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Disseminated Intravascular Coagulation


Disseminated Intravascular Coagulation  


Roger S. Riley, M.D., Ph.D. April, 2005

Disease Facts
DIC, consumption coagulopathy, consumptive thrombo-hemorrhagic disease, defibrination syndrome. DIC is one of the most common and clinically important acquired disorders of hemostasis. The true incidence of DIC is unknown because the disease is difficult to diagnosis. DIC occurs in acute and chronic forms of DIC. DIC is widespread intravascular activation of the coagulation system ("runaway hemostasis") caused by a disruption in the intricate control mechanisms of hemostasis. DIC is not a specific disease, but the sequelae of many pathologic conditions with various effects on the hemostatic system (See Table). These conditions lead to release of proinflammatory cytokines, uncontrolled thrombin generation, widespread microvascular thrombosis, impairment of anticoagulant pathways, activation or impairment of the fibrinolytic system, and other effects. Tissue damage and the deposition of fibrin also result in the release and activation of plasminogen activators and the generation of plasmin in amounts that overwhelm its inhibitor, (2-antiplasmin). Plasmin degrades factors VIII, V, and I and produces fibrin/fibrinogen degradation products. These substances, as well as the products of incompletely polymerized fibrin, impair platelet function and normal fibrin polymerization. Microvascular thrombosis leads to tissue ischemia, necrosis, and organ dysfunction, and the release of tissue factor, which further accelerates the process. In acute DIC, the consumption of platelets and clotting factors occurs more rapidly than they can be replenished and bleeding results. The bleeding can be severe or even fatal. Chronic DIC (“compensated DIC,” “nonovert DIC”) occurs when time or intensity of the trigger mechanism is such that the the regulatory mechanisms of coagulation are able to control systemic activation of coagulation, and the liver and bone marrow are able replace the missing coagulation factors and platelets. The following table lists the pathogenic mechanism of DIC in different diseases. Disease
Tissue damage, trauma



DIC Pathogenic Factors
Release of thromboplastic substances with activation of extrinsic coagulation pathway. Increased proinflammatory cytokines with TF-mediated coagulation activation, suppression of anticoagulation, and PAI-1mediated inhibition of fibrinolysis. Decreased blood flow with loss of hemodilution. Ischemia and multiple organ failure. Release of endotoxin with induction of inflammatory cytokines. Tissue factor expression and suppression of thrombomodulin. Downregulation of protein C-protein S system. Hypotension and septic shock. Tumor cell-related factors with procoagulant and fibrinolytic properties, cytokine release by leukemia cells, effect of chemotherapy, infectious complications

Shock Gram-negative septicemia Acute leukemia

Serial laboratory studies may be needed in early DIC. as well as hemorrhage into wound sites. and catheters. No single laboratory assay is pathognomonic of DIC. hypotension. Unfortunately. The bone marrow examination is contraindicated in DIC. chronic DIC) leads to an excess of activated coagulation products. amniotic fluid embolism. predisposing to thrombosis. proteinuria. the production of fibrin degradation products. HELLP) Vascular disorders (aortic aneurysms.Disseminated Intravascular Coagulation   2 Feature Pathogenesis Disease Advanced malignancy Microangiopathic hemolytic anemias (TTP. especially release of placental tissue factor Chronic local coagulation activation with consumption of platelets and coagulation factors. intravenous lines. and bleeding. Thrombocytopenia is the usual laboratory finding leading to the consideration of DIC. and shows a characteristic combination of thrombocytopenia. acidosis. hemangiomas) Liver disease Hyperthermia Snakebite Disease Facts DIC Pathogenic Factors Various mechanisms including release of procoagulant substances by tumor cells Decreased blood flow with loss of hemodilution. direct activation of coagulation by venom Clinical Presentation The clinical presentation and consequences of DIC depend on the etiology and the rapidity of the initiating event. Fever. and enhanced fibrinolysis. Various mechanisms. The intravascular fibrin strands produce microangiopathic hemolytic anemia. chemotherapyinduced. Peripheral blood smear examination is essential. and hypoxia may also occur. vascular infarction. decreased fibrinogen and plasmin levels. DIC is more common in injured or seriously ill hospitalized than in outpatients. malignant hypertension. leukocytosis with a left shift. and large young platelets in fulminant cases. with depletion of platelets and procoagulant factors. the diagnosis must be made through consideration of both laboratory and clinical findings. HUS. The usual signs include bleeding into deep tissues. Instead. and venous thrombosis. with elevated levels of fibrinogen degradation products (FDPs) and D-dimers. Acute events lead to intravascular coagulation. mild polychromatophilia. Ischemia and multiple organ failure. Slow or chronic activation of coagulation (compensated DIC. release of plasminogen activators by abnormal endothelium Impaired ability to clear procoagulants from the circulation and synthesize clotting factors Endothelial injury and tissue damage Endothelial damage. HEELP) Obstetric complications (preeclampsia. Acute DIC may be fatal unless the condition is promptly diagnosed and appropriate treatment undertaken (DIC = “Death is Coming”). schistocytes. but will show adequate megakaryocytes in spite of thrombocytopenia. schistocytes may be absent in chronic DIC. Laboratory Features . Coagulation evaluation reveals a prolonged prothrombin time (PT) and activated thromboplastin time (aPTT).

