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Semin Thromb Hemost 2001; 27(6): 569-576
DOI: 10.1055/s-2001-18862
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Advances in the Understanding of the Pathogenetic Pathways of Disseminated Intravascular Coagulation Result in More Insight in the Clinical Picture and Better Management Strategies

Marcel Levi1,2 , Evert de Jonge3 , Tom van der Poll2,4 , Hugo ten Cate1,5
  • 1Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam
  • 2Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam
  • 3Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam
  • 4The Laboratory of Experimental Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 5Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands
Further Information

Publication History

Publication Date:
06 December 2001 (online)

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ABSTRACT

Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to widespread deposition of fibrin in the circulation. There is ample experimental and pathological evidence that the fibrin deposition contributes to multiple organ failure. The massive and ongoing activation of coagulation may result in depletion of platelets and coagulation factors, which may cause bleeding (consumption coagulopathy). Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. DIC is not a disease in itself but is a complication of a variety of disorders. However, the pathogenesis of DIC follows similar pathways in almost all of these situations, with a pivotal role of proinflammatory cytokines. The cornerstone of the management of DIC is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found to be beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation and restoration of physiological anticoagulant pathways by means of the administration of (activated) protein C concentrate or antithrombin concentrate.

KEYWORD

Disseminated intravascular coagulation - DIC - multiple organ dysfunction syndrome - MODS - coagulation - cytokines - treatment

