Semin Thromb Hemost 2010; 36(4): 458-467
DOI: 10.1055/s-0030-1254055
© Thieme Medical Publishers

Laboratory Testing in Disseminated Intravascular Coagulation

Emmanuel J. Favaloro1
  • 1Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, NSW, Australia
Further Information

Publication History

Publication Date:
07 July 2010 (online)

ABSTRACT

The diagnosis of disseminated intravascular coagulation (DIC) relies on clinical signs and symptoms, identification of the underlying disease, the results of laboratory testing, and differentiation from other pathologies. The clinical features mainly depend on the underlying cause of the DIC. The laboratory diagnosis of DIC uses a combination of tests because no single test result alone can firmly establish or rule out the diagnosis. Global tests of hemostasis may initially provide evidence of coagulation activation and later in the process provide evidence of consumption of coagulation factors, but their individual diagnostic efficiency is limited. Fibrinolytic markers, in particular D-dimer, are reflective of activation of both coagulation and fibrinolysis, so that a normal finding can be useful for ruling-out DIC. Decreased levels of the natural anticoagulants (in particular, antithrombin and protein C) are frequently observed in patients with DIC, but their measurement is not normally incorporated into standard diagnostic algorithms. New tests are being explored for utility in DIC, and some additional tests may be useful on a case-by-case basis, depending on the proposed cause of the DIC or their local availability. For example, clot waveform analysis is useful but currently limited to a single instrument. Also, procalcitonin is an inflammatory biomarker that may be useful within the context of septic DIC, and activated factor X clotting time is an emerging test of procoagulant phospholipids that also seems to hold promise in DIC.

