Coagulation disturbances in the critically ill patient with special reference to prediction of outcome

Research output: ThesisDoctoral Thesis (compilation)


Critically ill patients in intensive care units (ICU) often have coagulation disturbances. Clinical manifestations such as thromboembolism and/or bleeding may result from activation and consumption of coagulation factors and inhibitors. Disseminated intravascular coagulation (DIC) is a severe condition with an often-poor prognosis. Global haemostatic tests are inexpensive, widely available, and may be performed 24 hours a day. In contrast, more sophisticated coagulation tests, such as protein C, antithrombin, and activated protein C-protein C inhibitor (APC-PCI) complex, are expensive, can be performed only in a limited number of healthcare facilities specializing in coagulation disorders, and often only during office hours.

In the present study 92 patients admitted to a general ICU constituted the study group. The inclusion criteria consisted of one or more of the following: platelet count <100×10e9 /L; International Normalized Ratio (INR) >1.36; or activated partial thromboplastin time (APTT) >45 seconds. A control group with a comparable age and sex distribution, but not fulfilling the laboratory criteria, was established. Groups were followed up to 180 days. Survival upon discharge from the ICU and hospital was significantly lower in the study group, especially in patients with disorders that can be related to internal medicine. Odds ratios showed that prolonged APTT, in particular, predicted a lower survival rate at the time points evaluated.

The coagulation inhibitors protein C and antithrombin were also analysed. Univariate analysis of variance showed that INR and APTT were independent predictors of protein C and, to some extent, antithrombin. Using a Cox regression model, decreased protein C, but not antithrombin, predicted lower survival at 5 years.

Using the same patient material in a theoretical model assuming best-case scenario, we hypothesized that protein C treatment of patients with low levels would increase survival to the same level as a cohort with higher protein C. Total costs per life saved at 30 days (upper limit of 95 % CI) were calculated at SEK 408,000 [recombinant human activated protein C; drotrecogin alfa (activated)] and 435,000 (protein C zymogen), which may be compared to the value of a statistical life at the same age (SEK 7.66 million).

We also studied 38 patients who underwent aortic surgery. The level of the coagulation test APC-PCI complex was very high immediately following surgery and remained so, although declining, during the first two days. Higher complex levels at 6-12 hours and 12-18 hours after admission to the ICU were observed in patients who did not survive their stay in the unit.
Original languageEnglish
Awarding Institution
  • Clinical Coagulation, Malmö
  • Berntorp, Erik, Supervisor
Award date2006 May 30
ISBN (Print)91-85481-88-2
Publication statusPublished - 2006

Bibliographical note

Defence details

Date: 2006-05-30
Time: 09:15
Place: Jubileumsaulan, Medicinskt Forskningscentrum, ingång 59, Universitetssjukhuset MAS, Malmö

External reviewer(s)

Name: Ingerslev, Jørgen
Title: Professor
Affiliation: Århus Universitetshospital/Skejby Sygehus, Århus, Denmark


<div class="article_info">G Nilsson, J Astermark, S Lethagen, E Vernersson and E Berntorp. <span class="article_issue_date">2002</span>. <span class="article_title">The prognostic value of global haemostatic tests in the intensive care unit setting.</span> <span class="journal_series_title">Acta Anaesthesiol Scand</span>, <span class="journal_volume">vol 46</span> <span class="journal_pages">pp 1062-7</span>.</div>
<div class="article_info">G Nilsson, J Astermark, S Lethagen, E Vernersson and E Berntorp. <span class="article_issue_date">2005</span>. <span class="article_title">Protein C levels can be forecasted by global haemostatic tests in critically ill patients and predict long-term survival.</span> <span class="journal_series_title">Thromb Res</span>, <span class="journal_volume">vol 116</span> <span class="journal_pages">pp 15-24</span>.</div>
<div class="article_info">G Nilsson, S Höjgård and E Berntorp. <span class="article_issue_date"></span>. <span class="article_title">Treatment of the critically ill patient with protein C: aspects on survival and cost.</span> (manuscript)</div>
<div class="article_info">G Nilsson, K Strandberg, J Astermark, E Vernersson, J Stenflo and E Berntorp. <span class="article_issue_date"></span>. <span class="article_title">The APC-PCI complex concentration predicts outcome of aortic surgery.</span> (submitted)</div>

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems

Free keywords

  • Medicine (human and vertebrates)
  • protein C
  • mortality
  • intensive care
  • health economics
  • global haemostatic tests
  • blood coagulation disorders
  • APC-PCI complex
  • abdominal aortic aneurysm operation
  • antithrombin
  • Medicin (människa och djur)


Dive into the research topics of 'Coagulation disturbances in the critically ill patient with special reference to prediction of outcome'. Together they form a unique fingerprint.

Cite this