Flashcards in Hemostatsis/Coag Cascade Deck (81):
1
Phases of Hematostatsis
Primary Hematostasis
Secondary Hemostatsis- coagulation phase
Termination of coag rxns
fibrinolysis
2
result of primary hemostatsis
platelet plug formation
3
result of secondary hemostatsis
fibrin formation/stabilization
4
vascular injury exposes
subendothelium (procoagulant)
5
first step of primary hemostasis
vasoconstriction
6
formation of platelet plug requires
vWF
platelets
fibrinogen
7
where is vwf synthesized
endothelial cells
megakaryocytes
8
what is vwf stored as large multimers in
weibel-palade bodies in endothelum
alpha granules in plasma cells
9
lifespan of a platelet
7-10 days
10
where is fibrinogen made
liver
11
3 categories of alpha granules
adhesive proteins
coagulant proteins
growth factors, selectins
12
adhesive proteins
fibronectin
vWF
13
coagulant proteins
fibrinogen
factor V
14
growth factors, selectins
PDGF, VEGF
P-selectin
15
dense
adp
atp
serotonin
calcium
16
Thromboxane A2
more vasoconstriction
platelet agg
platelet activation
17
fibrinogen binds to platelet via
GpIIb/IIIa R
18
platelet factor 3 activity
exposure of PS and PE on platelet surface allows coag factors to bind to platelets
19
secondary hemostasis is required to form
thrombus
20
fibrin
forms a mesh around platelets, stabilizes the platelet plus while blood vessel heals
21
coagulation factors circulate as
inactive (zymogen) as well as active forms
22
which factors are not synthesized by liver
Factor VIIII
vWF
23
what is factor VIII synthesized by
liver
vascular endothelium
24
dep on vit K for fx
2,7,9,10,S,C,Z
25
protein S, C, & Z are
endogenous anticoagulant factors
26
tissue factor
monocytes circulate in resting state and are stimulated by vascular injury to produce TF-- physiological
27
TF forms a complex w/ circulating factor VII
activation of factor VII to VIIa
28
factor Ix requires
Ca and factor 8 as cofactor to bind to platelet membrane phospholipid
--accelerates activation of factor X to Xa by 100,00 fold
29
factor 2
prothrombin
30
factor 2a
thrombin
31
prothrombinase complex
factor Va anchors factor 10a and prothrombin (2) in close proximity on platelet phospholipid
32
thrombin burst
small amount of thombin feeds back and activates XI to XIa by catalyzing 9-9a and 10-10a, etc
33
clotting functions of thrombin
hydrolyzes fibrinogen to form fibrin
involved in many feedback activities
activates factor 8 to stabilize fibrin
protects established clot (thrombus) from fibrinolysis
inhibits coag when needed
34
controlling coagulation
-hemodillution
hepatic clearance
endogenous anticoags
fibrinolysis (plasmin)
35
Antithrombin
produced by liver, endothelial cells
binds and inhibits factor Xa and thrombin
36
heparin
increases anticoag activity of AT
37
activated protein C
thrombin binds thrombomodulin on endothelial cell surface changing its structure--> can now activate proten C but not others
APC + S-->inactivates factors Va and VIIIa
38
tissue factor pathway inhibitor
produced by endothelial cells
binds to and activates factor Xa
inactivates TF/VIIa complex
39
plasminogen
synthesized by liver and circulates--> binds to fibrin-->cleaved to plasmin
40
plasmin cleaves
fibrin-->D dimers
41
PAI-1
stored n platlets; inhibits tPA
42
alpha 2 antiplasmin
major inhibitor of plasmin
43
plasma
fluid fraction of unclotted, whole blood
contains all soluble components including coag factors, fibrinogen, etc
44
serum
fluid remaining after blood has been allowed to clot; contains all soluble components except for coag factors
45
coag factors are performed with
plasma
46
citrate
anticoag for coagulation tests
binds Ca making ti unavailable for coagulation reactions
47
bleeding time
measures primary hemostasis
48
PFA-100
measures how long it takes for platelets to clot
49
PT
time required to form fibrin clot when citrated patient plasma is added to thromboplastin Ca mixture
measures extrinsic
50
PT normal time
12.2-14.8
51
INR
standardizes PT
=patient PT/mean PT
normal=1
anticoag=2-3
52
aPTT
activated partial thromboplastin time; not natural- lab driven
time required to form fibrin clot when citrated patient plasma is added to PHOSPHOLIPID+ Ca+ contact activator
53
contact activators
glass
kaolin
celiate
ellagic acid
54
aPTT is prolonged with
issues in the common and intrinsic pathways
55
prolonged PT could mean
mild liver disease
early vitamin K def
early warfarin
factor 7 issue
56
prolonged aPTT could mean
hemostatic factor dysfunction (hemophilia)
vWF disease
heparin
57
prolonged PT and PTT
severe liver disease
consumptive coagulopathy
hemodilution
severe vitamin K def
therapeutic warfarin
hypofibrinogenemia/dysfibrinogenemia
direct thrombin inhibitors
58
therapeutic warfarin inhibits factors
2,7,9,10
59
mixing studies and inhibitor
doesnt fix clotting
60
mixing study and factor def
fixes clotting
61
how does thrombin clotting time test work
exogenous thrombin + patient plasma
62
thrombin time prolonged in
hypofibrinogenemia
dysfibrinogenemia
heparin, thombin inhibitors
63
what does thrombin clotting time detect
fibrinogen abnormalities
64
D-dimer is a maker of
clot formation/breakdown
65
three ways to get a quantitative thrombocytopenia
increased destruction
sequestration in spleen
decreased production
66
what does heparin do to platelets?
low platelets, but no bleeding-- paradoxical state of hypercoagulation
67
8 ways to get destruction/consumption of platelets
autoimmune mediated processes
medications
DIC
TTP
HELLP syndrome in pregnancy
HUS
severe bleeding
vWF, type 2b
68
enlarged spleen can hold up to
90% of platlets
69
enlarged spleen vs normal spleen and platelets
normal spleen- can hold 30%
enlarged spleen- 90%
70
come causes of splenmegaly and platelet sequestration
portal htn (hepatic cirrhosis, thrombosis of portal or hepatic vein)
myeloproliferative diseases
71
decrease in production of platelets (6)
primary bone marrow disorders (leukemia, aplastic anemia, etc)
bone marrow infiltrative process
viral infections (hep, hiv)
toxic exposures to megakaryocytes
nutritional deficiencies
hereditary disorders
72
6 categories of hereditary qualitative disorders
bernard-soulier
glanzmann thromboasthenia
storage disorders
delta granule disorders
signal transduction disorders (decrease in release of granules)
scott syndrome
73
berniar soluier disease
defect in GP1B R
74
Glanzzmann Thrombasthenia
defect in GPIIb/IIIa R
75
storage disorders
gray platelet syndrome (absent alpha granules)
quebec platelet syndrome (inc uPa in alpha granules so they are degraded)
76
delta granule disorders
decrease in release of ADP due to hermansky pudak, chediak-higashi syndrome
77
scott syndrome
defect in assembly on platlet surface
78
8 ways to get aquired qualitative platelet disorders
aspirin
nsaid
gpIIb/IIIa inhibitors
ADP R inhibitors
SSRI
Herbal
uremia
myeloproflierative disorders
79
aspirin
irreversibly acetylates cyclooxygenase-->results in inhibition of thromboxane A2 production
80
GPIIb/IIIA inhibitor
abciximab
81