Brainscape's Knowledge GenomeTM

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


See full index

POM > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

What is the difference between fibrinolytic factors and coagulation factors?

A

fibrinolytic - anticoagulant proteins stop clotting

Coagulation factors - platelets- cause clotting

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

What is haemostasis and what three ways is it achieved?

A

Halting of blood

  1. vasoconstriction
  2. Primary haemostasis - formation of unstable platelet plug
  3. Secondary haemostasis - formation of a stable fibrin clot (coagulation)

Fibrinolysis after

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

What is haemostasis important to know?

A

Diagnosing and treating bleeding disorders

identify risk factors for thrombosis
treat thrombotic disorders

Monitor the drugs used to treat bleeding and thrombotic disorders

control bleeding in individuals who don’t have an underlying bleeding disorder

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

What causes vasoconstriction?

A

Injury occurs

nerves attached to endothelial cells and thesmooth muscle cellsdetect the injury and trigger areflexivecontractionof thesmooth musclesnear site called vascularspasm >

vessel narrows, reduceblood flowand decrease blood loss through the damaged artery >

secretion ofnitric oxideandprostaglandinsdecreases

endothelial cells secrete a protein calledendothelin which causes thesmooth musclesto contract

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

What do endothelial cells release which causes smooth muscle cells to relax/contract?

A

endothelial cells normally secretenitric oxideandprostaglandinsinto the blood which cause nearbysmooth musclesto relax

Secrete endothelin to contract

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

State the 5 basic steps to primary haemostasis.

A
  1. Endothelial injury
  2. exposure
  3. adhesion
  4. activation
  5. aggregation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is a platelet? How is it made

A

Discoid, non-nucleated, granule containing cells derived from myeloid stem cells

Formed in bone marrow by fragmentation of megakaryocyte cytoplasm

circulate for 10 days

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

Why are plasma membrane glycoproteins significant in homeostasis?

A

Important for platelet interactions

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

Once an endothelial injury occurs how do platelets bind to endothelium wall?

A

Collagen is exposed so platelets bind either…

  1. directly to collagen via the GP1a receptor
  2. Indirectly via VWF - released by endothelial cells and
    platelets bind via their GP1b receptor

Both are glycoprotein receptors

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

What happens when platelets are activated?

A

their shape changes from disc to rounded with spicules to encourage platelet-platelet interaction

They release

  • a-granules
  • dense granules

the platelet membrane invaginates to form canalicular system through which the contents are released: ADP. Fibrinogen, VWF

(thromboxane A2 (derived from arachidonic acid) - first produced then released)

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

What is thromboxane A2? How is it made?

A

A vasoconstrictor and has a role in platelet aggregation

Platelets are stimulated to produce prostaglandin thromboxane A2 from arachidonic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What effect does release of ADP and thromboxane A2 have?

A

Positive feedback - lead to further platelet recruitment, activation and adhesion by binding to P2Y12 and thromboxane A2 receptors respectively

Platelet activation causes a conformational change in the GPIIa/IIIa receptor so fibrinogen can bind
this causes further activation and links the platelets together to form the platelet plug
(platelet aggregation)

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

What prevents inappropriate platelet aggregation?

A

Active flow of blood

Prostacyclin (PGI2) which suppresses platelet activation by causing vasodilation

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

What are the two antiplatelet drugs and what conditions are they used to treat?

A

Aspirin and clopidogrel

prevention and treatment of cardiovascular and cerebrovascular disease

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

How does aspirin act as an anti-platelet drug?

A

Binds irreversibly to COX enzyme which inhibits prostaglandin production and thus thromboxane A2 production by platelets preventing their aggregation

Effects last 7 days till renewed

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

How is thromboxane A2 made?

what two things does it do?

A

membrane phospholipid > Phospholipase A2 enzyme > arachidonic acid > COX enzyme > Prostaglandin PGH2 > thromboxane synthase > thromboxane A2
TP-b receptor - vasoconstrict
TP-a receptor - platelet adhesion and aggregation

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

How is prostacyclin (PGI2) made?

what does it do?

