The importance of factor XIII as a component of fibrin sealants.
BACKGROUND
The need for factor XIII (FXIII) in fibrin sealant is subject to discussions. Some commercially available fibrin sealants (FS) contain high levels of FXIII (up to 70-80 U/mL) while others contain low levels or none. The objective of the present studies was to investigate the need for FXIII in FS.


METHODS
Beriplast P, a commercial FS containing 40-80 U/mL FXIII, was compared with FS with different concentrations of FXIII or FXIII depleted FS. In Study 1, Beriplast P or FS with 4 U/mL FXIII was allowed to cross-link for 0.25, 1, and 2 min and the resulting fibrin gamma- and beta-chains as well as gamma-gamma-chain dimers were analyzed by SDS-PAGE and densitometry. In Study 2, a series of six FS was prepared from fibrinogen containing 0 (FS-FXIII), 17.5, 35, 70, 140, and 280 U/mL FXIII. The intrasealant strength was determined using a biomechanical test (twin-bottle test). In Study 3, 18 rabbits underwent bilateral partial kidney resection (acute model); right (n = 18) and left (n = 18) kidneys were treated with Beriplast P or FS with 4 U/mL FXIII (FS + 4U FXIII). In Study 4, rabbits were randomly assigned to receive FXIII depleted FS (FS-FXIII) (n = 15); FS + 3 U/mL FXIII (n = 10); FS + 10 U/mL FXIII (n = 10); or Beriplast P (n = 15), after partial rabbit kidney resection (chronic model). The primary endpoint for Studies 3 and 4 was hemostasis.


RESULTS
In Study 1, Beriplast P produced significantly more fibrin gamma-chain cross-linking in the observed period than FS with 4 U/mL FXIII. In Study 2, fibrin clot strength increased as a function of FXIII concentration with a maximum of 70 U/mL. In Study 3, significantly more animals achieved hemostasis in the Beriplast P treated group than in the FS + 4U FXIII group (P = 0.03 at 15 s; P < 0.001 at 1 and 2 min). In Study 4, FS containing FXIII (all concentrations) achieved more efficient hemostasis and reduced the need for respray compared with FS-FXIII. Beriplast P was associated with a lower incidence of postoperative adhesions compared with the other treatment groups. At autopsy, the majority of clots formed from FXIII containing FS exhibited mild to moderate clot lysis, whereas the majority of clots in the FS-FXIII group showed severe lysis.


CONCLUSIONS
FXIII, when added to fibrinogen concentrate in FS, improved fibrin cross-linking and clot strength. FXIII containing FS achieved more effective hemostasis than FXIII depleted FS. FXIII is an essential component of commercial FS and should be present in FS at an optimal concentration of about 40-80 U/mL.
Dickneite
Gerhard
G
Aventis Behring GmbH, D-35002, Marburg, Germany.
Metzner
Hubert J
HJ
Kroez
Monika
M
Hein
Berndt
B
Nicolay
Uwe
U
D000818:Animals; D005176:Factor XIII / Q000494:pharmacology*; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects*; D009392:Nephrectomy; D011817:Rabbits; D013718:Tensile Strength
D015718:Fibrin Tissue Adhesive; D005176:Factor XIII