Research
Print page Print page
Switch language
Bispebjerg Hospital - a part of Copenhagen University Hospital
Published

Association between biomarkers of endothelial injury and hypocoagulability in patients with severe sepsis: a prospective study

Research output: Contribution to journalJournal articleResearchpeer-review

  1. The incretin effect in critically ill patients: a case-control study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. European legislation impedes critical care research and fails to protect patients' rights

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Sepsis-related Organ Failure Assessment Score is a strong predictor of survival in acute-on-chronic liver failure

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Cerebral autoregulatory performance and the cerebrovascular response to head-of-bed positioning in acute ischemic stroke

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Reversal of a Suspected Paradoxical Reaction to Zopiclone with Flumazenil

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Thromboelastography in patients with severe sepsis: a prospective cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Coagulation competence and fluid recruitment after moderate blood loss in young men

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Sisse Rye Ostrowski
  • Nicolai Haase
  • Rasmus Beier Müller
  • Morten Hylander Møller
  • Frank Christian Pott
  • Anders Perner
  • Pär Ingemar Johansson
View graph of relations

INTRODUCTION: Patients with severe sepsis often present with concurrent coagulopathy, microcirculatory failure and evidence of vascular endothelial activation and damage. Given the critical role of the endothelium in balancing hemostasis, we investigated single-point associations between whole blood coagulopathy by thrombelastography (TEG) and plasma/serum markers of endothelial activation and damage in patients with severe sepsis.

METHODS: A post-hoc multicenter prospective observational study in a subgroup of 184 patients from the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial. Study patients were admitted to two Danish intensive care units. Inclusion criteria were severe sepsis, pre-intervention whole blood TEG measurement and a plasma/serum research sample available from baseline (pre-intervention) for analysis of endothelial-derived biomarkers. Endothelial-derived biomarkers were measured in plasma/serum by enzyme-linked immunosorbent assay (syndecan-1, thrombomodulin, protein C (PC), tissue-type plasminogen activator and plasminogen activator inhibitor-1). Pre-intervention TEG, functional fibrinogen (FF) and laboratory and clinical data, including mortality, were retrieved from the trial database.

RESULTS: Most patients presented with septic shock (86%) and pulmonary (60%) or abdominal (30%) focus of infection. The median (IQR) age was 67 years (59 to 75), and 55% were males. The median SOFA and SAPS II scores were 8 (6 to 10) and 56 (41 to 68), respectively, with 7-, 28- and 90-day mortality rates being 21%, 39% and 53%, respectively. Pre-intervention (before treatment with different fluids), TEG reaction (R)-time, angle and maximum amplitude (MA) and FF MA all correlated with syndecan-1, thrombomodulin and PC levels. By multivariate linear regression analyses, higher syndecan-1 and lower PC were independently associated with TEG and FF hypocoagulability at the same time-point: 100 ng/ml higher syndecan-1 predicted 0.64 minutes higher R-time (SE 0.25), 1.78 mm lower TEG MA (SE 0.87) and 0.84 mm lower FF MA (SE 0.42; all P < 0.05), and 10% lower protein C predicted 1.24 mm lower TEG MA (SE 0.31).

CONCLUSIONS: In our cohort of patients with severe sepsis, higher circulating levels of biomarkers of mainly endothelial damage were independently associated with hypocoagulability assessed by TEG and FF. Endothelial damage is intimately linked to coagulopathy in severe sepsis.

TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00962156. Registered 13 July 2009.

Original languageEnglish
JournalCritical care (London, England)
Volume19
Pages (from-to)191
ISSN1466-609X
DOIs
Publication statusPublished - 2015

ID: 45693055