Fig. 4
Preparatory pharmacokinetic (PK) studies (a, b) and hemostatic treatment (c) by infusion of exogenous FXIII. Plasma-derived FXIII concentrates were infused at a dose of 1200 U in Nov. 201X + 2 (17.6 U/kg, equivalent to about 35 % increase) in preparation for biopsy (a) and 1440 U in June 201X + 3 (24.8 U/kg, equivalent to about 50 % increase) in preparation for bypass surgery (b), and during the perioperative period in July 201X + 3 (c). Both FXIII activity (filled squares) and antigen levels (filled diamonds) were measured before and at the indicated time intervals (a, b) or postoperation dates just before the daily exogenous FXIII infusions (at the top; c). Broken lines depict calculated FXIII activities after the infusion of exogenous FXIII concentrates. Discrepancies between FXIII activity and antigen levels indicate the formation and existence of FXIII antigen–antibody complexes between “free” anti-FXIII-A autoantibodies and exogenous FXIII concentrates (c). As expected, his FXIII activity reasonably increased from 18 to 53 % on the next day after FXIII concentrates infusion despite he underwent surgical procedure the day before (i.e., in spite of surgical bleeding in addition to the inhibition by anti-FXIII-A autoantibodies and the accelerated clearance of infused FXIII). His FXIII activity kept further increase to 103, 91, 116, 131, and 147 %, because about 30 U/kg FXIII concentrates were administered for the following 3 days and 15 U/kg for another 3 days. We tried to keep his FXIII activity around 100 % of normal at least for several days after surgery in order to prevent the notorious ‘delayed bleeding’ of severe FXIII deficiency. His FXIII activity then decreased to 59 % 10 days after the discontinuation of FXIII concentrates administration