L51 Hemostasis II Flashcards
Coagulation Factor characteristics
serine proteases, zymogens until activated
synthesized in the liver
V and VIII can be taken up by platelets and stors in alpha granules to be released later
TFIII in many cell types, mostly by subendo cells and resides on the plasma membrane
-ONLY PROTEIN FACTOR THAT DOESNT REQUIRE CLEAVAGE
Special factors (3)
I Fibrinogen (crosslinks to form mesh)
IV Calcium Common cofactor
XIII transglutaminase
-ultimate goal: cleave fibrinogen to fibrin to make a good clot
VII
IX
X
II
XII
XI
GLA-post trans vitK dependant carboxylation, to enhance protease interactions with plasma membrane binds TF activates IX, X activates 10 activates II II THrombin
bottom NOT GLA
activates XI in vitro
activates iX (booster)
cofactorsL III VIII V
warfarin
affects VII IX X II in decreasing order
(GLA-vitK dependent carboxylation)
warfarinL interfecres with Vit K recycling in carboxylation reaction reducing the efficiency of the coagulation complex
teh shorter the half life, the sooner its function is compromised
vitK deficiency: bleed out…bad clot formation
coagulation complex requires four components
protease
protease cofactor
calcium (IV)
PL-
THEN ITS MAXIMAL
three coagulation complexes
Initiation: TF VIIa
Tenase IXa VIIIa
Prothrombinase complex: Xa Va
Tenase and prothrombinase primarily take place in platelets
Initiation and amplification
endo cells
TF from damaged endothelial binds VII
VII autoactivated to VIIa
TF/VIIa + Ca + PL = initiation complex
Cleaves IX — IXa (TENASE)
AND
Cleaves X —Xa directly
Xa has SOME ability to activate thrombin, plus Va is being released from activated platets
Xa/Va much more efficient prothrombin to thrombin conversion
why use each cascade
tenase to prothrombinase through IXa mostly on activated platelets
INITIATION (start clot formation)
prothrombinase DIRECTLY through Xa mostly on subendo cells
smaller burst of thrombi activates V and VIII, more platelets and Factor XI (amplification)
hemophilia A and B
A
- defeciancy in FACTOR VIII
- 80% of hemophilia cases
mimicked by von willebrand def (vWF acts to stabilize VIII in circulation and extend its 1/2 life)
B
deficiency in FActor IX
20% hemophilia cases
variable symptoms
joinds succeptible bc joints are low in TF
Fibrinogen activation
fibrinogen firculates as a dimer joined at the center by an E domain and D domains at each end
thrombin cleaves alpha and beta fibropeptides from teh E domail allowing E to bind to a complementary D domain
POLYMERIZE
ionic bonds
Harden the clot
VIIIa transglutaminase produced in two places
circulatiing where it is activated by thrombin
platelet granules where it is activated by calcium
XIIIa forms crosslinks between lysice and glutamine residues to covalently bond the fibrin strands HARD CLOT
Plasmin
Fibrinolysis
activation of plasminogen stim in two ways
t-PA (plasminogen activator)
-recombinant t-PA=clinical anticoagulant” straptokinase
and UROKINASE
procoagulantsL endogenous: plasminogen activator protien PAI
-prevents activation of plasminogen whereas a2 asntiplasmin neutralizes free circulating plasmin
D dimer
one product of clot dissolution is D dimer
two crosslinked D domains
quantitiation of D dimers in blood indicates occurance of thrombus formation and breakdown
-rule out DVT or PE
used to diagnose and monitor disseminated intravasular coagulation (DIC) in conj with additional lab coagualtion tests (PTT PT, platelets)
Thrombomodulin TM
protien located on endothelial cell surfaces that can binds thrombin IIa
this binding removes thrombin from circulation
FURTHER: thrombin/TM complex becomes ANTI coagulant , by cleaning and activating Protien C
Activated Protien C APC degrades Va and VIIIa
-prevents inappropriate thrombus
slide 29
ATIII
IIa, Xa IXa
slide 30
