Review Article| Volume 129, ISSUE 5, e177-e184, May 2012

Diagnosis and treatment of disseminated intravascular coagulation: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)

Published:September 19, 2011DOI:



      The diagnosis and treatment of disseminated intravascular coagulation (DIC) remain extremely controversial.


      The Italian Society for Thrombosis and Haemostasis commissioned a project to develop clinical practice guidelines for the diagnosis and treatment of DIC.


      Key questions about the diagnosis and treatment of DIC were formulated by a multidisciplinary working group consisting of experts in clinical medicine and research. After a systematic review and discussion of the literature, recommendations were formulated and graded according to the supporting evidence. In the absence of evidence, evidence of low quality, or contradictory evidence, a formal consensus method was used to issue clinical recommendations.

      Results and Conclusions

      In suspected DIC, we suggest the use of the diagnostic scores ISTH (grade C), JMHW (grade C) or JAAM (grade D) over stand alone tests. The cornerstone of the management of DIC remains the treatment of the underlying triggering disease. We do not suggest the use of antithrombin (grade D), dermatan sulphate (grade D), gabexate (grade D), recombinant factor VIIa (grade D), activated protein C (grade D), thrombomodulin (grade B). The use of unfractionated heparin or low-molecular-weight heparin is not suggested except for thromboembombolic prophylaxis in patients a high risk who do not have active bleeding (grade D). In patients with severe sepsis/septic shock and DIC we suggest the use of human recombinant activated protein C (grade D). In patients with DIC and active bleeding we suggest the use of transfusion therapy (platelets, plasma, cryoprecipitate) (grade D).


      APACHE (Acute Physiology and Chronic Health Evaluation), DIC (Disseminated intravascular coagulation), FDP (fibrin degradation products), FFP (fresh-frozen plasma), ISTH (International Society on Thrombosis and Hemostasis), JAAM (Japanese Association for Acute Medicine), JMHW (Japanese Ministry of Health and Welfare), LMWH (low-molecular-weight heparin), PT (prothrombin time), RCT (randomized clinical trial), rFVIIa (recombinant activated factor VII), rhAPC (recombinant human activated protein C), SIGN (Scottish Intercollegiate Guideline Network), SISET (Società Italiana per lo Studio dell'Emostasi e Trombosi/Italian Society for Thrombosis and Haemostasis), UFH (unfractionated heparin)


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        • Levi M.
        • Ten Cate H.
        Disseminated intravascular coagulation.
        N Engl J Med. 1999; 341: 586-592
        • Levi M.
        Disseminated intravascular coagulation.
        Crit Care Med. 2007; 35: 2191-2195
        • Iorio A.
        • Ageno W.
        • Cosmi B.
        • Imberti D.
        • Lussana F.
        • Siragusa S.
        • et al.
        Objectives and methodology: Guidelines of the Italian Society for Haemostasis and Thrombosis.
        Thromb Res. 2009; 124: e1-e5
      1. Scottish Intercollegiate Guidelines Network, SIGN 50: A guideline developers' handbook, SIGN Publication No. 50. February 2001, last updated May 2004. Available from:

