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DIC

DIC

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DIC
DIC

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Disseminated Intravascular Coagulation

Feature
Synonyms

Disseminated Intravascular Coagulation  

1

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

Epidemiology

Pathogenesis

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

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

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

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