REFERENCES

  • 1 Taylor Jr F B, Toh C H, Hoots W K, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH) . Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation.  Thromb Haemost. 2001;  86(5) 1327-1330
  • 2 Franchini M, Lippi G, Manzato F. Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation.  Thromb J. 2006;  4 4
  • 3 Kobayashi T, Terao T, Maki M, Ikenoue T. Diagnosis and management of acute obstetrical DIC.  Semin Thromb Hemost. 2001;  27(2) 161-167
  • 4 Barbui T, Falanga A. Disseminated intravascular coagulation in acute leukemia.  Semin Thromb Hemost. 2001;  27(6) 593-604
  • 5 Levi M, de Jonge E, van der Poll T. Sepsis and disseminated intravascular coagulation.  J Thromb Thrombolysis. 2003;  16(1–2) 43-47
  • 6 Zeerleder S, Hack C E, Wuillemin W A. Disseminated intravascular coagulation in sepsis.  Chest. 2005;  128(4) 2864-2875
  • 7 Opal S M. The host response to endotoxin, antilipopolysaccharide strategies, and the management of severe sepsis.  Int J Med Microbiol. 2007;  297(5) 365-377
  • 8 Lippi G, Guidi G C. Laboratory diagnostics in septic disseminated intravascular coagulation.  European Haematol. 2009;  3 19-24
  • 9 Levi M, van der Poll T. Coagulation in sepsis: all bugs bite equally.  Crit Care. 2004;  8(2) 99-100
  • 10 Lippi G, Cervellin G. Disseminated intravascular coagulation in trauma injuries.  Semin Thromb Hemost. 2010;  36(4) 378-387
  • 11 Horan J T, Francis C W. Fibrin degradation products, fibrin monomer and soluble fibrin in disseminated intravascular coagulation.  Semin Thromb Hemost. 2001;  27(6) 657-666
  • 12 Hack C E. Fibrinolysis in disseminated intravascular coagulation.  Semin Thromb Hemost. 2001;  27(6) 633-638
  • 13 Levi M, van der Poll T. The role of natural anticoagulants in the pathogenesis and management of systemic activation of coagulation and inflammation in critically ill patients.  Semin Thromb Hemost. 2008;  34(5) 459-468
  • 14 Toh C H. Laboratory testing in disseminated intravascular coagulation.  Semin Thromb Hemost. 2001;  27(6) 653-656
  • 15 Favaloro E J, Adcock D M. Standardization of the INR: how good is your laboratory's INR and can it be improved?.  Semin Thromb Hemost. 2008;  34(7) 593-603
  • 16 Bick R L. Disseminated intravascular coagulation: pathophysiological mechanisms and manifestations.  Semin Thromb Hemost. 1998;  24(1) 3-18
  • 17 Lippi G, Favaloro E J. Activated partial thromboplastin time: new tricks for an old dogma.  Semin Thromb Hemost. 2008;  34(7) 604-611
  • 18 Prechel M, Walenga J M. The laboratory diagnosis and clinical management of patients with heparin-induced thrombocytopenia: an update.  Semin Thromb Hemost. 2008;  34(1) 86-96
  • 19 Selleng K, Selleng S, Greinacher A. Heparin-induced thrombocytopenia in intensive care patients.  Semin Thromb Hemost. 2008;  34(5) 425-438
  • 20 Levi M, Löwenberg E C. Thrombocytopenia in critically ill patients.  Semin Thromb Hemost. 2008;  34(5) 417-424
  • 21 Wada H, Sakuragawa N, Mori Y et al.. Hemostatic molecular markers before the onset of disseminated intravascular coagulation.  Am J Hematol. 1999;  60(4) 273-278
  • 22 Wada H, Sakuragawa N. Are fibrin-related markers useful for the diagnosis of thrombosis?.  Semin Thromb Hemost. 2008;  34(1) 33-38
  • 23 Lippi G, Franchini M, Targher G, Favaloro E J. Help me, Doctor! My D-dimer is raised.  Ann Med. 2008;  40(8) 594-605
  • 24 ISTH SSC DIC Meeting Report 2003. From the 49th Scientific and Standardization Committee Meeting (Birmingham, UK). Available at: http://www.isth.org/Publications/SSCMinutes/tabid/85/Default.aspx Accessed January 1, 2010
  • 25 de Jonge E, van der Poll T, Kesecioglu J, Levi M. Anticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience.  Semin Thromb Hemost. 2001;  27(6) 667-674
  • 26 Levi M, Toh C H, Thachil J, Watson H G. British Committee for Standards in Haematology . Guidelines for the diagnosis and management of disseminated intravascular coagulation.  Br J Haematol. 2009;  145(1) 24-33
  • 27 Wiedermann C J. Clinical review: molecular mechanisms underlying the role of antithrombin in sepsis.  Crit Care. 2006;  10(1) 209
  • 28 Wilson R F, Mammen E F, Robson M C, Heggers J P, Soullier G, DePoli P A. Antithrombin, prekallikrein, and fibronectin levels in surgical patients.  Arch Surg. 1986;  121(6) 635-640
  • 29 Ersoy B, Nehir H, Altinoz S, Yilmaz O, Dundar P E, Aydogan A. Prognostic value of initial antithrombin levels in neonatal sepsis.  Indian Pediatr. 2007;  44(8) 581-584
  • 30 Fourrier F, Chopin C, Goudemand J et al.. Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies.  Chest. 1992;  101(3) 816-823
  • 31 Mesters R M, Helterbrand J, Utterback B G et al.. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications.  Crit Care Med. 2000;  28(7) 2209-2216
  • 32 Toh C H, Hoots W K. SSC on Disseminated Intravascular Coagulation of the ISTH . The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview.  J Thromb Haemost. 2007;  5(3) 604-606
  • 33 Cauchie P, Cauchie Ch, Boudjeltia K Z et al.. Diagnosis and prognosis of overt disseminated intravascular coagulation in a general hospital—meaning of the ISTH score system, fibrin monomers, and lipoprotein-C-reactive protein complex formation.  Am J Hematol. 2006;  81(6) 414-419