        • Bakhtiari K.
        • Meijers J.C.M.
        • 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: 2416-2421
        • Yanada M.
        • Matsushita T.
        • Suzuki M.
        • Kiyoi H.
        • Yamamoto K.
        • Kinoshita T.
        • et al.
        Disseminated intravascular coagulation in acute leukemia: clinical and laboratory features at presentation.
        Eur J Haematol. 2006; 77: 282-287
        • Gando S.
        • Iba T.
        • Eguchi Y.
        • Ohtomo Y.
        • Okamoto K.
        • Koseki K.
        • et al.
        A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: Comparing current criteria.
        Crit Care Med. 2006; 34: 625-631
        • Sawamura A.
        • Hayakawa M.
        • Gando S.
        • Kubota N.
        • Sugano M.
        • Wada T.
        • et al.
        Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma.
        Thromb Res. 2009; 124: 706-710
        • 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: 595-600
        • Matsumoto T.
        • Wada H.
        • Nishioka Y.
        • Nishio M.
        • Abe Y.
        • Nishioka J.
        • 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: 185-192
        • Hayakawa M.
        • Gando S.
        • Hoshino H.
        A prospective comparative study of three sets of criteria for disseminated intravascular coagulation.
        Clin Appl Thromb Haemost. 2007; 13: 65-72
        • Wada H.
        • Gabazza E.C.
        • Asakura H.
        • Koike K.
        • Okamoto K.
        • Maruyama I.
        • et al.
        Comparison of diagnostic criteria for disseminated intravascular coagulation (DIC): diagnostic criteria of the International Society of Thrombosis and Hemostasis (ISTH) and of the Japanese Ministry of Health and Welfare for overt DIC.
        Am J Hematol. 2003; 74: 17-22
        • Kawasugi K.
        Hideo Wada H, Hatada T, Okamoto K, Uchiyama T, Kushimoto S, et al.
        Prospective evaluation of hemostatic abnormalities in overt DIC due to various underlying diseases. Thromb Res. 2011; 128: 186-190
        • Angstwurm M.W.A.
        • Dempfle C.-E.
        • Spannagl M.
        New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores.
        Crit Care Med. 2006; 34: 314-320
        • Gando S.
        • Saitoh D.
        • Ogura H.
        • Mayumi T.
        • Koseki K.
        • Ikeda T.
        • 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: 145-150
        • Takemitsu T.
        • Wada H.
        • Hatada T.
        • Ohmori Y.
        • Ishikura K.
        • Takeda T.
        • et al.
        Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation.
        Thromb Haemost. 2011; 105: 40-44
        • Iwai K.
        • Uchino S.
        • Endo A.
        • Saito K.
        • Kase Y.
        • Takinami M.
        Prospective external validation of the new scoring system for disseminated intravascular coagulation by Japanese Association for Acute Medicine (JAAM).
        Thromb Res. 2010; 126: 217-221
        • Kinasewitz G.T.
        • Zein J.G.
        • Lee G.L.
        • Nazir S.A.
        • Taylor F.B.
        Prognostic value of a simple evolving disseminated intravascular coagulation score in patients with severe sepsis.
        Crit Care Med. 2005; 33: 2214-2221
        • Dhainaut J.F.
        • Shorr A.F.
        • Macias W.L.
        • Kollef M.J.
        • Levi M.
        • Reinhart K.
        • et al.
        Dynamic evolution of coagulopathy in the first day of severe sepsis: Relationship with mortality and organ failure.
        Crit Care Med. 2005; 33: 341-348
        • Nakamura Y.
        • Tomura S.
        • Tachibana K.
        • Chiba Y.
        • Marumo F.
        Enhanced fibrinolytic activity during the course of haemodialysis.
        Clin Nephrol. 1992; 38: 90-96
        • Wiedermann C.J.
        • Kaneider N.C.
        A systematic review of antithrombin concentrate use in patients with disseminated intravascular coagulation of severe sepsis.
        Blood Coagul Fibrinolysis. 2006; 17: 521-526
        • Fourrier F.
        • Chopin C.
        • Huart J.J.
        • Runge I.
        • Caron C.
        • Goudemand J.
        Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation.
        Chest. 1993; 104: 882-888
        • Blauhut B.
        • Kramar H.
        • Vinazzer H.
        • Bergmann H.
        Substitution of antithrombin III in shock and DIC: a randomized study.
        Thromb Res. 1985; 39: 81-89
        • Inthorn D.
        • Hoffmann J.N.
        • Hartl W.H.
        • Mulbayer D.
        • Jochum M.
        Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction.
        Shock. 1997; 8: 328-334
        • Maki M.
        • Terao T.
        • Ikenoue T.
        • Takemura T.
        • Sekiba K.
        • Shirakawa K.
        • et al.
        Clinical evaluation of antithrombin III concentrate (BI 6.013) for disseminated intravascular coagulation in obstetrics.
        Gynecol Obstet Invest. 1987; 23: 230-240
        • Lavrentieva A.
        • Kontakiotis T.
        • Bitzani M.
        • Parlapani A.
        • Thomareis O.
        • Scourtis H.
        • et al.
        The efficacy of antithrombin administration in the acute phase of burn injury.
        Thromb Haemost. 2008; 100: 286-290
        • Langley P.G.
        • Hughes R.D.
        • Forbes A.
        • Keays R.
        • Williams R.
        Controlled trial of antithrombin III supplementation in fulminant hepatic failure.
        J Hepatol. 1993; 17: 326-331
        • Cofrancesco E.
        • Boschetti C.
        • Leonardi P.
        • Gianese F.
        • Cortellaro M.
