Brainscape's Knowledge GenomeTM

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


See full index

Y2 - HAEM > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

What are the basic steps in the haemostatic plug formation, and other responses to vessel injury, starting with vessel injury?

A
  • Vessel injury necessitates haemostatic plug formation
  • Local smooth muscle constriction
  1. Formation of an unstable platelet plug - platelet adhesion and aggregation to form plug
  2. Stabilisation of the plug with fibrin - blood coagulation
  3. Dissolution of clot and vessel repair - fibrinolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

In the haemostatic plug formation, why might the unstable platelet plug not be sufficiently stabilised, and what might be an adverse effect of incomplete platelet plug stabilisation?

A
  • Fibrin may not have spread all the way through the platelet plug in order to stabilise it
  • This can result in platelet embolisation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give 2 functions of the endothelium

A
  1. Maintain barrier between blood and procoagulant subendothelial structures (collagen - important in the platelet response and tissue factor - expressed on the surface of a number of cells and triggers coagulation)
  2. Synthesis of PGI2, thrombomodulin, vWF, plasminogen activators
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Outline the step-wise process in the formation of the platelet plug

A
  1. Endothelial cell lining is exposed in vessel injury, exposing the collagen on the basement membrane
  2. vWF (Von Willebrand Factor) binds to the collagen on the exposed basement membrane
  3. Rheological shear forces of flowing blood unravels the vWF and exposes it for binding
  4. Platelets either bind the vWF using glycoprotein 1b receptors (glp-1b receptors) or bind the collagen directly using glp-1a receptors
  5. Binding of the platelets partially activates it and causes them to release ADP and thromboxane which further activates it in a positive feedback mechanism
  6. Once the platelets are activated, the platelets can now bind circulating fibrinogen using glp-2b or glp-3a receptors
  7. This causes platelet aggregate formation as there is a sort of chain link formation with fibrinogen bridging between platelets - i.e. 2< bind one fibrinogen
  8. Fibrinogen is ultimately converted to fibrin to stabilise the initially unstable platelet plug
  9. When coagulation is activated, thrombin is generated. Thrombin can also activate platelets and the glp-2b and glp-3a receptors on platelets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Outline the steps of prostaglandin metabolism in endothelial cells and in platelets (i.e. the synthesis of prostacyclin and thromboxane), also which one synthesises which of these prostaglandins?

A

Endothelial cells - Prostacyclin synthesis

  1. Membrane phospholipid (+Phospholipase) → ​Arachidonic acid
  2. Arachidonic acid (+Cyclooxygenase) → Endoperoxides (PGG2, PGH2)
  3. Endoperoxides (PGG2, PGH2) (+Prostacylin synthetase) → Prostacyclin (PGI2)

Platelets - thromboxane synthesis

  1. Membrane phospholipid (+Phospholipase) → Arachidonic acid
  2. Arachidonic acid (+Cyclooxygenase) → Endoperoxides (PGG2, PGH2)
  3. Endoperoxides (PGG2, PGH2) (+Thromboxane synthetase) → Thromboxane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the function of the following prostaglandins and where are they synthesised?

1) Endoperoxidases (PGG2, PGH2)
2) Thromboxane
3) Prostacyclin

A

1)

  • Synthesised in both endothelial cells and platelets
  • Potent inducer of platelet aggregation

2)

  • Synthesised in platelets
  • Potent inducer of platelet aggregation

3)

  • Synthesised in endothelial cells
  • Potent inhibitor of platelet function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does aspirin essentially do and how does it do this?

A
  • Anti-platelet drug
  • Aspirin is a COX-1 ANTAGONIST irreversibly inactivates cyclooxygenase enzymes
  • This prevents the formation of endoperoxidases (PGG2, PGH2)
  • Endoperoxidases are the substrates that eventually form thromboxane, therefore without any endoperoxidase, you cannot form thromboxane
  • Therefore less thromboxane is produced, thromboxane is usually secreted by platelets to promote platelet activation
  • Therefore, by inhibiting thromboxane synthesis, aspirin inhibits the activity of platelets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

1) What anti-platelet drugs are used as anti-thrombotic agents and how do they function - no need to go into extensive detail just brief
2) In what circumstances would you want to use anti-thrombotic agents?

A

1)

  • COX-1 antagonists - to prevent pro-platelet thromboxane secretion e.g. aspirin
  • ADP receptor antagonist - to prevent pro-platelet function e.g. clopidogrel, prasugrel
  • Glp 2b / 3a antagonists - to prevent platelet aggregation e.g. abciximab, tirofiban, eptifibatide

2)

  • Angina
  • MI
  • Angioplast - cardiac intervention
  • Stents - cardiac intervention
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

1) What is the normal range of platelets in the blood?
2) What are the other symptomatic gradations of platelet levels of thrombocytopenia (low platelets) and at what numerical boundaries do they occur?

