Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(-)-inhibitor complexes in sepsis.
Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(-)-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(-4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.
Nuijens
J H
JH
Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Huijbregts
C C
CC
Eerenberg-Belmer
A J
AJ
Abbink
J J
JJ
Strack van Schijndel
R J
RJ
Felt-Bersma
R J
RJ
Thijs
L G
LG
Hack
C E
CE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003167:Complement Activation; D003174:Complement C1 Inactivator Proteins / Q000032:analysis*; D005174:Factor XII / Q000032:analysis*; D015956:Factor XIIa; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D018805:Sepsis / Q000097:blood*; D012697:Serine Endopeptidases / Q000032:analysis*; D012772:Shock, Septic / Q000097:blood
D003174:Complement C1 Inactivator Proteins; D005174:Factor XII; D007610:Kallikreins; D012697:Serine Endopeptidases; D015956:Factor XIIa