Coagulation and Fibrinolysis Flashcards
proteases
2,7,9,10
11,12,13
exist as zymogens
serine proteases
cofactors
5, 8
VWF
Tissue factor-bound to cell
clottingorer
2, 10, 5,7 9, 8 ,12 ? cjecl
steps of hemostasts
aterliolary vasoconstriction
priary hemo
secondary hemo
regulation of thrombous fomration
-antithrombotic activity
local vasoconstriction
occurs becuase of endothelin (vasoconstictor)
natural mechanism to restrict blood flow
decrease sheer force-allow paltelets to get in there
primary hemostasis
all about paltelets
platelet adhesion, shape chage, granule release, recruitment, aggregaton
vWF
how to platelets form
fro megakaryocytse
not much nucelos-may contain RNA/proteins important for thier functn
platelets size
size correlates with reactivity
larger platelets are prothrombotic
monolayer normal vs injured
nomral-platelets just fly around in blood
injured-basement membrane exposed-strucutreal and ecm proteins are recognied-collagen and VWF
- platelts attach here-become activitated-silent receptors that undrego conformational change and can bind
- degranulate-vwf and other trucutra/activating factors pop out
- degranulate weh nattach to basement membrane
4 steps for formation of platelet plug
adherence, activaion, granule release, change shape, aggregation
vwf disease
defeinceny of vwf
can happen b/c less or mutated vwf
or problems in receptr for vwf
result in bleeding
vwf fucntin
large circulating protein
made in endo cells and platelets
primary and secondary hmostatis
at site of injury-vwf binds to exposed collagen
- facilitates platelet tethering
- platelets without vwf- attach but not as stong as with vwf
chaperone for factor 8
what happens after endo exposed and vwf binds
sheer causes multimer to expose (VWF)
-platelets can now stick down and ttch to colagen at basement membrane
what releases vasocontrsictors/platele activators
collagen and platelets
whats inside platelets
have graunlaes that store adhesive proteins, prothrombotic factors, cytrokines, growth factor
how to treat angina
(reduced blood flow to heart)
target platlet activation/stickiess
-decrease platelet adhesion and allow more blood flow
petehciae
spontaneous small bruising, small amounts of blood leak out of blood vessels
petechaie vs purpura vs eccymoses
smaler tolarger bruise caused from not enough platelet
Platlet trophic factors + whjat happens when platelet count low
maintain cell-cell contacts
when platelets counts is low-rbc ca go through hole thatnormally platelet would be in the way of
secondary hemostasis
first hemostasis is not very strong-need stong sealet in form of cross-linked fibrin
how is fibrin create
clotting cascade results in formation of fibrin from fibrinogen
- small part of fibrinogen cut off
- rest of ibrinogen multimerizes to make fibrin
what does factor 13 do
cross links fibrin
why are serine proteases zymogenic
need to be ready to be recruited at moments notice
intrinsic vs extrinsic pathway
intrinsic-beginss with accumulation of factor 7 and tissue factor
-factor 12 activated with negative charge-nothing else needed
extrinsic-need ttissue factor to make blood clot
DONT FUCKING FORGET
THAT THIS IS HAPPENING ALL THE TIME IN CELLS
Extrinxic pathway
vessel wall injury exposes TISSUE FACTOR and increases TF expression by endothelial cells/monocytes
circulating factor 7 binds to TF, becomes 7a
7 activates 9
9 activates 10
10 activates 2
thrombin is 2a (only moderate amount)
-not as much as when 8 comes into play
2a cleaves fibrinogen to fibrin
TF
tissue factor-normally not exposed or exist in blood stream
exist in sub epithelium
ebola
tells body to make tissue facgtor-consupmotion of clotting factors-have herorages becuase none left
factor 7
always a little active-but low concentration so cant initate coagulation witout tssue factor
common pathway
9a activating 10,
10a activating 2 (prothrombin) to make 2a
-apparently small amount of thrombin formed
2a cleaving firbrinogen to make fibrin
thombin activiates
cleaves fibinogen to fibrin
activates more factor 9 and 8
factor 8
sex linked recessive disrder
gets activated by thrombin-criculates in complex with VWF
VWF chaperones factor 8
-stabilies and extends half life of factor 8 (60 fold)
soluble cofactor-functions as catalyst
VWF functions 2
VWF links platelets of subendothelial BM
Binds to and stabilizes factor 8
factpr 8 and 9
form complex
activate factor 10 ALOT FASTER
-alot more thrombin and fibrin
factor 8 or9 defecenincy
8-hemophilia a-factor 8 defecineny-sponteous bleeding
defecinecy in 9-hemo b-not as severe
both are x linked recessive
factors 10 and 5
accelerates prothrombin activation
complex together-converrts at 300000x faster
factor 5
soluble co-factor
catalyst
activated by thrombin
accelerates factor 10a conversion of protrombin (2) to thrombin
three complexes essential for coagulation
tissue factor, factor 7a,9=10 initiation
factor 9a, 8a=10 amplifciation 1
10, 5a=2 (prothrombin) amplification 2
idk about this one….