A

1)

  • 150-400 x 109/L

2)

  • < 100 x 109 / L → No spontaneous bleeding, but bleeding with trauma
  • < 40 x 109 / L → Spontaneous bleeding common
  • < 10 x 109 / L → Severe spontaneous bleeding common - happens in leukaemia often
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

1) What is the pathophysiology of autoimmune thrombocytopaenia?
2) What clinical sign can be seen in autoimmune thrombocytopaenia?

A

1)

  • Antibodies against Glp-2b / Glp-3a prevent platelet aggregation

2)

  • Purpura
  • Multiple bruises
  • Ecchymoses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List 3 tests to monitor platelets and their function

A
  1. Platelet count
  2. Bleeding time
  3. Platelet aggregation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the bleeding time test - how is it performed, what is the normal bleeding time range and when is it used and what does it test?

A
  • A standardised incision is made and the time between the start of bleeding and the cessation of bleeding is measured
  • Normal bleeding time = 3-8 minutes
  • Used when the platelet count is normal but excessive bleeding may be taking place - can be used in renal disease
  • It tests the platelet - vessel wall interaction, if excessively long, it indicates abnormal platelet-vessel wall interaction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When is the platelet aggregation test used to test platelets?

A
  • In suspected inherited platelet defects
  • In suspected vWF disease (von Willebrand Factor disease)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Outline all the steps in the clotting cascade and mention which parts constitute the intrinsic, extrinsic and common pathways - you can just draw out the diagram - see ppt if diagram not very visible here

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

What is the role of the platelet in the the coagulation cascade?

A
  • Accelerates the cascade
  • FVIIIa on platelet surface brings together FIX and FX to accelerate the proteolytic activation of FX to FXa
  • FXa converts prothrombin into thrombin in the presence of FVa on the surface of platelets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Platelet life span?

A
  • 10 days roughly
17
Q

What cell is this?

A

A megakaryocyte

18
Q

Describe the maturation pathway for the development of megakaryocytes and thus detail how platelets are released and into circulation

A
  • Haematopoietic stem cells from bone marrow
  • Matures into Meg-CFC
  • Matures into Promegakaryocyte
  • Matures into Megakaryocyte
  • Megakaryocyte binds to the sinusoidal endothelial cells, penetrates through a bit and then releases loads of platelets into circulation
19
Q

1) Describe the mode of action of the anticoagulant - ‘Warfarin’
2) Is Warfarin a slow or fast acting anti-coagulant and in what conditions might it be used for as a therapeutic anticoagulant?

A

1)

Warfarin inhibits the vitamin K-epoxide reductase which normally converts glutamic acid residues in the nascent clotting factors (FII, VII, IX, X) into γ-carboxyglutamic acid which interacts with calcium and the platelet membrane phospholipid - i.e. platelets - therefore these clotting factors cannot interact with platelets, thereby impeding clotting by preventing thrombin formation

2)

  • Long-term anti-coagulant
  • Following venous thrombosis
  • To treat atrial fibrillation
20
Q

1) Describe the mode of action of the anticoagulant - ‘Heparin’
2) Is heparing a slow acting or fast acting anti-coagulant and what conditions might it be used for as a therapeutic anticoagulant?

A

1)

  • Inhibits the following coagulation proteases by irreversibly forming complexes with them: thrombin (IIa), FXa, F9a, F11a
  • It does this by accelerating the action of a natural plasma thrombin inhibitor - anti-thrombin

2)

  • Immediate anti-coagulation
  • Venous thromboembolism
  • Pulmonary embolism
21
Q

1) Give 3 lab coagulation tests, describing what they test like mechanistically including which pathways of the coagulation cascade that they test
2) Clinically, what are the practical uses of 2 of these 3 lab coagulation tests?

A

1)

  1. APTT = Activated Partial Thromboplastin Time
  • Initiates coagulation through FXII
  • Detects abnormalities in the intrinsic and common pathways
  1. PT = Prothrombin time
  • Initiates coagulation through tissue factor
  • Detects abnormalities in extrinsic and common pathways
  1. TCT = Thrombin Clotting Time
  • Add thrombin
  • Shows abnormality in the conversion of fibrinogen into fibrin
  • Detects abnormalities in common pathwa

2)

* APTT and PT are used together for screening for causes of bleeding disorders

* APTT is used to monitor heparin therapy in thrombosis

* PT is used for monitoring warfarin treatment in thrombosis

22
Q

Describe the process of fibrinolysis and the substances involved in the process, including what type of substances they are

A
  • Fibrin clot is broken down
  • Plasminogen (a zymogen) is broken down by tPA (tissue plasminogen activator - a proteinase) assemble on the surface of a stable fibrin clot and interact to form plasmin
  • Plasmin breaks down the fibrin clot and releases fibrin degradation products
23
Q

Give 2 things that can be administered therapeutically as ‘clot-busters’ i.e. things that activate fibrinolysis and give one example condition in which they are used clinically

A
  1. tPA
  2. Streptokinase
  • After an MI (myocardial infarction)
24
Q

What is the basic pathophysiology of DIC (disseminated intravascular coagulation) and what is one sign that can be seen in the blood indicative of DIC and explain why you’ll see this?

