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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

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50% Lysis (min)

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  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

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