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Flashcards in Hemostasis Deck (63):
1

What is the major process in primary hemostasis?

FIRST vessel reflexively constricts
platelets form a plug to minimize blood loss

2

What is the major process in secondary hemostasis?

Clotting cascade forms a fibrin clot that anchors and stabilizes the platelet plug

3

______ is central to the hemostatic response because i tis a potent platelet activator and it converts soluble fibrinogen to an insoluble fibrin clot

thrombin

4

The _________ surface is an important site for assembly and localization of the membrane bound enzyme complexes of coagulation

Activated platelet surfac

5

Gradual transition to ______ facilitates removal of a clot and wound healing

fibrinolysis

6

List three pro-thrombotic components

1. Platelets/ vWF: formation of hemostatic plug
2. Coagulation cascade: thrombin--> fibrin clot formation
3. Fibrinolysis inhibitors: soluble protease inhibitors that down regulate fibrinolysis and prevent degradation of the clot

7

List three anti-thrombotic components

1. Intact endothelium
2. Fibrinolysis: second enzyme cascade converts plasminiogen to plasmin which lyses the fibrin clot
3. Coagulation inhibitors: soluble protease inhibitors that down-regulate the coagulation cascade and remove activated coagulation factors

8

List three classes of drugs that can be used to prevent hemostasis and their major targets

1. antiplatelet drugs: target formation of primary platelet plug
2. anticoagulants: prevent formation of fibrin clot
3. antifibrinolytics: prevent breakdown of fibrin clot

9

List the steps in primary hemostasis

1. Platelet adhesion: interaction of platelet Gp-Ib with vWF
2. Platelet activation: by thrombin, collagen, ADP
3. Platelet aggregation: cross linking of activated platelets by fibrinogen binding to Gp IIb/IIIa
4. Secretion of platelet granules
5. Retraction of the newly formed thrombus

10

Platelet ______ results in conformational change and activation of Gp IIb/IIIa, granule release, and thrombus contraction

activation

11

Megakaryocyte differentiation is characterized by _____ in which DNA replication occurs but the nucleus does not divide

endomitosis

12

The production of platelets is controlled by the cytokine _____

TPO, thrombonpoietin

13

About 30% of platelets are stored in the spleen and can be released in response to _____

epinephrine

14

There is usually an ____ relationship between platelet number and mean platelet volume

inverse

15

Describe the relationship between platelet sequestration, platelet desttruction, and megakaryocyte hyperplasia

As platelets are sequestered, but not destroyed, in a large spleen, there is no compensatory megakaryocyte hyperplasia in the marrow in patients with thrombocytopenia due to hypersplenism. In contrast, when the platelet count is reduced due to rapid destruction, there is megakaryocytic hyperplasia.

16

Large circulating platelets on the blood smear in a patient with thrombocytopenia suggests:

peripheral destruction of platelets
Rapid platelet production leads to increased size of circulating platelets

17

List the two hemostatic functions of vWF

- major carrier of VIII, prolongs half life of VIII
- mediates platelet tethering and adhesion to exposed subendothelium

18

Where is vWF found/ stored

endothelial cells, megakaryocytes, subendothelial connective tissue

19

wVW is released by endothelial cells in the blood, which can be enhanced by ________

DDAVP

20

If there is inherited or acquired deficiency of________, large VWF-platelet aggregates can form
in the circulation and occlude small blood vessels causing tissue injury.

ADAMTS13

This causes the disease thrombotic thrombocytopenic purpura (TTP)

21

_______ promotes vWF unfolding

high shear stress- as in arterial circulation

22

List platelet agonists that trigger platelet activation

collagen (in ECM)
thrombin (generated by TF)
epinephrine
ADP
serotonin
TXA2 produced by COX1

23

Describe the contents of a granules and dense granules

a granules: proteins such as fibrinogen, vWF and factor V that promote clot formation as well as chemokines that recruit inflammatory cells

Dense granules: ADP/ATP and serotonin which activates additional platelets

24

______ is normally sequestered on the inner membrane of a platelet but is exposed after platelet activation. It enhances the assembly of membrane bound coagulation enzyme complexes

phosphatidylserine

25

Describe the terms intrinsic pathway and extrinsic pathway

Extrinsic pathway: plasma clotting in response to addition of tissue homogenates- factors "extrinsic to the blood". Measured by PT

Intrinsic pathway: clotting of plasma in a glass tube using only factors intrinsic to the blood. Measured by aPTT

26

What is the initiation phase of the clotting cascade?

formation of TF-VIIa complex, must exceed a specific threshold in order to trigger clotting mechanism

27

What occurs in the propagation phase of the clotting casdcade

Amplifies clotting response through factor IXa-VIIIa complex

28

Which components of the coagulation cascade are vitamin K dependent?

II, VII, IX, X, C and S

29

Describe how the phospholipid platelet surface is involved in activation of zymogens

Acts as a surface to bring a protease, a cofactor/ helper protein, and a zymogen into close contact

30

Describe factor XI

a serine protease but not vitamin K dependent

31

Describe factor XIII

enzyme that is activated by thrombin, works by cross linking fibrin to stabilize a thrombus

32

What is the function of antithrombin?

