Activation of both the complement system and the contact system of intrinsic coagulation is implicated in the pathophysiology of sepsis. Because C1 inhibitor (C1-Inh) regulates the activation of both cascade systems, we studied the characteristics of plasma C1-Inh in 48 patients with severe sepsis on admission to the Intensive Care Unit at the Free University of Amsterdam. The ratio between the level of functional and antigenic C1-Inh (functional index) was significantly reduced in the patients with sepsis compared with healthy volunteers (P = 0.004). The assessment of modified (cleaved), inactive C1-Inh (iC1-Inh), and complexed forms of C1-Inh (nonfunctional C1-Inh species) revealed that the reduced functional index was mainly due to the presence of iC1-Inh. On SDS-PAGE, iC1-Inh species migrated with a lower apparent molecular weight (Mr 98,000, 91,000, and 86,000) than native C1-Inh (Mr 110,000). Elevated iC1-Inh levels (greater than or equal to 0.13 microM) were found in 81% of all patients, sometimes up to 1.6 microM. Levels of iC1-Inh on admission appeared to be of prognostic value: iC1-Inh was higher in 27 patients who died than in 21 patients who survived (P = 0.003). The mortality in 15 patients with iC1-Inh levels up to 0.2 microM was 27%, but in 12 patients with plasma iC1-Inh exceeding 0.44 microM, the mortality was 83%. The overall mortality in the patients with sepsis was 56%. We propose that the cleavage of C1-Inh in patients with sepsis reflects processes that play a major role in the development of fatal complications during sepsis.
J H Nuijens, A J Eerenberg-Belmer, C C Huijbregts, W O Schreuder, R J Felt-Bersma, J J Abbink, L G Thijs, C E Hack
Usage data is cumulative from December 2020 through December 2021.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.