Hemodynamics Part I: hemostasis Flashcards Preview

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Flashcards in Hemodynamics Part I: hemostasis Deck (92):
1

hemostasis occurs as the result of ...

well regulated and balanced process of maintaining blood in a fluid state while allowing for controlled and focused clotting to prevent blood loss

2

3 general components that contribute to hemostasis

endothelium/vascular wall

platelts

coagulation cascade

3

sequence of clot formation (5)

1. brief vasoconstriction
2. endothelial damage exposes subendothelium casuing platelts to become activated and adhere.
3. TF is released and activates the coagulation cascade forming fibrin
4. platelet activation furthers coagulation
5. fibrin and platelets form a clot thereby plugging the defect to prevent blood loss

4

factors which activate endothelium and shift the function to the procoagulant state include (4)

infectious agents
hemodynamic forces
cytokines
plasma mediators

5

antithrombotic mechanisms of the endothelium

- acts as barrier to suendothelium
- prostacyclin PGI2 and NO inhibit platelet aggregation (thrombin and several cytokines stimulate PGI2 and NO synthesis)
- adenosine diphosphatase degrades ADP thereby inhibiting platelet aggregation

6

anticoagulant activites of endothelium

- heparin-like molecules are cofactors to antithrombin
-thrombomodlin converts thrombin to an anticoagulant
- fibrinolytic (endothelial cells make tPA)

7

prothrombotic mechanisms of the endothelium

- endothelial cells synthesize von Willebrand factor, which serves to firmly bind platelets to the subendothelium
- endotoxin and some cytokines induce enothelial cells to make tissue factor
- endothelial cells secrete plasminogen activator inhibitor

8

under normal conditions, endothelial cells inhibit platelet adherence and blood clotting

injury or activation of endothelial cells results in procoagulant state

9

from what do platelet cells derive?

magakaryocytes

10

platelet adhesion: vWF links the subenothellium to _________ on platelets

glycoprotein Ib receptors

this mediates firma dherence of platelets to vessel wall

11

_____- activates the platelets causing the release of their granules

adhesion

12

platelet granule contents

calcium
ADP
platelet factor 4
serotonin

13

function of calcium

critical coagulation cascade

14

function of ADP

mediates platelet aggregation which drives increasing platelet aggregation at the site (along with thromboxane)

15

function of platelet factor 4

binding of heparin by platelet factor 4 results in its inactivation

16

function of serotonin

induces vasoconstriction

17

fibrinogen links platelets via _____

GpIIb-IIIa

18

GpIIb - IIIa inhibitors are used to -------

inhibit thrombosis

19

where does thrombin bind

platelet surface

20

platelet activation causes expression of __________ on surface of platelets

phospholipid complexes on suface of platelts which act as surfaces to bind coagulation factors and calcium --> promotes coagulation

21

actions of thrombin

thrombin converts fibrinogen to fibrin monomer but also effects local vasculature, inflammation and fibrinolysis

22

forms glue for platelet plug

fibrin crosslinks

23

when is tissue factor released?

when tissue is injured

24

where do the intrinsic and extrinsic pathways converge?

factors IX and X

25

what surface is best for maximum coagulation factor activity?

phospholipid surface

26

warfarin (Coumadin)

prolongs prothrombin time PT (extrinsic)

27

heparin

prolongs partial thromboplastin time PTT (intrinsic )

28

TENET XV

intrinsic longer pathway PTT

29

fibrinogen --> fibrin

via thrombin

30

3 anticoagulants

antithrombin III

protein C

Plasmin

31

action of antithrombin III

directly inactivates serine proteases thrombin and Xa (also IXa, XIa and XIIa)

32

what potentiates the action of antithrombin III

heparin

33

cleaves the cofactors Va and VIIIa

protein C

34

breaks down fibrin

plasmin

35

enhances the activity of protein C

protein S

36

activates protein C

thrombomodulin

37

activated by thrombin

thrombomodulin

binds to thrombin to alter its conformation

38

inhibits VIIa tissue factor complex (extrinsic arm)

tissue pathway factor inhibitor

39

where is plasmin activity optimized?

at sites of fibrin deposition

40

how is free plasmin inactivated

by circulating alpha2 antiplasmin

41

what inactivates tPA

PAI plasminogen activator inhibitor

42

how do endothelial cells modulate coagulation/anticoagulation balance?

by releasing PAI

43

what increases PAI?

thrombin and various cytokines

44

what breaks down fibrin?

plasmin (from plasminogen)

45

what 3 substance activate plasminogen?

urokinase

tPA

streptokinase

46

prevent clot formation and extension

anticoagulants

47

interfere with platelet activty

antiplatelet drugs

48

dissolve existing thrombi

thrombolytic agents

49

blood clot that forms abnormally within a blood vessel

thrombus

50

a dislodged blood clot which travels through the bloodstream

embolus

51

naturally occurring anticoagulant produced by basophils and mast cells to prevent formation and extension of blood clots

heparin

52

does heparin disintegrate clots that have already formed?

