Skip to main content
Log in

RETRACTED ARTICLE: Thrombomodulin in intensive care patients

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

This article was retracted on 21 June 2023

This article has been updated

Abstract

Objective

Changes of endothelial-related coagulation was studied in intensive care patients.Design: Descriptive, prospective.Setting: Clinical investigation, intensive care unit of an university hospital.

Patients

40 consecutive critically ill patients with severe trauma (n=20) or postoperative complications (n=20) were studied. 14 patients suffered from sepsis, 12 patients suffered from acute renal failure.

Interventions

12 patients with acute renal failure were continuously hemofiltrated. All patients were on continuous sedation (fentanyl and midazolam) and mechanical ventilation.

Measurements

In addition to standard coagulation variables, thrombomodulin (TM), protein C and protein S as well as thrombin/antithrombin III (TAT) plasma concentrations were measured from arterial blood samples using enzymelinked immuno-sorbent assays (ELISA). Measurements were carried out on the day of admission (trauma patients) or on the day of diagnosis of sepsis and during the next 4 days.

Main results

Throughout the entire investigation period, TM plasma concentrations in patients with sepsis (baseline: 90±25 μg/l, 4th day: 152±28 μg/l) were significantly higher than in non-septic patients (baseline: 60±29 μg/l, 4th day: 42±15 μg/l). 15 of the 40 patients died within or after the end of the investigation period. TM plasma concentrations of survivors were lower (maximum: 63±18μg/l) than in the non-survivors (maximum: 159±22 μg/l) (p<0.05). Hemofiltered patients showed higher TM plasma levels, which further increased during the hemofiltration procedure. Protein C and (free) protein S were without significant group differences. TAT plasma levels were elevated above normal in all patients (no group differences).

Conclusions

Besides plasmatic and platelet-related coagulation, endothelium-associated coagulation appears to be also important for maintenance of hemostasis. TM plasma concentrations were elevated in all our critically ill patients, particularly when sepsis was evident. This appears to be most likely due to endothelial membrane damage with increased release of membrane-bound TM into the circulating blood in these patients. The importance of the elevated plasma levels of circulating soluble TM on hemostasis in these patients is an ongoing debate and warrants further studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Change history

References

  1. Scherer R, Kox WJ (1993) Consumptive coagulopathies in the critically ill. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine, Springer, Berlin Heidelberg New York Tokyo, pp 629–637

    Google Scholar 

  2. Lorente JA, Garcia-Frade J, Landin L, dePablo R, Torrado C, Renes E, Garcia-Avello A (1993) Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 103: 1536–1542

    Article  CAS  PubMed  Google Scholar 

  3. Bone RC (1992) Sepsis and cogulation. An important link. Chest 101:594–595

    Article  CAS  PubMed  Google Scholar 

  4. Gibbs NM, Crawford PM, Michalopoulos N (1992) Postoperative changes in coagulant and anticoagulant factors following abdominal aortic surgery. J Cardiothorac Vasc Anesth 6:680–685

    Article  CAS  PubMed  Google Scholar 

  5. Sterm DM, Esosito C, Gerlach H, Gerlach M, Ryan J, Handley D, Nawroth P (1991) Endothelium and regulation of coagulation. Diabetes Care 14 [Suppl 1]: 160–166

    Article  Google Scholar 

  6. Wu KK (1992) Endothelial cells in hemostatis, thrombosis, and inflammation. Hosp Pract 145-166

  7. Gerlach H, Esposito C, Stern D (1990) Modulation of endothelial hemostatic properties: an active role in the host response. Ann Rev Med 41:15–24

    Article  CAS  PubMed  Google Scholar 

  8. Maruyama I (1992) Thrombomodulin, an endothelial anticoagulant: its structure, function and expression. Jpn Circ J 56:187–191

    Article  CAS  PubMed  Google Scholar 

  9. Takano S, Kimura S, Ohdama S, Aoki N (1990) Plasma thrombomodulin in health and diseases. Blood 76: 2024–2029

    Article  CAS  PubMed  Google Scholar 

  10. Thompson EA, Salem HH (1997) The role of thrombomodulin in the regulation of hemostatic interactions. Progr Hematol 15:51–70

