Laboratory Testing in Disseminated Intravascular Coagulation

Emmanuel J Favaloro

doi:10.1055/s-0030-1254055

Seminars in Thrombosis and Hemostasis, Table of Contents

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

Laboratory Testing in Disseminated Intravascular Coagulation

Emmanuel J. Favaloro¹

¹Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, NSW, Australia

Abstract

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.

KEYWORDS

Disseminated intravascular coagulation - DIC - diagnosis - hemostasis - laboratory testing

Full Text

References

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