Abstract

Disseminated Intravascular Coagulation (D.I.C.) also called consumption coagulopathy, is a life threatening condition that provokes thrombosis and hemorrhage, coupled with a serious underlying disease. The pathogenesis of Disseminated Intravascular Coagulation (D.I.C.) can be considered primarily due to an uncontrolled and excessive production of thrombin, that leads to a widespread and systemic intravascular fibrin deposition in the circulation. DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. (1) (British Journal of Haematology 2004 vol. 124 pp. 567-576)  Disseminated intravascular dissemination (DIC) may occur during sepsis, trauma and tissue destruction, cancer, and obstetrical complications. For DIC there are two clinical forms, an acute and a chronic DIC.  Acute DIC is a decompensated DIC and develops when blood is exposed to large amounts of tissue factor over a brief period time that leads to massive generation of thrombin and consequently to an acute triggering of coagulation that does not allow enough time to compensatory mechanisms to recover. The symptoms provoked by these events are a systemic bleeding diathesis due to consumption of coagulation factors and severe thrombocytopenia and tissue ischemic injury and a microangiopathic hemolytic anemia due to widespread intravascular fibrin deposition. (2) (www.uptodate.com 2014)  Microvascular thrombi and consequently dysfunction may interest the kidney, liver, lungs, and central nervous system.
Compensated or chronic DIC develops when blood is exposed to small amounts of tissue factor and compensatory mechanisms have time to recover and, differently from acute DIC, a slower rate of consumption of coagulation factors may be balanced by increased synthesis of these proteins. In particular the liver and bone marrow can replace the depleted coagulation factors and platelets respectively. Because of this, the patients with chronic DIC are  either asymptomatic with an increased level of fibrin degradation product or have symptoms of venous and/or arterial thrombosis. In some cases may present a mild skin or mucosal bleeding. (2) (www.uptodate.com 2014)  The laboratory diagnosis of  acute DIC include a reduced platelet count, plasma fibrinogen level, plasma factor V and plasma factor VIII. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Thrombin Time (TT) are prolonged. Fibrin degradation products and D-dimer are elevated. The laboratory diagnosis of chronic DIC include a variable platelet count, a normal PT, APTT, TT, Fibrinogen, Plasma factor V, Plasma factor VIII and elevated fibrin degradation products and D-dimer. DIC must be differentiate from the coagulopathy associated with primary liver disease, from TTP-HUS, from primary fibrinogenolysis and from Heparin-Induced Thrombocytopenia (HIT). (2) (www.uptodate.com 2014)
a) Severe liver disease leads to a decreased synthesis of coagulation factors, increasing the bleeding risk, and of coagulation inhibitors, increasing the thrombotic risk, and leads to thrombocytopenia which is principally due to hypersplenism, a consequence of portal hypertension, but may also be due to decreased thrombopoietin (TPO) levels, auto-antibody destruction, and bone marrow suppression due to liver disease. (3) (www.uptodate.com 2014) In addition, liver disease may be associated with chronic or intermittent fibrinolysis, fibrinogenolysis, and elevated levels of fibrinogen degradation products (FDPs). In some cases may be difficult to differentiate the coagulopathy associated with primary severe liver disease from the liver dysfunction observed in patients with acute DIC. (2) (www.uptodate.com 2014)
b) DIC can be differentiated from TTP-HUS because if DIC results from activation of the coagulation system, TTP-HUS results from primary platelet activation, due to a congenital or acquired defect of ADAMTS13.
c) Primary fibrinogenolysis occurs when plasmin is generated in the absence of thrombosis. It is rare and may be present in certain conditions, such as direct infusion of thrombolytic agents and in patients with prostate cancer. (2) (www.uptodate.com 2014) (4) (Cancer Investigation 2000 vol. 18 pp. 191-196)
d) The differential diagnosis with HIT may be due to an unexplained thrombocytopenia with a platelet count less than 50%  of  a prior value in a patient who has begun heparin therapy within preceding 5 to 10 days, or in a patient receiving prolonged treatment with low molecular weight heparin (LMWH). (2) (www.uptodate.com)
For treatment of DIC, is crucial the therapy of the underlying disease such as sepsis, trauma, or burns in which there is a high mortality rate from 40 to 80%  (5) (Thrombosis Research 1998 vol. 89 pp. 59-64) or of other diseases such as  acute promyelocytic leukemia, cancer, abruptio placentae, HELLP syndrome, eclampsia and severe preeclampsia, septic abortion. Risk factors of death include increasing age and the severity of the organ dysfunction and hemostatic abnormalities. (2) www.uptodate.com)  Treatment with platelet transfusion and fresh frozen plasma is normally used in case of serious bleeding, in case of high risk of bleeding such as after surgery or in patients who require invasive procedures. This treatment is not used as a prophylactic treatment in patients who are not bleeding or who are not at high risk of bleeding. Patients with marked ( < 20,000/mcL) or moderate thrombocytopenia ( < 50,000/mcL) and serious bleeding must receive platelet transfusions at the dosage of 1 to 2 units per 10 kg per day.  Patients with active bleeding and a high elevated prothrombin Time (PT) and/or a fibrinogen concentration < 50 mg/dL may receive fresh frozen plasma (FFP) at the dosage of 10-15 mL/kg or cryoprecipitate for fibrinogen replacement to keep the fibrinogen level > 100 mg/dL. The administration of heparin is only used in patients with chronic, compensated DIC  who have predominantly thrombotic manifestations such as migratory thromboflebitis. (2) (www.uptodate.com) Low dose of heparin may be used in DIC associated with acute promyelocitic leukemia. The administration of  antifibrinolytic agents, such as epsilon-aminocaproic acid (EACA) or aprotinin is contraindicated because the blockade of the fibrinolytic system may increase the risk of thrombotic complications. (2) (www.uptodate.com) 
   
References  :
 
1 ) Levi Marcel :  Current understanding of disseminated intravascular coagulation. British Journal of Haematology 2004;  124 : 567-576
2 ) Leung Lawrence L.K., Mannucci Pier Mannuccio, Tirnauer Jennifer S.  : Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults. www.uptodate.com 2014
3 ) Shah Neeral L., Northup Patrick G., Caldwell Stephen H. et al. :  Coagulation abnormalities in patients with liver disease. www.uptodate.com  2014
4 ) Sallah S. Gagnon G.A. : Reversion of primary hyperfibrinogenolysis in patients with hormone-refractory prostate cancer using docetaxel. Cancer Investigation 2000; 18 : 191-196
5 ) Garcia-Avello A., Lorente J.A., Cesar-Perez J. Et al.  : Degree of hypercoagulability  and hyperfibrinolysis is related to organ failure and prognosis after burn trauma. Thrombosis Research 1998; 89 : 59-64 

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