Fibrinolysis Flashcards
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.
FIBRINOLYSIS
Fibrinolysis is the degradation of
fibrin into ________
• Final stage of ______
Excessive fibrinolysis predisposes
a person to uncontrolled bleeding.
- monomers or polymers
- hemostatic activation
Active form is the plasma serine protease plasmin, digests fibrin/fibrinogen
- Plasminogen
- 92,000
- 24-26hr
- 15-21 mg/dL
Serine protease secreted by activated endothelium, activates plasminogen
- Tissue plasminogen activator (TPA)
- 68,00
- Unknown
- 4-7 ug/dL
Serine protease secreted by kidney cells, activates plasminogen
- Urokinase plasminogen activator (UPA)
- 54,000
- Unknown
- 2-4 ng/mL
Serpin secreted by endothelium, inhibits tissue plasminogen activator
- Plasminogen activator inhibitor-1 (PAl-1)
- 52,000
- 1hr
- 14-28 mg/dL
Serpin, inhibits free plasmin
- a-Antiplasmin
- 51,000
- Unknown
- 7 mg/dL
Suppresses fibrinolysis by removing fibrin C-terminal lysine binding sites blocking TPA and plasminogen binding
- Thrombin activatable fibrinolysis inhibitor (TAF)
- 55,000
- 8-10min
- 5 ug/mL
- plasma zymogen synthesized by the liver
- Activated into plasmin by _______
- Single-chain protein possessing five
glycosylated loops called ______
- Plasminogen
- plasminogen activators
- kringles
Enable plasminogen along with the
_______ to bind lysine moieties
on the fibrin molecule during polymerization
- plasminogen activators
PLG gene is located on chromosome _____
- 6q26-q27
Plasma concentration of PLG is approximately _______
- 200mg/L
is a serine protease that systematically digests fibrin
polymer by the hydrolysis of arginine-related and lysine related peptide bond
- Plasmin
• 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 ______.
- Plasmin
- Fibrinolysis
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 _____
- 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
⚫Excessive amounts of
plasminoge activators from
damaged cells / malignant cells
⚫Converts plasminogen to plasmin in
the absence of ______
- Primary Fibrinolysis
- fibrin formation
Secondary Fibrinolysis
● _____ :uncontrolled , inappropriate formation of
fibrin within the blood vessels
●
●
●
●
- DIC
- Infection
- Neoplasm
- Snake bite
- HTR
• 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
- Tissue Plasminogen Activator
- fibrinolysis
- lysine bonds with fibrin
- thrombus with plasminogen
tPA along with _______ will
position themselves on the surface of the
________
When _____ and _____ activates the
plasminogen, that signals the start or
activation of fibrinolysis
- plasminogen and urokinase plasminogen activator
- thrombus or clot
- tPA and uPA
• Circulating tPA is bound to _________ which
regulates the activity of tPA
- Plasminogen Activator Inhibitor-1
inhibits the activation of plasminogen
resulting into the continuation of the
production of thrombus
- PAI-1
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
- UROKINASE PLASMINOGEN ACTIVATOR
- urinary tract epithelial cells, monocytes, and macrophages
Primary inhibitor of plasminogen activation
Inhibits tPA and uPA
• Single-chain glycoprotein serpin
• Produced by ______, ______, _______, ______ , _______ , _______ , ________, and _______
- Plasminogen Activator Inhibitor -1 ( PAI-1)
- endothelial cells,
megakaryocytes, smooth muscle cells
, fibroblasts, monocytes, adipocytes,
hepatocytes, and other cell types
• Increased PAI-1 levels correlate with
reduced fibrinolytic activity and increased
risk of ______
- Primary inhibitor of plasminogen activation
- thrombosis
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 _____.
- a2-ANTIPLASMIN (a2-AP)
- 70mg/L
- chromosome 17p13
- plasma and platelets.
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 ______
- THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR
- 75 nm and 10 mins
- thrombin-thrombomodulin complex
- carboxyterminallysine
- TPA and plasminogen to fibrin
- plasmin
Plasmin cleaves fibrin (and
fibrinogen) producing a series
of identifiable fibrin fragments:
_, _, _, _, and ______ (_____)
- DEGRADATION PROCESS
- X, Y, D, E, and D-dimer (D-D)
______ described as the
central E domain with the two
D domains (D-E-D), minus some
peptides cleaved by plasmin
- Fragment X
______ is the E domain
after cleavage of one D domain
(D-E)
- Fragment Y
Eventually these
fragments are further
digested to individual __
and ______
- D and E domains
_________, is composed of
two D domains from
separate fibrin molecules
(not fibrinogen)
crosslinked by the action
of ______
- D-D fragment, called Ddimer
- factor XIIIa
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 ______.
- Degradation of Cross-linked fibrin
- plasmin
- two D and one E moietiees (D2E Fragment)
- D-dimer
