blood clotting

Question 1

factors involved in intrinsic pathway

Answer 1

12, 11, 9 + 8, 10

Question 2

factors involves in extrinsic pathway

Answer 2

7, 10

Question 3

common pathway

Answer 3

10 activated (with help of 5)
10a turns prothrombin –> thrombin
thrombin turns fibrinogen –> fibrin
fibrin forms soft clot

Question 4

which factors are Ca dependent for activation?

Answer 4

7, 9, 10, thrombin

Question 5

what binds Ca during clot formation?

Answer 5

g-carboxyglutamate

Question 6

what is g-carboxyglutamate?

Answer 6

unusual aa present on pro-factor, will bind Ca well bc of negative charges, needed for factor to be activated

Question 7

m/c form of hemophilia

Answer 7

hemophilia A, involves mutation in factor 8, thus unable to activate factor 10 via intrinsic pathway

Question 8

central regulated step of clotting? factors involved?

Answer 8

prothrombin –> thrombin

factors- Ca, Factor Va, Factor Xa, phospholipids

Question 9

describe the action of thrombin

Answer 9

highly specific serum protease, cleaves only arginine-glycine bonds

Question 10

how is the intrinsic pathway initiated?

Answer 10

platelets binding to damaged tissue surface, releasing ADP

Question 11

what is required for formation of g-carboxyglutamate? why?

Answer 11

vitamin K, bc enzyme used to carboxylate glutamate is called “vit K dependent carboxylase”

Question 12

how does warfarin work?

Answer 12

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

Question 13

what is another vit k analogue?

Answer 13

dicumarol

Question 14

why do pts taking warfarin need to limit vitamin K consumption?

Answer 14

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

Question 15

what occurs when fibrinogen –> fibrin?

Answer 15

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

Question 16

what is responsible for hard clot formation?

Answer 16

factor 13 a is a transmaidase that covalently cross-links glutamine and lysine residues in fibrin to form a hard clot

Question 17

anti-thrombotic effects of thrombin

Answer 17

activates protein C
protein C activates protein S
together they destroy factor 5a and 8a to down regulate clot formation

Question 18

factor V leiden

Answer 18

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

Question 19

pro-thrombotic effects of thrombin, through up regulation of:

Answer 19

factors 5,7,8,12,13

Question 20

action of antithrombin III

Answer 20

serum protease inhibitor that inhibits thrombin and prevents unnecessary clot formation, also inhibits steps in intrinsic pathway

Question 21

MOA of heparin

Answer 21

increases the binding of antithrombin III to thrombin, thus increasing anti-coagulation

Question 22

MOA of aspirin

Answer 22

irreversible COX1 inhibitor that inhibits platelet aggregation

Question 23

why do Ca antagonists cause bleeding? example?

Answer 23

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

Question 24

MOA of eliquix/xarelto

Answer 24

10a inhibitors

Question 25

MOA pradaxa

Answer 25

thrombin inhibitor

Question 26

clot dissolution pathway

Answer 26

TPA activates plasminogen –> plasmin

plasmin breaks down clot into soluble fibrin byproducts

Question 27

what type of enzyme is plasmin?

Answer 27

protease

Question 28

what will increase the activity of TPA?

Answer 28

protein C

Question 29

what will decrease the activity of plasmin?

Answer 29

antiplasmin

Question 30

what is steptokinase?

Answer 30

similar to TPA, made by bacteria