Guideline sources The following summarized guidelines for the evaluation and management of disseminated intravascular coagulation are prepared by our editorial team based on guidelines from the International Society on Thrombosis and Haemostasis (ISTH 2015; 2013), the Italian Society for Haemostasis and Thrombosis (SISET 2012), and the British Committee for Standards In Haematology (BCSH 2009). 1 2 3 4 5 5 6 7 8 Definition DIC is a clinicopathologic syndrome characterized by systemic activation of widespread coagulation resulting in severe bleeding and organ failure. 5 Epidemiology DIC is mostly caused by hypercoagulation (infection, particularly sepsis) and hyperfibrinolysis (acute promyelocytic leukemia, obstetric diseases, or aortic aneurysms). 6 Pathophysiology The incidence of DIC in the United States is estimated at 18.6 cases per 100,000 person-years. 5 i https://web.pathway.md/diseases/recGyBhLwbD48Ylbm 1/7 6/29/23, 10:19 PM Disseminated intravascular coagulation Pathway Disease course Clinical manifestations include latent and compensated activation of coagulation (no obvious clinical symptoms) and overt DIC (microvascular thrombosis; multi-organ dysfunction includes renal insufficiency, respiratory failure, hypotension, circulatory failure, or impaired cerebral function; macrovascular thrombi results in venous or arterial obstruction and embolization) Sustained thrombin generation results in severe bleeding and increased risk of death. 7 Prognosis and risk of recurrence The in-hospital mortality of DIC in critically ill patients is 45%. 8 Calculator ISTH criteria criteria for dissemi Guidelines 1. Screening and diagnosis Diagnosis: As per ISTH 2013 guidelines, recognize that there is no gold standard for the diagnosis of DIC and a single test that is, by itself, capable of accurately diagnosing DIC. As per BCSH 2009 guidelines, diagnose DIC based on both clinical and laboratory evaluation. B 2. Classification and risk stratification Scoring systems: As per ISTH 2013 guidelines, use a scoring system for the diagnosis of DIC, recognizing that the ISTH score correlates with key clinical observations and outcomes. B As per SISET 2012 guidelines, consider using any of the following scoring systems to make the diagnosis in patients with suspected DIC: the ISTH score C the JMHW score C the JAAM score. C Show 2 more As per BCSH 2009 guidelines, use the ISTH DIC scoring system to obtain objective measurement of DIC. B 3. Diagnostic investigations https://web.pathway.md/diseases/recGyBhLwbD48Ylbm 2/7 6/29/23, 10:19 PM Disseminated intravascular coagulation Pathway Laboratory tests: Avoid using stand-alone laboratory tests in patients with suspected DIC. D Consider obtaining D-dimer as a fibrin-related marker considering an increase up to 10 times the ULN as moderate and an increase above this threshold as strong. C 4. Medical management General principles: as per ISTH 2013 guidelines, treat the underlying condition as the cornerstone of treatment of DIC. B Prothrombin complex concentrate: As per ISTH 2013 guidelines, consider administering PCC in actively bleeding patients if FFP transfusion is not possible. As per BCSH 2009 guidelines, consider administering factor concentrates, such as PCC, if transfusion of FFP is not possible in patients with bleeding because of fluid overload, recognizing that these will only partially correct the defect because they contain only selected factors, whereas in DIC there is a global deficiency of coagulation factors. C Fibrinogen replacement: As per ISTH 2013 guidelines, consider administering fibrinogen concentrate or cryoprecipitate in actively bleeding patients with persisting severe hypofibrinogenemia (< 1.5 g/L) despite FFP replacement. C As per BCSH 2009 guidelines, consider administering fibrinogen concentrate or cryoprecipitate in patients with severe hypofibrinogenemia (< 1 g/L) persisting despite FFP replacement. C Recombinant factor VIIa: avoid using routine recombinant activated factor VII in bleeding patients with solid tumors or obstetric complications and DIC. D Activated protein C: As per ISTH 2013 guidelines, insufficient evidence to support the use of activated protein C in patients with DIC. Consider using on a case-by-case basis. I As per SISET 2012 guidelines, consider administering recombinant human activated protein C in patients with severe sepsis/septic shock, APACHE II score > 25 (EMEA: at least 2 organs compromised) and DIC. C Show 2 more As per BCSH 2009 guidelines, consider administering recombinant human-activated protein C (continuous infusion, 24 g/kg/hour for 4 days) in patients with severe sepsis and DIC. B Show 2 more Intravenous heparin: As per ISTH 2013 guidelines, consider administering therapeutic doses of heparin in patients with DIC where thrombosis predominates. Prefer LMWH over UFH. C As per BCSH 2009 guidelines: Consider administering therapeutic doses of heparin in patients with DIC with predominating thrombosis, such as arterial or VTE, severe purpura fulminans associated with acral ischemia or vascular skin infarction. https://web.pathway.md/diseases/recGyBhLwbD48Ylbm 3/7 6/29/23, 10:19 PM Disseminated intravascular coagulation Pathway Consider administering continuous infusion UFH in patients with perceived coexisting high risk of bleeding. Consider administering weight adjusted doses (such as 10 g/kg/hour) without the intention of prolonging the activated PTT ratio 1.5-2.5 times the control. Observe clinical signs of bleeding because monitoring the activated PTT in these patients may be complicated. C Antithrombin concentrate: As per SISET 2012 guidelines, avoid using thrombomodulin in patients with hematological cancer or infection and DIC. D As per BCSH 2009 guidelines, do not administer antithrombin in patients with DIC not receiving heparin. D Recombinant thrombomodulin: As per ISTH 2013 guidelines, insufficient evidence to support the use of recombinant human thrombomodulin in patients with DIC. Consider using on a case-by-case basis. I As per SISET 2012 guidelines, avoid using antithrombin in patients with DIC secondary to severe sepsis/septic shock, obstetric complications, burn injury or advanced liver disease. D Dermatan sulfate and gabexate: Avoid using dermatan sulfate in patients with DIC and hematological malignancy. D Avoid using in patients with DIC and sepsis, malignancy, or in patients undergoing surgery. D Antifibrinolytic agents: As per ISTH 2013 guidelines: Avoid using antifibrinolytic agents in patients with DIC. D Consider administering antifibrinolytic agents in patients with DIC presenting with severe bleeding characterized by a marked hyperfibrinolytic state such as leukemia C or trauma. C As per BCSH 2009 guidelines, consider administering lysine analogs, such as tranexamic acid (for example 1 g every 8 hours), in patients with DIC characterized by a primary hyperfibrinolytic state and presenting with severe bleeding. C 5. Inpatient care Thromboprophylaxis: As per ISTH 2013 guidelines, administer prophylaxis for VTE with prophylactic doses of UFH B or LMWH in critically ill, non-bleeding patients with DIC, recognizing that there is no direct evidence of the effects of anticoagulants on DIC. A As per SISET 2012 guidelines, avoid administering UFH or LMWH in patients with DIC except for thromboembolic prophylaxis in patients at high risk not having active bleeding. D 6. Therapeutic procedures Indications for transfusion therapy: https://web.pathway.md/diseases/recGyBhLwbD48Ylbm 4/7 6/29/23, 10:19 PM Disseminated intravascular coagulation Pathway Consider performing transfusion (platelets, plasma, cryoprecipitate) in patients with DIC and active bleeding. C Avoid performing transfusion solely based on laboratory parameters in patients with chronic DIC or without active bleeding. D Platelet transfusion: As per ISTH 2013 guidelines, administer platelets in patients with DIC with active bleeding