Dr White, Clotting Cascade, Cp2, Biochemistry

Front 1

the process of forming a barrier to blood loss is called

Back 1

hemostasis

Front 2

hemostasis occurs in 3 steps

Back 2

primary=forms primary plug, clumping of platelets
secondary=forms blood clot, insoluble strands of fibrin are deposited
third is fibrinolysis=removal fibrin clot

Front 3

how is fibrin made...basic

Back 3

fibrinogen is soluble is altered into fibrin (insoluble)

Front 4

zymogen

Back 4

is an inactive form of an enzyme that can be activated by proteolysis. they are sequentially activated

Front 5

biologically inactive zymogens are activated in

Back 5

the liver

Front 6

pro form

Back 6

keeps zymogen inactive

Front 7

each zymogen serves first as a ___ then as a___

Back 7

substrate, then enzyme

Front 8

what is the final enzyme that acts on fibrin

Back 8

thrombin, converts fibrinogen to fibrin

Front 9

Prothrombin (Factor 2)

Back 9

cleaved to form thrombin Ifactor IIa) then thrombin changes fibrinogen into fibrin which will form the clot

Front 10

start of clot formation

Back 10

vascular injury-->exposes collagen-->platelet activation-->tissue factors released and activate thrombin which makes fibrin clot

Front 11

what catalyzes the hyrolysis of peptide bond in activation of prothrombin to thrombin

Back 11

serine proteases (serine is the active site)

Front 12

A segment of fibrin fits into

Back 12

D segment of fibrin in s staggered formation (like bricks in a wall) initially forms a soft clot because connections in E and D domains are formed by hydrogen bonds (weak)

Front 13

Hard clot formation

Back 13

covalent bonds formed between fibrin subunits, slower process. Factor XIIIa=transglutaminase.

Front 14

Where is the bond formed that forms the hard clot? what factor does this?

Back 14

covalent bonds between NH2 of glutamine and NH3 of lysine. Factor XIIIa, transglutaminase does this

Front 15

What activates transglutamine to help it form the hard clot

Back 15

thrombin activates transglutaminase

Front 16

where is prothrombin made

Back 16

in the liver, modified by post-translational modification

Front 17

how is prothrombin activated

Back 17

glutamic acids get modification, get extra COOH group attched to them. the carboxylation of several glutamic acid residues ads another charge so it's a 2- charge.

Front 18

How does prothrombin work

Back 18

damaged vessels release Ca2+ so modified prothrombin 2- binds to it perfectly. provides specificity

Front 19

Modification of prothrombin requires

Back 19

vitamin K. Recycling of vitamin K is essential and therapeutically important

Front 20

warfarin and dicoumerol work by

Back 20

competitive inhibitors of epoxide reductase,structure similar to Vitamin K, anti clotting drugs. inhibits addition of carboxylic acid groups.

Front 21

Intrinsic pathway of clotting

Back 21

does not require any protein outside of the vasculature to activate it.

Front 22

Summary of intrinsic pathway

Back 22

broken vessel (contact factors)-->factor XII/XIIa-->acts on factor XI/XIa--> IX/IXa-->joins with cofactor VIIIa-->this complex changes factor X to Xa-->complexes with factor V to form Va-Xa complex which eventually cleaves prothrombin to thrombin

Front 23

activating factor IX to IXa require

Back 23

phospholipids on interior of platelets. becaome exposed when platelet is disrupted. phospholipid surface of platelets and dameged vessels are essential

Front 24

where does classic hemophilia occur

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factor VIIIa and IXa

Front 25

amplification of clotting cascade

Back 25

activation of a handful of factor XIIa activates hundreds which activates thousands. exponential response

Front 26

Extrinsic pathway

Back 26

requires an active component that is not part of blood in normal conditions. this is Tissue factor III

Front 27

extrinsic pathway is activated by

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contact of factor VII with tissue factor converts it to VIIa/TF complex which activates Factor X to Xa (this is a second way to convert X to Xa)

Front 28

the intrinsic pathway and extrinsic pathway converge to form common pathway where?

Back 28

from factor X to fibrin clot formation is considered the common pathway

Front 29

What are the vitamin K dependent factors

Back 29

factor X, IX, VII

Front 30

positive feedback in clotting cascade occurs with which factors?

Back 30

thrombin, Factor XIa, Xa, VIIa

Front 31

PTT test

Back 31

partial thromboplastin time. clotting time from factor XII to fibrin clot. normal is 20-39 seconds. Activator substance such as kaolin is added to plasma to activate contact factors

Front 32

Prothrombin time (PT test)

Back 32

looks at clotting time from factor VII to fibrin clot. reference time is 30 seconds. Addition of tissue factor starts the test

Front 33

Regulation of clotting cascade is done how?

Back 33

1) thrombin binds fibrin and inactivates it. Can also cut factor VIIIa, Xa, Va. can cut prothrombin too.
2) Thrombin cleaves protein C to Ca and this activation of protein C decreases production of thrombin

Front 34

what are some anticlotters

Back 34

ASA, Warfarin, dicoumeroal, heparin, TPA(tissue plasminogen activator-->dissovles clot)