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S.N Biochemistry 3 > Hemostasis > Flashcards

Hemostasis Flashcards

1
Q

Action of Va and what is it?

A

Cofactor. Binds to platelet memb. And forms a complex with factor Xa and prothrombin

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2
Q

Players of the Extrinsic pathway?

A

TF (Tissue Factor) VII X and Ca2+ They result in the formation of Xa!

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3
Q

What is the mechanism of action of Heparin?

A

Binds antithrombin

the bound antithrombin inactivates thrombin and fXa

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4
Q

Describe the Extrinsic pathway

A

TF activates VII -> TF acts as cofactor for VIIa -> VIIa activates X (requires Ca2+)

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5
Q

How does fibrinogen exist in the circulation?

A

Dimers

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6
Q

When does the protein C zymogen activates?

How is it greatly promoted?

A

When it binds to thrombin

Greatly promoted by the presence of thrombomodulin and EPCR

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7
Q

What does Thrombin catalyzes?

A

Cleavage of fibrinogen to initiate fibrin clot formation

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8
Q

How does fVII activates?

What are the substrates of factor VIIa?

A

Activated when bound to TF

fX and fIX

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9
Q

Prothrombinase complex players

A

Va Xa Ca2+

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10
Q

How does the tPA can be inhibited?

A

PAI-1

Plasmin Activator Inhibitor-1

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11
Q

Where does factor V synthesized?

A

Liver Spleen Kidney

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12
Q

Action of protein C?

A

Inactivates factors V and VIII

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13
Q

Where does the assembly of prothrombinase complex takes place?

A

On the phosphatidyl serine exposing memb. Surface of activated platelet

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14
Q

Describe the special features of the D and E regions of fibrinogen

A

E- middle region, interaction between all chains

D- C terminal of beta and gamma chains

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15
Q

Thrombin receptor names and structure

A

PAR 1/PAR3/PAR4

(Protease Activated Receptor)

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16
Q

What happens during platelet activation?

A

Platelet adhere to exposed collagen fibers via specific R on the platelet surface

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17
Q

Structure of Fibrinogen?

A

Soluble -plasma glycoprotein Dimer (Aa, Bb, gamma)2 covalently linked by 29 disulfide bonds

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18
Q

Players of Intrinsic pathway

A

XII XI IX VIII Requires Ca2+

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19
Q

What two pathways leads to Fibrin clot? Which one is faster?

A
  1. Intrinsic 2. Extrinsic- faster. (remember less factors are involved so it is faster)
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20
Q

What can activate protein C?

A

Thrombomodiulin bound thrombin

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21
Q

Actions of XIIa

A
  1. XI -> XIa 2. Releases Bradykinin (vasodilator) from HMG kininogon
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22
Q

What is the common pathway?

A

Proteolytic conversation of prothrombin to thrombin (fX with co factor fV)

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23
Q

Actions of XIa and cofactor

A

IX -> IXa Ca2+ is cofactor

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24
Q

What are the fibrin degregation products?

A

D-dimer/D-E complex

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25
Q

What is Plasmin?

A

serine protease

used for the degeneration of fibrin

26
Q

Thrombin R actions

A

Induces platelets aggregation, activates endothelial cells, activates protein C

27
Q

What causes activation of the extrinsic

A

External trauma

28
Q

What are the two isoforms of the gamma subunit of fibrinogen and what are they significance?

A

Gamma A and gamma’

gamma’- 10% of the gamma subunits

increase►Arterial thrombosis.

decreases ►venous thrombosis.

29
Q

What is the structure of fibrinogen?

A

2xalpha+2xbeta+2xgamma

held together by disulfide bonds (s-s)

30
Q

Define factor VIII

A

Circulating glycoprotein Cofactor! Serves as a receptor on platelet surface for factor IXa+ X

31
Q

What is protein C?

A

Zymogen. The active form is Active Protein C.

serin protease

proteolytically inactivates fV and fVIII

32
Q

What is the role of platelet in hemostasis?

A
33
Q

What does NET mean? What is the function fo it?

A

Neutrophill Extracellular Trap

needed for NETosis=degranulation (mainly of DNA)

34
Q

What promotes activation of protein C?

A

Presence ofthrombomodulin and EPCR (Endothelial Protein C Receptor)

35
Q

What is the main endogenous plasmin activator?

A

tPA

36
Q

How does Va inactivates?

A

Protein C

37
Q

What anticoagulants produced by the endothelial cells?

A

NO

tPA

heparan sulfate

prostacyclin

38
Q

Structure of Xa

A

Two chain serine protease

39
Q

What is the role of kringle domain in the structure of tPA and plasminogen?

A

Lys binding

40
Q

What molecules does fibrinogen cleavage releases ?

A

Fibrinopeptide A/B

(FPA/FPB)

41
Q

Actions of Thrombin

A

Fibrinogen -> Fibrin Prothrombin= II Thrombin= IIa

42
Q

How can we treat Leiden mutation?

A

Blood thinners

43
Q

What are the actions of Xa and where does it happen?

A

Prothrombin -> Thrombin Occurs on the platelet memb. Surface

44
Q

Theombin R activation

A

Theombin binds extracellular N-domain -> cleaavage of N terminal -> SFLLRN ligand binds -> activation

45
Q

What is Gla domain?

A

Many glutamate residues modified by vit K dependand carboxylation to form gamma carboxyglutamate

High affinity to calcium ions!

46
Q

Why is Aspirin used in the prevention of myocardial infarction?

A

It inhibitd the COX activity in platelets

47
Q

Describe the shape of unstimulated platelet

A

Disk shape

48
Q

Localization of TF?

A
  • Sub endothelial epit.
  • Activated myocites
49
Q

How does plasmin circulate in the body?

A

inactive zymogen- plasminoge

50
Q

Where do platelet tend to flow inside the blood vessel?

A

Walls- faster adhesion and activation

51
Q

What is Leiden mutation?

A

Mutation in fV

52
Q

Actions of FXIIIa

A

It is a transglutaminase

covalently cross links Lys and Gln residues of anti parallel chains -> isopeptide bonds between them

53
Q

What activates XIII?

A

First thrombin and then we need Ca2+

54
Q

Prothrombin structure

A

Single chain glycoprotein with Ser-His-Asp in the active site

55
Q

What does Leiden mutation causes? and how?

A

Increase in blood clotting

56
Q

What mediates the initial binding of plasminogen to fibrin?

A

K5

57
Q

Who acts as the serine protease in the Intrinsic pathway? Who is the cofactor?

A

IXa VIIIa is cofactor

58
Q

Write down substrates of thrombin? (5)

A

XI

V

VIII

XIII

Fibrinogen

59
Q

How does FXIII travel in the blood?

A

Bound to fibrinogen

60
Q

Give the inhibitors of fibrinolysis

A

S.N Biochemistry 3 (14 decks)

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