Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Pathogenesis and etiology of disseminated intravascular coagulation

INTRODUCTION

Disseminated intravascular coagulation (DIC), also called consumption coagulopathy and defibrination syndrome, is a systemic process producing both thrombosis and hemorrhage. It is initiated by a number of defined disorders and consists of several components, including exposure of blood to procoagulants, formation of fibrin in the circulation, fibrinolysis, depletion of clotting factors, and end-organ damage. Treatment is best directed at correcting the underlying cause.

The pathogenesis and etiology of DIC will be reviewed here. The clinical manifestations, diagnosis, and treatment of DIC are discussed separately. (See "Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults".)

PATHOGENESIS OF DIC

Overview of pathogenesis — The pathogenesis of disseminated intravascular coagulation (DIC) is primarily due to an uncontrolled and excessive production of thrombin, leading to widespread and systemic intravascular fibrin deposition (algorithm 1) [1].

DIC is initiated by a number of disorders, and it consists of the following components:

Exposure of blood to procoagulants

            

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Mar 24, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Levi M. Current understanding of disseminated intravascular coagulation. Br J Haematol 2004; 124:567.
  2. Matsuda T. Clinical aspects of DIC--disseminated intravascular coagulation. Pol J Pharmacol 1996; 48:73.
  3. Banner DW. The factor VIIa/tissue factor complex. Thromb Haemost 1997; 78:512.
  4. Levi M, van der Poll T, ten Cate H, van Deventer SJ. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia. Eur J Clin Invest 1997; 27:3.
  5. Franco RF, de Jonge E, Dekkers PE, et al. The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation. Blood 2000; 96:554.
  6. Sase T, Wada H, Nishioka J, et al. Measurement of tissue factor messenger RNA levels in leukocytes from patients in hypercoagulable state caused by several underlying diseases. Thromb Haemost 2003; 89:660.
  7. Pixley RA, De La Cadena R, Page JD, et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J Clin Invest 1993; 91:61.
  8. Ono T, Mimuro J, Madoiwa S, et al. Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood 2006; 107:528.
  9. Spero JA, Lewis JH, Hasiba U. Disseminated intravascular coagulation. Findings in 346 patients. Thromb Haemost 1980; 43:28.
  10. Siegal T, Seligsohn U, Aghai E, Modan M. Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases. Thromb Haemost 1978; 39:122.
  11. van Gorp EC, Suharti C, ten Cate H, et al. Review: infectious diseases and coagulation disorders. J Infect Dis 1999; 180:176.
  12. McGehee WG, Rapaport SI, Hjort PF. Intravascular coagulation in fulminant meningococcemia. Ann Intern Med 1967; 67:250.
  13. Winkelstein A, Songster CL, Caras TS, et al. Fulminant meningococcemia and disseminated intravascular coagulation. Arch Intern Med 1969; 124:55.
  14. Thijs LG, de Boer JP, de Groot MC, Hack CE. Coagulation disorders in septic shock. Intensive Care Med 1993; 19 Suppl 1:S8.
  15. Gando S, Kameue T, Nanzaki S, Nakanishi Y. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome. Thromb Haemost 1996; 75:224.
  16. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341:586.
  17. Esmon CT, Fukudome K, Mather T, et al. Inflammation, sepsis, and coagulation. Haematologica 1999; 84:254.
  18. Dempfle CE. Coagulopathy of sepsis. Thromb Haemost 2004; 91:213.
  19. Levi M, ten Cate H, Bauer KA, et al. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93:114.
  20. Colman RW. Contact systems in infectious disease. Rev Infect Dis 1989; 11 Suppl 4:S689.
  21. de Jonge E, Dekkers PE, Creasey AA, et al. Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood 2000; 95:1124.
  22. Edwards RL, Rickles FR. Macrophage procoagulants. Prog Hemost Thromb 1984; 7:183.
