4.9 Clotting Cascade Flashcards
1
Q
what is the last thing platelets do
A
secrete PL layer which is important to localize the lesion
2
Q
what else helps localize where you’re going to clot
A
collagen and binding of vonWB
3
Q
how many clotting factors are there
A
13
4
Q
goal of clotting factors
A
generate thrombin
5
Q
action of thrombin
A
cleaves fibrinogen to make fibrin
6
Q
Componets needed for clotting
A
enzyme, substrate, cofactor (like Ca), and PL surface
7
Q
1
A
fibrinogen
8
Q
1a
A
fibrin
9
Q
2
A
protrhombin
10
Q
2a
A
thrombin
11
Q
3
A
tissue factor
12
Q
4
A
Ca ion
13
Q
5
A
prothrombin accelerator
14
Q
6
A
doesn’t really exist, is actually just 5a
15
Q
7
A
proconvertin,
co-thromboplasmin
16
Q
8
A
antihemophillic factor
17
Q
9
A
christmas factor
18
Q
10
A
prothrombinase, stuart prower fac
19
Q
11
A
thromboplasmin antecedent
20
Q
12
A
hageman factor
21
Q
13
A
fibrinase,
fibrin stabilizing factor
22
Q
Intrinsic
A
12 11 9 –>10 2 1 8
23
Q
Extrinsic
A
3 7 –> 10 2 1 8
24
Q
Crosstalk areas
A
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
