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OBJECTIVE To review new insights in the pathogenetic mechanisms involved in the development of disseminated intravascular coagulation (DIC) in septic patients, in order to develop new directions for therapeutic intervention. METHODS Articles and published peer-reviewed abstracts on the mechanism of the initiation of DIC in sepsis. METHODS Studies selected for detailed review were those reporting specifics about the mechanism of activation of coagulation and fibrinolysis in experimental human and animal models of sepsis. Data extraction guidelines for assessing data quality included validity of the model, quality of the laboratory assessment of activation of coagulation and fibrinolysis, and methodological considerations, such as the presence of control experiments and statistical analysis. RESULTS After the presence of endotoxin in the circulation, significant coagulation activation can be detected. This activation is preceded by an increase in the serum levels of various cytokines, such as tumor necrosis factor and interleukins. Inhibition of the increase in tumor necrosis factor results in inhibition of coagulation activation. Measurement of molecular markers for the activation of coagulation proteins at various levels indicates that the activation of coagulation is mediated by the tissue factor-dependent pathway, which is further confirmed by experiments in which the inhibition of the tissue factor-dependent pathway resulted in complete inhibition of coagulation activation. The activation of coagulation seems to be amplified by impaired function of the protein C-protein S inhibitory pathway. An imbalance between coagulation and fibrinolysis, ultimately leading to plasminogen activator inhibitor type 1-mediated inhibition of fibrinolysis, may further promote the procoagulant state. CONCLUSIONS The increased knowledge of the various pathogenetic mechanisms of coagulation activation and fibrinolysis in sepsis may have therapeutic implications; however, their efficacy needs to be assessed in appropriate clinical trials.
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
February 1994,
JAMA,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
October 2005,
Chest,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
December 2001,
Seminars in thrombosis and hemostasis,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
January 2003,
Journal of thrombosis and thrombolysis,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
May 1991,
Vnitrni lekarstvi,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
January 2016,
Journal of intensive care,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
September 1979,
The Southeast Asian journal of tropical medicine and public health,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
January 1983,
Bibliotheca haematologica,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
January 1970,
Hamatologie und Bluttransfusion,
M Levi, and
H ten Cate, and
T van der Poll, and
S J van Deventer
November 2000,
Intensive care medicine,