REFERENCES

  • 1 Levi M, ten Cate H. Disseminated intravascular coagulation.  N Engl J Med . 1999;  341 586-592
    CrossrefPubMedGoogle Scholar
  • 2 Seligsohn U. Disseminated intravascular coagulation. In: Handin RI, Lux SE, Stossel TP, eds. Blood: Principles and Practice of Hematology Philadelphia: Lippincott 2000
    Google Scholar
  • 3 Marder V J, Feinstein D, Francis C, Colman R W. Consumptive thrombohemorrhagic disorders. In: Colman RW, Hirsh J, Marder VJ, Salzman E, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 3rd ed Philadelphia: Lippincott 1994: 1023-1063
    Google Scholar
  • 4 Mammen E F, Anderson G F, Barnard M I. Disseminated intravascular coagulation in man.  Thrombosis et Diathesis Haemorrhagica . 1969;  36(Suppl) 171-176
    PubMedGoogle Scholar
  • 5 Levi M, ten Cate H, van der Poll T. Disseminated intravascular coagulation. State of the art.  Thromb Haemost . 1999;  82 695-705
    PubMedGoogle Scholar
  • 6 Verstraete M, Vermylen C, Vermylen J. Excessive consumption of blood coagulation components as a cause of hemorraghic diathesis.  Am J Med . 1965;  35 899-905
    PubMedGoogle Scholar
  • 7 Rodriguez-Erdmann F. Bleeding due to increased intravascular blood coagulation. Hemorrhagic syndromes caused by consumption of blood-clotting factors (consumption-coagulopathies).  N Engl J Med . 1965;  273 1370-1378
    PubMedGoogle Scholar
  • 8 Dupuy M. Injections de matière cérébrale dans les veines.  Gaz Med Paris . 1834;  2 524-528
    PubMedGoogle Scholar
  • 9 Trousseau A. Phlegmasia alba dolens.  Clin Med Hotel Dieu Paris . 1865;  695
    PubMedGoogle Scholar
  • 10 Ratnoff O D, Pritchard J A, Colopy J E. Hemorraghic states during pregnancy.  N Engl J Med . 1955;  253 97-102
    CrossrefPubMedGoogle Scholar
  • 11 McKay D G. Disseminated Intravascular Coagulation. An Intermediary Mechanism of Disease New York: Hoeber; 1965
    Google Scholar
  • 12 Deykin D. The clinical challenge of disseminated intravascular coagulation.  N Engl J Med . 1970;  283 636-644
    PubMedGoogle Scholar
  • 13 Colman R W, Robboy S J, Minna J D. Disseminated intravascular coagulation. A reappraisal.  Annu Rev Med . 1979;  30 359-374
    CrossrefPubMedGoogle Scholar
  • 14 Feinstein D I. Treatment of disseminated intravascular coagulation.  Semin Thromb Hemost . 1988;  14 351-362
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Schwartzman R J, Hill J B. Neurologic complications of disseminated intravascular coagulation.  Neurology . 1982;  32 791-797
    CrossrefPubMedGoogle Scholar
  • 16 Merskey C, Johnson A J, Kleiner G J, Wohl H. The defibrination syndrome. Clinical features and laboratory diagnosis.  Br J Haematol . 1967;  13 528-549
    CrossrefPubMedGoogle Scholar
  • 17 Schneider C L. Fibrin embolism with defibrination as one of the end results during placenta abruptio.  Surg Gynecol Obstet . 1951;  92 27-34
    PubMedGoogle Scholar
  • 18 Lasch H G, Heene D L, Huth K, Sandritter W. Pathophysiology, clinical manifestations and therapy of consumption-coagulopathy (``Verbrauchskoagulopathie'').  Am J Cardiol . 1967;  20 381-391
    CrossrefPubMedGoogle Scholar
  • 19 Müller-Berghaus G. Pathophysiologic and biochemical events in disseminated intravascular coagulation. Dysregulation of procoagulant and anticoagulant pathways.  Semin Thromb Hemost . 1989;  15 58-87
    PubMedGoogle Scholar
  • 20 Müller-Berghaus G, Blombäck M, ten Cate W J. Attempts to define disseminated intravascular coagulation. In: Müller-Berghaus G, Madlener K, Blombäck M, ten Cate JW, eds. DIC. Pathogenesis, Diagnosis and Therapy of Disseminated Intravascular Fibrin Formation Amsterdam: Elsevier Science Publishers 1993: 3
    Google Scholar
  • 21 Brandtzaeg P, Joo G B, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease.  Thromb Res . 1990;  57 271-278
    CrossrefPubMedGoogle Scholar
  • 22 Hesselvik J F, Blombäck M, Brodin B, Maller R. Coagulation, fibrinolysis, and kallikrein systems in sepsis.  Relation to outcome. Crit Care Med . 1989;  17 724-733
    CrossrefPubMedGoogle Scholar
  • 23 Voss R, Matthias F R, Borkowski G, Reitz D. Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit.  Br J Haematol . 1990;  75 99-105
    CrossrefPubMedGoogle Scholar
  • 24 Alkjaersig N, Fletcher A P, Sherry S. Pathogenesis of the coagulation defect developing during pathological plasma proteolytic (fibrinolytic) states.  J Clin Invest . 1962;  41 917-934
    CrossrefPubMedGoogle Scholar
  • 25 Levi M, van der Poll T, de Jonge E, ten Cate H. Relative insufficiency of fibrinolysis in disseminated intravascular coagulation.  Sepsis . 2000;  3 103-109
