9- Haemostasis Flashcards
(95 cards)
1
Q
What is haemostasis?
A
The body’s response to injury/bleeding by stopping blood flow?
2
Q
What are the 5 main stages of haemostasis
A
- Vasoconstriction
- Platelet plug formation
- Coagulation pathways
- Coagulation inhibitors
- Fibrinolysis
3
Q
What is exposed when you have a vessel injury?
A
Collagen
4
Q
What is the first haemostatic line of defence?
A
vasoconstriction of the blood vessels
5
Q
Name some chemical vasoconstrictors
A
Serotonin, Thromboxane A2
6
Q
What is the second haemostatic line of defence?
A
Platelet plug formation
7
Q
What is another name for platelets?
A
Thrombocytes
8
Q
What stimulates the production of platelets?
A
Thrombopoietin
9
Q
Where is thrombopoietin produced?
A
In the liver
10
Q
Where are platelets produced?
A
In the bone marrow
11
Q
What stem line do platelets (thrombocytes) come from?
A
Myeloid stem line
12
Q
What is the precursor of thrombocytes?
A
Megokaryocytes
13
Q
What is the precursor of megakaryocyte?
A
Megakaryoblasts
14
Q
How many platelets is one megakaryocyte equal to?
A
1 megakaryocyte = 4000 platelets
15
Q
What is the diameter of a platelet/thrombocyte?
A
2-4um
16
Q
What is the lifespan of circulating platelets?
A
9-10 days
17
Q
What is the normal platelet count?
A
150 - 400x10^9
18
Q
What does a platelet contain?
A
No nucleus, mainly contains granules needed for haemostatic process (e.g- calcium, ADP, Serotonin (vasoconstictor), and clotting factors such as vWF, factor V, factor VIII)
19
Q
What is the ratio of red blood cell to platelet to white blood cell?
A
700:40:1
20
Q
What are the 3 main stages of platelet plug formation?
A
- Adhesion
- Release of granular contents
- Aggregation
21
Q
What does exposed collagen do?
A
attracts platelets, which stick to the damage surface thus activating the platelet
22
Q
What does the activated platelet then do?
A
Release its granular contents (e.g, calcium, ADP, Serotonin, vWF, factor V, factor VIII)
23
Q
What is aggregation?
A
granular contents which begin to clump together to form a haemostatic platelet plug
24
Q
How does the platelet adhere to exposed collagen on blood vessel?
A
adheres via glycoproteins and vWF
25
What does adhesion activate?
Activates prostoglandin synthesis
26
What does prostoglandin stimulate?
prostoglandin stimulates ADP release from dense bodies, causing the platelets to swell promoting adhesion
27
What does ADP stimulated by prostoglandin cause?
Causes platelets to swell and adhere better
28
What kind of feedback mechanism does ADP release lead to?
positive feedback, more ADP and TXA2 released, further adhesion, more platelet aggregation
29
What does further platelet aggregation around blood vessels lead to?
formation of the platelet plug plug
30
What induced platelet aggregation?
ADP, Thromoboxane A2 and phospholipids
31
What is the next step once the platelet has been activated?
Coagulation Pathways
32
How does an activated platelet appear on an electron microscope?
Green, psuedophilia like extentions
33
How does a non-activated platelet appear on an electron microscope?
Blue, round disc shaped
34
What is the third haemostatic line of defence?
Coagulation factors
35
Name some coagulation factors
- tissue factor (FIII)
-pro thrombin (FII)
- thrombin (FIIA)
others are known by factor number:
- factor 8 (VIII)
- factor 9 (IX)
36
Where are coagulation factors produced?
in the liver
37
What 2 things do coagulation factors need to be produced?
- vitamin k
| - calcium
38
How do you show a factor is activated?
a = activated
39
How many coagulation pathways are there?
3 pathways
1. extrinsic pathway
2. intrinsic pathway
3. common pathway
40
What is the main initiator of the coagulation process?
'tissue factor" which is exposed on the damaged blood vessle
41
What is the first clotting factor which binds to tissue factor
clotting factor VII, activates and binds to the tissue factor forming "factor VII-Tissue factor complex"
42
What does tissue factor VIIa complex activate?
factor X
43
What does factor X activate in the extrinsic pathway?
Small amount of prothrombin to be converted to thrombin
44
How is the activation of prothrombin regulated?
tissue factor pathway inhibitor
45
How is the intrinsic pathway different to the extrinsic?
it is slower than extrinsic but more efficient
46
What 2 factors does the intrinsic pathway utilise?
- factor IX (9)
| - Cofactor VIII (8)
47
Briefly describe the intrinsic pathway
factor XII bingd to clotting factors VIII and IX and platelet factors to form factor X activator complex. This activated FX to FXa
48
What does factor X activate in the intrinsic pathway?
