance found in leeches
  • it is the most potent, known and natural inhibitor of thrombin and acts to only inhibit thrombin
  • it is only the inactivated thrombin that is bound to fibrin, so hirudin is very selective and does not afffect other factors
26
Q

What is fibrinolysis?

A

the process of breaking down fibrin that forms the blood clot

27
Q

When is the fibrinolysis pathway activated?

A
  • at the same time as the blood coagulation pathway

- activation of clotting factors stimulate coagulators which activate the plasminogen activators

28
Q

What are the plasminogen activators?

A
  • agents such as tissue type plasminogen activator (TTPA)
  • urokinase type plasminogen activator (UKPA)
  • killokrene
  • neutrophil elastase
29
Q

What is the role of the plasminogen activators?

A
  • any one of them can come along and convert plasmin to plasminogen
  • plasmin then comes anlong and lyses and dissolves the fibrin found in the blood clot.
30
Q

what are the fibrinolytic agents?

A
  • although fibrin is not easy to break down, there are fibrinolytic agents used for patients that come in with MI or stroke
  • they have very short therapeutic windows
31
Q

What are the two different groups of fibrinolytic agents?

A
  1. tissue plasminogen activators like streptokinase and urokinase
  2. fibrin specific agents like alteplase and duteplase
32
Q

How do tissue plasminogen activators work?

A
  • interact with both free plasminogen and plasminogen which is bound to fibrin, and convert the plasminogen to plasmin.
  • plasmin is then able to lyse the fibrin in the blood clots.
33
Q

How do fibrin specific agents work?

A
  • these preferentially bind and activate plasminogen that is bound to fibrin
  • they are more selective and will only activate this found plasminogen to stimulate the lysis of fibrin
34
Q

What is the main difference between the mechansims of tissue plasminogen activators and fribrin specific agents?

A

-fibrin specific agents do not act on free plasminogen

35
Q

What is platelet aggregation?

A
  • the first process that is stimulated following damage to the vascular endothelium
  • platlets sense damage and start to adhere to the site of damage
  • they respond to the exposure of glycoproteins on the damaged vascualr endothelium
  • platelets chagne shape and start to express glycoprotein receptors and are activated
36
Q

What is the result of the platelet aggregation and blood coagulation cascades being ativated?

A
  • thrombin is produced ( from the blood coagulation cascade) and also activates activation factors
  • recruitment, adherence and activation of more platelets occurs through the release of 5-HT, ADP, cycli endoperoxidases and the synthesis of thromboxane A2
  • results in linkage of adjacent platelets, fibrinogen binding to those glycoprotein receptors, which causes platelet aggregation
37
Q

What is the main anti-platelet agent?

A
  • low dose aspirin
  • works by modulating the balance between TXA2 and prostacyclin PGI2
  • normally the pathway sits more on the PGI2 side, but aspirin inhibits COX, resulting in reduction of TXA2 in platelets and normal levels of PGI2 in endothelial cells
  • inhibits TXA2 stimulation of platelet aggregation
  • maintains PGI2 inhibition of platelet agregation
38
Q

What is prostacyclin PGI2?

A

It is produced by the vascular endothelium and inhibits platelet aggregation

39
Q

How long does it take for platelets to synthesise after administration with aspirin?

A

7-10 days

40
Q

What are higher doses of aspirin needed for?

A

-inhibit COX in vascular endothelium

41
Q

What are low doses of aspirin used for?

A

-intermittently decreasing the synthesis of TXA2 without affecting PGI2 synthesis

42
Q

What are the new antiplatelet agents?

A
  • TXA2 synthesis inhibitors
  • TXA2 receptor antagonists
  • Ticlopidine
43
Q

What is TXA2 synthesis inhibitor?

A
  • these inhibit the synthesis of thromboxane A2

- results in inhibition of platelet aggregation

44
Q

What is TXA2 receptor antagonists?

A
  • these prevent thromboxane A2 from binding to TXA2 receptors
  • results in inhibition of platelet aggregation
45
Q

What is Ticlopidine?

A
  • inhibits ADP-dependent aggregation by inhibiting the expression of GP IIb/IIIA receptors
  • this prevents platelet aggregation
46
Q

What are the glycoprotein IIa and III b receptor antagonists?

A
  • Abciximab
  • Tirofiban
  • Epoprostenol
47
Q

What is Abciximab?

A
  • MAB fab fragment directed against the glycoprotein IIb and IIIa receptors
  • bloks fibrinogen binding to these receptors
48
Q

What is tirofiban?

A

GP 2B/IIIA receptor antagonists

-blocks fibrinogen binding to these receptors

49
Q

What is Epoprostenol?

A
  • synthetic prostacyclin

- acts by inhibiting expression of GP IIb/IIIA receptors and prevent platelet aggregation.

Medsci305 (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions