Clotting Cascade Flashcards

1
Q

is fibrin or fibrinogen soluble?

A

fibrinogen

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2
Q

what parts of a zymogen are located in the liver?

A

pre for secretion
pro to keep it inactive
functional protein

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3
Q

what parts does the blood plasma contain?

A

Pro

functional protein

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4
Q

in coagulating blood, what does it contain

A

functional protein only

therefore biologically active

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5
Q

what enzyme catalyzes prothrombin –> thrombin?

A

prothrombinase

Serine protease

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6
Q

what is factor 9 deficiency called?

what disease is it associated with?

A

Christmas disease

Hemophilia B

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7
Q

where does thrombin cut?

A

Arg-Gly

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8
Q

what subunits is fibrinogen made of?

where does thrombin cut? what happens to these portions?

A

alpha, beta, gamma

cuts off A and B sites
A fits into gamma subunit of another fibrinogen

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9
Q

what domain are the A sites located at of fibrinogen?

where are the B sites located?

A

E

E

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10
Q

where do E domains go after being cut?

A

match complementary sites of D domain

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11
Q

what do B sites do after being cut?

A

interact to from 3D wall

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12
Q

what kind of interaction occurs between D and E domains?

A

H-bonds (soft clot)

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13
Q

in the formation of a hard clot, what bonds are formed?

A

covalent bonds between NH2 of Gln and NH3 of Lys

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14
Q

once the hard clot is formed what catalyzes the conversion of fibrin to cross-linked fibrin?

A

Factor 13a (Transglutaminase)

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15
Q

what activates Factor 13a?

A

Thrombin

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16
Q

what must happen to prothrombin?

what is this important for?

A

must be modified post-translationally

clot localization

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17
Q

how does glutamate of prothrombin get modified?

by what enzyme?

what is formed and with what charge?

A

COO- group attached

carboxylase

gamma-carboxy-glutamate -2 charge

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18
Q

what is significant about the -2 charge on prothrombin after post-translational modification?

A

provides specificity and localization to damaged vessels

binds perfectly to Ca2+ that is released

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19
Q

what does carboxylation of prothrombin require?

A

Vitamin K

20
Q

how do Warfarin(Coumadin) and Dicuomerol work?

A

competitive inhibitors of epoxide reductase

inhibit addition of COO- groups to prothrombin

21
Q

Dicoumerol and Warfin resemble what structure?

what happens to prothrombin levels?

A

Vitamin K

DECREASE

22
Q

which pathway does not require a protein outside of blood to be activated?

A

Intrinsic

23
Q

What factor activates the intrinsic pathway via surface activation?
what converts this factor in active factor??

A

Factor 12

Kallikrein –> 12a

24
Q

Factor 12a activates which factor?

what else is required?

A

11 –> 11a

Calcium

25
Q

Factor 11a along with what else will activate what?

A

PF3 and calcium activate:

9 –> 9a

26
Q

what else helps to activate factor 9a?

A

Factor 8 –> 8a

conversion requires Thrombin

27
Q

From factor 9a what is formed next?

A

9a-8a complex called TENASE

28
Q

the start of the common pathway beings with what?

what else is required for this activation?

A

Tenase activates Factor 10 –> 10a

PF3 and Calcium

29
Q

what helps to activate factor 10a?

A

Factor 5, converted to factor 5a with Thrombin

30
Q

what is the 10a-5a complex called?

what does it do? what else is required?

A

prothrombinase

converts Prothrombin –> Thrombin
needs help of PF3 and calcium

31
Q

what does the extrinsic pathway require?

where is it found?

A

Tissue Factor (Factor 3)

surfaces of cells lining blood vessels (TM protein)

32
Q

how is the extrinsic pathway activated?

A

contact of Factor 7 with Factor 3

33
Q

outline the steps of the extrinsic pathway

A

7 –> 7a via TF
7a + TF –> 7a, TF complex
10 –> 10a via 7a/TF complex, PF3, Calcium
10a/5a complex (prothrombinase) w/help of PF3 and Ca activates:
prothrombin –> thrombin

34
Q

describe the thrombin spark

A

a microburst of thrombin gets created from the extrinsic pathway w/platelets

35
Q

Which factors are vitamin K dependent?

A

7,9,10

36
Q

what is the Partial Thromboplastin Time (PTT) test?

what is the activator substance?

what is normal?

A

clotting time from Factor 7 to fibrin clot (intrinsic and common pathways)

kaolin

35 seconds

37
Q

what is the Prothrombin Time (PT) test?

what is added to this test?

what is normal?

A

clotting time from Factor 7 to fibrin clot extrinsic and common pathways

Tissue thromboplastin

10-12 seconds

38
Q

what is the initiating factor in vivo to begin clotting cascade?

A

TF (Factor 3)

39
Q

outline clotting cascade in vivo

A

F3 activates 7–>7a
7a and TF complex w/PF3 and calcium activate 9–>9a
8–>8a via thrombin also acts on 9
9a + 8a form Tenase, activates w/PF3 and Calcium 10–>10a
5–>5a via Thrombin helps to activate 10a
10a + 5a is prothrombinase which activates prothrombin–>thrombin

40
Q

what factors can thrombin cut to inactivate?

what else can it inactivate?

A

5, 8, 10

prothrombin

41
Q

What can thrombin complex with?

what does this form?

A

thrombomodulin

TTM complex

42
Q

what does the TTM complex do?

A

cleaves Protein C into active protein Ca

43
Q

What can Protein Ca do?

what does this protein have a lot of?

A

inactivate 5a and 8a to DEC thrombin

gamma-carboxyglutamate

44
Q

how to anticlotters work?

A

DEC calcium

45
Q

what binds to thrombin and and 10a and inactivates them?

it also activates antithrombin III

A

heparin

46
Q

what is the “end game” factor that dissolves a clot/fibrinolysis?

A

Tissue plasminogen factor (TPA)

47
Q

what are the 3 stages of hemostasis?

A

primary - form. of primary plug
secondary - form. of blood clot
third - removal of clot