4) Biochemistry of factors Flashcards
3 biochemical categories of coag proteins based on function
substrate
cofactor
enzyme
each zymogen is first a ———– (proenzyme)
substrate
2 biochemical changes that activate a zymogen
proteolytic cleavage
conformational change
only substrate acted on which does not become an enzyme
fibrinogen
enhance function of factors they interact with
cofactors
tissue factor is cofactor for…
VII
V is cofactor for…
X
VIII is cofactor for…
IX
HMWK is cofactor for…
prekallikrein
XIIIa is not a serine protease but rather a…
transglutaminase
why does ↓ XII lead to clotting?
↓ kallikrein, ↓ double chain u-PA
↓ fibrinolysis
PIVKAs
(dysfunctional) proteins induced by vitamin K absence
3 groups of factors based on physical properties
contact factors
prothrombin proteins
fibrinogen factors
- activation of intrinsic system in vitro
- activated by negatively charged surfaces
- no essential role in vivo in activating cascade
contact factors
contact factors
- XII
- XI
- prekallikrein
- HMWK
- vitamin K dependent
- low MW
prothrombin proteins
prothrombin proteins
- II (prothrombin)
- VII
- IX
- X
why is vitamin K needed for the prothrombin proteins?
- contain glutamic acid
- undergoes gamma-carboxylation to become gamma-carboxyglutamic acid
- becomes Ca-binding receptor
- without K, carboxylation is disturbed
- no Ca binding
action of warfarin
inhibits vitamin K dependent factors
- not found in serum, consumed in clotting
- high MW
fibrinogen factors
fibrinogen factors
- I (fibrinogen)
- V
- VIII
- XIII
fibrinogen factors are acted on by ——- during coagulation
thrombin
Hageman
XII
plasma thromboplastin antecedent
XI
Fletcher
prekallikrein
Fitzgerald
HMWK
stable factor
VII
Christmas
IX
Stuart-Prower
X
labile factor
V
anti-hemophilic factor
VIII
fibrin stabilizing factor
XIII
2 forms of VIII found in body
- VIII:vWF —inactive form carried by vWF (stabilized)
- VIII:c —active form that breaks away when activated by thrombin
function of vWF in secondary hemostasis
carrier protein for VIII
extrinsic tenase
TF-Ca-VIIa
“extrinsic”
TF is not normally found in blood
“intrinsic”
factors are already present in blood
intrinsic tenase
PF3-IXa-Ca-VIII
2 ways to activate intrinsic pathway in vivo
- by the extrinsic pathway at factor IX
- by thrombin at factor XI
prothrombinase
PL-Xa-Ca-V
thrombin stimulates endothelials to…
release vWF
express TF
3 steps of formation of insoluble fibrin clot from fibrinogen
- hydrolytic cleavage of A & B peptides
- spontaneous polymerization of fibrin monomers
- stabilization by XIIIa (D crosslinking)
increases resistance to proteolytic digestion by plasmin
D crosslinking
steps of fibrinolysis and FDPs
- small fragments cleaved, forming fragment X
- D cleaved, forming fragment D + fragment Y
- Y cleaved, forming D and E fragments
marker for pathologic clotting, especially DVT
D-dimers
D-dimer test has —— negative predictive value and ——- positive predictive value
good
poor
test systems cannot detect ——–
XIII
inhibitor of thrombin, Xa, IXa, XIa, and XIIa
antithrombin II
heparin greatly enhances effect of —— on thrombin and Xa
antithrombin II
thrombin activates protein C when…
in high concentration and bound to thrombomodulin
important in inflammation, vascular permeability, and chemotaxis
kinin system
pathologic condition of developing Ab to factors
protease inhibitors
bridge from extrinsic to intrinsic (2)
- extrinsic tenase activates IX
- thrombin activates XI
no enzyme activity (cofactors)
most labile
V
VIII
effect of vW disease on secondary hemostasis
VIII deficiency