Kalwinsky DK. Hematol Oncol Clin North Am 17:149. diagnosis. 2004 Higuchi T. 2004 Levi M: Pathogenesis and treatment of DIC. Falanga A. malignancy..e. Bick RL: Disseminated intravascular coagulation current concepts of etiology. Best Pract Res Clin Haematol 16:463. 2003 Toh CH: Laboratory testing in disseminated intravascular coagulation. ten Cate H: Disseminated intravascular coagulation. Barbui T. and treatment. Dennis M: Disseminated intravascular coagulation: old disease. van der Poll T: New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology. Treatment References Barbui T. activated protein C. A number of laboratory assays under evaluation focus on therombin generation (i. new hope. Br J Haematol 124:567. 1997 Levi M: Current understanding of disseminated intravascular coagulation. pathophysiology. self-propagating clinical disaster of simultaneous bleeding and clotting can rapidly lead to the death of the patient. surgery. soluble fibrin). 2001. However. clinical trials with antithrombin III. van der Poll T: Sepsis and disseminated intravascular coagulation. 2003 Carter M. Otherwise. In the meantime. elevated D-dimers levels are normally found after trauma. prothrombin fragment 1+2). 1989 Dahlback B: Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases. J Intern Med 257:209. activated protein C inhibitor and plasmin-antiplasmin complexes). Ann Med 36:41. 2005 Levi M. Unfortunately. Until recently. 106:43-51. 2001 Toh CH. and the end products of thrombin activity (i. the D-dimer level is the most useful. Manzato F: Update on the treatment of disseminated intravascular coagulation. replacement of the deficient platelets and clotting factors is required. 2001. an uncontrollable. 2003 Slofstra SH. 27:593-604.Disseminated Intravascular Coagulation  Laboratory Features (Cont’d)  3 Of these laboratory tests.e. and tissue factor pathway inhibitor (TFPI) appear promising. FFP and/or cryoprecipitate were used to replace the missing clotting factors. Disseminated intravascular coagulation in acute leukemia. Hematol Oncol 15:209. Shimizu T.e.. Falanga A. J Thromb Thrombolysis 16:43. Thromb Res 115 Suppl 1:54. Dahl GV. Semin Thromb Hemost. since an elevated values indicate the formation and breakdown of fibrin thrombi. 2003 Franchini M. Leukemia 3:298. and other conditions where DIC is common. et al: Childhood acute promyelocytic leukemia: a rare variant of nonlymphoid leukemia with distinctive clinical and biologic features. Bmj 327:974. thrombin activation of the protein C and fibrinolytic pathways (i. Hematol J 4:295. 2005 Falanga A. and the cautious use of heparin may reverse the cycle of consumption and clot formation. Coagulopathy of acute promyelocytic leukemia. de Jonge E. fibrinopeptide A. Acta Haematol. de Jonge E. The only definitive therapy for DIC is control of the initiating disease process. Mori H. 2004 Levi M. Spek CA. Rickles FR: Pathogenesis and management of the bleeding diathesis in acute promyelocytic leukaemia. et al: Coagulation patterns of disseminated intravascular coagulation in acute promyelocytic leukemia. 2003 . Semin Thromb Hemost 27:653. Hematology 9:81..

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