4.9 Clotting Cascade Flashcards Preview

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Flashcards in 4.9 Clotting Cascade Deck (109):
1

what is the last thing platelets do

secrete PL layer which is important to localize the lesion

2

what else helps localize where you're going to clot

collagen and binding of vonWB

3

how many clotting factors are there

13

4

goal of clotting factors

generate thrombin

5

action of thrombin

cleaves fibrinogen to make fibrin

6

Componets needed for clotting

enzyme, substrate, cofactor (like Ca), and PL surface

7

1

fibrinogen

8

1a

fibrin

9

2

protrhombin

10

2a

thrombin

11

3

tissue factor

12

4

Ca ion

13

5

prothrombin accelerator

14

6

doesn't really exist, is actually just 5a

15

7

proconvertin,
co-thromboplasmin

16

8

antihemophillic factor

17

9

christmas factor

18

10

prothrombinase, stuart prower fac

19

11

thromboplasmin antecedent

20

12

hageman factor

21

13

fibrinase,
fibrin stabilizing factor

22

Intrinsic

12 11 9 -->10 2 1 8

23

Extrinsic

3 7 --> 10 2 1 8

24

Crosstalk areas

7 also to 9, 10 also to 7

25

Extrinsic path begins with

endothlial ijury releaseing 3

26

3 is a cofactor that

complexes with 7 forming 3/7a

27

3/7a activates

10 to 10a (in the same ways as 9a)

28

at the 3/7a step a burst of

thrombin is produced_this is needed early on to form the secondary plug

29

Intrinsic path begins with

exposure of collagen causing a complex of
prekallikrein,
HMW kininogen,
factor 9, and
factor 7 to from

30

Prekallikrein is converted to

kallikrein

31

Kallikrein activates

12 to 12a

32

12a activates

11 to 11a and cleaves more prekallikrein to more kallikrein

33

11a activates

9 to 9a

34

9a activates

10 to 10a on surface of platelets

35

10 can only be activate by 9 a if

the tenase complex is fromed on the PL layer of the platelet plug

36

tenase complex

8a, 9a, 10, Ca

37

8 is activated by

early fromed thrombin from extrinsic pathway

38

8a is the

receptor for 9a and 10 (cofactor for cleavage of 10 by 9a)

39

2 --> 2a (prothrombin --> thrombin)

10a, 5a, 2, and Ca complex on PL to allow 2 to be cleaved into 2a

40

5a is a cofactor in the formation of 2a similar to

8a in the formation of 10a

41

thrombin activates

8 to 8a

42

function of 8a

a transglutimase that crosslinks fibrinmaing it more stable

43

thrombin activates factors

11, 8, 5, and plays a major role in early platelet activation

44

thrombin also activates

protein C

45

Protein C

in the presence of protein S and PL degrades 5a and 8a --> INHIBITORY PATH

46

antithrombin 3 inhibits

thormbin (major) and 9a, 10a, 11a, 12a

47

heparin enhances

antithrombin 3 activity 1000 fold

48

warfarin/comadin

anticoagulation factor

49

vit K

cofactor in clotting and warfarin inhibits the thing that Vit k binds?

50

Ca is needed for clevage of

11 by 12a, 9 by 11a, 10 by 9a, 2 by 10a

51

5a is needed for

clevage of 2 by 10a

52

PL layer needed to gererate

10a and 2a(thrombin)

53

slide 45

picture of this

54

from which factor onward is there an amplification and crossover of intrinsic and extrinsic paths

9a

55

severe deficiences in which factors do NOT result in serious bleeding

12 and 11

56

Thrombosis

pathological coagulation of blood, number 1 cause of mortality and morbidity in USA

57

Virchow's Triad

endothelial injury,
stasis/turbulence,
hypercoagulability

58

endothelial injury

even just stress and not complete death of endothelial cells can cause change to the phenotype

59

Stasis/turbulence

understand moving stasis - formation of eties

60

hypercoagulability is determined by

genetic and environmental factors

61

Endothelial injury can be due to

trauma,
ischemia (MI),
atherosclerosis,
endotoxins,
cigarette smoke,
autoimmunity

62

Common pathway

exposure of subendothelial connective tissue to plasma and/or phenotypic changes in endothelial cells

63

on a smear of a heavy smoker

you see weird looking cells that are killed endothelial cells

64

left ventricle thrombus

get into carotids leading to stroke

65

right ventricle thrombus

getin into capilaries of lungs

66

septal defects and thrombi

normally if there is a septal defect the pressure on the right is more than the left so flow occurs nromally, but if the valsalva maneuver occurs then there can be a reversal of flow causing problems

