Fibrinolysis

Question 1

It is a system where by the temporary
fibrin clot is systematically and
gradually dissolved as the vessel
heals in order to restore normal blood flow.

Answer 1

FIBRINOLYSIS

Question 2

Fibrinolysis is the degradation of
fibrin into ________
• Final stage of ______
Excessive fibrinolysis predisposes
a person to uncontrolled bleeding.

Answer 2

• monomers or polymers
• hemostatic activation

Question 3

Active form is the plasma serine protease plasmin, digests fibrin/fibrinogen

Answer 3

• Plasminogen
• 92,000
• 24-26hr
• 15-21 mg/dL

Question 4

Serine protease secreted by activated endothelium, activates plasminogen

Answer 4

• Tissue plasminogen activator (TPA)
• 68,00
• Unknown
• 4-7 ug/dL

Question 5

Serine protease secreted by kidney cells, activates plasminogen

Answer 5

• Urokinase plasminogen activator (UPA)
• 54,000
• Unknown
• 2-4 ng/mL

Question 6

Serpin secreted by endothelium, inhibits tissue plasminogen activator

Answer 6

• Plasminogen activator inhibitor-1 (PAl-1)
• 52,000
• 1hr
• 14-28 mg/dL

Question 7

Serpin, inhibits free plasmin

Answer 7

• a-Antiplasmin
• 51,000
• Unknown
• 7 mg/dL

Question 8

Suppresses fibrinolysis by removing fibrin C-terminal lysine binding sites blocking TPA and plasminogen binding

Answer 8

• Thrombin activatable fibrinolysis inhibitor (TAF)
• 55,000
• 8-10min
• 5 ug/mL

Question 9

• plasma zymogen synthesized by the liver
• Activated into plasmin by _______
• Single-chain protein possessing five
  glycosylated loops called ______

Answer 9

• Plasminogen
• plasminogen activators
• kringles

Question 10

Enable plasminogen along with the
_______ to bind lysine moieties
on the fibrin molecule during polymerization

Answer 10

• plasminogen activators

Question 11

PLG gene is located on chromosome _____

Answer 11

• 6q26-q27

Question 12

Plasma concentration of PLG is approximately _______

Answer 12

• 200mg/L

Question 13

is a serine protease that systematically digests fibrin
polymer by the hydrolysis of arginine-related and lysine related peptide bond

Answer 13

• Plasmin

Question 14

• The most important in fibrinolysis is
• is the only protein that is able to
degrade fibrin clot.
• The rest of the proteins will either inhibit or induced ______.

Answer 14

• Plasmin
• Fibrinolysis

Question 15

The Actions of Plasmin
⚫Destroys _____ and _____
⚫Produces _____, which increase vascular
permeability and interfere with thrombininduced fibrin formation.
⚫Produces ____
⚫Destroys ___ __, ____, ___, ___and _______
⚫Indirectly enhances or amplifies
conversion of ______
⚫Enhances or amplifies conversion of
______________
⚫Cleaves _____

Answer 15

• fibrinogen and fibrin
• Fibrin degradation product
• D-Dimer
• Factor V, VIII, IX, XI and other plasma proteins
• Factor XII to XIIa
• PK to kallikrein, liberating kinins from kininogen
• C3 fragments

Question 16

⚫Excessive amounts of
plasminoge activators from
damaged cells / malignant cells
⚫Converts plasminogen to plasmin in
the absence of ______

Answer 16

• Primary Fibrinolysis
• fibrin formation

Question 17

Secondary Fibrinolysis
● _____ :uncontrolled , inappropriate formation of
fibrin within the blood vessels
●
●
●
●

Answer 17

• DIC
• Infection
• Neoplasm
• Snake bite
• HTR

Question 18

• Secreted by the endothelial cells
• Hydrolyzes fibrin-bound plasminogen converting it to plasmin thus initiating _____.
• Two kringle regions, form _______
• Localizes at the surface of __________ where it begins the digestion process

Answer 18

• Tissue Plasminogen Activator
• fibrinolysis
• lysine bonds with fibrin
• thrombus with plasminogen

Question 19

tPA along with _______ will
position themselves on the surface of the
________
When _____ and _____ activates the
plasminogen, that signals the start or
activation of fibrinolysis

Answer 19

• plasminogen and urokinase plasminogen activator
• thrombus or clot
• tPA and uPA

Question 20

• Circulating tPA is bound to _________ which
regulates the activity of tPA

Answer 20

• Plasminogen Activator Inhibitor-1

Question 21

inhibits the activation of plasminogen
resulting into the continuation of the
production of thrombus

Answer 21

• PAI-1

Question 22

Secreted by ________,
_______, and _______
• Becomes incorporated into the mix of
fibrin-bound plasminogen and TPA at the
time of thrombus formation
• One kringle region
• Does not bind firmly to fibrin

Answer 22

• UROKINASE PLASMINOGEN ACTIVATOR
• urinary tract epithelial cells, monocytes, and macrophages

Question 23

Primary inhibitor of plasminogen activation
Inhibits tPA and uPA
• Single-chain glycoprotein serpin
• Produced by ______, ______, _______, ______ , _______ , _______ , ________, and _______

Answer 23

• Plasminogen Activator Inhibitor -1 ( PAI-1)
• endothelial cells,
  megakaryocytes, smooth muscle cells
  , fibroblasts, monocytes, adipocytes,
  hepatocytes, and other cell types

Question 24

• Increased PAI-1 levels correlate with
reduced fibrinolytic activity and increased
risk of ______

Answer 24

• Primary inhibitor of plasminogen activation
• thrombosis

Question 25

Primary Fast-acting inhibitor of free plasmin Inhibits fibrinolysis ______ • Single-chain glycoprotein serpin • Synthesized in the liver • The gene (symbol PLI) is located on ________ It is present in the ______ and also in _____.

Answer 25

- a2-ANTIPLASMIN (a2-AP) - 70mg/L - chromosome 17p13 - plasma and platelets.

Question 26

Plasma procarboxypeptidase synthesized in the liver _____ ; very short half-life (_____) • Activated by _______ • Inhibits fibrinolysis by cleaving exposed _______ residues from partially degraded fibrin Prevents the binding of ________ and blocking the formation of ______

Answer 26

- THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR - 75 nm and 10 mins - thrombin-thrombomodulin complex - carboxyterminallysine - TPA and plasminogen to fibrin - plasmin

Question 27

Plasmin cleaves fibrin (and fibrinogen) producing a series of identifiable fibrin fragments: _, _, _, _, and ______ (_____)

Answer 27

- DEGRADATION PROCESS - X, Y, D, E, and D-dimer (D-D)

Question 28

______ described as the central E domain with the two D domains (D-E-D), minus some peptides cleaved by plasmin

Answer 28

- Fragment X

Question 29

______ is the E domain after cleavage of one D domain (D-E)

Answer 29

- Fragment Y

Question 30

Eventually these fragments are further digested to individual __ and ______

Answer 30

- D and E domains

Question 31

_________, is composed of two D domains from separate fibrin molecules (not fibrinogen) crosslinked by the action of ______

Answer 31

- D-D fragment, called Ddimer - factor XIIIa

Question 32

When a normally cross-linked fibin clot is dissolved by _____, isolated D and E fragments are not the characteristic end stage fragments. Rather, a variety of complexes are found, most characteristically one composed of __________, which is called a ______.

Answer 32

- Degradation of Cross-linked fibrin - plasmin - two D and one E moietiees (D2E Fragment) - D-dimer