Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation.
BACKGROUND
Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality.


OBJECTIVE
Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC.


METHODS
From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination.


RESULTS
At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02).


CONCLUSIONS
High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.
Kienast
J
J
Department of Internal Medicine, Hematology/Oncology, Westfaelische Wilhelms University, Muenster, Germany.
Juers
M
M
Wiedermann
C J
CJ
Hoffmann
J N
JN
Ostermann
H
H
Strauss
R
R
Keinecke
H-O
HO
Warren
B L
BL
Opal
S M
SM
D000368:Aged; D000990:Antithrombin III / Q000009:adverse effects / Q000627:therapeutic use*; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D004311:Double-Blind Method; D005006:Ethnicity; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D000990:Antithrombin III