Term
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Definition
Antithrombin III/endogenous heparins
Tissue factor pathway inhibitor
Proteins C and S |
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Term
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Definition
neutralizes heparin
Contained in alpha granules of platelets |
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Term
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Definition
sythesized and stored by platelets (alpha granules)
released on activation
promotes angiogenesis |
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Term
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Definition
cytokine, activated by integrins
stored in alpha granules of platelets |
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Term
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Definition
important in vasculogenesis and angiogenesis
stored in alpha granules of platelets |
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Term
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Definition
results in cell prolif, diff, survival
protects mucosa
stored in alpha granules of platelets |
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Term
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Definition
-endocytosed by MKcytes
soluble plasma glycoprotein, synthesised by liver
Soluble plasma glycoptn
Converted by thrombin into fibrin during blood coagulation
Cross-linked by factor VIII --> clot
*stabilized by thrombospondin |
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Term
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Definition
(Contained in alpha granules of platelets)
immunoglobulins, stored in alpha granules of platelets, involved in inflammation/wound healing |
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Term
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Definition
(also Contained in alpha granules of platelets)+ in ECM + plasma
glycoptn of ECM that binds to transmembrane integrins + EC components like collagen, fibrin, and proteoglycans |
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Term
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Definition
(Contained in alpha granules of platelets, synthesized by MKcytes)
-Cofactor
-Binds to activated platelets, activated by thrombin (spliced, 2 resultant parts bound together by calcium)
-Activated factor X needs activated factor V + Ca2+ to convert prothrombin--> thrombin
-factor Va is degraded by activated ptn C
-Needed for thrombin generation
Deficiency: predisposed for either hemorrhage or thrombosis |
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Term
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Definition
Platelet agonist
(Contained in alpha granules of platelets)
**One of the most potent activators of platelets*
Zymogen prothrombin becomes thrombin
Converts fibrinogen to fibrin
-Activates platelets via PARs (protease actiated receptors)1 and 4 (Gq and G12)
-clips a peptide on PAR to allow it to bind/activate itself
Activates Ptn C in presence of thrombomodulin to decrease clotting
-result in activation of membrane phospholipases and liberation of arachidonate (-->TxA2), mobil Ca2+, and actin-myosin intxns -->further platelet aggregation |
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Term
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Definition
(Contained in alpha granules of platelets)
One of the principal inhibitors of coagulation
Degrades Factor Va |
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Term
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Definition
(Contained in alpha granules of platelets, synthesized by MKcytes)
von Willebrand factor
-important in platelet adhesion to wound sites + binding to factor VIII
-binds to collagen when exposed
-binds to platelet GP1b when complexed to GPV and GPIX (best under high shear stress)
-broken down by ADAMTS13
-produced constitutively from Weibel-palade bodies (endothelium) and alpha granules of platelets (MKcytes)
-its D domain binds to factor VIII
-A1 domain binds to heparin, platelet GP1b receptor
-A3 domain binds to collagen
-C1 domain binds to platelet integrin αIIbβ3 when this is activated
-Monomers are cross linked by cysteine residues to large multimers |
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Term
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Definition
(Contained in alpha granules of platelets, synthesized by MKcytes)
-bound to vWf while inactive in circulation (makes it lasttttt, incr half life)
-degrades rapidly when not bound to vWf
-thrombin releases factor VIII from vWf |
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Term
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Definition
(Contained in alpha granules of platelets)
metalloprotease that cleaves vWf to be broken down by other proteases |
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Term
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Definition
aka thrombin-sensitivie ptn (TSP-1): released from platelets that have been stimulated by thrombin
(Contained in alpha granules of platelets) and in plasma
*binds to fibrinogen to stabilize fibrinogen-platelet interaction
-anti-angiogenesis, apoptosis, activ TGF-beta
-received by CD36, CD47, and integrins |
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Term
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Definition
(Contained in alpha granules of platelets, endocytosed by MKcytes)
Zymogen, cleaved to be plasmin by tPA (using fibrin cofactor), uPA, kallikrein, or facor XII
Protease that acts to degrade fibrin clots
-cleaves fibrin, fibronectin, thrombospondin, laminin, and von Willebrand factor. |
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Term
| Processing of alpha granule contents |
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Definition
| After activation, they fuse with Surface Canalicular system to export contents |
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Term