  23. Jansen PM, Pixley RA, Brouwer M, et al. Inhibition of factor XII in septic baboons attenuates the activation of complement and fibrinolytic systems and reduces the release of interleukin-6 and neutrophil elastase. Blood 1996; 87:2337.
  24. Nieuwland R, Berckmans RJ, McGregor S, et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95:930.
  25. Murray HW, Tuazon CU, Sheagren JN. Staphylococcal septicemia and disseminated intravascular coagulation. Staphylococcus aureus endocarditis mimicking meningococcemia. Arch Intern Med 1977; 137:844.
  26. Stossel TP, Levy R. Intravascular coagulation associated with pneumococcal bacteremia and symmetrical peripheral gangrene. Arch Intern Med 1970; 125:876.
  27. de Virgilio C, Klein S, Chang L, et al. Clostridial bacteremia: implications for the surgeon. Am Surg 1991; 57:388.
  28. Grewal PK, Uchiyama S, Ditto D, et al. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 2008; 14:648.
  29. Stéphan F, Hollande J, Richard O, et al. Thrombocytopenia in a surgical ICU. Chest 1999; 115:1363.
  30. Hulka F, Mullins RJ, Frank EH. Blunt brain injury activates the coagulation process. Arch Surg 1996; 131:923.
  31. Selladurai BM, Vickneswaran M, Duraisamy S, Atan M. Coagulopathy in acute head injury--a study of its role as a prognostic indicator. Br J Neurosurg 1997; 11:398.
  32. Olson JD, Kaufman HH, Moake J, et al. The incidence and significance of hemostatic abnormalities in patients with head injuries. Neurosurgery 1989; 24:825.
  33. Gando S, Nanzaki S, Kemmotsu O. Disseminated intravascular coagulation and sustained systemic inflammatory response syndrome predict organ dysfunctions after trauma: application of clinical decision analysis. Ann Surg 1999; 229:121.
  34. Scherer RU, Spangenberg P. Procoagulant activity in patients with isolated severe head trauma. Crit Care Med 1998; 26:149.
  35. Barbui T, Finazzi G, Falanga A. The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood 1998; 91:3093.
  36. Rickles FR, Levine M, Edwards RL. Hemostatic alterations in cancer patients. Cancer Metastasis Rev 1992; 11:237.
  37. Rao LV. Tissue factor as a tumor procoagulant. Cancer Metastasis Rev 1992; 11:249.
  38. Gordon SG, Mielicki WP. Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue. Blood Coagul Fibrinolysis 1997; 8:73.
  39. Gordon SG, Franks JJ, Lewis B. Cancer procoagulant A: a factor X activating procoagulant from malignant tissue. Thromb Res 1975; 6:127.
  40. Gilbert WM, Danielsen B. Amniotic fluid embolism: decreased mortality in a population-based study. Obstet Gynecol 1999; 93:973.
  41. Sutton DM, Hauser R, Kulapongs P, Bachmann F. Intravascular coagulation in abruptio placentae. Am J Obstet Gynecol 1971; 109:604.
  42. Eskes TK. Abruptio placentae. A "classic" dedicated to Elizabeth Ramsey. Eur J Obstet Gynecol Reprod Biol 1997; 75:63.
  43. Crane S, Chun B, Acker D. Treatment of obstetrical hemorrhagic emergencies. Curr Opin Obstet Gynecol 1993; 5:675.
  44. Davies S. Amniotic fluid embolism and isolated disseminated intravascular coagulation. Can J Anaesth 1999; 46:456.
  45. Sibai BM, Ramadan MK, Usta I, et al. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993; 169:1000.
  46. Sibai BM, Ramadan MK. Acute renal failure in pregnancies complicated by hemolysis, elevated liver enzymes, and low platelets. Am J Obstet Gynecol 1993; 168:1682.
  47. Sibai BM, Spinnato JA, Watson DL, et al. Pregnancy outcome in 303 cases with severe preeclampsia. Obstet Gynecol 1984; 64:319.
  48. Castro MA, Goodwin TM, Shaw KJ, et al. Disseminated intravascular coagulation and antithrombin III depression in acute fatty liver of pregnancy. Am J Obstet Gynecol 1996; 174:211.
  49. Parasnis H, Raje B, Hinduja IN. Relevance of plasma fibrinogen estimation in obstetric complications. J Postgrad Med 1992; 38:183.
