RECOMBINANT FACTOR-XIII SUPPLEMENTED CLOTS RESIST LYSIS BY PLASMIN AND LEUKOCYTE ELASTASE

We have examined the lysis of fibrin and plasma clots supplemented with supraphysiological concentrations of recombinant factor XIII (rFXIII) prior to clotting with thrombin. rFXIII supplements of up to 200 mug/mL reduced the lysis rate of fibrin clots by either plasmin or leucocyte elastase in a dose-dependent fashion. Plasma clots supplemented with rFXIII were larger and more resistant to plasmin lysis relative to controls. These effects were all greater when the clots were incubated for 20 h compared to 1 h. To determine whether these in vitro findings might have an in vivo correlate, rFXIII supplemented and unsupplemented fibrin clots labelled with I-125-fibrin were implanted into the peritoneum of mice and lysis followed by the appearance of I-125 in the urine. Supplemented clots released significantly less I-125 over the first 10 days post-surgery. We conclude that supraphysiological concentrations of rFXIII reduce lysis to both plasmin and leucocyte elastase in vitro and that supplemented clots show a similar resistance in vivo.