    PubMedGoogle Scholar
  • 26 Vervloet M G, Thijs L G, Hack C E. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock.  Semin Thromb Hemost . 1998;  24 33-44
    PubMedGoogle Scholar
  • 27 Levi M, van der Poll T, ten Cate H, van Deventer J S. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia.  Eur J Clin Invest . 1997;  27 3-9
    CrossrefPubMedGoogle Scholar
  • 28 Avvisati G, ten Cate W J, Sturk A. Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia.  Br J Haematol . 1988;  70 43-48
    CrossrefPubMedGoogle Scholar
  • 29 Dombret H, Scrobohaci M L, Ghorra P. Coagulation disorders associated with acute promyelocytic leukemia. Corrective effect of all-trans retinoic acid treatment.  Leukemia . 1993;  7 2-9
    PubMedGoogle Scholar
  • 30 Albarracin N S, Haust M D. Intravascular coagulation in promyelocytic leukemia. A case study including ultrastructure.  Am J Clin Pathol . 1971;  55 677-685
    PubMedGoogle Scholar
  • 31 Avvisati G, ten Cate W J, Büller H R, Mandelli F. Tranexamic acid for control of haemorrhage in acute promyelocytic leukaemia.  Lancet . 1989;  2 122-124
    PubMedGoogle Scholar
  • 32 Taylor Jr B F, Toh C H, Hoots K, Wada H, Levi M. Towards a definition, clinical and laboratory criteria and a scoring system for disseminated intravascular coagulation.  Thromb Haemost 2001 (in press).
    PubMedGoogle Scholar
  • 33 Müller-Berghaus G, Levi M, ten Cate H. Disseminated intravascular coagulation. In: Verstraete M, Topol E, Fuster V, eds. Cardiovascular Thrombosis Thrombocardiology. Philadelphia: Lippincott 1998: 781
    Google Scholar
  • 34 Thijs L G, de Boer P J, de Groot M, Hack C E. Coagulation disorders in septic shock.  Intensive Care Med . 1993;  19(Suppl 1) S8-15
    CrossrefPubMedGoogle Scholar
  • 35 Baglin T. Disseminated intravascular coagulation. Diagnosis and treatment.  BMJ . 1996;  312 683-687
    CrossrefPubMedGoogle Scholar
  • 36 Gando S, Kameue T, Nanzaki S, Nakanishi Y. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome.  Thromb Haemost . 1996;  75 224-228
    PubMedGoogle Scholar
  • 37 Bone R C. Gram-positive organisms and sepsis.  Arch Intern Med . 1994;  154 26-34
    CrossrefPubMedGoogle Scholar
  • 38 Bhamarapravati N. Hemostatic defects in Dengue hemorrhagic fever.  Rev Infect Dis . 1989;  11(Suppl 4) S826-S829
    CrossrefPubMedGoogle Scholar
  • 39 Heller M V, Marta R F, Sturk A. Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever.  Thromb Haemost . 1995;  73 368-373
    PubMedGoogle Scholar
  • 40 Clemens R, Pramoolsinsap C, Lorenz R. Activation of the coagulation cascade in severe falciparum malaria through the intrinsic pathway.  Br J Haematol . 1994;  87 100-105
    CrossrefPubMedGoogle Scholar
  • 41 Mohanty D, Ghosh K, Nandwani S K. Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant activity in acute malaria.  Am J Hematol . 1997;  54 23-29
    CrossrefPubMedGoogle Scholar
  • 42 Fera G, Semeraro N, de Mitrio V, Schiraldi O. Disseminated intravascular coagulation associated with disseminated cryptococcosis in a patient with acquired immunodeficiency syndrome.  Infection . 1993;  21 171-173
    CrossrefPubMedGoogle Scholar
  • 43 Hayes E B, Gubler D J. Dengue and Dengue hemorrhagic fever.  Pediatr Infect Dis J . 1992;  11 311-317
    PubMedGoogle Scholar
  • 44 Sumarmo, Wulur H, Jahja E. Clinical observations on virologically confirmed fatal Dengue infections in Jakarta, Indonesia.  Bull World Health Organ . 1983;  61 693-701
    PubMedGoogle Scholar
  • 45 Kuberski T, Rosen L, Reed D, Mataika J. Clinical and laboratory observations on patients with primary and secondary Dengue type 1 infections with hemorrhagic manifestations in Fiji.  Am J Trop Med Hyg . 1977;  26 775-783
    PubMedGoogle Scholar
  • 46 Egbring R, Slenczka W, Baltzer G. Clinical manifestations and mechanism of the haemorrhagic diathesis in Marburg viral disease. In: Martini GA, Siegert R, eds. Marburg Virus Disease New York: Springer-Verlag 1971: 41
    Google Scholar
  • 47 Gear J S, Cassel G A, Gear A J. Outbreak of Marburg virus disease in Johannesburg.  BMJ . 1975;  4 489-493
    CrossrefPubMedGoogle Scholar
  • 48 WHO International Study Team. Ebola haemorrhagic fever in Sudan.  Bull World Health Organ . 1978;  56 247-270
    PubMedGoogle Scholar
  • 49 International Commision. Ebola haemorrhgic fever in Zaire.  Bull World Health Organ . 1978;  56 271-293
    PubMedGoogle Scholar
  • 50 Roumen R M, Hendriks T, van der Ven. Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure.  Ann Surg . 1993;  218 769-776
    CrossrefPubMedGoogle Scholar
