Fibrinolysis

Question 1

The process that breaks down fibrin clots after wound healing?

Answer 1

Fibrinolysis

Question 2

When does fibrinolysis begin?

Answer 2

A few hours after fibrin polymerization and cross-linking.

Question 3

What are the key activators of fibrinolysis?

Answer 3

Tissue Plasminogen Activator (TPA)

Urokinase Plasminogen Activator (UPA)

Question 4

When are TPA and UPA released?

Answer 4

In response to inflammation and coagulation.

Question 5

What are the key fibrinolytic proteins that assemble on fibrin during clotting?

Answer 5

Plasminogen
Plasmin
TPA
UPA
PAI-1

Question 6

These are loops that bind to lysine and fibrinogen proteins, concentrating them on the fibrin clot.

Answer 6

Kringle Loops

Question 7

What enzyme degrades fibrin to restore normal blood flow?

Answer 7

Plasmin

Question 8

What activates fibrin-bound plasminogen several hours after thrombus formation?

Answer 8

Tissue plasminogen activator (TPA) and urokinase plasminogen activator (UPA)

Question 9

What happens if there is excessive fibrinolysis?

Answer 9

Bleeding due to premature clot lysis.

Question 10

What happens if there is inadequate fibrinolysis?

Answer 10

Clot extension and thrombosis.

Question 11

How is plasminogen converted to plasmin?

Answer 11

Fibrin-bound plasminogen is cleaved at Arginine 561-Valine 562 by tissue plasminogen activator (TPA) or urokinase plasminogen activator (UPA).

Question 12

What type of enzyme is plasmin, and what does it do?

Answer 12

Plasmin is a serine protease that hydrolyzes arginine- and lysine-related peptide bonds in fibrin.

Question 13

How does plasmin contribute to fibrinolysis?

Answer 13

Digests fibrin polymers, dissolving clots and restoring blood vessel patency.

Question 14

How is plasmin activity localized to fibrin?

Answer 14

Plasmin binds fibrin via lysine residues, preventing widespread systemic activity.

Question 15

What is the feedback mechanism for accelerating clot digestion?

Answer 15

Fibrin breaks down, exposed lysine residues attract more plasminogen and TPA, speeding up clot digestion.

Question 16

What are the potential risks of plasmin regulation?

Answer 16

Free plasmin can digest plasma fibrinogen, factor V, factor VIII, and fibronectin, leading to potentially fatal primary fibrinolysis.

Question 17

What is the safety mechanism that regulates plasmin?

Answer 17

Plasma a2-antiplasmin rapidly binds and inactivates any free plasmin in circulation, preventing uncontrolled fibrinolysis.

Question 18

What is the source of Tissue Plasminogen Activator?

Answer 18

Endothelial cells (ECs).

Question 19

What is the function of Tissue Plasminogen Activator?

Answer 19

Hydrolyzes fibrin-bound plasminogen to initiate fibrinolysis.

Question 20

How does TPA localize at the thrombus surface?

Answer 20

Binds to fibrin through kringle regions.

Question 21

What is the clinical use of synthetic recombinant TPA?

Answer 21

Dissolves pathological clots in venous and arterial thrombotic diseases.

Question 22

Source of Urokinase Plasminogen Activator?

Answer 22

Urinary tract epithelial cells, monocytes, macrophages

Question 23

Function of Urokinase Plasminogen Activator?

Answer 23

Activates plasminogen (minor effect)

Question 24

Clinical use of purified Urokinase Plasminogen Activator

Answer 24

Thrombolysis (MI, stroke, DVT)

Question 25

Function of Plasminogen Activator Inhibitor 1 (PAI-1)

Answer 25

Inhibits TPA and UPA

Question 26

Source of Plasminogen Activator Inhibitor 1 (PAI-1)

Answer 26

ECs, megakaryocytes, smooth muscle cells

Question 27

Storage site of Plasminogen Activator Inhibitor 1 (PAI-1)

Answer 27

Platelets

Question 28

Clinical significance of PAI-1 deficiency

Answer 28

Chronic mild bleeding

Question 29

Conditions associated with elevated PAI-1

Answer 29

Metabolic syndrome, obesity, atherosclerosis, sepsis, stroke

Question 30

Function of α2-Antiplasmin (AP)

Answer 30

Inhibits free plasmin

Question 31

N-Terminus role of α2-Antiplasmin (AP)

Answer 31

Binds fibrin via Factor 13a

Question 32

C-Terminus role of α2-Antiplasmin (AP)

Answer 32

Binds plasmin, slows fibrinolysis

Question 33

Therapeutic analogues of α2-Antiplasmin (AP)

Answer 33

Tranexamic acid, ε-aminocaproic acid

Question 34

Source of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI)

Answer 34

Liver (plasma procarboxypeptidase)

Question 35

Activation of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI)

Answer 35

Thrombin-thrombomodulin complex

Question 36

Function of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI)

Answer 36

Prevents plasminogen and TPA binding to fibrin

Question 37

Effect of reduced TAFI activation

Answer 37

Increased fibrinolysis, bleeding

Question 38

Effect of increased TAFI activation

Answer 38

Decreased fibrinolysis, thrombosis

Question 39

Source of Fibrin Degradation Products (FDPs)

Answer 39

Plasmin cleavage of fibrin

Question 40

Major fragments of FDPs

Answer 40

X, Y, D, E, D-D

Question 41

Role of FDPs in hemostasis

Answer 41

Inhibit platelet activation and fibrin polymerization

Question 42

Composition of Fragment X

Answer 42

D-E-D (E domain with two D domains)

Question 43

Composition of Fragment Y

Answer 43

D-E (E domain with one D domain)

Question 44

Further degradation of Fragments X and Y

Answer 44

Into D and E domains

Question 45

Composition of D-Dimer

Answer 45

Two D domains cross-linked by Factor 13a

Question 46

Specificity of D-Dimer

Answer 46

Marker of cross-linked fibrin degradation

Question 47

Clinical significance of elevated D-Dimer

Answer 47

Indicates thrombosis and fibrinolysis

Question 48

Conditions detected by D-Dimer

Answer 48

DIC, DVT, pulmonary embolism

Question 49

Main method for detecting fibrinolytic activity

Answer 49

Immunoassays

Question 50

Targets of immunoassays of fibrinolytic activity?

Answer 50

Fibrin degradation products (FDPs) D-Dimer antigen

Question 51

Principle of D-Dimer immunoassay

Answer 51

Uses monoclonal antibodies

Question 52

Formats of D-Dimer tests

Answer 52

Automated lab tests, point-of-care tests (whole blood)