A
  • There’s systemic clots all over in DIC when unecessary
  • This directly impedes microvasculature all over the body, but more importantly…
  • Excessive consumption of clotting factors and platelets, this leads to higher risk of haemorrhage
  • Clinical sign: very high fibrin degradation products
  • Because, as a lot of clots form with fibrin, lots of fibrinolysis must also occur which releases lots of fibrin degradation products which can essentially be seen as markers of DIC
25
Q

How does TFPI (tissue factor pathway inhibitor) inhibit the coagulation cascade?

A
  • TFPI-FXa can bind/inactivate TF-FVIIa active site via Kunitz domain 1 (K1)
26
Q

What activates protein C - brief, just name and where it is and then outline in one sentence how activated protein C down-regulates thrombin generation to inhibit the coagulation cascade? Thus what type of process is it?

A
  • Activated by thrombin-thrombomodulin complex on endothelial cell
  • Activated Protein C down-regulates thrombin generation by proteolytically inactivating procoagulant factors FVa and FVIIIa
  • So it is a negative feedback mechanism by thrombin
27
Q

Describe 2 functions of Activated Protein C?

A
  1. Down-regulating thrombin formation - NOT inhibiting
  2. Preventing the spread of a haemostatic plug beyond the site of injury
28
Q

How is the haemostatic plug prevented from spreading beyond the site of injury?

A
  • Activated Protein C along with co-factor S binds to prevent the spread
29
Q

Outline the step-wise process of activation of Protein C to form activated Protein C

A
  1. Thrombin (FIIa) contains serine proteases which cleaves fibrinogen to form fibrin
  2. Thrombin binds thrombomodulin on endothelial cell readily
  3. Protein C is localised to the endothelial cell surface beside the thrombin-thrombomodulin complex by binding to EPCR (Endothelial Protein C Receptor)
  4. Thrombin now cleaves Protein C to release an
  5. The activation peptide activates the Protein C zymogen to form Activated Protein C
30
Q

How does anti-thrombin prevent coagulation elsewhere from the site of injury?

A
  • Inhibits any thrombin or FXa that escapes the haemostatic plug
31
Q

What does anti-thrombin do?

A
  • It’s a serine protease inhibitor
  • Inactivates many activated coagulation serine proteases (thrombin, FIXa, FXa, FXIa)
  • Mops up free serine proteases that escape the site of vessel injury from the haemostatic plug
32
Q

In the extrinsic pathway describe the arrangement of the clotting factor its associated with and the tissue factor, and what its function is in relation to it

A
  • FVII / VIIa binds cell surfaces via the Gla domain
  • All domains of the clotting factor interact with the tissue factor
  • The tissue factor accelerates the function of FVII / VIIa
  • FVIIa goes on to activate FIX → FIXa conversion and FX → fXa conversion
33
Q

1) FVII is a ….. ….. …..
2) FVII is secreted by the …..

A

1) FVII is a serine protease zymogen
2) FVII is secreted by the liver

34
Q

1) How many domains are in the FVII, FIX, FX and PC molecules?
2) The structure of the FVII,FIX and FX molecule are described as a ….. ….. structure
3) Describe the common structure of FVII, FIX, FX and PC molecules by domains and which contains the active site and which contains calcium and which interfaces with the phospholipid membranes
4) All of FVII, FIX, FX and PC molecules circulate in plasma in ….. form and are activated by what process?

A

1)

  • 4

2)

  • Homologous modular

3)

  • Serine Protease domain which contains the active site
  • EGF2
  • EGF1
  • Gla with calcium - this interfaces with the membranes

4) Circulate in zymogen form and are activated by proteolysis

35
Q

1) List all the molecules that contain the Gla domain?
2) What is the principal function of the Gla domain?

A

1)

  • FVII
  • FIX
  • FX
  • FXI
  • Prothrombin
  • Protein C
  • Protein S

2)

  • Binds to phospholipid surfaces such as membranes
36
Q

1) List all the molecules that contain the serine protease domain?
2) What does the serine protease domain contain that facilitates its function as a protease and where does it cleave its substrates?

A

1)

  • FVII
  • FX
  • Prothrombin
  • FIX
  • FXI
  • Protein C

2)

  • Serine proteases contain a catalytic triad of His / Asp / Ser
  • Cleave substrates after specific Arg (and Lys residues)
37
Q

How does Activated Protein C downregulate thrombin formation?

A

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

38
Q

Describe the ultrastructure features of platelets

A
  • Glycogen
  • Phospholipid membrane
  • Mitochondrion
  • Open canallicular system
  • Microtubules for actomyosin
  • Anuclear
  • Thrombin receptor
  • α granules: growth factor, fibrinogen, factor V, vWF
  • Dense granules: ADP, ATP, Serotonin, Ca2+
  • Surface glycoproteins: GlpIa, GlpIb, Glp IIb, Glp IIIa

Y2 - HAEM (11 decks)

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