Clotting Cascade Flashcards by Alex Hamidi

is fibrin or fibrinogen soluble?

fibrinogen

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what parts of a zymogen are located in the liver?

pre for secretion
pro to keep it inactive
functional protein

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what parts does the blood plasma contain?

Pro

functional protein

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in coagulating blood, what does it contain

functional protein only

therefore biologically active

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what enzyme catalyzes prothrombin –> thrombin?

prothrombinase

Serine protease

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what is factor 9 deficiency called?

what disease is it associated with?

Christmas disease

Hemophilia B

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where does thrombin cut?

Arg-Gly

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what subunits is fibrinogen made of?

where does thrombin cut? what happens to these portions?

alpha, beta, gamma

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

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what domain are the A sites located at of fibrinogen?

where are the B sites located?

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where do E domains go after being cut?

match complementary sites of D domain

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what do B sites do after being cut?

interact to from 3D wall

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what kind of interaction occurs between D and E domains?

H-bonds (soft clot)

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

covalent bonds between NH2 of Gln and NH3 of Lys

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

Factor 13a (Transglutaminase)

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what activates Factor 13a?

Thrombin

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what must happen to prothrombin?

what is this important for?

must be modified post-translationally

clot localization

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how does glutamate of prothrombin get modified?

by what enzyme?

what is formed and with what charge?

COO- group attached

carboxylase

gamma-carboxy-glutamate -2 charge

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

provides specificity and localization to damaged vessels

binds perfectly to Ca2+ that is released

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what does carboxylation of prothrombin require?

Vitamin K

how do Warfarin(Coumadin) and Dicuomerol work?

competitive inhibitors of epoxide reductase

inhibit addition of COO- groups to prothrombin

Dicoumerol and Warfin resemble what structure?

what happens to prothrombin levels?

Vitamin K

DECREASE

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

Intrinsic

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

Factor 12

Kallikrein –> 12a

Factor 12a activates which factor?

what else is required?

11 –> 11a

Calcium

Factor 11a along with what else will activate what?

PF3 and calcium activate: | 9 --> 9a

what else helps to activate factor 9a?

Factor 8 --> 8a conversion requires Thrombin

From factor 9a what is formed next?

9a-8a complex called TENASE

the start of the common pathway beings with what? what else is required for this activation?

Tenase activates Factor 10 --> 10a PF3 and Calcium

what helps to activate factor 10a?

Factor 5, converted to factor 5a with Thrombin

what is the 10a-5a complex called? what does it do? what else is required?

prothrombinase converts Prothrombin --> Thrombin needs help of PF3 and calcium

what does the extrinsic pathway require? where is it found?

Tissue Factor (Factor 3) surfaces of cells lining blood vessels (TM protein)

how is the extrinsic pathway activated?

contact of Factor 7 with Factor 3

outline the steps of the extrinsic pathway

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

describe the thrombin spark

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

Which factors are vitamin K dependent?

7,9,10

what is the Partial Thromboplastin Time (PTT) test? what is the activator substance? what is normal?

clotting time from Factor 7 to fibrin clot (intrinsic and common pathways) kaolin 35 seconds

what is the Prothrombin Time (PT) test? what is added to this test? what is normal?

clotting time from Factor 7 to fibrin clot extrinsic and common pathways Tissue thromboplastin 10-12 seconds

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

TF (Factor 3)

outline clotting cascade in vivo

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

what factors can thrombin cut to inactivate? what else can it inactivate?

5, 8, 10 prothrombin

What can thrombin complex with? what does this form?

thrombomodulin TTM complex

what does the TTM complex do?

cleaves Protein C into active protein Ca

What can Protein Ca do? what does this protein have a lot of?

inactivate 5a and 8a to DEC thrombin gamma-carboxyglutamate

how to anticlotters work?

DEC calcium

what binds to thrombin and and 10a and inactivates them? it also activates antithrombin III

heparin

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

Tissue plasminogen factor (TPA)

what are the 3 stages of hemostasis?

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