FIBRINOLYSIS Flashcards by Arriane Cyrel (MTI)

is defined as the dissolution of clot by plasmin.

Fibrinolysis

How well did you know this?

Not at all

Perfectly

is derived from plasminogen, which is produced by the liver.

Plasmin

How well did you know this?

Not at all

Perfectly

Dissolution of clot to restore and reestabish blood flow

FIBRINOLYSIS

How well did you know this?

Not at all

Perfectly

Clot=

Thrombosis = ↑ Blood pressure = Aneurysm

How well did you know this?

Not at all

Perfectly

-Dissolution of clots

FIBRINOLYSIS

How well did you know this?

Not at all

Perfectly

-systematic, accelerating hydrolysis of fibrin by bound plasmin

FIBRINOLYSIS

How well did you know this?

Not at all

Perfectly

-Proteins involved:

Plasminogen
Tissue plasminogen activator
Urokinase
Plasminogen activator inhibitor-1
a2-Antiplasmin Thrombin-activatable
fibrinolysis inhibitor

How well did you know this?

Not at all

Perfectly

Plasma serine protease, plasmin digests fibrin/fibrinogen

Plasminogen

How well did you know this?

Not at all

Perfectly

Serine protease secreted by activated endothelium, activates plasminogen

Tissue plasminogen activator

How well did you know this?

Not at all

Perfectly

Serine protease secreted by kidney, activates plasminogen

Urokinase

How well did you know this?

Not at all

Perfectly

Secreted by endothelium, inhibits tissue plasminogen activator

Plasminogen activator inhibitor-1

How well did you know this?

Not at all

Perfectly

Inhibits plasmin

a2-Antiplasmin

How well did you know this?

Not at all

Perfectly

Suppresses fibrinolysis by removing fibrin C-terminal lysine binding sites

Thrombin-activatable fibrinolysis inhibitor

How well did you know this?

Not at all

Perfectly

: Serine protease; substrate for activation; activates plasmin (digests fibrin to fibrinogen)

Plasminogen

How well did you know this?

Not at all

Perfectly

: digests fibrin/fibrinogen

Plasmin

How well did you know this?

Not at all

Perfectly

: injured blood vessel that releases procoagulant substances like collagen and tissue factor

Activated endothelium

How well did you know this?

Not at all

Perfectly

Endothelium → Activation of plasminogen →

TPA → Plasmin

How well did you know this?

Not at all

Perfectly

: regulator of TPA/Urokinase plasminogen activator

Plasminogen activator inhibitor-1

How well did you know this?

Not at all

Perfectly

: specifically inhibits free plasmin

a2-Antiplasmin

How well did you know this?

Not at all

Perfectly

: activated by thrombin

TAFI

How well did you know this?

Not at all

Perfectly

: form the kidneys and can also be produced by monocyte and macrophage

UPA

How well did you know this?

Not at all

Perfectly

• Serine protease activated to plasmin

PLASMINOGEN

How well did you know this?

Not at all

Perfectly

• Produced by the liver

PLASMINOGEN

How well did you know this?

Not at all

Perfectly

• Structure: five glycosylated loops (kringles)

PLASMINOGEN

How well did you know this?

Not at all

Perfectly

is made up of lysine amino acid

Plasminogen

: located at the C-terminal end of every loop

Lysine

allows binding to TPA or UPA in plasminogen to activate it

Lysine

binding site of the activators of plasminogen

Lysine

attaches lysine to activate plasminogen (FIBRINOLYTIC SYSTEM)

TPA/UPA

Other activators: (COAGULATION SYSTEM)

FXIIa, Kallikrein, and Thrombin + Protein C, Protein S, Protein Z, thrombomodulin

(EXOGENOUS)

urokinase and streptokinase

not produced by the body but can imitate the action of urokinase from the kidney

EXOGENOUS

synthetically produced outside the body

EXOGENOUS

can come from bacteria, medications, and food

EXOGENOUS

Functions of Plasmin

Promotes clot dissolution Activates complement system Fragments FXIIa

activated form of plasminogen, which digests the clot

Plasmin

: excess plasmin is released and destroyed by antiplasmin

→ Normal

: excessive free plasmin is released, antiplasmin is depleted, plasmin destroys other components

→ Abnormal

(substrates for plasmin: [?])