which factors are depend
2, 7, 9, 10 (serine proteases)
proteins C, S, z-ANTICOAGULATNATS
what does vit k do
2, 7, 9, 10 all have glutamates at amino terminus-need additional negative charge
-probded by carboxlation (vitamin k dependent)
net negative charge-enables interaction with Ca and membrane interaction
vitamin k is oxized then reduced-then can give carboxylation
warfari
blocks oxidation of vit k
vitamin k deficiency
cased by giving antibiotics to newborns-kill thier vit k synthesizing colonic flora
intrinsic pathway activation
contact activaton with negative glass tube
tf independent
Intrinsic pathway proteins
factor 7
high molecular weight kiniogen
factor-11-ONLY ONE THAT RESULTS IN EXCESS bLEEDING IF DONT HAVE
Prekallikrien
how is factor 12 activatd
contact with negatively charged surface (usualy phosphate residues)
]normall just circulating in blood stream
HMKG use
required for facttor 11 to attach to negatively charged surface and become factor 11a
factor 11a
binds and activates factor 9, which actviates 10, which cleaves prothrombin to thrombin, to make fibrin
thrombin activates more factor 11
functions in propogation phase of clot-in conjunction iwth 9a
-assocated with hemo c-minor
11 and 5 and 8 and 9 and 11 (but mostly 11 and 5 i htink)
both activated by thrombin to amplify (check)
fibrinogen vs fibrin
only a small cleave
fibrin when cleaved
can self assemble into multimers and into fibers
- spontaoues
- essentally the glue that holds platlets totgher alliowing for clotting
factor 13
transgluaminase
activated bythrombin
- cross links fibrin chains
- extensive cross-linking increases fibrin from dimers to trimers to tetramers
- defects very rare-need this or die
covalent bonds
how to get coagulation to shut off
coagulation/cofactrs adhere to membranes-confined process locally to area of injury
-thrombomodulin
thrombomoldulun
high affinity recepotr for thrombin 2
- meutralizes thrombins procoagulalant activity
- cofactor for thrombin dependnt activation of protein c
always at surface of cell
thrombin sink-stops thrombin from getting too far away from site of cut
Protein c
turns of factors 5 and 8 *(cleave but not sure)
thrombin+ thrombomodulin complex activate protein c
protein c and s
inhibiors of pro-coagulant system
-anticoaulants
vitamin k depedent
activated by thrombin+thrombomodulin complex
factor 5 leiden mutation
single base pair substituion
icnreased resistance o protein c
-ensures 5 does not get turned off
inherited thrombophilic disorder-cuases clotting to occur
5% higher chance for dvt
fibrinolysis
as clotting becomes activated, fibrinolysis becomes actiacated
- creates force that keep clot from gettin into ECM
- also keeps clot from spreading
plasminogen
activated by thrombin or TPA
becomes plasmin (when activated)
degreads fibrin and keeps clot from spreading
TPA
tssue plasmonogen activator
used to chew up and spit out clots in MI or stroke