        Dermatan sulphate for the treatment of disseminated intravascular coagulation (DIC) in acute leukemia: a randomised, heparin-controlled pilot study.
        Thromb Res. 1994; 74: 65-75
        • Sakuragawa N.
        • Hasegawa H.
        • Maki M.
        • Nakagawa M.
        • Nakashima M.
        Clinical evaluation of low-molecular-weight heparin (FR-860) on disseminated intravascular coagulation (DIC). A multicenter co-operative double-blind trial in comparison with heparin.
        Thromb Res. 1993; 72: 475-500
        • Umeki S.
        • Adachi M.
        • Watanabe M.
        • Yaji S.
        • Soejima R.
        Gabexate as a therapy for disseminated intravascular coagulation.
        Arch Intern Med. 1988; 148: 1409-1412
        • Aoki N.
        • Matsuda T.
        • Saito H.
        • Takatsuki K.
        • Okajima K.
        • Takahashi H.
        • et al.
        A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation.
        Int J Hematol. 2002; 75: 540-547
        • Jaimes F.
        • De La Rosa G.
        • Morales C.
        • Fortich F.
        • Arango C.
        • Aguirre D.
        • et al.
        Unfractioned heparin for treatment of sepsis: a randomized clinical trial (The HETRASE Study).
        Crit Care Med. 2009; 37: 1185-1196
        • Oguma Y.
        • Sakuragawa N.
        • Maki M.
        • Nakagawa M.
        • Hasegawa H.
        Clinical effect of low-molecular-weight heparin (Fragmin) on DIC: a multicenter cooperative study in Japan.
        Thromb Res. 1990; 59: 37-49
        • Sallah S.
        • Husain A.
        • Nguyen N.P.
        Recombinant activated factor VII in patients with cancer and hemorrhagic disseminated intravascular coagulation.
        Blood Coagul Fibrinolysis. 2004; 15: 577-582
        • Baudo F.
        • Caimi T.M.
        • Mostarda G.
        • De Cataldo F.
        • Morra E.
        Critical bleeding in pregnancy: a novel therapeutic approach to bleeding.
        Minerva Anestesiol. 2006; 72: 389-393
        • Nishiyama T.
        • Matsukawa T.
        • Hanaoka K.
        Is protease inhibitor a choice for the treatment of pre- or mild disseminated intravascular coagulation?.
        Crit Care Med. 2000; 28: 1419-1422
        • Bernard G.R.
        • Vincent J.-L.
        • Laterre P.-F.
        • LaRosa S.P.
        • Dhainaut J.-F.
        • Rodriguez A.L.
        • et al.
        Efficacy and safety of recombinant human activated protein C for severe sepsis.
        N Engl J Med. 2001; 344: 699-709
        • Dhainaut J.-F.
        • Yan S.B.
        • Joyce D.E.
        • Pettilä V.
        • Basson B.
        • Brandt J.T.
        • et al.
        Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.
        J Thromb Haemost. 2004; 2: 1924-1933
        • Kobayashi T.
        • Terao T.
        • Maki M.
        • Ikenoue T.
        Activated Protein C Is Effective for Disseminated Intravascular Associated with Placental Abruption.
        Thromb Haemost. 1999; 82: 1363
        • Rivard G.E.
        • David M.
        • Farrell C.
        • Schwarz H.P.
        Treatment of purpura fulminans in meningococcemia with protein C concentrate.
        J Pediatr. 1995; 126: 646-652
        • Ettinghausen C.E.
        • Veldmann A.
        • Beeg T.
        • Schneider W.
        • Jager G.
        • Kreuz W.
        Replacement therapy with protein C concentrate in infants and adolescents with Meningococcal sepsis and purpura fulminans.
        Semin Thromb Haemost. 1999; 25: 537-541
        • Rintala E.
        • Kauppila M.
        • Seppala O.-P.
        • Voipio-Pulkki L.-M.
        • Pettila V.
        • Rasi V.
        • et al.
        Protein C substitution in sepsis-associated purpura fulminans.
        Crit Care Med. 2000; 28: 2373-2378
        • de Kleijn E.D.
        • de Groot R.
        • Hack C.E.
        • Mulder P.G.H.
        • Engl W.
        • Moritz B.
        • et al.
        Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: A randomized, double-blinded, placebo-controlled, dose-finding study.
        Crit Care Med. 2003; 31: 1839-1847
        • Churchwell K.B.
        • McManus M.L.
        • Kent P.
        • Gorlin J.
        • Galacki D.
        • Humphreys D.
        • et al.
        Intensive blood and plasma exchange for treatment of coagulopahty in meningococcemia.
        J Clin Apher. 1995; 10: 171-177
        • Saito H.
        • Maruyama I.
        • Shimazaki S.
        • Yamamoto Y.
        • Aikawa N.
        • Ohno R.
        • et al.
        Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial.
        J Thromb Haemost. 2007; 5: 31-41
        • Stanworth S.J.
        • Brunskill Sj
        • Hyde C.J.
        • McClelland D.B.L.
        • Murphy M.F.
        Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials.
        Br J Haematol. 2004; 126: 139-152
        • Levi M.
        • Toh C.H.
        • Thachil J.
        • Watson H.G.
        Guidelines for the diagnosis and management of disseminated intravascular coagulation.
        Br J Haematol. 2009; 145: 24-33
        • Wada H.
        • Asakura H.
        • Okamoto K.
        • Iba T.
        • Uchiyama T.
        • Kawasugi K.
        • et al.
        Expert consensus for the treatment of disseminated intravascular coagulation in Japan.
        Thromb Res. 2010; 125: 6-11
        • Iba T.
        • Asakura H.
        Comparison between British and Japanese guidelines for the diagnosis and treatment of disseminated intravascular coagulation.
        Br J Haematol. 2010; 149: 461-462
        • Levi M.
        Japanese consensus for disseminated intravascular coagulation (DIC): Is it a small world after all?.
        Thromb Res. 2010; 125: 4-5