NO

53

how is heparin given?

intravenously or by subcutaneous injection

54

how does heparin work?

binds and activates antithrombin III (inhibits thrombin, factor IXa, factor Xa)

55

how is warfarin administered?

oral medication

56

how does warfarin decrease blood coagulation?

by interfering with vitamin K metabolism

57

what are the vitamin K dependent clotting factors>

VII
IX
X
II

58

what clotting factors does heparin attack?

9a
10a
2

59

what clotting factors does coumadin attack?

9
7
10
2

60

dabigatran

direct thrombin inhibitor

61

rivaroxaban

direct factor Xa inhibitor

62

apixaban

direct factor Xa inhibitor

63

TFPI tissue factor pathway inhibitor

new anticoagulation drug

64

extrinsic assessment of coagulation

prothrombin time PT

65

what drug increased the prothrombin time

warfarin (coumadin)

66

which factors require vitamin K for synthesis

factors II, VII, IX, X, protein C and protein S

67

describe the international normalized ratio INR

compares patient PT to the normal PT which compensates for differences in tissue factor

68

intrinsic assessment of coagulation

partial thromboplastin time PTT

69

what prolongs the PTT

heparin
hemophilia
antiphospholipid antibody

70

what are the only factors not included in PTT

factors VII and XIII

71

how would you distinguish between an inhibitor and factor deficiency

mixing pt sample with normal plasma:

if inhibitor: no clotting
if deficiency: clotting

72

low dose heparin PT and PTT

PT normal
PTT prolonged

73

high dose heparin PT and PTT

PT prolonged
PTT prolonged

74

low dose warfarin PT adn PTT

PT prolonged
PTT normal

75

high dose warfarin PT and PTT

PT prolonged
PTT prolonged

76

what is warfarin necrosis?

thighs, breasts, and buttocks multiple or single lesion, with localized pain and erythema that develops into a painful necrotic eschar

low levels of protein C --> transient hypercoagulable state causing local thrombosis of dermal vessels

77

describe heparin induced thrombocytopenia

platelet factor 4 is released by plateltes and bidns heparin thus blocking its action and pormoting coagulation

antibodies to heparin bind heparin/platelet factor 4 complex ----> endothelila injury and platelet activation (prothombotic state)

78

bernard-soulier diesease

platelet abnormality

defect of platelet adhesion

autosomal recessive

lacking glycoprotein Ib

79

glanzmann's thrombasthenia

platelet abnormality: defect of platelet aggregation

autosomal recessive

lacking glycoprotein IIb/IIIA

80

TTP thrombotic thrombocytopenic Purpura

platelet abnormality: antibodies direct against the von Willebrand factor cleaving protease, ADAMTS-13

81

Idiopathic thrombocytopenic purpura ITP

platelet abnormality

antibodies directly agianst platelets

82

aplastic anemia/ pancytopenia

platelet abnormality

all the cell lines are gone- marrow destroyed

83

von Willerbrand's disease

coagulopathy

deficiency of von Willebrand's antigen

easily bruised, nosebleed, etc.

most common bleeding disorder

84

factor VIII deficiency

hemophilia A

x-linked recessive most common hemophilia

85

factor IX deficiency

hemophilia B

x-linked recessive coagulopathy

86

factor XI deficiency

hemophila C

mildest hemophilia associated with the EJws

87

factor XII deficiency

not clinically important

neither is the presence of lupus anticoagulant

88

purpura petechia and ecchymoses are most likely

platelet deficiency

89

trouble stopping blleding most likely

coagulation factor deficiency

90

DIC

NOT a specific diagnosis

widespread activation of the caogulation system (thrombin) that from tiny thrombi throughout body leading to thrombocytopenia and consumptive coagulopathy (organ failure and bleeding)

91

peripheral blood smear of DIC

observe sheared RBC

92

what do D-DIMER assays measure

plasmin-cleaved insoluble cross-linked fibrin (indirect measure of thrombin which is required for fibrin formation)

used in diagnosis of DIC