  50. Sarkar M, Mulliken JB, Kozakewich HP, et al. Thrombocytopenic coagulopathy (Kasabach-Merritt phenomenon) is associated with Kaposiform hemangioendothelioma and not with common infantile hemangioma. Plast Reconstr Surg 1997; 100:1377.
  51. Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1992; 326:1456.
  52. Warrell RP Jr, Kempin SJ. Treatment of severe coagulopathy in the Kasabach-Merritt syndrome with aminocaproic acid and cryoprecipitate. N Engl J Med 1985; 313:309.
  53. Hall GW. Kasabach-Merritt syndrome: pathogenesis and management. Br J Haematol 2001; 112:851.
  54. Bick RL. Hereditary hemorrhagic telangiectasia and disseminated intravascular coagulation: a new clinical syndrome. Ann N Y Acad Sci 1981; 370:851.
  55. Fisher DF Jr, Yawn DH, Crawford ES. Preoperative disseminated intravascular coagulation associated with aortic aneurysms. A prospective study of 76 cases. Arch Surg 1983; 118:1252.
  56. Aboulafia DM, Aboulafia ED. Aortic aneurysm-induced disseminated intravascular coagulation. Ann Vasc Surg 1996; 10:396.
  57. Mazoyer E, Enjolras O, Bisdorff A, et al. Coagulation disorders in patients with venous malformation of the limbs and trunk: a case series of 118 patients. Arch Dermatol 2008; 144:861.
  58. Dompmartin A, Acher A, Thibon P, et al. Association of localized intravascular coagulopathy with venous malformations. Arch Dermatol 2008; 144:873.
  59. Smadja C, Franco D. The LeVeen shunt in the elective treatment of intractable ascites in cirrhosis. A prospective study on 140 patients. Ann Surg 1985; 201:488.
  60. Capon SM, Goldfinger D. Acute hemolytic transfusion reaction, a paradigm of the systemic inflammatory response: new insights into pathophysiology and treatment. Transfusion 1995; 35:513.
  61. Wiedmer T, Hall SE, Ortel TL, et al. Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria. Blood 1993; 82:1192.
  62. Tun Pe. Heparin therapy in Russell's viper bite victims with disseminated intravascular coagulation: a controlled trial. Southeast Asian J Trop Med Public Health 1992; 23:282.
  63. Pereira SP, Langley PG, Williams R. The management of abnormalities of hemostasis in acute liver failure. Semin Liver Dis 1996; 16:403.
  64. Himmelreich G, Jochum M, Bechstein WO, et al. Mediators of leukocyte activation play a role in disseminated intravascular coagulation during orthotopic liver transplantation. Transplantation 1994; 57:354.
  65. Bakker CM, Metselaar HJ, Gomes MJ, et al. Intravascular coagulation in liver transplantation--is it present or not? A comparison between orthotopic and heterotopic liver transplantation. Thromb Haemost 1993; 69:25.
  66. Violi F, Ferro D, Basili S, et al. Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis. Gastroenterology 1995; 109:531.
  67. Dematte JE, O'Mara K, Buescher J, et al. Near-fatal heat stroke during the 1995 heat wave in Chicago. Ann Intern Med 1998; 129:173.
  68. Mustafa KY, Omer O, Khogali M, et al. Blood coagulation and fibrinolysis in heat stroke. Br J Haematol 1985; 61:517.
  69. García-Avello A, Lorente JA, Cesar-Perez J, et al. Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma. Thromb Res 1998; 89:59.
  70. Walubo A, Seger D. Fatal multi-organ failure after suicidal overdose with MDMA, 'ecstasy': case report and review of the literature. Hum Exp Toxicol 1999; 18:119.
  71. Kendrick WC, Hull AR, Knochel JP. Rhabdomyolysis and shock after intravenous amphetamine administration. Ann Intern Med 1977; 86:381.
  72. Branson HE, Katz J, Marble R, Griffin JH. Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983; 2:1165.
  73. Yuen P, Cheung A, Lin HJ, et al. Purpura fulminans in a Chinese boy with congenital protein C deficiency. Pediatrics 1986; 77:670.
  74. Smith OP, White B, Vaughan D, et al. Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet 1997; 350:1590.
  75. Fourrier F, Lestavel P, Chopin C, et al. Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates. Intensive Care Med 1990; 16:121.