Blood Clotting Flashcards Preview

Blood and Lymph > Blood Clotting > Flashcards

Flashcards in Blood Clotting Deck (35)
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1
Q

What can abnormal clotting cause?

A

vascular occlusion and infarction

2
Q

What are the 4 major players of Forming a clot?

A

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

3
Q

Describe von Willebrand Factor

A

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

4
Q

What happens once von Willebrand Factor is activated?

A

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

5
Q

Is fibrin normally found in blood?

A

no, but its precursor fibrinogen is

6
Q

Is aggregation of platelets alone enough to seal large wounds?

A

no

7
Q

what converts fibrin to fibrinogen

A

protease thrombin

8
Q

Describe how protease thrombin works

A

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

9
Q

why is fibrinogen more soluble

A

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

10
Q

Describe Factor XIII

A

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

11
Q

where is thrombin limited to

A

the site of injury

12
Q

what produces thrombin

A

prothrombin by factor Xa

13
Q

what does the inactive fragment of thrombin contain

A

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

14
Q

what is the one protease factor unique to the extrinsic pathway

A

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

15
Q

What is the Contact Phase Activation

A

initiating rxns of the intrinsic pathway

16
Q

what 2 proteases are required for contact phase activation

A

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

17
Q

Describe the steps of the Intrinsic Pathway

A

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

18
Q

what is the most important clotting inhibitor

A

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

19
Q

what activates ATIII

A

heparin

20
Q

Describe Thrombomodulin

A

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

21
Q

where is thrombomodulin found and why is this important

A

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

22
Q

what does Plasmin do

A

degrade the fibrin clot

23
Q

what is Plasmin formed from

A

inactive precursor plasminogen which binds the fibrin clot with high affinity

24
Q

fibrin complex is activated by what activator

A

tissue type plasminogen activator (tPA)

25
Q

describe tPA

A

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

26
Q

when is active plasmin formed

A

only in the fibrin clot where it is needed

27
Q

what else can activate plasminogen

A

Urokinase and Streptokinase(allosterically without proteolytic cleavage)

28
Q

When is Plasminogen administered

A

event of acute MI if administered within an hour

29
Q

what effect does Ca2+ have on clotting

A

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

30
Q

name 2 commonly used anticoagulants

A

Heparin and Coumadin(warfarin)

31
Q

What steps are used to assess blood clotting

A

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

32
Q

prolonged bleeding time is indicative of what

A

platelet disorders

33
Q

what is activated partial thromboplastin time used for

A

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

34
Q

what is prolonged Prothrombine time indicative of

A

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

35
Q

Describe Hemophilia

A

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