PLATELET
hemostasis
blood vessel
subendothelial ECM: collagen, basement membrane, VWF, microfibril, elastin, mucopolysaccharides, fibronectin, laminin
role of endothelial cells
antithrombin properties:
produce prostacyclin & NO
secrete CD39 (ADPase)
glycocalyx
TFPI
receptor for thrombin & PC
tPA & uPA
prothrombin:
secrete VWF
increased expression of adhesion molecules
express TF
secretion of PAI-1 & TAFI
injury:
vasoconstriction
reduce blood flow to affected area
prevent exsanguination
facilitate plat & coagulation contact with TF & subendothelial collagen
amine & TXA2
platelet
normal: 250x10^9/L
lifespan: 8-12d
content
peripheral zone: glycocalyx
sol-gel: utubule coil, open canalicular system, dense tubular system
inner organelle: granules, mitochondria, actin
production site: BM
time: 7-10d
regulator: TPO in liver, kidney, BM
VWF
multimeric
cleave by ADAM
binding site: collagen, plat, heparin, FVIII
synthesis site: endothelial cells & megakaryocytes
store as globular protein - WB bodies
supp plat adhesion
protect FVIII
primary hemostasis
adhesion: plat tethering, GP1b-IX-VI, VWF, collagen
activation: interaction of GP2b3a, plat change shape, granules secretion, expose to phosphatidylserine, TXA2 synthesis
aggregation: crosslinked plat thro fibrinogen bridge, VWF, GP2b3a
procoagulant activity
coagulation factors
prothrombin to thrombin
fibrinogen to fibrin
unstable to localized stable plug
cell based model
protease + cofactor + phospholipid + calcium
secondary hemostasis
extrinsic/initiation
intrinsic/amplification: thrombin burst
common/propagation
natural inhibitors
TFPI: extrinsic
AT: serpin, inhibit FIIa, IXa, Xa, XIa, XIIa, TPA, urokinase, trypsin, plasmin
PC & S: activated by thrombomodulin, inhibit cofactor FVa, FVIIIa, PAI1
a2 macroglobulin, a2 antiplasmin, a1 antitrypsin, C1 esterase
fibrinolysis = tertiary hemostasis
plasmin degrade fibrin/fibrinogen to FDP/D-dimer
clot dissolution
serpin: plasminogen, tPA, uPA
inhibitor serpin: a2 antiplasmin, PAI
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