Clotting system Flashcards
How are platelets activated?
Vascular injury contact and attach to one another to make a plug
What attaches to platelets go catalyze a serious of reactions in thrombin generation?
Coagulation factors
What does thrombin catalyze the deposition of?
Fibirin
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
What is expressed when vascular injury occurs?
Extracellular collagen and von Willebrand factor (vWF)
What is a receptor protein in platelets and can attach to collagen?
GPIa
What happens when GPIb is exposed?
Becomes able to bind to vWF which causes a confrontational shift
What occurs when GPIIb or GPIIIa is exposed?
More binding of collagen and vWF
Fibringen is called what in active form?
Fibrin
Factor II (prothrombin) has what function?
Serine protease
What is tissue factor function?
Receptor and cofactor
What is the function for Ca2+?
Cofactor
What is the function for factor V?
Cofactor
What is the function for factor VII?
Serine protease
What is the function for factor VIII?
Cofactor
What is the function for factor IX (christmas factor)?
Serine protease
What is the function of factor X (Stuart-Prower factor)?
Serine protease
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
