Fibrinolysis

Question 1

APCR - Activated protein C resistance

Answer 1

• Risk factors for thrombosis

- Presence of the F5 Leiden mutation –> F5a resist to the degradation by APC

Question 2

APCR & Clot-based assay

Answer 2

Add APC to a plasma to induce the prolonged APTT

• Prolonged clotting time –> normal
• Unchanged clotting time –> F5L present

Question 3

Activation of plasminogen to plasma

Answer 3

• t-PA (tissue plasminogen activator): serine protease produced by endothelial cells
• t-PA from injury site enter to fibrin clot, convert plasminogen to plasmin
• Plasmin digest: fibrin (then cleared by macrophage), fibrinogen, F5, F8, F2, F12, protein S, protein C

Question 4

Activators for Plasminogen to Plasmin:

Answer 4

tPA, Urokinase (from kidney), F11a, F12a, Kallikrein

Question 5

Inhibitor of Fibrinolysis

Answer 5

• Plasminogen Activator Inhibitor 1, 2 (PAI): Inhibit tPA, urokinase
• Alpha2-antiplasmin, alpha2-macroglobulin (A2AP): Inhibit plasmin
• Thrombin-activatable fibrinolysis inhibitor (TAFI): inhibit the cleavage from fibrin to FDP by keeping plasminogen from binding to fibrin.

Question 6

Products from Fibrinogen cleavage

Answer 6

Fragment X, Y, D and E

Question 7

Products from Fibrin cleavage

Answer 7

Fragment D-dimers due to crosslinked by F13a

More larger molecules pf varying composition: DD/E, YD/DY, YY/DXD

Question 8

D-Dimer functions

Answer 8

Specific marker from Fibrin degradation

Excellent marker for DIC and others

Question 9

D-Dimer assay

Answer 9

• Macroscopic latex agglutination
• Dilution of plasma or serum –> mixed with latex particles
• Results:
  + No agglu: D-dimer < 0.5 FEU
  + Agglu in undiluted but not in 1:2 dilution: D-dimer 0.5 - 1.0 ug/mL
  + Both have agglu: D-dimer > 1.0 ug/mL