A

membrane phospholipid > Phospholipase A2 enzyme > arachidonic acid > COX enzyme > Prostaglandin PGH2 > prostacyclin synthase > prostacyclin PGI2
vasodilation - prevents platelet activation

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

How does clopidogrel stop haemostasis ?

A

Irreversibly blocks the ADP receptors (P2Y12) on platelets

Effects last 7 days until renewed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is von willebrand factor?

A
  • a glycoprotein that is synthesised by endothelial cells and megakaryocytes (incorporated into platelet granules) and circulates in plasma as multimers of different sizes.

mediates the adhesion of platelets to sites of injury and promotes platelet-platelet aggregation

is a specific carrier for factor VIII (FVIII)

20
Q

Why is secondary haemostasis important?

A

Primary is only useful for small vessel injury, in large vessels it will fall apart

Fibrin will stabilise the platelet plug

21
Q

what basic principle does the blood coagulation pathway focus on?

A

Generation of thrombin (factor IIa) which cleaves fibrinogen (factor I) to generate a fibrin clot that stabilises the platelet plug at sites of vascular injury

22
Q

How many factors are there?

name as many

A 
Factors 1-13
I - fibrinogen
II- prothrombin - essential
III - tissue factor 
IV- calcium ion 
V- co factor
VI
VII - essential
VIII - anti-haemophilic factor
IX - essential
X - essential
XIII fibrin stabilising 
2+7=9 and 10
23
Q

What are the three phases of secondary haemostasis?

A

Initiation
Amplification
Propagation

24
Q

Explain the process of forming a fibrin clot

A

Initiation
Tissue Factor (III) exposed on surface of endothelial cells, leucocytes and extravascular surfaces
This activates factor 7 => 7a
This then activates
9 => 9a; 10 => 10a
10a then activates 2(prothrombin) => 2a(thrombin)

Amplification
thrombin mediates activation of co-factors 5 and 8 and the zymogen 11 and platelets

Propagation
11 activates more 9 => 9a
which along with 8a amplifies 10 => 10a
burst of 2a thrombin

Cleaves circulating fibrinogen to make fibrin

25
Q

Where are clotting factors synthesised?

A

Mostly in the liver and except VIII and VWF (made in endothelial cells)

26
Q

Why is vitamin K needed?

A

Factors II (prothrombin), VII, IX and X are dependent on Vitamin K for gamma carboxylation of their glutamic acid residues, which is essential for the function of these clotting factors.

27
Q

What are the two ways natural anti-coagulation occurs?

A

-Protein C and protein S (co-factor)
thrombin binds to thrombomodulin on endothelial cell surface causing protein C to become APC (activated protein C)
in the presence of S inactivates 8a and 5a

-antithrombin inactivates thrombin and 10a
the action of antithrombin is made more potent by heparin released from macrophages

28
Q

What are three antiplatelet drugs and how do they work?

A

-Heparin
Potentiates action of antithrombin => inactivates 10a and 2a (thrombin)
Administered IV or SC

-Warfarin
Vit K antagonist => interferes with protein carboxylation
Reduces synthesis of Factors 2, 7, 9, 10 in the liver
Administered orally, takes several days to take effect as it deals with synthesis of new factors
Needs to be monitored by regular blood testing

DOACs (Direct Oral Anticoagulants)
Directly inhibits thrombin or 10a (without the involvement of antithrombin)

29
Q

What is the fibrinolytic system?

How does it work?

A

Mechanism to lyse clots-
primary fibrinolytic enzyme - Plasmin circulates as plasminogen
it is activated by tissue plasminogen activator (t-PA) however this only happens when it comes together on lysine residues on fibrin

30
Q

What does the breakdown of fibrin lead to? What does plasmin also break down and what is it inhibited by?

A

Fibrin degradation products

Also breaks down other plasma proteins ie factors 5 and 8 and fibrinogen

inhibited by anti-plasmin (which circulates in blood) and alpha 2 macroglobulin

31
Q

What is thrombolytic therapy and where is it used?

What are the risks of it?

