Brainscape's Knowledge GenomeTM

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


See full index

Year 2 haem mine > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

what is haemostasis?

A

“the cellular and biochemical processes that enables both the 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
2
Q

what is haemostasis for?

A

“to prevent blood loss from intact and injured vessels, enable tissue repair”

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

what tips the balance between bleeding and thrombosis towards bleeding?

A

increase in fibrinolytic factors and anticoagulant proteins.
decrease in coagulant factors and platelets

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

what is the basic summary/structure for a haemostatic plug formation?

A
  • response to injury to endothelial cell lining
  • vessel constriction: vascular SM cells contract locally, limits blood flow to injured vessel
  • formation of an unstable platelet plug: platelet adhesion, platelet aggregation, limits blood loss and provides surface for coagulation
  • stabilisation of the plug with fibrin: blood coagulation, stops blood loss
  • vessel repair and dissolution of clot: cell migration/proliferation and fibrinolysis, restores vessel integrity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

action of the EC (endothelial cell in the artery)

A

acts as an anticoagulant barrier

-TM, EPCR, TFPI, GAG

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

action of subendothelium in the vessel wall of artery

A 
procoagulant
basement membrane
elastin, collagen 
VSMC- TF
fibroblasts- TF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the haemostatic blood formation key for?

A

mainly important in small blood vessels

local contractile response to injury

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

what is the lifespan of platelets?

A

approx. 10 days

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

how are platelets formed?

A

from megakaryocytes
MK looses its ability to divide, however continue to replicate its DNA becomes polyploid, cytoplasm enlarge. MK matures, becomes granular and form platelets that will be released in the circulation.

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

why is the platelet cytoskeleton important?

A

Important for platelet morphology, shape change, pseudopods,
contraction and clot retraction.
And in platelet activation: conversion from a passive to an interactive cell

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

what are the many roles of platelets?

A 
cancer
haemostasis + thrombosis 
inflammation 
infection 
atherosclerosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

how do the platelets and VWF circulate in a normal blood vessel?

A

Under normal physiological conditions, platelets circulate in close contact to the endothelial cell lining of the blood vessel wall & VWF circulate in a globular conformation with its plt binding site cryptic.

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

1) describes what happens in platelet adhesion

A

upon injury of the blood vessel, several components of the subendothelium (eg collagen, fibronectin, laminin) become exposed, to which platelets will get recruited- key is exposed collagen
VWF can bind to collagen via its A3 domain and with shear forces of flowing blood unravel VWF.
VWF unravelling exposes platelet binding sites- (GpIb) - platelets get tethered
Binding of VWF to platelet Gp1b recruits platelets to site of vessel damage

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

other ways in which platelets can bind to collagen?

and when?

A

Platelets can also bind directly to collagen via GPVI & α2β1
(only at low shear – i.e. not in arteries/capillaries)

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

2) describe platelet activation

A

collagen and thrombin also activates platelets
Platelets bound to collagen/VWF release
ADP and thromboxane – further activate platelets and allow recruitment of additional platelets
Activated platelets (αIIbβ3) recruit additional platelets
Platelets will bind to each other via fibrinogen on activated aIIbb3 integrin leads to Platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

3) describe platelet aggregation

A

αIIbβ3 also binds fibrinogen– platelet plug develops
Helps slow bleeding & provides surface for coagulation (support for initiation of the coagulation cascade).
Thrombin is released.
Platelet shape changes- leading to a spreading platelet

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

what disorders can you get in the first stage of haemostasis/ platelet plug formation?

A

no VWF, lack of platelets

18
Q

what is a lack of platelets called?

A

thrombocytopenia

19
Q

signs of thrombocytopenia?

A

Immune Thrombocytopenia (ITP):
purpura,
multiple bruises,
ecchymoses (a discoloration of the skin resulting from bleeding underneath)

20
Q

where are the 3 places where coagulation factors are made?

A
  1. The liver – most plasma haemostatic proteins
  2. Endothelial cells – VWF, TM, TFPI
  3. Megakaryocytes – VWF, FV
21
Q

what do clotting factors circulate as and how are they activated?

A

Clotting factors circulate as inactive precursors
Either serine protease zymogens or cofactors
Activated by specific proteolysis
Serine protease contain a catalytic triad His/Asp/Ser

22
Q

describe initiation of coagulation

A

FVII/FVIIa bind cell surfaces via Gla domain

All domains of FVII/FVIIa interact with TF

TF makes FVIIa 2x106 times more active

23
Q

what does tissue factor do?

A

Cellular receptor and cofactor for FVII/VIIa

Only procoagulant factor that does not require proteolytic activation

primary initiator of coagulation
47kDa integral membrane
normally located at extravascular sites
i.e not usually exposed to the blood (VSMC, fibroblasts etc…)

24
Q

where is TF expressed higher?