I, V, VIII, XIII

Plasmin cannot recognize the difference between

fibrinogen and fibrin

Fibrinogen will be depleted and exhausted from the liver until I, V, VIII depletes = [?] due to excess plasmin not destroyed by antiplasmin

prolonged bleeding

(participates in the activation of C1a, C1b, and other complement factors)

Activates complement system

(along with K, activates plasminogen to plasmin; plasmin feeds back to XII to fragment it)

Fragments FXIIa

Types of Plasmin

1. Bound plasmin 2. Free plasmin

: digest clots (needed by the body)

1. Bound plasmin

: digest fibrinogen, FV, VIII and fibronectin

2. Free plasmin

imp in plt adhesion; can destroy a lot when free in the circulation & without antiplasmin

2. Free plasmin

- activates fibrinogen to become fibrin

Thrombin

- Fibrin (composition: [?] – soluble)

fibronopeptide A and fibronopeptide B

- independent; weaker; subjected to proteolysis =

soluble (no clot)

- Cross-linked fibrin is insoluble and acted upon by plasmin forming

FDPs (fibrin degradation products)

-: connects and cross-links domains/fibrinopeptides A and B

FXIII

FDPs

- Fibrin degradation products

(has both alpha and beta knobs)with 2 D domains

E central domain

connects with other D to create fibrin link

connects D dimer

Alpha knob

connects D domain

Beta knob

- is activated to plasmin

Plasminogen

- Plasmin works on fibrin and split them into

FDPs

- TPA and UPA is inhibited by

Plasminogen Activator Inhibitor (PAI-1) and Lipoprotein A (Lp-a)

– these two are controlled by TPA and UPA

Plasminogen Activator Inhibitor (PAI-1) and Lipoprotein A (Lp-a)

- Free plasmin (plasmin that did not participate in the clot) is inhibited by

a-2 antiplasmin

-: activates fibrinogen to fibrin, XIII to XIIIa and TAFI to TAFIa

Thrombin

(needed to control plasmin)

TAFIa

TAFI

- Thrombin-Activatable Fibrinolysis Inhibitor (TAFI)

Plasminogen is activated to Free plasmin and Bound plasmin (attached to a clot) by [?]

TPA

attaches to bound plasmin degrading fibrin to firbin degradation products (FDPs: X, Y, D, E, D-dimer)

TPA

: targets bound plasmin

3) Thrombin-activatable fibrinolysis inhibitor (TAFI)

: targets free plasmin; works on the dangerous free plasmin

2) a-2 antiplasmin

: targets activator of plasminogen

1) Plasminogen activator inhibitor-1 (PAI-1)

deactivates fibrinolysis at once/primary inhibitor/regulator of fibrinolysis

1) Plasminogen activator inhibitor-1 (PAI-1)

Fibrin (& Fibrinogen) Degradation Products (FDP):

X, Y, D (DD DIMER), E

• Four principal products by plasmin:

Fragment X,Y,D (D-D dimer) and E

: early degradation products

• X and Y

: late degradation products

• D and E

: indication of in-vivo fibrinolysis

• D-D dimer

tested for px w/ DIC where coagulation occurs inside the body by administering anticoagulants to inhibit some factors and stop coagulation

• D-D dimer

production indicates that coagulation has stopped and clot has dissolved

• D-D dimer

indicates successful fibriolysis

• D-D dimer

[?]: above; [?]: below

Fibronopeptide A Fibronopeptide B

Fibronopeptide A is degraded by plasmin by working first on the alpha chain =

Fragment X

E and D is degraded by plasmin by working first on the D domain =

Fragment Y

composed of 1 E dmain and 1 D domain

Fragment Y

Does not contain alpha chain and 1 D-dimer

Fragment Y

E and D connects = (indication of in vivo fibrinolysis)

D-d dimer

Effects of FDP:

inhibits coagulation

: with anticoagulant effect (V and VIII)

Fragment Xand Y

: inhibit fibrin polymerization

Fragment Y and D

do not allow fibrin to connect w/ each other/no cross-linking

Fragment Y and D

: inhibits thrombin (the body cannot coagulate in the presence of FDP – control of coagulation and anticoagulant)

Fragment E