Elevated plasma levels of the anaphylatoxins C3a and C4a are associated with a fatal outcome in sepsis.
OBJECTIVE
Both complement and contact system of coagulation have been implicated in the pathophysiology of sepsis. We therefore measured levels of the complement activation products C1-C1-inhibitor complexes and C3a in serial plasma samples (obtained every six hours) from 48 patients with clinically suspected sepsis, and related these levels to the clinical outcome. C4a was also measured in samples obtained on admission.


RESULTS
C3a levels were elevated in 47 patients at least once during the observation period. These levels appeared to be considerably higher in patients who died than in patients who survived. This difference was found for the levels on admission (p = 0.0003), as well as for the highest (p = 0.0010) and the lowest (p less than 0.0001) levels encountered in each patient. The mortality in patients with plasma C3a levels of 13 nmol/liter or less on admission (27 patients) was 33 percent, compared with 86 percent in patients with levels of 14 nmol/liter or more. Patients with septic shock had significantly higher C3a levels than normotensive patients (p values between 0.046 and 0.004). No significant differences in C3a were found between patients who had respiratory distress syndrome and those who did not. C4a levels in plasma samples obtained on admission were elevated in 43 patients. These levels correlated very significantly with C3a levels (p less than 0.0001), and showed similar associations with a fatal outcome. C1-C1-inhibitor complexes were elevated in 23 patients at least once during the observation period. These patients had significantly higher levels of C4a and C3a than patients with normal amounts of C1-C1-inhibitor complexes. Patients who died had higher levels of C1-C1-inhibitor complexes than patients who survived. However, this difference was not significant.


CONCLUSIONS
On the basis of our results, we propose that activation of the complement system via the classical pathway is involved in the development of fatal complications in sepsis.
Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam.
C E
CE
Hack
J H
JH
Nuijens
R J
RJ
Felt-Bersma
W O
WO
Schreuder
A J
AJ
Eerenberg-Belmer
J
J
Paardekooper
W
W
Bronsveld
L G
LG
Thijs
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000706:Anaphylatoxins / Q000032:analysis*; D001424:Bacterial Infections / Q000097:blood*; D003172:Complement C1 / Q000032:analysis; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D003176:Complement C3 / Q000032:analysis*; D015926:Complement C3a; D003181:Complement C4 / Q000032:analysis*; D015934:Complement C4a; D003171:Complement Pathway, Classical; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis*; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000097:blood; D012772:Shock, Septic / Q000097:blood
D000706:Anaphylatoxins; D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D003176:Complement C3; D003181:Complement C4; D010455:Peptides; D015926:Complement C3a; D015934:Complement C4a