and a platelet count of < 50 10 /L or in patients at high risk of bleeding and a platelet count of < 20 10 /L. B As per BCSH 2009 guidelines, do not rely primarily on laboratory results to administer platelets or plasma (components) in patients with DIC. Reserve it for patients presenting with bleeding. D Show 2 more Fresh frozen plasma transfusion: As per ISTH 2013 guidelines, consider administering FFP in patients with active bleeding with either prolonged PT/activated PTT (> 1.5 times normal) or decreased fibrinogen (< 1.5 g/dL). Consider administering FFP in patients with DIC requiring an invasive procedure with similar laboratory abnormalities. C As per BCSH 2009 guidelines, consider administering FFP in bleeding patients with DIC and prolonged PT and activated PTT. C Show 2 more Plasmapheresis: avoid performing plasma exchange in patients with sepsis and DIC. D 7. Specific circumstances Patients with malignancy: consider administering platelets to maintain a platelet count > 50 10 /L in patients with DIC and active bleeding. C Show 3 more 8. Follow-up and surveillance Serial laboratory assessment: as per ISTH 2013 guidelines, obtain repeated tests to monitor the dynamic changes based on laboratory results and clinical observations. B Clinical findings Symptoms Past medical history Bleeding Acute pancreatitis Petechia Acute promyelocytic leukemia Liver cirrhosis Past obstetric history Malignancy Pancreatic cancer Pregnancy Sepsis https://web.pathway.md/diseases/recGyBhLwbD48Ylbm 5/7 6/29/23, 10:19 PM Disseminated intravascular coagulation Pathway Traumatic injury Integument exam Vascular exam Erythematous macules Eschar Limb ischemia Gangrene Geographic plaques Lab findings Hemorrhagic bullae ALF Mucosal bleeding Prolonged PTT Purpura Prolonged serum PT Purpura fulminans serum D-dimer Hematological findings serum fibrinogen Schistocytes Imaging findings blood platelet count Intracranial hemorrhage References 1. H Wada, J Thachil, M Di Nisio et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013 Feb 4. Open 2. Marcello Di Nisio, Francesco Baudo, Benilde Cosmi et al. Diagnosis and treatment of disseminated intravascular coagulation: guidelines of the Italian Society for Haemostasis and Thrombosis SISET . Thromb Res. 2012 May;129 5):e177 84. Open 3. M Levi, C H Toh, J Thachil et al. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009 Apr;145 1 24 33. Open 4. J Thachil, A Falanga, M Levi et al. Management of cancer-associated disseminated intravascular coagulation: guidance from the SSC of the ISTH. J Thromb Haemost. 2015 Apr;13 4 671 5. Open 5. Balwinder Singh, Andrew C Hanson, Rabe Alhurani et al. Trends in the incidence and outcomes of disseminated intravascular coagulation in critically ill patients 2004 2010 a population-based study. 2013 May;143 5 1235 1242.2013 May;143 5 1235 1242. Open 6. Hideo Wada, Takeshi Matsumoto, Yoshiki Yamashita. Diagnosis and treatment of disseminated intravascular coagulation DIC according to four DIC guidelines. 2014 Feb 20;2 1 15.2014 Feb 20;2 1 15. Open 7. Chrysoula Papageorgiou, Georges Jourdi, Eusebe Adjambri et al. Disseminated Intravascular Coagulation: An Update on Pathogenesis, Diagnosis, and Therapeutic Strategies. 2018 Dec;24 9_suppl):8S 28S.2018 Dec;24 9_suppl):8S 28S. Open 8. Yukiko Kimura, Jennifer E Weiss, Kathryn L Haroldson et al. Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis. 2013 May;65 5 745 52.2013 May;65 5 745 52. Open 9. Bick RL. Disseminated intravascular coagulation: objective clinical and laboratory diagnosis, treatment, and assessment of therapeutic response. Semin Thromb Hemost. 1996;22 1 69 88. Open 10. Bakhtiari K, Meijers JC, de Jonge E et al. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. 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Hideo Wada, Esteban C Gabazza, Hidesaku Asakura 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 Sep;74 1 17 22. Open https://web.pathway.md/diseases/recGyBhLwbD48Ylbm 7/7