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

Intensive Care Med. 2012 Aug;38(8):1326-35. doi: 10.1007/s00134-012-2620-2. Epub 2012 Jun 27.


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.

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use
  • Antithrombin III / analysis
  • Blood Coagulation Disorders / mortality*
  • Blood Coagulation Factors / analysis
  • Female
  • Fibrin / metabolism
  • Hospital Mortality*
  • Humans
  • Intensive Care Units
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Prospective Studies
  • Protein C / analysis
  • Prothrombin Time
  • Shock, Septic / mortality*
  • Thrombin / metabolism*


  • Anticoagulants
  • Blood Coagulation Factors
  • Protein C
  • Antithrombin III
  • Fibrin
  • Thrombin