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Persistent hypocoagulability in patients with septic shock predicts greater hospital mortality: impact of impaired thrombin generation

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Abstract

Purpose

Sepsis induces hypercoagulability, hypofibrinolysis, microthrombosis, and endothelial dysfunction leading to multiple organ failure. However, not all studies reported benefit from anticoagulation for patients with severe sepsis, and time courses of coagulation abnormalities in septic shock are poorly documented. Therefore, the aim of this prospective observational cohort study was to describe the coagulation profile of patients with septic shock and to determine whether alterations of the profile are associated with hospital mortality.

Methods

Thirty-nine patients with septic shock on ICU admission were prospectively included in the study. From admission to day 7, analytical coagulation tests, thrombin generation (TG) assays, and thromboelastometric analyses were performed and tested for association with survival.

Results

Patients with septic shock presented on admission prolongation of prothrombin time, activated partial thromboplastin time (aPTT), increased consumption of most procoagulant factors as well as both delay and deficit in TG, all compatible with a hypocoagulable state compared with reference values (P < 0.001). Time courses revealed a persistent hypocoagulability profile in non-survivors as compared with survivors. From multiple logistic regression, prolonged aPTT (P = 0.007) and persistence of TG deficit (P = 0.024) on day 3 were strong predictors of mortality, independently from disease severity scores, disseminated intravascular coagulation score, and standard coagulation tests on admission.

Conclusions

Patients with septic shock present with hypocoagulability at the time of ICU admission. Persistence of hypocoagulability assessed by prolonged aPTT and unresolving deficit in TG on day 3 after onset of septic shock is associated with greater hospital mortality.

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Acknowledgments

The authors thank the medical and nursing staff of the ICU at the University Hospital of Liege for their contribution to the study, Pierre Goffin, Marie-Pierre Damas, and Charlotte Ponte for their scientific contribution as medical research students, Joelle Lefrancq for helping with patient recruitment, and lab technicians and biologists for TG/ROTEM participation. Fonds d’Investissement de Recherche scientifique, CHU Liege, Fonds de la Recherche scientifique médicale, Brussels, Belgium.

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Authors and Affiliations

  1. Medicosurgical Intensive Care Unit, University Hospital Centre of Liege, Sart Tilman, Liege, Belgium

    Paul B. Massion, Didier Ledoux, Jean-Luc Canivet & Pierre Damas

  2. Laboratory Hematology and GIGA-Research, University Hospital Centre of Liege, Sart Tilman, Liege, Belgium

    Pierre Peters, Valentine Zimermann & André Gothot

  3. Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Pierre P. Massion

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  1. Paul B. Massion
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Correspondence to Paul B. Massion.

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Massion, P.B., Peters, P., Ledoux, D. et al. Persistent hypocoagulability in patients with septic shock predicts greater hospital mortality: impact of impaired thrombin generation. Intensive Care Med 38, 1326–1335 (2012). https://doi.org/10.1007/s00134-012-2620-2

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  • DOI: https://doi.org/10.1007/s00134-012-2620-2

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