Factor XIII in severe sepsis and septic shock.
OBJECTIVE
In sepsis, activation of coagulation and inhibition of fibrinolysis lead to microvascular thrombosis. Thus, clot stability might be a critical issue in the development of multiple organ dysfunction syndrome. Activated FXIII (FXIIIa) forms stable fibrin clots by covalently cross-linking fibrin monomers. Therefore, we investigated the impact of FXIII antigen and activity levels on disease severity and fatality in sepsis patients.


METHODS
FXIII subunit A (FXIIIA) and FXIII cross-linking activity (FXIIICA) were measured in 151 controls, in 32 patients with severe sepsis and 8 with septic shock. In addition, FXIII subunit B (FXIIIB) was measured in the sepsis patients. Moreover, clotting parameters were determined.


RESULTS
Patients suffering from sepsis (n=40) had significantly (p<0.005) lower FXIIIA levels (median [range]: 36.5% [8.8-127.4%]) and FXIIICA levels (76.5% [9.4-266%]) as compared to healthy controls (n=151, 119% [31.3-283.2] and 122.4% [40.6-485.3], respectively). No difference in FXIIIA, FXIIIB and FXIIICA levels between survivors and non-survivors, nor between patients with severe sepsis and septic shock was found. The specific activity of FXIII (FXIIICA/FXIIIA, SA(FXIII)) was significantly (p<0.001) higher in sepsis patients (2.0 [0.8-5.3]) as compared to healthy controls (1.0 [0.4-5.1]). SA(FXIII) significantly (p<0.05) increased with fatality (non-survivors [n=13] vs. survivors [n=27]: 3.3 [1.2-5.0] vs. 1.9 [0.8-5.3]) and disease severity (septic shock vs. severe sepsis: 3.4 [1.8-4.3] vs. 1.9 [0.8-5.3]).


CONCLUSIONS
We show decreased FXIIICA and FXIIIA levels, but higher SA(FXIII) in sepsis as compared to controls. Increased SA(FXIII) correlates with disease severity and fatality in sepsis patients.
Zeerleder
Sacha
S
Sanquin Research at CLB, Amsterdam, The Netherlands. s.zeerleder@sanquin.nl
Schroeder
Verena
V
Lämmle
Bernhard
B
Wuillemin
Walter A
WA
Hack
C Erik
CE
Kohler
Hans Peter
HP
D026122:Factor XIIIa / Q000032:analysis*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology / Q000401:mortality; D012772:Shock, Septic / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D015996:Survival Rate
D026122:Factor XIIIa