67

stasis/turbulents disrupts

laminar flow

68

stasis/turbulence stresses

endothelium

69

stasis/turbulence diminishes

anticoagulants

70

stasis/turbulents concentrates

procoagulants

71

does moving stasis disturb flow

no

72

stasis/turbulence excludes

inhibitors

73

during stasis/turbulence

more activate clotting factors, and potential for clotting is reduced, along with inhition of clotting

74

where is the most common place for thrombotic events

deep veins

75

why is the most common place for thrombotic events the deep veins

bc under the valves of deep veins there are eties of turbulence

76

hypercoagulability can occur due to

inherited deficiencies in anticoagulants,
heparin induced thrombocytopenia,
antiphospholipid antibodies,
medications/prostheses,
sickle cell disease

77

how does heparin induce thrombocytopenia

when a large MW heparin is givin,
Ab forms agains it that cross react with platelets.
So the next time you give the heparin there is a huge rise in Ab that bind the platelets and use them up

78

what disease is associated with antiPL antibodies

lupus, seen in young wooen - these tend to coressreact with platelets too

79

hypercoag - leiden mutation for factor 5( replacing glut for arg) makes factor 5 resistant to ceavage by

protein C - seen in 2 - 15% of caucasians

80

hypercoag - mutation in prothrombin causing

prothrombin to inc - seein in 1-2% of population

81

homocysteinemia is correlated with_..and can be treated with_..

cardiovascular disease__.vitamins

82

deficiencies in Protein S and C

hypercoaguable bc no cleavage of factor 5

83

who should be suspected for inherited hypercoaguable states?

patients under 50 who thrombose with no underlying cause

84

hypercoag - fibrolytic activity

this is an inhibition of coagulation bc it eats up the ealy nascent clots - loss of this ability makes you more hypercoaguable

85

effects of aniPL

recurrent arterial/venous thromboses,
miscarriages,
cardiac valve vegetations,
thrombocytopenia

86

post mortem clots

chicken fat and currant jelly due to gravity

87

antemortem clots

Lines of Zahn - blood is moving so it looks like its stirred with a stick

88

Mural thrombi

walled - in the walls of the heart

89

Fate of Thrombi

Propogation,
Dissolution,
organization and recanalization,
embolization

90

what does heparin do

helps to prevent propagation, it DOES NOT dissolve clots

91

Emboli

detached intravascular solid, liquid, or gas that is cared by blood to a distant site

92

99% of emboli are

are thromboemboli

93

other emboli

nitrogen,
air,
fat,
artherosclerotic plaque

94

Pulmonary thromboembolism

clinically important event and frequent cause of sudden death,
may or maynot cause infarction,
majority from deep leg veins

95

organs least prone to infarction after thromboembolism

lung and
liver

due to collateral blood supply

96

so probability of infarction goes up as you go more

distal

97

in pulmonary thromboembolism sudden death is due to more

proximal events ---- tend to be bigger and kill you

98

in pulmonary thromboembolism, infarction is more likely to occur

in more peripheral (distal?) tissue due to capillary drop off

99

if a clot formd after death

it would fall away from the walls

100

if the lung tissue still looks healthy when you see a pulmonary thromboembolism

this means the person died suddenly with no time to develop disease and destroy tissue

101

difference btw infarct and hemmoragic thromboembolism

infarct is rock hard bc tissue is dead and surrounding blood is pumping into dead tissue, but hemmoragic would be squishy

102

when you start to see organization there are

fibroblasts - tells you that the clot happened a long time ago

103

Fat emboli

occurs after crush injuries to bone where small liquid blobules of fat shower curgulation

104

what does fat do to platelets

activates platelets and injures endothelium leading to thrombosis

105

Amniotic fluid embolism

rare but dangerous bc of the biochemical effects of the amniotic fluid in the mother's blood, and squamous cells and lanugo hair lodge in the mother's pulmonary vessels, sends mother into shock, massive DIC

106

Gas embolisme most frequently occurs as

decompression sickness seen in divers and casson workers

107

to see symptoms of gas embolism need

more than 100cc gas

108

orthepedic surgery and gas emolism

since bone breaks are prone to vessels being exposed to air, air can be sucked into the patient bc the vessels in the bone are held wide open - if enough air comes in it can kill the patient

109

Arterial emboli arise from

most arise from mural thrombi in heart, other form
aneurysms,
artherosclerotic plaques, or
valves