    Google Scholar 

  11. Dittman WA, Majerus PW (1990) Structure and function of thrombomodulin: a natural anticoagulant. Blood 75:329–336

    Article  CAS  PubMed  Google Scholar 

  12. Esmon CT (1989) The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 264:4743–4746

    Article  CAS  PubMed  Google Scholar 

  13. Mann KG, Krishnaswamy S, Lawson JH (1992) Surface-dependent hemostasis. Semin Hematol 29:213–226

    CAS  PubMed  Google Scholar 

  14. Bone RC, Fein AM, Balk RA et al (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 104:1644–1655

    Article  Google Scholar 

  15. Baker SP, O'Neill B (1976) The injury severity score: an update. J Trauma 16:882–888

    Article  CAS  PubMed  Google Scholar 

  16. Boffa MC, Karochkine M, Berard M (1991) Plasma thrombomodulin as a marker of endothelium damage. Nouv Rev Fr Hematol 33:529–530

    CAS  PubMed  Google Scholar 

  17. Noworth PP, Handley DA, Esmon CT, Stern DM (1986) Interleukin I induces endothelial cell procoagulant while suppressing cell surface anticoagulant activity. Proc Natl Acad Sci USA 83: 3460–3464

    Article  Google Scholar 

  18. Moore KL, Esmon CT, Esmon NL (1989) Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. Blood 73:159–165

    Article  CAS  PubMed  Google Scholar 

  19. Amano K, Tateyama M, Inaba H, Fukutake F, Fuimaki M (1992) Fluctuations in plasma levels of endothelin in patients with DIC. Thromb Haemost 68:404–406

    Article  CAS  PubMed  Google Scholar 

  20. Ogawa S, Gerlach H, Esposito C, Pasagian-Macaulay A, Brett J, Stern D (1990) Hypoxia modulates the barrier and coagulant function of the cultured bovine endothelium: increased monolayer permeability and induction of procoagulant properties. J Clin Invest 85:1090–1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yamazaki M, Asakura H, Sato T, Tsugawa Y, Matsumura M, Kawamura Y, Ohka T, Matsuda T (1992) Changes in plasma levels of thrombomodulin during haemodialysis. Blood Coagul Fibrinolysis 3:113–117

    Article  CAS  PubMed  Google Scholar 

  22. Sakurabayashi I, Itou, Ishii S, Kawai T, Ito H, Honma S (1985) Studies on granulocyte elastase in plasma. Jpn J Clin Hematol 33:1113–1118

    CAS  Google Scholar 

  23. Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Morishita E, Yamazaki M, Matsuda T (1991) Plasma levels of soluble thrombomodulin increase in cases of disseminated intravascular coagulation with organ failure. Am J Hematol 38:281–287

    Article  CAS  PubMed  Google Scholar 

  24. Uchiyama H, Hiraishi S, Ishii H, Kazama M (1989) Plasma thrombomodulin is originated by damage of endothelial cell. Thromb Haemost 62: 276–280

    Google Scholar 

  25. Komada T, Dittman WA, Majerus PW (1988) A role for thrombomodulin in the patho-genesis of thrombin-thromboembolism in mice. Blood 71: 728–733

    Article  Google Scholar 

  26. Ishii H, Majerus PW (1985) Thrombomodulin is present in human plasma and urin. J Clin Invest 76:2178–2183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ishii H, Uchiyama H, Kazama M (1991) Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemost 65:618–623

    Article  CAS  PubMed  Google Scholar 

  28. Dittman WA (1991) Thrombomodulin. Biological and cardiovascular applications. Trends Cardiovasc Med 1: 331–336

    Article  CAS  PubMed  Google Scholar 

  29. Feindt P, Volkmer I, Seyffert UT, Haack H (1991) The role of protein C as an inhibitor of blood clotting during extracorporeal circulation. Thorac Cardiovasc Surgeon 39:338–343

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Boldt, J., Wollbrück, T., Sonneborn, S. et al. RETRACTED ARTICLE: Thrombomodulin in intensive care patients. Intensive Care Med 21, 645–650 (1995). https://doi.org/10.1007/BF01711542

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01711542

Key word

Navigation