Blood Clotting

Question 1

What can abnormal clotting cause?

Answer 1

vascular occlusion and infarction

Question 2

What are the 4 major players of Forming a clot?

Answer 2

1) Endothelial cells
2) Subendothelial tissue
3) Platelets
4) Clotting factors

Question 3

Describe von Willebrand Factor

Answer 3

mediates platelet adhesion to exposed extracellular matrix when the endothelial lining of blood vessel is damaged, present in plasma and the extracellular matrix; adhered platelets become activated by agents that increase the [Ca2+] of platelets

Question 4

What happens once von Willebrand Factor is activated?

Answer 4

receptor for fibrinogen becomes exposed on the platelet memebrane, Fibrinogen binds this and causes platelet aggregation

Question 5

Is fibrin normally found in blood?

Answer 5

no, but its precursor fibrinogen is

Question 6

Is aggregation of platelets alone enough to seal large wounds?

Answer 6

no

Question 7

what converts fibrin to fibrinogen

Answer 7

protease thrombin

Question 8

Describe how protease thrombin works

Answer 8

1) cleaves 2 peptide binds between A(alpha) and B(beta) chains releasing 2 peptides (fibrinopeptides A and B)
2) remaining peptide= fibrin monomer
3) once monomer are formed, they aggregate into fibrous structure

Question 9

why is fibrinogen more soluble

Answer 9

b/c the fibrinopeptides are covered in negatively charged aspartate and gultamate residues (which repel fibrinogen and prevent aggregation)

Question 10

Describe Factor XIII

Answer 10

transglutaminase which catalyzes the crosslinking of fibrinogen monomers that form a soft gel instead of a clot

Question 11

where is thrombin limited to

Answer 11

the site of injury

Question 12

what produces thrombin

Answer 12

prothrombin by factor Xa

Question 13

what does the inactive fragment of thrombin contain

Answer 13

10 residues of (gamma)-carboxyglutamate (produced by hepatocytes in rxn requiring vit K)

Question 14

what is the one protease factor unique to the extrinsic pathway

Answer 14

factor VIIa. active only in the presence of tissue factor(exposed after injury)

Question 15

What is the Contact Phase Activation

Answer 15

initiating rxns of the intrinsic pathway

Question 16

what 2 proteases are required for contact phase activation

Answer 16

1) Kallikrein
2) Factor XIIa
also requires HMWK (high molecular weight kininogen)

Question 17

Describe the steps of the Intrinsic Pathway

Answer 17

Factor XIIa activates Factor XI which activates Factor IX which activates Factor X (this step requires Factor VIIIa)

Question 18

what is the most important clotting inhibitor

Answer 18

ATIII (others include alpha1-antiprotease and alpha2-macroglobulin)

Question 19

what activates ATIII

Answer 19

heparin

Question 20

Describe Thrombomodulin

Answer 20

on the surface of endothelial cells, binds circulating thrombin(which will now not be able to bind to substrates) instead Protein C is activated which degrades factor Va and VIIIa

Question 21

where is thrombomodulin found and why is this important

Answer 21

only on intact endothelium, this helps prevent clot formation on areas with no endothelial damage

Question 22

what does Plasmin do

Answer 22

degrade the fibrin clot

Question 23

what is Plasmin formed from

Answer 23

inactive precursor plasminogen which binds the fibrin clot with high affinity

Question 24

fibrin complex is activated by what activator

Answer 24

tissue type plasminogen activator (tPA)

Question 25

describe tPA

Answer 25

1) a serine protease that binds to fibrin
2) does not require proteolytic activation
3) minimal activity in the absence of fibrin

Question 26

when is active plasmin formed

Answer 26

only in the fibrin clot where it is needed

Question 27

what else can activate plasminogen

Answer 27

Urokinase and Streptokinase(allosterically without proteolytic cleavage)

Question 28

When is Plasminogen administered

Answer 28

event of acute MI if administered within an hour

Question 29

what effect does Ca2+ have on clotting

Answer 29

can inhibit clotting if Ca2+ is removed, all (gamma)-carboxyglutamate containing factors (2,7,9,10) depend on Ca2+

Question 30

name 2 commonly used anticoagulants

Answer 30

Heparin and Coumadin(warfarin)

Question 31

What steps are used to assess blood clotting

Answer 31

1) Bleeding time
2) Activated partial thromboplastin time
3) Prothrombin time

Question 32

prolonged bleeding time is indicative of what

Answer 32

platelet disorders

Question 33

what is activated partial thromboplastin time used for

Answer 33

to measure efficacy of heparin and test the intrinsic and common final pathway

Question 34

what is prolonged Prothrombine time indicative of

Answer 34

deficiencies of the extrinsic and final common pathway, used routinely to measure coumadin therapy

Question 35

Describe Hemophilia

Answer 35

A is a deficiency of factor 8, B is a deficiency of factor 9 both factors 8 and 9 activate factor 10, X-linked mostly affecting males, only Tx is injection of factor 8