Patients with severe sepsis vary markedly in their ability to generate activated protein C

被引:122
作者
Liaw, PCY
Esmon, CT
Kahnamoui, K
Schmidt, S
Kahnamoui, S
Ferrell, G
Beaudin, S
Julian, JA
Weitz, JI
Crowther, M
Loeb, M
Cook, D
机构
[1] Henderson Res Ctr, Hamilton, ON L8V 1C3, Canada
[2] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada
[3] McMaster Univ, Dept Biochem, Hamilton, ON L8S 4L8, Canada
[4] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8S 4L8, Canada
[5] McMaster Univ, Dept Surg, Hamilton, ON L8S 4L8, Canada
[6] McMaster Univ, Dept Pathol, Hamilton, ON L8S 4L8, Canada
[7] McMaster Univ, Dept Mol Med, Hamilton, ON L8S 4L8, Canada
[8] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK USA
[9] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Norman, OK 73019 USA
[10] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Norman, OK 73019 USA
[11] Howard Hughes Med Inst, Oklahoma City, OK USA
关键词
D O I
10.1182/blood-2004-03-1203
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Activated protein C (APC) supplementation significantly reduces mortality in patients with severe sepsis, presumably by down-regulating coagulation, inflammation, and apoptosis. In vivo, endogenous APC is generated from protein C (PC) "on demand" in response to elevated thrombin levels. Thrombomodulin and endothelial cell protein C receptor are endothelial receptors required to generate APC endogenously. Since these receptors may be down-regulated in sepsis, we measured plasma markers of APC generation in 32 patients with severe sepsis to determine whether APC generation is impaired and whether markers of APC generation correlate with 28-day mortality. Relative to normals, all patients had elevated F1 + 2 and thrombin-antithrombin complex (TAT) levels (markers of thrombin generation and inhibition, respectively), and 28 of 32 patients had reduced PC levels. In 20 patients, APC levels paralleled elevated F1 + 2 levels, whereas 12 patients had low APC levels despite elevated F1 + 2 levels, suggesting that APC generation is impaired in the latter. No significant differences exist between survivors and nonsurvivors with respect to baseline PC levels, F1 + 2 levels, and APACHE II (acute physiology and chronic health evaluation) scores. Baseline APC levels were higher in survivors (P = .024), and baseline F1 + 2/APC ratios were lower in survivors (P = .047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis. (C) 2004 by The American Society of Hematology.
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收藏
页码:3958 / 3964
页数:7
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