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Definition
coagulation, inflammation, wound repair
PF4, PDGF, TGF-beta, VEGF, EGF
fibrinogen, igG, IgA, IgM, fibronectin, factor V, vWf, thrombospondin, plasminogen
fuse with surface canalicular system to export contents
Deficiency: Gray platelet syndrome |
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Term
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Definition
serotonin, catecholamines, Ca2+, Mg2+, ADP, ATP
fuse directly with PM to release contents
deficiency: Hermansy-Pudlak |
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Term
| Surface canalicular system |
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Definition
| allows rapid release of (alpha) granule contents |
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Term
| DTS (dense tubular system) |
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Definition
remnants of ER from MKcytes
-sequesters Ca2+ |
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Term
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Definition
synthesize vWF, factor V, and factor VIII
endocytose fibrinogen and plasminogen |
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Term
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Definition
Fibrinogen receptor, aggregation
Integrin (cell surface adhesion molecule)
-platelet receptor for fibrinogen, fibronectin
-Activated by PKC (which is activated by Ca2+ and DAG) to bind vWf
-required for platelet aggregation
Deficiency: Glanzmann's thrombasthenia |
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Term
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Definition
Integrin (cell surface adhesion molecule)
-collagen receptor
-activated by PKC (which is activated by DAG + Ca2+) |
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Term
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Definition
Integrin (cell surface adhesion molecule)
-fibronectin receptor |
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Term
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Definition
Integrin (cell surface adhesion molecule)
-collagen receptor
-when binds, outside-in signaling via PLC and DAG/IP3
-->Ca2+ release |
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Term
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Definition
vWf receptor, adhesion
Integrin (cell surface adhesion molecule)
-vWf receptor on platelets
Important for adhesion
Deficiency: Bernard-Soulier syndrome |
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Term
| Endothelial cells' role in hemostasis |
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Definition
Produce anti-thrombotic factors
-prostacyclin, ADPases, heparins, thrombomoduli
Can also produce vWf and factor VIII |
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Term
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Definition
integral membrane ptn on surface of endothelial cells
Co-factor for thrombin
Converts it into an anti-coagulant ENZ from pro-coagulant ENZ |
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Term
| G proteins involved with platelets |
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Definition
Gq - mediates signaling via IP3/DAG (needed for thrombus formation)
G12 - changes in actin cytoskeleton
Gi - decreases cAMP levels (stimulatory in platelets)
Gs - increases cAMP levels (inhibitory in platelets) |
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Term
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Definition
platelet agonist
-released from platelets in contact w/collagen or thrombin
-activates platelets via G ptn receptors PY12 and PY2 (Gi and Gq)
-mobilizes fibrinogen binding sites (conf change in GPIIb/IIIa complex so fibrinogen can bridge platelets in Ca2+-dependent process) |
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Term
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Definition
Thromboxane
Most potent platelet agonist (activator)
-activates platelets via G ptn receptors TPα and TPβ (Gq and G12)
-formed from AA (arachidonic acid) by COX1
-Can diffuse across the PM to activate more platelets
*secretion phase of platelet plug formation*
- Assists in blood vessel constriction |
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Term
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Definition
Platelet agonist
-activates platelets via G ptn receptor α2 adrenergic (Gi) |
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Term
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Definition
*secretion phase of platelet plug formation*
liberated from PL membrane by PL-A2
-COX1 makes it into TxA2 |
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Term
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Definition
Initiates almost all hemostatic processes
-activates factor VI --> VIIa in secondary hemostasis |
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Term
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Definition
| Primary trigger to result in activation of membrane phospholipases + liberation of arachidonate (converted to TxA2), mobilization of Ca2+ and actin-myosin intxns, secretion of ADP, TxA2, and serotonin; causing further platelet aggregation and constric of VSM |
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Term
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Definition
vitamin K antagonist
-relevant in purpura fulminans (inability to turn off clotting mech)
-drops anti-coagulants II, VII, IX, X, ptn C and S |
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Term
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Definition
exposed when platelet is activated
-binder for coagulatioin ptns |
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Term
| What happens in vascular injury? |
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Definition
-Subendothelial collagen exposed
-vWf needed for platelets to adhere (secreted by endothelial cells)
-TxA2 and ADP released --> aggregation |
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