Clotting system Flashcards by gopi patel

How are platelets activated?

Vascular injury contact and attach to one another to make a plug

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What attaches to platelets go catalyze a serious of reactions in thrombin generation?

Coagulation factors

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What does thrombin catalyze the deposition of?

Fibirin

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Describe platelets.

Enucleated cells of the blood and are vital to clot initiation
Smooth and discoid when inactive w/ canalicular system
Pseudopodia extended when active

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What is expressed when vascular injury occurs?

Extracellular collagen and von Willebrand factor (vWF)

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What is a receptor protein in platelets and can attach to collagen?

GPIa

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What happens when GPIb is exposed?

Becomes able to bind to vWF which causes a confrontational shift

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What occurs when GPIIb or GPIIIa is exposed?

More binding of collagen and vWF

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Fibringen is called what in active form?

Fibrin

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Factor II (prothrombin) has what function?

Serine protease

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What is tissue factor function?

Receptor and cofactor

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What is the function for Ca2+?

Cofactor

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What is the function for factor V?

Cofactor

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What is the function for factor VII?

Serine protease

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What is the function for factor VIII?

Cofactor

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What is the function for factor IX (christmas factor)?

Serine protease

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What is the function of factor X (Stuart-Prower factor)?

Serine protease

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What is the function of factor XI?

Serine protease

What is the function factor XII?

Ca2+ dependent transglutaminase

What does regulatory protein thrombomodulin do?

Endothelial cell receptor, binds tropin

What does regulatory protein C do?

Activated by thrombomodulin-bound thrombin; serine protease

What does regulatory protein S do?

Cofactor

Binds activated protein C

What is the structure of a clotting protease?

Catalystic head - protease domain (serine)
2 EDF-like domains (not a growth factor) - stem for head, binding sites for regulators/cofactors 
Gla domain (membrane surface) chilates Ca2+

What is necessary for the gamma-carboxyglutamate modification?

Vitamin K (modifies Gla)

What does warfarin do?

Potent anticoagulant which functions by mimicking the structure of vit K

What do factors V and VIII have in common?

Must be activated by proteolutic cleavage Sit on anionic phospholipids surface Associate with both an active serine protease and substrate

What is factor V a cofactor for?

fXa

What is factor VIII a cofactor for?

fIXa

What are the tree parts to the coagulation cascade?

Extrinsic, Intrinsic, Common

What is the clinical readout for how fast the extrinsic pathway forms a clot?

Prothrombin time (PT)

What is the clinical readout of how fast the intrinsic pathway forms a clot?

Activated partial thromboplastin time (aPTT)

What leads to hemophilias A and B?

VIII and IX

What lead to major bleeding disorder?

VII

What are the three phases coagulation?

Initiation Priming (amplification) Propagation

What is the coagulation cascade initiated by?

Tissue factor (TF)

What does TF bind to and what occurs?

fVIII which autocatalyzes to form active TF/fVIIa complex

How does amplification occur?

Small levels of thrombin generated and are used to activate cofactors

What does thrombin do?

Activates fV to fVa Activates fXI to fXIa Triggers release to fVIIIa from vWF

What increases the half-life of fVIII?

vWF

What occurs in the propagation phase?

The activated intrinsic factors and cofactors that have been generated are active IIa generates a thrombin burst which catalyzes the deposition on insoluble fibrin at wound site

What is formed when fibrinogen is cleaved by thrombin?

Insoluble fibrin

What enzyme causes cross-linking of fibrin in a soft clot?

fXIIIa

What will cleave fibrin to break down clots?

Plasminogen activated to plasmin