1 / 10

50% Lysis (min)

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

aoife
Télécharger la présentation

50% Lysis (min)

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. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 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)

  2. Now the Hike Gets Exciting: What Happens in Plasma?

  3. 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

  4. Xa33/13 is Generated in Lysing Plasma FXa-serpin FX FXa Xa33 0 1 75 30 3960 2535 1020 1500 3000 4500 Minutes

  5. 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).

  6. 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

  7. 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).

  8. 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)

  9. [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

  10. Centre for Blood Research cbr.ubc.ca Kim Talbot Scott Meixner

More Related