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Flashcards in blood clotting Deck (30):
1

factors involved in intrinsic pathway

12, 11, 9 + 8, 10

2

factors involves in extrinsic pathway

7, 10

3

common pathway

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

4

which factors are Ca dependent for activation?

7, 9, 10, thrombin

5

what binds Ca during clot formation?

g-carboxyglutamate

6

what is g-carboxyglutamate?

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

7

m/c form of hemophilia

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

8

central regulated step of clotting? factors involved?

prothrombin --> thrombin
factors- Ca, Factor Va, Factor Xa, phospholipids

9

describe the action of thrombin

highly specific serum protease, cleaves only arginine-glycine bonds

10

how is the intrinsic pathway initiated?

platelets binding to damaged tissue surface, releasing ADP

11

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

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

12

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

13

what is another vit k analogue?

dicumarol

14

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

15

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

16

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

17

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

18

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

19

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

factors 5,7,8,12,13

20

action of antithrombin III

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

21

MOA of heparin

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

22

MOA of aspirin

irreversible COX1 inhibitor that inhibits platelet aggregation

23

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

24

MOA of eliquix/xarelto

10a inhibitors

25

MOA pradaxa

thrombin inhibitor

26

clot dissolution pathway

TPA activates plasminogen --> plasmin
plasmin breaks down clot into soluble fibrin byproducts

27

what type of enzyme is plasmin?

protease

28

what will increase the activity of TPA?

protein C

29

what will decrease the activity of plasmin?

antiplasmin

30

what is steptokinase?

similar to TPA, made by bacteria