Lecture 5 1/24/24

Question 1

What is the definition of hemostasis?

Answer 1

interruption of blood flow through an injured vessel

Question 2

What are the goals of hemostasis?

Answer 2

-form clot quickly
-confine clot to where needed
-limit propagation
-dissolve clot when no longer needed

Question 3

What are the three main processes of hemostasis?

Answer 3

-formation of platelet plug (primary)
-formation of fibrin through coagulation cascade (secondary)
-formation of plasmin for clot breakdown (fibrinolysis)

Question 4

How do the processes of hemostasis occur, in relation to each other?

Answer 4

-primary and secondary hemostasis occur about the same time
-fibrinolysis occurs in quick succession to primary and secondary hemostasis

Question 5

What are the antithrombotic properties associated with “at rest” blood vessels?

Answer 5

-blood flow
-bioactive molecules

Question 6

How do bioactive molecules prevent thrombus formation?

Answer 6

-vasodilation
-inhibition of platelet function/aggregation
-inhibition of coagulation
-fibrinolysis

Question 7

What are the prothrombotic properties associated with “activated” blood vessels?

Answer 7

-exposure of subendothelial cells/activation of coagulation cascade
-turbulent blood flow
-bioactive molecules

Question 8

What is tissue factor?

Answer 8

protein found in the collagenous extracellular matrix that is the beginning of secondary hemostasis/coagulation

Question 9

How do bioactive molecules promote thrombus formation?

Answer 9

-vasoconstriction
-inhibition of fibrinolysis

Question 10

How do platelets morphologically differ when at rest compared to activated?

Answer 10

-discoid/plate-shaped at rest
-spherical with multiple projections when activated

Question 11

What are the components of platelet structure?

Answer 11

-cytoskeleton
-open canalicular system to increase surface area
-dense tubular system of ER

Question 12

What are the alpha granules associated with the platelets?

Answer 12

-vWF
-fibrinogen
-factors 5, 7, 8, 11, 13
-PAI

Question 13

What are the dense granules associated with the platelets?

Answer 13

-serotonin
-ADP
-Ca++

Question 14

What is the role of the platelets’ alpha and dense granules?

Answer 14

pro-coagulation

Question 15

What is the function of GpVI and Alpha2Beta1 proteins on the platelet surface?

Answer 15

-binds to collagen
-part of primary hemostasis
-backup plan if vWF is absent/not functioning

Question 16

What is the function of Gp1b?

Answer 16

-vWF receptor
-part of primary hemostasis

Question 17

What is the role of GpIIb-IIIa?

Answer 17

-fibrinogen receptor
-involved in primary and secondary hemostasis

Question 18

How do Gp1b and GpIIb-IIIa differ structurally?

Answer 18

-Gp1b is always active and ready to bind
-GpIIb-IIIa is not active when platelet is at rest

Question 19

What is the goal of primary hemostasis?

Answer 19

formation of the primary platelet plug

Question 20

Which “players” are involved in primary hemostasis?

Answer 20

-platelets
-Von Willebrand factor (vWF)
-vessel wall

Question 21

What are the three phases of primary hemostasis?

Answer 21

-platelet adhesion
-platelet activation
-platelet aggregation

Question 22

What are the characteristics of vWF?

Answer 22

-synthesized by endothelial cells
-circulates in blood in zymogen form
-undergoes a conformational change after binding to collagen that allows for interaction with Gp1b

Question 23

What is important about the Gp1b-vWF bond?

Answer 23

it provides stabilization against sheer forces and is difficult to disrupt

Question 24

What occurs during the platelet activation stage, once the platelets are attached to collagen?

Answer 24

-shape change
-granule secretion
-conformational changes in surface proteins (GpIIb-IIIa)

Question 25

What compounds are released by activated platelets?

Answer 25

-thromboxane -ADP -PAF -vWF -serotonin -FV -fibrinogen -Ca++

Question 26

What are the overall effects of platelet activation?

Answer 26

-further activation -platelet aggregation

Question 27

How do platelets aggregate?

Answer 27

fibrinogen molecules bind to GpIIb-IIIa on two different platelets, linking them together

Question 28

What marks the end of primary hemostasis?

Answer 28

the formation of the primary platelet plug with fibrinogen acting as the "glue"

Question 29

What is flippase?

