Flashcards in blood clotting Deck (30):
factors involved in intrinsic pathway
12, 11, 9 + 8, 10
factors involves in extrinsic pathway
10 activated (with help of 5)
10a turns prothrombin --> thrombin
thrombin turns fibrinogen --> fibrin
fibrin forms soft clot
which factors are Ca dependent for activation?
7, 9, 10, thrombin
what binds Ca during clot formation?
what is g-carboxyglutamate?
unusual aa present on pro-factor, will bind Ca well bc of negative charges, needed for factor to be activated
m/c form of hemophilia
hemophilia A, involves mutation in factor 8, thus unable to activate factor 10 via intrinsic pathway
central regulated step of clotting? factors involved?
prothrombin --> thrombin
factors- Ca, Factor Va, Factor Xa, phospholipids
describe the action of thrombin
highly specific serum protease, cleaves only arginine-glycine bonds
how is the intrinsic pathway initiated?
platelets binding to damaged tissue surface, releasing ADP
what is required for formation of g-carboxyglutamate? why?
vitamin K, bc enzyme used to carboxylate glutamate is called "vit K dependent carboxylase"
how does warfarin work?
blood thinner, vitamin K analog- acts as substitute for bit K in the redox reaction that leads to the formation of g-carboxyglutamate, thus g-carboxyglutamate cannot form properly and the Ca dependent factors (7,9,10, thrombin) cannot be activated and clot cannot form
what is another vit k analogue?
why do pts taking warfarin need to limit vitamin K consumption?
warfarin is a vitamin K analogue and it acts as a competitive inhibitor of the enzyme needed to form g-carboxyglutamate, if pt increases vitamin K in the diet, the effects of warfarin will be overcome, g-carboxyglutamate will be formed and clots can form as well
what occurs when fibrinogen --> fibrin?
fibrinogen has negatively charged peptides that make it soluble, thrombin will cleave off those peptides to yield the insoluble fibrin, that then forms the soft clot
what is responsible for hard clot formation?
factor 13 a is a transmaidase that covalently cross-links glutamine and lysine residues in fibrin to form a hard clot
anti-thrombotic effects of thrombin
activates protein C
protein C activates protein S
together they destroy factor 5a and 8a to down regulate clot formation
factor V leiden
mutation in factor 5 that makes it resistant to inactivation by protein C, leads to hyper coagulable state, m/c cause of DVT with air travel
pro-thrombotic effects of thrombin, through up regulation of:
action of antithrombin III
serum protease inhibitor that inhibits thrombin and prevents unnecessary clot formation, also inhibits steps in intrinsic pathway
MOA of heparin
increases the binding of antithrombin III to thrombin, thus increasing anti-coagulation
MOA of aspirin
irreversible COX1 inhibitor that inhibits platelet aggregation
why do Ca antagonists cause bleeding? example?
Ca antagonists will take all the ca away and leave none for activation of 7,9,10, thrombin; example is ethylene glycol that is converted to oxalic acid that then binds Ca
MOA of eliquix/xarelto
clot dissolution pathway
TPA activates plasminogen --> plasmin
plasmin breaks down clot into soluble fibrin byproducts
what type of enzyme is plasmin?
what will increase the activity of TPA?
what will decrease the activity of plasmin?