  • 34 Kobayashi N, Maegawa K, Takada M, Tanaka H, Gonmori H. Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan.  Bibl Haematol. 1983;  (49) 265-275
  • 35 Voves C, Wuillemin W A, Zeerleder S. International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients.  Blood Coagul Fibrinolysis. 2006;  17(6) 445-451
  • 36 Wada H, Gabazza E C, Asakura H et al.. Comparison of diagnostic criteria for disseminated intravascular coagulation (DIC): diagnostic criteria of the International Society of Thrombosis and Hemostasis and of the Japanese Ministry of Health and Welfare for overt DIC.  Am J Hematol. 2003;  74(1) 17-22
  • 37 Gando S, Iba T, Eguchi Y et al.. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria.  Crit Care Med. 2006;  34(3) 625-631
  • 38 Gando S, Saitoh D, Ogura H et al.. Natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey.  Crit Care Med. 2008;  36(1) 145-150
  • 39 Gando S, Saitoh D, Ogura H et al.. Disseminated intravascular coagulation (DIC) diagnosed based on the Japanese Association for Acute Medicine criteria is a dependent continuum to overt DIC in patients with sepsis.  Thromb Res. 2009;  123(5) 715-718
  • 40 Kushimoto S, Gando S, Saitoh D et al.. Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria. Comparison between sepsis and trauma.  Thromb Haemost. 2008;  100(6) 1099-1105
  • 41 Lee J H, Song J W, Song K S. Diagnosis of overt disseminated intravascular coagulation: a comparative study using criteria from the International Society versus the Korean Society on Thrombosis and Hemostasis.  Yonsei Med J. 2007;  48(4) 595-600
  • 42 Kershaw G, Jayakodi D, Dunkley S. Laboratory identification of factor inhibitors: the perspective of a large tertiary hemophilia center.  Semin Thromb Hemost. 2009;  35(8) 760-768
  • 43 Levi M, Opal S M. Coagulation abnormalities in critically ill patients.  Crit Care. 2006;  10(4) 222
  • 44 Wada H, Usui M, Sakuragawa N. Hemostatic abnormalities and liver diseases.  Semin Thromb Hemost. 2008;  34(8) 772-778
  • 45 Downey C, Kazmi R, Toh C H. Novel and diagnostically applicable information from optical waveform analysis of blood coagulation in disseminated intravascular coagulation.  Br J Haematol. 1997;  98(1) 68-73
  • 46 Downey C, Kazmi R, Toh C H. Early identification and prognostic implications in disseminated intravascular coagulation through transmittance waveform analysis.  Thromb Haemost. 1998;  80 65-69
  • 47 Toh C H, 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(7) 2522-2529
  • 48 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 1) S15-S22
  • 49 Matsumoto T, Wada H, Nishioka Y et al.. Frequency of abnormal biphasic aPTT clot waveforms in patients with underlying disorders associated with disseminated intravascular coagulation.  Clin Appl Thromb Hemost. 2006;  12(2) 185-192
  • 50 Bakhtiari K, Meijers J C, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation.  Crit Care Med. 2004;  32(12) 2416-2421
  • 51 Toh C H. Transmittance waveform of routine coagulation tests is a sensitive and specific method for diagnosing non-overt disseminated intravascular coagulation.  Blood Rev. 2002;  16(Suppl 1) S11-S14
  • 52 Toh C H, Giles A R. Waveform analysis of clotting test optical profiles in the diagnosis and management of disseminated intravascular coagulation (DIC).  Clin Lab Haematol. 2002;  24(6) 321-327
  • 53 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(6) 1654-1660
  • 54 Mina A, Favaloro E J, Mohammed S, Koutts J. A laboratory evaluation into the short APTT.  Blood Coagul Fibrinolysis. 2010;  21(2) 152-157
  • 55 Exner T, Joseph J, Low J, Connor D, Ma D. A new activated factor X-based clotting method with improved specificity for procoagulant phospholipid.  Blood Coagul Fibrinolysis. 2003;  14(8) 773-779
  • 56 Enjeti A K, Lincz L F, Seldon M. Detection and measurement of microparticles: an evolving research tool for vascular biology.  Semin Thromb Hemost. 2007;  33(8) 771-779
  • 57 Enjeti A K, Lincz L F, Seldon M. Microparticles in health and disease.  Semin Thromb Hemost. 2008;  34(7) 683-691
  • 58 van Dreden P, Rousseau A, Fontaine S, Woodhams B J, Exner T. Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids.  Blood Coagul Fibrinolysis. 2009;  20 494-502
  • 59 Connor D E, Exner T, Ma D D, Joseph J E. Detection of the procoagulant activity of microparticle-associated phosphatidylserine using XACT.  Blood Coagul Fibrinolysis. 2009;  20 558-564
  • 60 Seo J W, Kim H K, Kim J E, Park S, Cho H I. Prognostic values of the factor Xa-activated clotting time and endogenous thrombin potential in patients suspected of having disseminated intravascular coagulation.  Thromb Res. 2009;  123(4) 565-572
  • 61 Hong K H, Kim H K, Kim J E, Jung J S, Han K S, Cho H I. Prognostic value of immature platelet fraction and plasma thrombopoietin in disseminated intravascular coagulation.  Blood Coagul Fibrinolysis. 2009;  20(6) 409-414
  • 62 Herzum I, Renz H. Inflammatory markers in SIRS, sepsis and septic shock.  Curr Med Chem. 2008;  15(6) 581-587
  • 63 Schneider H G, Lam Q T. Procalcitonin for the clinical laboratory: a review.  Pathology. 2007;  39(4) 383-390

Dr. E.J. FavaloroPh.D. M.A.I.M.S. 

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital

WSAHS, Westmead, NSW 2145, Australia

Email: emmanuel.favaloro@swahs.health.nsw.gov.au