Secondary hemostasis
o coagulation factor response
platelets
vessels
coagulation factors
HEMOSTATIS OVERVIEW
Hemostasis:
Primary hemostasis
o platelet and vascular response (vessel
injury)
o initiated by exposure of platelets to
subendothelial components (blood vessel):
collagen
microfilaments
basement membrane
o acute injury
change shape
centralization of organelles
ADP
Promotes 2 platelet
aggregation
Recruits additional
platelets
ATP
Serotonin
Further vasoconstriction
Stop bleeding;
Allow for vessel repair
(through formation of
a stable fibrinplatelet plug)
coagulation factors:
o enzyme precursors (zymogens)
selectively hydrolyze
arginine- or lysinecontaining peptide bonds
o nonenzymatic cofactors
Zymogen activation:
o conformational change (1)
Enhance zymogen
activation process
Zymogen -> serine proteases
o Biochemical amplification of the coagulation
process
o Production of serine proteases - rate of
further transformation of zymogens;
activity levels of cofactors
Kinin
o Chemotaxis
o Sensation of pain
o Mediate inflammatory responses
o Increase vascular permeability
o Vasodilation and hypotension
o Induce contraction of smooth muscle
o Contact activation phase (intrinsic pathway)
o C activation
Kinin system
o contains factors that are activated by the
coagulation and fibrinolytic systems
o factors:
kallikrein
conversion of HMWK to
kinin
fibrinolytic system
kinins: bradykinin
2.
3.
Contact group
Vitamin K
o Necessary to -carboxylate the
preformed enzyme precursors of
factors II, VII, IX, and X
o -carboxylation
highest MW
most labile
consumed in coagulation
cofactor in intrinsic
pathway
produced in liver
antihemophilic factor
o VIII:vWF important in normal
platelet function
o HMW portion:
synthesized by the
endothelial cells and
megakaryocytes
PHOSPHOLIPIDS CONTRIBUTING TO
COAGULATION
Tissue Factor
Factor XI activation
Factor IX activation
tissue factor
o tissue thromboplastin
o from cell membranes into plasma
factor VII
o -carboxyglutamic acid residue of factor VII
binds the PL portion of tissue factor in the
presence of Ca
alternate pathway
Xa-Va-Ca-PL
V to Va by thrombin
prothrombin to thrombin
o common pathway
activator:
autocatalytic
acts on fibrinogen
enhanced by Ca
thrombomodulin
cofactor protein S
stimulates fibrinolysis (
plasminogen activator
activity)
Activated protein C
inhibits tissue
plasminogen activator
inhibitor (TPAI)
prevention of interference
with plasmin production
thrombin + thrombomodulin = no
longer enhance factor V or VIII
activity, stimulate platelet
aggregation, or fibrinogen
conversion to fibrin
vulnerable to plasmin
STEP 3: clot stabilization
o requires factor XIII, Ca, and thrombin
o thrombin activates XIII
coagulation
to plasmin by plasminogen
activators
liver
increased concentrations
inflammation
activate plasminogen
intrinsically
o Extrinsic Plasminogen Activation
urokinase
therapeutic destruction of
thrombi
activates plasminogen
induce fibrinolysis
streptokinase
plasminogen part of any clot; tendency of fibrin to
absorb plasminogen
excessive free plasmin antiplasmin is depleted;
plasmin begins destroying components other that
fibrin
o
o
FDP
Inhibit coagulation
Form incoagulable or slowly coagulable
complexes with fibrin monomers or
fibrinogen
COAGULATION
o Antithrombin III (AT-III)
Conformational change
Heparin
rate of factor
inactivation, NOT
magnitude
Heparin-like substance
Acidic
mucopolysaccharide
Naturally-occuring heparin
Heparan sulfate
Inhibits fibrinolysis
Vitamin K-dependent
Cofactor S
Greatly enhanced:
thrombin +
thrombomodulin ; (1:1)
with protein S
Thrombin specificity is
altered (when +
thrombomodulin)
Plasmin + 2-antitrypsin
similar to thrombin-AT-III
complex
inactivating serine
protease
Fibrin
o