Bleeding following cardiac surgery involving cardiopulmonary bypass (CPB) remains a major concern. Coagulation factor XIII (FXIII) functions as a clot-stabilising factor by cross-linking fibrin. Low post-operative levels of FXIII correlate with increased post-operative blood loss. To evaluate preliminary safety and pharmacokinetics of recombinant FXIII (rFXIII-A(2)) in cardiac surgery, patients scheduled for coronary artery bypass grafting were randomised to receive a
single dose of either rFXIII-A(2) (11. 9, 25, 35 or 50 IU/kg) or placebo in a 4:1 ratio. Study drug was given post-CPB within 10 to 20 minutes after first protamine dose. Patients were evaluated until day 7 or discharge, with a follow-up visit at weeks 5-7. The primary end-point was incidence and severity of adverse events. Thirty-five patients were randomised to rFXIII-A(2) and eight to placebo. Eighteen serious adverse events were reported. These were all complications well recognised during cardiac surgery. Although one patient required an implantable defibrillator, all recovered without sequelae. One myocardial infarction in a patient receiving 35 IU/kg rFXIII-A(2) was identified by the Data Monitoring Committee after reviewing ECGs and cardiac enzymes. No other thromboembolic events were seen. Dosing with 25-50 IU/kg rFXIII-A(2) restored levels of FXIII to pre-operative levels, with a tendency towards an overshoot in receiving 50 IU/kg. rFXIII-A(2), in doses from 11. 9 IU/kg up to 50 IU/kg, was well tolerated. For post-operative FXIII replenishment, 35 IU/kg of rFXIII-A(2) may be the most appropriate dose.