Incorporation Of Alpha 2-Plasmin Inhibitor Into Fibrin Clots And Its Association With The Clinical Outcome Of Acute Ischemic Stroke Patients

Cross-linking of alpha 2-plasmin inhibitor (alpha 2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying alpha 2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of alpha 2-PI incorporation by measuring alpha 2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, alpha 2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and alpha 2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased alpha 2-PI incorporation into the fibrin clot. alpha 2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 +/- 4.6% vs. 47.4 +/- 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 +/- 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of alpha 2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, alpha 2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.