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The Coagulation System in Sepsis

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The Sepsis Text

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Conclusion

Extrinsic and intrinsic pathways of the coagulation system should no longer be considered as distinct entities, but rather as an integrated system providing optimal thrombin generation via the TF/factor VII complex. The role of factor XII and other contact system proteins in coagulation is less clear, and presumably is more important for fibrinolysis and inflammation.

There is no doubt that activation of coagulation, predominantly, if not exclusively, via the TF/factor VII pathway, occurs in animal and human models for sepsis. In the more severe sepsis animal models, this activation is associated with full-blown DIC. In these latter models inhibitors of TF/FVIIa improve mortality, even when given after the challenge. Surprisingly, all the evidence so far does not support that the beneficial effects of these inhibitors are due to their effects on clotting, but rather seem to be related to their effects on the inflammatory cascade. Identification of the molecular pathways of these anti-inflammatory effects is of critical importance since they seem to be key processes in the events leading to mortality in sepsis.

The interpretation of prolonged clotting times and decreased platelet numbers in patients with sepsis needs further study regarding their clinical implications since they may result from other processes than activation of coagulation.

The implications of moderately increased generation of thrombin in the absence of significant fibrinogen consumption, as occurs in the majority of septic patients, also needs a critical evaluation since such a generation actually may be beneficial by activating protein C.

Intervention studies with clotting inhibitors in patients should reveal the importance and the biological consequences of activation of the coagulation system in the pathogenesis of human sepsis.

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  1. C. Erik Hack
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Editors and Affiliations

  1. Department of Intensive Care, Erasme University Hospital, Brussels, Belgium

    Jean-Louis Vincent M.D.

  2. Service de Réanimation Polyvalente, Hôpital Saint-Joseph, Paris, France

    Jean Carlet M.D.

  3. Division of Infectious Diseases, The Memorial Hospital of Rhode Island, Pawtucket, RI

    Steven M. Opal M.D.

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Hack, C.E. (2002). The Coagulation System in Sepsis. In: Vincent, JL., Carlet, J., Opal, S.M. (eds) The Sepsis Text. Springer, Boston, MA. https://doi.org/10.1007/0-306-47664-9_39

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