  • 51 Colman R W, Rubin R N. Disseminated intravascular coagulation due to malignancy.  Semin Oncol . 1990;  17 172-186
    PubMedGoogle Scholar
  • 52 Sarris A H, Kempin S, Berman E. High incidence of disseminated intravascular coagulation during remission induction of adult patients with acute lymphoblastic leukemia.  Blood . 1992;  79 1305-1310
    PubMedGoogle Scholar
  • 53 Tytgat G N, Collen D, Verstraete M. Metabolism of fibrinogen in cirrhosis of the liver.  J Clin Invest . 1971;  50 169-170
    PubMedGoogle Scholar
  • 54 Coleman M, Finlayson N, Bettigole R E. Fibrinogen survival in cirrhosis. Improvement by ``low dose'' heparin.  Ann Intern Med . 1975;  83 79-81
    PubMedGoogle Scholar
  • 55 Carr J M, McKinney M, McDonagh J. Diagnosis of disseminated intravascular coagulation. Role of D-dimer.  Am J Clin Pathol . 1989;  91 280-287
    PubMedGoogle Scholar
  • 56 Coccheri S, Mannucci P M, Palareti G. Significance of plasma fibrinopeptide A and high molecular weight fibrinogen in patients with liver cirrhosis.  Br J Haematol . 1982;  52 503-509
    PubMedGoogle Scholar
  • 57 Oka K, Tanaka K. Intravascular coagulation in autopsy cases with liver diseases.  Thromb Haemost . 1979;  42 564-570
    PubMedGoogle Scholar
  • 58 Tempero M A, Davis R B, Reed E, Edney J. Thrombocytopenia and laboratory evidence of disseminated intravascular coagulation after shunts for ascites in malignant disease.  Cancer . 1985;  55 2718-2721
    PubMedGoogle Scholar
  • 59 Szlachetka D M. Kasabach-Merritt syndrome. A case review.  Neonatal Network . 1998;  17 7-15
    PubMedGoogle Scholar
  • 60 Gibney E J, Bouchier-Hayes D. Coagulopathy and abdominal aortic aneurysm.  Eur J Vasc Surg . 1990;  4 557-562
    PubMedGoogle Scholar
  • 61 Aboulafia D M, Aboulafia E D. Aortic aneurysm-induced disseminated intravascular coagulation.  Ann Vasc Surg . 1996;  10 396-405
    PubMedGoogle Scholar
  • 62 Straub P W, Kessler S, Schreiber A, Frick P G. Chronic intravascular coagulation in Kasabach-Merritt syndrome. Preferential accumulation of fibrinogen 131 I in a giant hemangioma.  Arch Intern Med . 1972;  129 475-478
    CrossrefPubMedGoogle Scholar
  • 63 Warrell R PJ, Kempin S J, Benua R S, Reiman R E, Young C W. Intratumoral consumption of indium-111 labeled platelets in a patient with hemangiomatosis and intravascular coagulation (Kasabach-Merritt syndrome).  Cancer . 1983;  52 2256-2260
    PubMedGoogle Scholar
  • 64 Neidhart J A, Roach R W. Successful treatment of skeletal hemangioma and Kasabach-Merritt syndrome with aminocaproic acid. Is fibrinolysis ``defensive''?.  Am J Med . 1982;  73 434-438
    CrossrefPubMedGoogle Scholar
  • 65 el-Dessouky M, Azmy A F, Raine P A, Young D G. Kasabach-Merritt syndrome.  J Pediatr Surg . 1988;  23 109-111
    CrossrefPubMedGoogle Scholar
  • 66 D'Amico J A, Hoffman G C, Dyment P G. Klippel-Trenaunay syndrome associated with chronic disseminated intravascular coagulation and massive osteolysis.  Cleveland Clin Q . 1977;  44 181-188
    PubMedGoogle Scholar
  • 67 Poon M C, Kloiber R, Birdsell D C. Epsilon-aminocaproic acid in the reversal of consumptive coagulopathy with platelet sequestration in a vascular malformation of Klippel-Trenaunay syndrome.  Am J Med . 1989;  87 211-213
    PubMedGoogle Scholar
  • 68 Alpert L I, Benisch B. Hemangioendothelioma of the liver associated with microangiopathic hemolytic anemia. Report of four cases.  Am J Med . 1970;  48 624-628
    CrossrefPubMedGoogle Scholar
  • 69 Bick R L. Hereditary hemorrhagic telangiectasia and disseminated intravascular coagulation. A new clinical syndrome.  Ann N Y Acad Sci . 1981;  370 851-854
    PubMedGoogle Scholar
  • 70 de Boer K, ten Cate W J, Sturk A, Borm J J, Treffers P E. Enhanced thrombin generation in normal and hypertensive pregnancy.  Am J Obstet Gynecol . 1989;  160 95-100
    PubMedGoogle Scholar
  • 71 Weiner C P. Preeclampsia-eclampsia syndrome and coagulation.  Clin Perinatol . 1991;  18 713-726
    PubMedGoogle Scholar
  • 72 Martin J NJ, Stedman C M. Imitators of preeclampsia and HELLP syndrome.  Obstet Gynecol Clin North Am . 1991;  18 181-198
    PubMedGoogle Scholar
  • 73 Weiner C P. The obstetric patient and disseminated intravascular coagulation.  Clin Perinatol . 1986;  13 705-717
    PubMedGoogle Scholar
  • 74 McDougall R J, Duke G J. Amniotic fluid embolism syndrome. Case report and review.  Anaesthesia Intensive Care . 1995;  23 735-740
    PubMedGoogle Scholar
  • 75 Ruggenenti P, Lutz J, Remuzzi G. Pathogenesis and treatment of thrombotic microangiopathy.  Kidney Int . 1997;  58(Suppl) S97-101
    PubMedGoogle Scholar
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