Answer 29

molecule that moves negatively charged phospholipids to the inside of the cell membrane

Question 30

What is floppase?

Answer 30

molecule that moves neutral phospholipids to the outside of the cell membrane

Question 31

What is scrambase?

Answer 31

molecule that moves negatively charged phospholipids outside and neutral phospholipids inside

Question 32

What happens when a platelet is activated?

Answer 32

-flippase and floppase are deactivated -scrambase is activated

Question 33

What is platelet factor 3?

Answer 33

the activated cell membrane of a platelet (neg. charged outer membrane)

Question 34

What is the overall function of platelet factor 3?

Answer 34

connect primary and secondary hemostasis

Question 35

Why is factor 10 able to bind to the negatively charged activated platelet, despite having a negative charge itself?

Answer 35

Ca2+ ions facilitate the binding of factor 10 to the platelet wall

Question 36

What is the main goal of secondary hemostasis?

Answer 36

activation of the coagulation cascade to form fibrin

Question 37

What are the "players" involved in secondary hemostasis?

Answer 37

-coagulation factors -platelet factor 3 -calcium

Question 38

What are the coagulation factors?

Answer 38

-fibrinogen -prothrombin -tissue factor -Ca2+ -factor 7 -factor 9 complexed with co-factor 8 -factor 10 complexed with co-factor 5 -factor 11 -factor 12 -factor 13

Question 39

What does the factor 10/co-factor 5 complex form?

Answer 39

prothrombinase

Question 40

What does the factor 9/co-factor 8 complex form?

Answer 40

tenase

Question 41

How do the soluble clotting factors circulate in plasma?

Answer 41

as pro-enzymes

Question 42

How does tissue factor differ from the other coagulation factors?

Answer 42

tissue factor is a membrane-bound protein typically found in the vascular space

Question 43

Which factors are involved in the extrinsic pathway of the coagulation cascade?

Answer 43

-tissue factor -factor 7

Question 44

Which factors are involved in the intrinsic pathway of the coagulation cascade?

Answer 44

-factor 12 -factor 11 -factor 9 -factor 8

Question 45

Which factors are involved in the common pathway of the coagulation cascade?

Answer 45

-factor 10 -factor 5 -prothrombin -fibrinogen

Question 46

What are the characteristics of coagulation cascade initiation?

Answer 46

-extrinsic pathway -via tissue factor -on the surface of fibroblasts -small amount of thrombin production

Question 47

What are the characteristics of coagulation cascade amplification?

Answer 47

-intrinsic pathway -via thrombin -on the surface of platelets -leads to more thrombin production

Question 48

What is the role of tissue factor and factor 7?

Answer 48

to activate the factor 10/co-factor 5 complex

Question 49

What is the role of the factor 10/co-factor 5 complex?

Answer 49

activate prothrombin into thrombin

Question 50

What is the role of factor 9/co-factor 8 complex?

Answer 50

activate more factor 10 during the amplification phase

Question 51

What is the role of thrombin?

Answer 51

to convert fibrinogen into fibrin

Question 52

What are the functions of factor 12?

Answer 52

-bradykinin generation -stimulation of fibrinolysis

Question 53

What are the specific physiologic inhibitors of secondary hemostasis?

Answer 53

-tissue factor pathway inhibitor -antithrombin -thrombomodulin -protein C -protein S

Question 54

What are the non-specific physiologic inhibitors of secondary hemostasis?

Answer 54

-alpha-2-macroglobulin -alpha-1antitrypsin

Question 55

What is the essential link between primary and secondary hemostasis?

Answer 55

-platelets provide negatively charged surface for coagulation factor assembly and release -thrombin activates platelets

Question 56

What is the essential link between secondary hemostasis and fibrinolysis?

Answer 56

-thrombin inhibits fibrinolysis -factor 12 promotes fibrinolysis

Question 57

What is the main goal of fibrinolysis?

Answer 57

formation of plasmin to break down the fibrin clot

Question 58

What are the "players" in fibrinolysis?

Answer 58

-plasminogen -plasminogen activators (tPA) -fibrin

Question 59

How does fibrinolysis work?

Answer 59

-plasminogen is an inactivated "bomb" within the fibrin clot -activation of plasminogen into plasmin destroys the clot and releases fibrinogen

Question 60

What are the inhibitors of fibrinolysis?

Answer 60

-antiplasmin -plasminogen activator inhibitor