- small amounts of prothrombin to thrombin
| - thrombin activates co-factor 8 from factor 9 helping to activate factor X to factor Xa
49
What is the main outcome of the common pathway?
Fibrin production
50
What are the 2 co-factors of prothrombinase?
Factor Xa and Factor Va
51
What does prothrombinase do?
Activates prothrombin to thrombin
52
What does thrombin do?
Thrombin converts fibrinogen to fibrin
53
What does activated FXa and Thrombin activate?
Factor Va
54
what does FXa and FVa make up
prothrombinase
55
Which pathway produces enough thrombin to convert fibrinogen to fibrin?
the common pathway
56
What is thrombin?
An enzyme in blood plasma that causes the clotting of blood by converting fibrinogen to fibrin
57
What factor stabilises the fibrin clot?
FACTOR 13 XIII, produces a stable haemostatic plug
58
What does a stable haemostatic plug allow?
no more blood loss, prevents damage and allows wound to start healing
59
What helps regulate the coagulation pathway ?
coagulation inhibitors
60
Name 3 coagulation inhibitors
1. Tissue factor pathway inhibitor
2. Antithrombin
3. Heparin co-factor
61
How does tissue factor pathway inhibitor work?
Acts on factor VIIa and Xa, used in extrinsic pathway
62
Which coagulation inhibitor works in the extrinsic pathway?
Tissue factor pathway inhibitor
63
How does antithrombin work?
Works on factor Xa and thrombin, used in common pathwy to help regulate coagulation process and thrombin feedback
64
Which coagulation inhibitor works in the common pathway?
Antithrombin
65
What does heparin cofactor act on?
Thrombin
66
What is the final stage of haemostasis?
Fibrinolysis
67
What is fibrin broken down by into?
Fibrin is degraded by plasmin into fibrin degredation products (FDP)
68
Why are FDPs (fibrin degredation products) helpful
they tell us the amount of clotting going on in the body. i.e. lots of FDP = excessive production therefore a clot may be present
69
Name some laboratory tests for haemostatisis?
1. Bleeding test
2. Prothromin time
3. Activated partial thromboplastin time
70
Which test can you do that looks at platelet numbers/functions
A bleeding test
71
What does a bleeding test look for?
1. tests for abnormal platelet function
| 2. tests platelet count
72
Normal platelet count?
150 - 400 x 10^9/L
73
What does prothrombin time look at?
How blood clots, the coagulation process
| measures factors in the extrinsic pathway : VII, X, V, prothrombin, Fibrinogen
74
What is normal prothrombin time?
10-14 seconds
75
In which patients would prothrombin time be prolonged?
- patients with liver disease as alot of the clotting factors are produced n the liver
- patients on oral anticoagulants (e.g- warfarin)
76
What is prothrombin time standardised as?
INR (International Normalised Ratio)
77
Name some oral anticoagulants
Warfarin
78
What is warfarin
An oral anticoagulant which decreases vitamin k dependant factors II, V, VII, IX and X
only prevents new factors being produced, doesn't affect pre-formed factors
79
What is warfarin prescribed for?
- atrial fibrillation
- deep vein thrombosis
- heart valve replacement
80
What is the INR range in patients on warfarin?
2.0 to 3.0
81
What does activated partial thrombinase time (APTT) measure?
measures factors in the intrinsic pathway: VIII, IX, XI, XII and also X, V, prothrombin and fibrinogen
82
What is normal APTT (activated partial thrombinase time )
3-40 seconds
83
When is APTT prolonged?
in haemophillia, heparin therapy
84
What does heparin do?
Increases the action of antithrombin on thrombin and FXa, acts immediately to prevent clots
85
Explain Low Molecular Weight Heparin?
Has high bioavailabltiy (93%), injected into abdomen subcutaneously
86
Why is heparin given in pregnancy instead if warfarin?
Warfarin can cross the placenta and cause harm to the baby
87
What do direct oral anticoagulants do?
Target Thrombin and Factor Xa directly (common to both pathways)
88
Thrombin's action in anticoagulants?
final effector of blood coagulation and most potent platelet agonist
89
FXa's action in anticoagulants?
Shown to activate clotting over wider concentration than thrombin
90
Name a thrombin inhibiting drug?
Dabigatran : PRADAXA
91
Name a Factir Xa inhibiting drug?
Rivaroxaban : XARELTO
92
Name some antiplatelet drugs
Aspirin
Clopidogrel
Ticlopidine
93
How does aspirin work as an antiplatelet drug?
inhibits COX enzyme required for platelet production of Thromboxane A2
94
How does clopidogrel work as an antiplatelet drug?
irreversibly blocks ADP receptor on platelet membrane (blocks IIb/IIa complex)
95
why do dentist need to know about haemostasis?
possibilty of bleeding prevention is key
