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.
Sanquin Research at CLB, Amsterdam, The Netherlands. s.zeerleder@sanquin.nl
Sacha
S
Zeerleder
Verena
V
Schroeder
Bernhard
B
Lämmle
Walter A
WA
Wuillemin
C Erik
CE
Hack
Hans Peter
HP
Kohler
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