Hemostasis

Question 1

Action of Va and what is it?

Answer 1

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

Question 2

Players of the Extrinsic pathway?

Answer 2

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

Question 3

What is the mechanism of action of Heparin?

Answer 3

Binds antithrombin

the bound antithrombin inactivates thrombin and fXa

Question 4

Describe the Extrinsic pathway

Answer 4

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

Question 5

How does fibrinogen exist in the circulation?

Answer 5

Dimers

Question 6

When does the protein C zymogen activates?

How is it greatly promoted?

Answer 6

When it binds to thrombin

Greatly promoted by the presence of thrombomodulin and EPCR

Question 7

What does Thrombin catalyzes?

Answer 7

Cleavage of fibrinogen to initiate fibrin clot formation

Question 8

How does fVII activates?

What are the substrates of factor VIIa?

Answer 8

Activated when bound to TF

fX and fIX

Question 9

Prothrombinase complex players

Answer 9

Va Xa Ca2+

Question 10

How does the tPA can be inhibited?

Answer 10

PAI-1

Plasmin Activator Inhibitor-1

Question 11

Where does factor V synthesized?

Answer 11

Liver Spleen Kidney

Question 12

Action of protein C?

Answer 12

Inactivates factors V and VIII

Question 13

Where does the assembly of prothrombinase complex takes place?

Answer 13

On the phosphatidyl serine exposing memb. Surface of activated platelet

Question 14

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

Answer 14

E- middle region, interaction between all chains

D- C terminal of beta and gamma chains

Question 15

Thrombin receptor names and structure

Answer 15

PAR 1/PAR3/PAR4

(Protease Activated Receptor)

Question 16

What happens during platelet activation?

Answer 16

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

Question 17

Structure of Fibrinogen?

Answer 17

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

Question 18

Players of Intrinsic pathway

Answer 18

XII XI IX VIII Requires Ca2+

Question 19

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

Answer 19

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

Question 20

What can activate protein C?

Answer 20

Thrombomodiulin bound thrombin

Question 21

Actions of XIIa

Answer 21

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

Question 22

What is the common pathway?

Answer 22

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

Question 23

Actions of XIa and cofactor

Answer 23

IX -> IXa Ca2+ is cofactor

Question 24

What are the fibrin degregation products?

Answer 24

D-dimer/D-E complex

Question 25

What is Plasmin?

Answer 25

serine protease used for the degeneration of fibrin

Question 26

Thrombin R actions

Answer 26

Induces platelets aggregation, activates endothelial cells, activates protein C

Question 27

What causes activation of the extrinsic

Answer 27

External trauma

Question 28

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

Answer 28

Gamma _A and gamma’ gamma’- 10% of the gamma subunits increase►Arterial thrombosis. decreases ►venous thrombosis.

Question 29

What is the structure of fibrinogen?

Answer 29

2xalpha+2xbeta+2xgamma held together by disulfide bonds (s-s)

Question 30

Define factor VIII

Answer 30

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

Question 31

What is protein C?

Answer 31

Zymogen. The active form is Active Protein C. serin protease proteolytically inactivates fV and fVIII

Question 32

What is the role of platelet in hemostasis?

Answer 32

Question 33

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

Answer 33

Neutrophill Extracellular Trap needed for NETosis=degranulation (mainly of DNA)

Question 34

What promotes activation of protein C?

Answer 34

Presence ofthrombomodulin and EPCR (Endothelial Protein C Receptor)

Question 35

What is the main endogenous plasmin activator?

Answer 35

tPA

Question 36

How does Va inactivates?

Answer 36

Protein C

Question 37

What anticoagulants produced by the endothelial cells?

Answer 37

NO tPA heparan sulfate prostacyclin

Question 38

Structure of Xa

Answer 38

Two chain serine protease

Question 39

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

Answer 39

Lys binding

Question 40

What molecules does fibrinogen cleavage releases ?

Answer 40

Fibrinopeptide A/B | (FPA/FPB)

Question 41

Actions of Thrombin

Answer 41

Fibrinogen -\> Fibrin Prothrombin= II Thrombin= IIa

Question 42

How can we treat Leiden mutation?

Answer 42

Blood thinners

Question 43

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

Answer 43

Prothrombin -\> Thrombin Occurs on the platelet memb. Surface

Question 44

Theombin R activation

Answer 44

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

Question 45

What is Gla domain?

Answer 45

Many glutamate residues modified by vit K dependand carboxylation to form gamma carboxyglutamate High affinity to calcium ions!

Question 46

Why is Aspirin used in the prevention of myocardial infarction?

Answer 46

It inhibitd the COX activity in platelets

Question 47

Describe the shape of unstimulated platelet

Answer 47

Disk shape

Question 48

Localization of TF?

Answer 48

- Sub endothelial epit. - Activated myocites

Question 49

How does plasmin circulate in the body?

Answer 49

inactive zymogen- plasminoge

Question 50

Where do platelet tend to flow inside the blood vessel?

Answer 50

Walls- faster adhesion and activation

Question 51

What is Leiden mutation?

Answer 51

Mutation in fV

Question 52

Actions of FXIII_a

Answer 52

It is a transglutaminase covalently cross links Lys and Gln residues of anti parallel chains -\> isopeptide bonds between them

Question 53

What activates XIII?

Answer 53

First thrombin and then we need Ca²⁺

Question 54

Prothrombin structure

Answer 54

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

Question 55

What does Leiden mutation causes? and how?

Answer 55

Increase in blood clotting

Question 56

What mediates the initial binding of plasminogen to fibrin?

Answer 56

K5

Question 57

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

Answer 57

IXa VIIIa is cofactor

Question 58

Write down substrates of thrombin? (5)

Answer 58

XI V VIII XIII Fibrinogen

Question 59

How does FXIII travel in the blood?

Answer 59

Bound to fibrinogen

Question 60

Give the inhibitors of fibrinolysis

Answer 60