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Hemostasis and clotting pathways Flashcards

week 2

1
Q

what are the three phases of Hemostasis?

A

Vascular constriction
platelet Plug formation
blood coagulation

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2
Q

Describe the mechanism of vasoconstriction

A

vascular spasm:
- injured epithelial cells release humoral immune response
- contraction of smooth muscle in small blood vessels

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3
Q

Describe the formation of the platelet plug (OVERALL)

A

injury: nitric oxide and PGI2 no longer inhibit PLTs

Adherence: vWF binds to PLT using GPIb and GPIa

Aggregation: This binding releases ADP and TXA2

Adherence: PLTs bind together with GPIIb/IIa w Fibrinogen = Fibrin Mesh

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4
Q

Name the three steps of PLT Plug formation?

A

Adherence
Activation
Aggregation

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4
Q

What is the role of GPIa?

A

attaches directly to subendothelial collagen

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5
Q

what is the role of GPIb-vBF?

A

attaches to collagen

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6
Q

Compare pri and sec hemostatic responses.

A

Mediation
P= blood vessels and PLTS
S= Coagulation and PLTS

Activated by:
P= small injuries
S= large issues

Length
P= rapid and short
S= delayed and long

pri- first responders
sec- construction crew

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7
Q

What is FI and what is its clotting factor and pathway?

A

Fibrinogen

Fibrinogen Group

Both

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8
Q

What is FII and what is its clotting factor and its pathway?

A

Prothrombrin

Vit K dependent

Both

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9
Q

What is FIII and its pathway?

A

Tissue factor

Extrinsic

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10
Q

What is FIV and its pathway?

A

Calcium

Both

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11
Q

What is VIII and what is its clotting factor and its pathway?

A

Antihemophilic factor A

Fibronogen Group

Intrinsic

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11
Q

What is IX and what is its clotting factor and its pathway?

A

Christmas Factor

Vit K dependent

Intrinsic

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12
Q

Outline the Intrinsic pathway

A

XII –> XIIa

XIIa – HMW–> XI

XI–> XIa

XIa –> IX

IX–Ca–> IXa

IXa–VIIP Ca –> X

X–> Xa

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13
Q

Outline the Extrinsic pathway

A

VII –> TF VIIa

TF VIIa – FIII P Ca –> X

X–> Xa

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14
Q

When does intrinsic pathway occur? simple events?

A

Contact with damaged surface

initial triggering event

  • sequential activation of 12 –> 11 –> 9 –> 8 –> 10
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15
Q

When does the extrinsic pathway occur? simple events?

A

Trauma

‘waterfall’ sequence/enzyme cascade

  • 3 (+) –> 7 – (=) –> 10
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16
Q

Outline the common pathway simply

A

prothrombin –> thrombin

Fibrinogen – thrombin–> fibrinogen monomer –> fibrin fibres –> cross-linked fibrin mesh

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17
Q

How does TBD act as an anti-clotter?

A

Complexes with thrombin –> activates protein C –> degrades VIIa and Va

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17
Q

How does Tissue Factor Pathway Inhibitor act as a Anti-clotting system?

A

Binds to trimolecular complex of ext pathway

Blocks protease activity of VIIA

18
Q

How does Protein C and S act as an anti-clotter?

A

Binds to TBD and inactivates Va and VIIa –> inhibits coagulation

19
Q

How does ATB act as an anti-clotter?

A

Inactivates thrombin and IXa, Xa, XIa and XIIa

Heparin binding activates ATB

20
Q

What does the Fibrinolytic system do?

A

Breaks down fibrin into degradation products

21
Q

What does Warfarin do?

A

inhibits Vit K dependent CF

decreases promthorbrin (FII) and procoagulant factors

21
What does Asprin do?
inhibits Cyclooxygenase --> inhibits TXA2 --> decerased PLT aggregation = increased bleeding
22
What is bleeding time and what can increase it?
Tests Primary Haemostatic response Thrombocytopenia and vWF deficiency increase bleeding time
22
What is Coagulation time and what increases it?
tests SECONDARY hemostatic response increased due to: Hemophilia A/B, Vit K Deficiency, liver disease
23
What is prothrombin time and what increases it?
Time for clot formation when FII and Ca added increased due to VIT k def, warfarin therapy, liver disease
24
what is Activated partial thromboplastin time? What increases it?
tests int and ect pathways increased due to haemophilia A/B, Vit K def, heparin therapy and liver disease
25
What is the role of TXA2 and what is it?
What: lipid mediator - Stimulates platelet activation by binding to receptors = PLT shape change, release of granules - promotes clumping of platelets - vasoconstrictor
26
what is the coagulation factor involved in haemophilia A and what is its role?
F VIII cofactor if tenase complex which activates FX
27
what are the functions of platelets in secondary hemostasis
provides a surface for coagulation (Phospholipid Bilayer) Releases coagulation factors (FV, ADO TXA2) Clot retraction
28
What is the role Von Willebrand factor in pri haemostais?
binds to collagen in injured endothelial cells to allow PLTs to adhere
29
what is the role of Strepokinase in the fibrinolytic pathway?
activates Plasminogen --> converts molecules into plasmin --> plasmin breaks down fibrin --> dissolves clot --> restores blood flow
30
Why is pregnancy considered a hypercoagulable state?
increased levels of clotting factors (VII, VIII, X and vWF) via hormone levels decreased natural anticoagulants (protein S) reduced fibrinolytic activity (suppressed)
31
What is the main role of Warfarin?
interference with Vitamin K-dependent synthesis of clotting factors
32
what is the mechanism of action of Warfarin?
inhibits Vitiman K reductase which recycles Vit K = reduced active v Vit k = reduced synthesis of FII, VII, IX and X
33
What is the role of Vitiman K in coagulation
some cofactors require it for synthesis is a cofactor for enzyme that adds carboxyl group to clotting factor = allowing to function properly
34
what timing tests monitors the effectiveness of warfarin?
Prothrombin time test
35
what are the vitiman K dependant co-factors?
FII, FVII, FIX, FX
36
what is FXa?
an enzyme that turns prothrombin into thrombin
37
what is the importance of thrombin?
Fibrin maker - turns fibrogen --> fibrin Platelet activator - tells PLTS to stick together Clotting Amplifier - boost clotting process
38
How does HIT lead to clot formation?
PF4-Heparin complex triggers IgG antibodies --> antibodies bind to PF4-heaprin complex associated with a PLT --> PLT activation --> releases more PF4 creating pos feedback loop = sig increase in thrombin --> clot formation
39
effect of liver disease on procoagulant actions
Liver is pri site of synthesis for many coagulation factors Impair liver's ability to utilise Vitamin K = deficiency in clotting factors
40
What is the role of Protein C in the coagulation Cascade?
Natural Anticoagulant when works w Protein S = inactivates Va and VIIIa
41
How does t-PA work?
aims to dissolve blood clots plasminogen activation (converts plasminogen into plasmin) Fibrinolysis plasmin breaks down fibrin --> removes structure of the clot
42
What are the anticoagulant factors that come from the endothelium?
PGI2 NO TFPI Thrombodulin EPCR
43
What are the 5 regulatory proteins of haemostasis?
vWF, Protein C, Protein S, Thrombomodulin and antithrombin III

HRM (9 decks)

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