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Coagulation CCMLS > Fibrinolysis > Flashcards

Fibrinolysis Flashcards

1
Q

plasminogen is produced where?

A

liver

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2
Q

when is fibrinolysis activated?

A

When coagulation cascade is activated

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3
Q

Main components of fibrinolysis are

A

plasminogen
plasminogen activators
plasmin
inhibitors of plasminogen activators/plasmin

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4
Q

Activators of plasminogen

A

intrinsic factors
extrinsic factors
urokinase
lipoprotein a
exogenous activators

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5
Q

intrinsic activators of plasminogen

A

12a, 11a, Kallekrein

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6
Q

how does kallekrein activate plasminongen?

A

converts urokinase to a more active form;
releases bradykinin from HK which stimulates release of tissue plasminogen activator (tPA)

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7
Q

extrinsic factors that activate plasminogen

A

tPA, uPA

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8
Q

where is urokinase plasminogen activator found?

A

plasma and urine

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9
Q

what is uPA major function?

A

in tissues it digests cellular maxtrix allowing cells to migrate

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10
Q

what allows tPA efficiency to increase?

A

when it is bound to fibrin along with plasminogen

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11
Q

where is tPA produced?

A

endothelial cells

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12
Q

when is tPA released?

A

in response to stimuli: thrombin, bradykinin, exercise, venous stasis, and DDAVP (drug therapy for VW disease)

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13
Q

what activates uPA?

A

plasmin
kallikrein

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14
Q

what effect does lipoprotein a have on plasminogen?

A

It is similar in structure to plasminogen and competes w/ plasmin for biding fibrin
It also inhibits activation of plasminogen by tPA and uPA

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15
Q

exogenous activators of plasminogen

A

streptokinase
staphylokinas
Y.pestis

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16
Q

how do exogenous activators affect plasminogen?

A

they assume enzymatic activity when bound to plasminogen
Streptokinase has no preference for bound plasminogen
Stapylokinase has a preference for bound plasminogen

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17
Q

examples of inhibitors of fibrinolysis

A

PAI (1,2,3)
TAFI
AP (alpha 2 antiplasmin)
alpha 2 macroglobulin

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18
Q

PAI

A

plasminogen activator inhibitors
form complex with plasminogen activators and inhibits their activity

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19
Q

PAI 1 inhibits…

A

inhibits tPA

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20
Q

PAI 2 inhibits…

A

inhibits uPA

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21
Q

PAI 3 inhibits…

A

inhibits protein c

22
Q

TAFI

A

thrombin activatable fibrinolysis inhibitor

23
Q

TAFI is activated by what?

A

thrombin-thrombomodulin complex

24
Q

How does TAFI inhibit plasminogen?

A

removes lysine and arinine residues from fibrin eliminating binding sites for plasminogen

25
Q

AP

A

alpha 2 antiplasmin

26
Q

how does Alpha 2 antiplasmin inhibit plasminogen?

A

crosslinks fibrin by f13a which increases resistance of fibrin to action of plasmin
binds circulating unbound plasmin inhibiting it

27
Q

how does alpha 2 macroglobulin function as an inhibitor?

A

it neutralizes plasmin if AP cannot neutralize all the plasmin present

28
Q

FDP

A

fibrin degradation products
fragments x, y, d, e

29
Q

fragment x

A

competes with fibrinogen for thrombin===less fibrin is formed

30
Q

fragment y & d

A

interferes with polymerization of fibrin monomers

31
Q

fragment e

A

inhibits thrombin

32
Q

FSP inhibits

A

platelet aggregation

33
Q

plasmin degrades what factors?

A

5, 8, 12

34
Q

liver function

A

produces most coagulation factors, activators, and inhibitors
removes activated coagulation factors, plasmin, and FSP

35
Q

Positive feedback

A

thrombin activates plts
thrombin activates factors 5, 8
f10a activates f7, 8

36
Q

negative feedback

A

thrombin inactivates factors 5, 8, 10a (thru TF pathway inhibitor), &7
fibrin slows thrombin release
FDP interferes w/ fibrin monomer polymerization

37
Q

biochemical inhibitors

A

soluble naturally occurring proteins that inhibit enzymes by forming a complex at active site

38
Q

AT

A

antithrombin
prod. by liver, endothelial cells, megakaryocytes

39
Q

what does Anti Thrombin inhibit?

A

all serine proteases:
thrombin, 12a, 11a, 9a, 10a, kallekrein, & plasmin by forming a 1:1 complex
acts slowly w/o heparin

40
Q

Anti thrombin activity is increased with what?

A

heparin
3-4x increase

41
Q

heparin must have what to work as an anticoagulant?

A

Anti Thrombin

42
Q

Where is heparin located?

A

granules of basophils and mast cells

43
Q

heparin cofactor 2

A

inhibits thrombin
1000x more effective bound to heparin

44
Q

protein c

A

produced in liver
activated by thrombomodulin:thrombin complex
w/ protein s inactivated f5a &8a

45
Q

protein s

A

on phospholipid surface
w/ protein c inactivates f5a & 8a

46
Q

APC

A

activated protein C

47
Q

Activated protein C is inactivated by what?

A

protein c inhibitor PAI 3, alpha 1 antitrypsin, and alpha 2 macroglobulin

48
Q

tissue factor pathway inhibitor

A

inhibits f7a-TF complex, f10a, & plasmin

49
Q

alpha 2 macroglobulin inhibits…

A

thrombin, f10a, plasmin, kallekrein

50
Q

how does alpha 2 macroglobulin inhibit?

A

binds enzyme undergoing a conformation change preventing enzyme from binding w/ substrate

51
Q

alpha 1 antitrypsin

A

inhibit proteases at tissue level

52
Q

c-1 inhibitor

A

inhibits complement system
inhibits f12a, 11a, kallekrein, and plasmin

Coagulation CCMLS (8 decks)

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