Thromb Haemost 2008; 100(01): 146-148
DOI: 10.1160/TH07-10-0622
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

The biphasic transmittance waveform: An early marker of sepsis in patients with neutropenia

Nazia Hussain
1   Haematology Department, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK
,
Dan Hodson
1   Haematology Department, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK
,
Robert Marcus
1   Haematology Department, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK
,
Trevor Baglin
1   Haematology Department, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK
,
Roger Luddington
1   Haematology Department, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK
› Author Affiliations
Further Information

Publication History

Received 19 October 2007

Accepted after major revision 01 May 2008

Publication Date:
22 November 2017 (online)

Summary

Transmittance waveform (TW) analysis has been proposed as a method of both prediction and monitoring of non-overt and overt disseminated intravascular coagulation. This study assessed the use of the rapid TW of the activated partial thromboplastin time in the detection of sepsis in 49 consecutive neutropenic haemato-oncology patients. A slope 1 cut-off value of –0.050 was found to be optimum giving 85% sensitivity with 92% specificity and positive and negative predictive values of 62% and 98%, respectively. Furthermore a worsening slope 1 value at 24 hours was indicative of a 60% increase in mortality risk. Haemato-oncology patients have a significantly increased risk of developing sepsis during intensive chemotherapy, exacerbated by the resultant neutopenia. This sepsis may progress extremely rapidly and is associated with a high mortality. Early diagnosis is therefore critical and is currently made on a predominantly clinical basis with supporting microbiological evidence 2–3 days later. This study showed that TW offers an early marker, predictive of sepsis in neutropenic patients. It correlates with subsequent microbiological results and may identify patients at greater risk of clinical deterioration who may require more intensive early therapy or observation. It may also provide a useful marker to monitor the effects of treatment.

 
  • References

  • 1 Cohen J. The immunopathogenesis of sepsis. Nature 2002; 420: 885-891.
  • 2 Rangel-Frausto MS, Pittet D, Costigan M. et al. The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study. J Am Med Assoc 1995; 273: 117-123.
  • 3 Members of the American College of Chest Physicians/Society of Crit Care Med Consensus Conference Committee: American College of Chest Physicians/Society of Crit Care Med Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20: 864-874.
  • 4 Levy MM, Fink MP, Marshall JC. et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International sepsis definitions conference. Crit Care Med 2003; 31: 1250-1256.
  • 5 Penack O, Beinart T, Buchheidt D. et al. Management of sepsis in neutropenia: guidelines of the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2006; 85: 424-433.
  • 6 Tang BM, Eslick GD, Craig JC. et al. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007; 07: 210-217.
  • 7 Uzzan B, Cohen R, Nicolas P. et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and alter surgery or trauma: a systematic review and meta-analysis. Crit Care Med 2006; 34: 1996-2003.
  • 8 Downey D, Kazmi R, Toh CH. Novel & diagnostically applicable information from optical waveform analysis of blood coagulation in disseminated intravascular coagulation. Br J Haematol 1997; 98: 68-73.
  • 9 Downey D, Kazmi R, Toh CH. Early identification and prognostic implications in disseminated intravascular coagulation through transmittance waveform analysis. Thromb Haemost 1998; 80: 65-69.
  • 10 Toh CH, Samis J, Downey C. et al. Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca++-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation. Blood 2002; 100: 2522-2529.
  • 11 Chopin N, Floccard B, Sobas F. et al. Activated partial thromboplastin time waveform analysis : A new tool to detect infection?. Crit Care Med 2006; 34: 1654-1660.
  • 12 Nesheim M, Samis J, Walker J. et al. Lipoprotein-complexed c-reactive protein and the biphasic transmittance waveform in critically ill patients. Blood Rev 2002; 16 (Suppl. 01) S15-22.
  • 13 Toh CH, Ticknor LO, Downey C. et al. Early identification of sepsis and mortality risks through simple, rapid clot-waveform analysis, implications of lipoprotein-complexed c -reactive protein formation. Intensive Care Med 2003; 29: 55-61.
  • 14 Dempfle CH, Lorenz S, Smolinski M. et al. Unity of activated partial thromboplastin time waveform analysis for identification of sepsis and overt disseminated intravascular coagulation in patients admitted to a surgical intensive care unit. Crit Care Med 2004; 32 (02) 520-524.
  • 15 Bewick V, Cheek L, Ball J. Statistics Review 13: Receiver Operating Characteristic Curves. Crit Care 2004; 08: 508-512.
  • 16 Loong TW. Understanding sensitivity and specificity with the right side of the brain. Br Med J 2003; 327: 716-719.
  • 17 Wada H, Wakita Y, Nakase T. et al. Outcome of disseminated intravascular coagulation in relation to the score when treatment was begun. Mie DIC Study Group. Throm Haemost 1995; 74: 848-852.
  • 18 Khan MA, Siddiqui K, Shamim A. et al. Emerging bacterial resistance patterns in febrile neutropenic patients: experience at a tertiary care hospital in Pakistan. J Pak Med Assoc 2004; 54: 357-360.
  • 19 Marik P. Definition of sepsis: Not quite time to dump SIRS?. Crit Care Med 2002; 30: 706-708.