Inhibits thrombin (IIa), Xa, IXa, XIa

33

Describe the function of Protein C and Protein S

Protein C: proteolytic inactivation of V and VIII

Protein S: supports inactivation of V and VIII

34

What is the function of tissue factor pathway inhibitor?

Forms a complex with factor Xa that inactivates the TF-VIIa complex

35

List the components of the coagulation cascade that are considered cofactors

tissue factor: membrane protein that binds VIIa to form a complex that activates X, does not require proteolytic activation for cofactor activity

Factors V and VIII: require activation by thrombin to function.
VIII binds IXa to form a complex that activates X
Va binds to Xa to form a complex that activates prothrombin

Protein S: vitamin K dependent cofactor for protein C

36

How does TF initiate coagulation?

After vascular injury, TF is exposed to the blood and binds circulating VIIa. TF-VIIa generates additional VII and small amounts of IX and X before being inhibited by tissue factor pathway inhibitor

A small amount of thrombin is generated by Xa which in turn activates V, VIII, and IX

37

Activation of factors of VIII and V in the initiation phase allows for the formation of _____ and ______ complexes

IXa/VIIIa and Xa/Va

--> explosive generation of thrombin in the propagation phase

38

In the propagation phase, thrombin also cleaves/ activates factor ____ which activates additional factor IX and contributes to the final rate of thrombin generation

XI

39

______ is an abundant plasma protein that is cleaved by thrombin to form an insoluble clot

fibrinogen (cleaved to fibrin)

40

What is the role of factor XIII in the coagulation cascade?

Cross links fibrin strands to stabilize the fibrin clot

41

List all of the pro-coagulant functions of thrombin

activation of factors V, VIII, XI and XIII,activation of platelets, and cleavage of fibrinogen to fibrin

42

At very low concentrations, thrombin is bound to _______ on endothelial surfaces, which acts as an anti-coagulant by accelerating activation of protein C

thrombomodulin

43

Describe the role of the contact factors in the coagulation cascade

Factor XII, HMWK, prekallikrein

Deficiency does not lead to a bleeding phenotype but does show up as a prolonged aPTT
These factors are not necessary for normal hemostasis

44

What is the role of factor XI? What happens in factor XI deficiency?

XI is activated by thrombin and activates factor IX

Deficiency causes a mild to moderate bleeding phenotype

45

List three circulating coagulation inhibitors

- tissue factor pathway inhibitor: inhibits TF-VIIa complex so inhibits initiation phase

- antithrombin III: markedly reduces rate of thrombin generation in the propagation phase by inhibiting thrombin

- activated protein C: helps terminate propagation by inactivating Va and VIIIa

46

______ inhibits IXa, Xa, and thrombin, acting as a scavenger of free proteases

AT3

47

The activity of AT3 is markedly accelerated by the drug _____

heparin

48

How is protein C activated?

Thrombin bound to thrombomodulin

49

The _____ response predominates on the arterial side and the _____ response is more critical on the venous side

platelets on arterial side
clotting cascade on venous side

50

List platelet inhibitory substances produced by normal endothelium

PGI2
Nitric oxide synthase- NO generated from arginine by eNOS
CD39 aka ectoDAPase, degrades ADP and ATP

51

List anticoagulant substances produced by normal endothelium

Heparin sulfate: binds AT3 to accelerate protease inhibition
Thrombomodulin: enhances generation of activated protein C

52

How does intact endothelium act as a profibrinolytic surface?

Produces enzymes that activate plasminogen

53

______ is a zymogen produced in the liver that is converted to activated protease then works to digest cross linked fibrin

plasminogen

54

Endothelial cells secrete _____ which activates plasminogen to plasmin and binds specifically to fibrin

tPA

55

Describe two fibrinolysis inhibitors

- a-antiplasmin: circulates in blood, inhibits circulating plasmin but is less effective at inhibiting plasmin bound to a fibrin clot- helps keep plasmin activity local to a fibrin clot and not systemic

- plasminogen activator inhibitor-1: released by endothelial cells, helps stabilize blood clots by delaying the onset of fibrinolysis

56

The PT measures factors:

VII, X, V, II, and fibrinogen

57

Prolonged PT with normal aPTT occurs in factor ____ deficiency

VII

58

The aPTT measures factors:

IX, XI, VIII, X, V, II, and fibrinogen

59

The aPTT is sensitive to changes in the ______ which prolong aPTT but do not cause bleeding

contact factors

60

The aPTT is commonly used to monitor the anticoagulant effects of ______

heparin

61

Describe how to interpret the findings of a mixing test

if a single coagulation factor deficiency is present, the mixing test will completely correct prolongation of the clotting
time. If a coagulation inhibitor is present, mixing will usually not correct the clotting time.

62

A _____ test can be used to assess vWF activity because it causes conformational changes in vWF triggering binding to GpIb

Ristocetin

63

The thrombin time test is very sensitive to the presence of _____

heparin