High tPA Negates Role of
Download
1 / 10

50% Lysis (min) - PowerPoint PPT Presentation


  • 53 Views
  • Uploaded on

High tPA Negates Role of FXa and Xa33/13 in Fibrinolysis. 3000. 2000. no addition. 50% Lysis (min). 1000. +Xa33/13. +FXa /. 0. 0.1. 1. 10. 100. [tPA] (  M). Now the Hike Gets Exciting: What Happens in Plasma?. Phase 1 Fibrinolysis Contributes to

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' 50% Lysis (min)' - idola-barry


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

High tPA Negates Role of

FXa and Xa33/13 in Fibrinolysis

3000

2000

no

addition

50% Lysis (min)

1000

+Xa33/13

+FXa/

0

0.1

1

10

100

[tPA] (M)


Now the Hike Gets Exciting:

What Happens in Plasma?


Phase 1 Fibrinolysis Contributes to

Large Variability Between Plasmas

Single Donor Plasma

Reference Plasma

.4

.4

.3

.3

Clot Amount

Turbidity (A405)

Clot Amount

Turbidity (A405)

.2

.2

.1

.1

0

0

0

2000

4000

6000

0

2000

4000

6000

Minutes

Minutes


Xa33/13 is Generated in Lysing Plasma

FXa-serpin

FX

FXa

Xa33

0

1

75

30

3960

2535

1020

1500

3000

4500

Minutes


FX and FXa, but not Xa33/13,

Enhance Fibrinolysis in Plasma

Single Donor Plasma

.4

no addition

.3

+Xa33/13

.2

Clot Amount

Turbidity (A405)

+FXa/

+FX

.1

0

0

1000

2000

3000

4000

Minutes

But, effective only at relatively high concentration (>0.5μM).


Xa33/13 Looses Plasminogen Binding

in Plasma During Fibrinolysis

Purified Fibrin

Plasma

Anti-FX

Pg-HRP

Anti-FX

Pg-HRP

Xa33/13

Time (min)

0 300

0 300

0 1000

0 1000


Xa-Fib Enhances Plasma Fibrinolysis

.4

no addition

.3

Clot Amount

Turbidity (A405)

.2

Xa-Fib

Control

.1

0

0

1000

2000

3000

Minutes

Effective at low concentration (0.01μM).


Xa-Fib Inhibits Thrombosis Better than tPA

Collaborator: Drs. Heyu Ni and Adili Reheman, CBS, U of T

Thrombus

Not Induced

Thrombus

Induced

Thrombus

Induced

+tPA (0.4 μM)

Thrombus

Induced

+Xa-Fib (0.02 μM)


[low]

Pg

Pg

Pn

Pn

Pn

tPA

tPA

tPA

K

K

Auxiliary Cofactor Model of Fibrinolysis

Pg

II

Va

Auxiliary

Cofactor

Xa

Xa

33/13

IIa

[low]

[high]

Intact Fibrin

Phase 1

Primed Fibrin

Phase 2

Degraded

Fibrin


Centre for

Blood

Research

cbr.ubc.ca

Kim Talbot

Scott Meixner


ad