A

Recombinant t-PA (using bacteria to make it)

administered intravenously to selected patients presenting with ischaemic stroke.

time-dependent and so t-PA needs to be given to eligible patients as quickly as possible

There is a high risk of bleeding associated with its use.

Thrombolytic therapy can also be given to patients with life threatening pulmonary emboli

32
Q

What are antifibrinolytic drugs and how do they work?

A

Tranexamic Acid => synthetic derivative of lysine, binds plasminogen

Prevents activation of plasminogen

Used to treat bleeding in trauma, surgery and for inherited bleeding disorders

33
Q

What is the prothrombin time test and what does it show?

A

Prothrombin Time (PT) Test

It measures primarily the clotting ability of factors 1, 2, 5, 7, 10

If any of these factors are too low, it takes longer than normal for the blood to clot.

The results of this test will be normal among most people with haemophilia A and B.

Extrinsic Pathway

34
Q

What is the activated partial thromboplastin time test and what does it show?

A

It measures the clotting ability of factors 8, 9, 11, 12.

The results of this test will show a longer clotting time among people with haemophilia A (VIII) or B (IX) and XI deficiency.

Intrinsic pathway

35
Q

What three things can cause bleeding?

A
  1. Reduction in platelet number or function Primary haemostasis –platelet plug
  2. Reduction in coagulation factors Secondary haemostasis – fibrin clot
  3. Increased fibrinolysis
36
Q

What is thrombosis?

A

Reduced anticoagulant proteins

Reduced fibrinolytic actvity e.g. pregnancy

Increased clotting factors
Factor 8 in pregnancy
Factor V Leiden (thrombophilia)
Myeloproliferative disorders

37
Q

Why is the balance between fibrinolytic factors and coagulation factors important?

A
  • allow the stimulation of blood clotting processes following injury, where blood changes from its liquid state (coagulation)
  • Limit the extent of the response to the area to prevent excessive or generalised clotting (thrombosis)
  • Start the process leading to breakdown of the clot as part of the healing process (fibrinolysis)
38
Q

Which factors are essential to the stable fibrin clot?

A

II- prothrombin - essential

VII - essential

IX - essential
X - essential

2+7=9 and 10

39
Q

How is the COX enzyme replaced?

A

endothelial cells can synthesise more COX where non nuclear platelets cannot

40
Q

What two receptors does thromboxane A2 bind to and what does this cause?

A

TP-α platelet adhesion and aggregation

TP-β vasoconstriction

41
Q

What is the effect of calcium ions during secondary haemostasis?

A

Calcium ionsplay an important role in the binding of activated clotting factors to the phospholipid surfaces of platelets.

42
Q

What is Virchows triad?

A

The three contributory factors to pathological clotting or thrombosis.

  • Blood: dominant in venous thrombosis
  • Vessel wall: dominant in arterial thrombosis
  • Blood flow: complex, contributes to both arterial and venous thrombosis
43
Q

What can caused reduced platelet number or function

A

Failure of production - drugs/viruses, bone marrow infiltration

Shortened survival - immune thrombocytopenia, increased splenic pooling

Reduction in function- inherited causes or aspirin (antiplatelet drugs

44
Q

What can cause reduction in coagulation factors?

A

Congenital
VWD
haemophilia A - Factor VIII deficiency
haemophillia B - Factor XI deficiency

Acquired
liver
Anticoagulant drugs
DIC -disseminated intravascular coagulation - condition in which blood clots form throughout the body, blocking small blood vessels)

Tx: Replacement with recombinant factors

45
Q

What can cause increased fibrinolysis?

A

Increased fibrinolysis

DIC, due to thrombolytic therapy tPA

46
Q

What changes in blood can increase the risk of venous thrombosis ?

A

• Reduced levels of anticoagulant proteins

• Reduced fibrinolytic activity
- pregnancy where there is an inhibition of plasminogen

• Increased levels of clotting factors or platelets

  • Levels of VIII rising in pregnancy
  • T​he activity of factor V is increased by a mutation - Factor V Leiden makes factor V more resistant to inactivation by protein C - inherited thrombophilia
  • Platelets are increased in number in some myeloproliferative disorders, where the bone marrow output is increased.
    

POM (42 decks)

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