A

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.

25
Q

describe factor VII

A 
serine protease zymogen
 48kDa plasma glycoprotein 
 expressed/secreted by the liver 
 domain structure;
 Gla Domain
 2x EGF-like domains
 Serine protease domain

circulates in plasma at ~10nM
~1% of plasma FVII circulates in its activated form (FVIIa)

26
Q

what does FVII do?

A

a homologous modular structure (4 domains)

*has a Gla domain - binding to phospholipid surfaces

EGF domain is involved in protein-protein interactions

all circulate in plasma in zymogen form

activated by proteolysis

27
Q

give some examples of Gla domain containing proteins

A

FVII
FX
Prothrombin
FIX

Protein C
Protein S

Gla domain - needed by the factors in order to bind to phospholipid surfaces

28
Q

what is the role of vit K in blood clotting

A

clotting factors are made as proteins in the liver, these have cluster of glutamic acid
This glutamic acid is recognised by an enzyme in the lover and this is converted in a post-translational modification in the presence of vit K to gamma carboxyglutamic acid (means an extra carboxyl group is added_
once the extra carboxyl group has been added, calcium can facilitate the binding of of the gamma carboxyglutamic acid to the activated platelet membrane phospholipid
so the gamma carboxylation allows the clothing factors to localise on the surface of the platelet.

29
Q

how does warfarin work?

A

inhibits vit K and so stops the gamma carboxylation
stopping the ability of the clotting factors to bind to the surface of the platelets
-enzyme inhibited is vit k epoxide reductase

30
Q

what does the TF-FVIIa trigger?

A

TF-FVIIa proteolytically activates FX & FIX

Removes activation peptide to yield active enzyme

31
Q

what does FXa do?

What’s key about this step?

A

FXa can activate prothrombin to generate thrombin

Activation is inefficient - only small quantities of thrombin are generated

32
Q

What does small quantities of thrombin do?

A

it activates factor 8 and factor 5
They both act as accelerating factors
factor 8a brings factor 9a and factor 10 together so that factor 9a can proteolytically activate factor 10 to 10a

33
Q

what does the tissue factor pathway inhibitor (TFPI) do?

A

TFPI-FXa can bind/inactivate TF-FVIIa active site via Kunitz domain 1 (K1)

34
Q

how does the protein C pathway work?

A

Protein C pathway – Thrombin binds to thrombomodulin on the surface of the endothelial cell. By binding to thrombomodulin, the thrombin activates protein C. Protein C localised to endothelial surface (where thrombin/TM are). Thrombin cleaves protein C to release activation peptide. Activates protein C zymogen to APC (serine protease).
Protein S acts as a cofactor protein C- inactivates factor 5a and factor 8a

Haemostatic plug prevented from spreading beyond site of injury

Activated protein C (APC) inhibits thrombin generation by proteolytically inactivating procoagulant cofactors FVa and FVIIIa

35
Q

coagulation cascade regulation summarised:

A

TFPI regulates the initiation of coagulation

Protein C pathway regulates the propagation phase of coagulation by down-regulating thrombin generation – it does not inhibit thrombin

36
Q

what is anti-thrombin?

A

Antithrombin (AT) is a 58kDa serine protease inhibitor (SERPIN)
AT inactivates many activated coagulation serine proteases (FXa, thrombin, FIXa, FXIa)
AT “mops up” and free serine proteases that escape the site of vessel damage.
**Antithrombin inhibits any thrombin or FXa that “escapes”, the FXa that is needed will stay at the clot site.

37
Q

what are the 3 inhibitory coagulation mechanisms?

A

(i) TFPI (tissue factor pathway inhibitor)
(ii) The protein C anticoagulant pathway (APC & protein S)
(iii) Antithrombin

38
Q

describe the process of fibrinolysis

A

there is a plasma protein called plasminogen and endothelial cells produce tissue plasminogen activator
normally no interaction

when a fibrin clot forms, these two proteins assemble on the surface of the clot and the plasminogen is converted to plasmin by tPA.
plasmin then breaks down the clot
tPA (tissue plasminogen activator) and bacterial activator streptokinase are used in therapeutic thrombolysis of MI (slot busters)

39
Q

examples of fibrin degradation products

A

FDP

elevated in DIC

40
Q

‘clinical’ haemostasis

what are the drugs and tests?

A

Drugs
anticoagulants - heparin, warfarin, DOACs
antiplatelet agents – aspirin, P2Y12 blockers

Tests
coagulation (PT, APTT)
platelet function tests
d-dimer

Year 2 haem mine (11 decks)

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