• DIC, also called consumption coagulopathy, is a systemic process producing both thrombosis and hemorrhage. It consists of the following components:   
  • Exposure of blood to procoagulants such as tissue factor and cancer procoagulant  
  • Formation of fibrin within the circulation  
  • Fibrinolysis  
  • Depletion of clotting factors  
  • End-organ damage 
• Purpura fulminans is a severe form of DIC resulting from thrombosis of extensive areas of the skin. 

• Sepsis  
• Trauma and tissue injury  and extensive surgery 
• Drugs
• PCC complex
• Amphetamines
• Transplant rejection
• Obstetric complications like septic abortion,Abruptio placentae and Amniotic fluid embolism
• Cancer
• Fulminant hepatic failure 
• Cirrhosis 
• Severe allergic reactions 
• Transfusion reactions
• Miscellaneous

• Interactions between coagulation and fibrinolytic pathways result in bleeding and thrombosis in the microcirculation in patients with DIC.  It leads to ischemic tissue damage leading to failure of multiple organs (especially lung, kidney, liver, and brain). Secondary fibrinolysis leads to vessel patency, fibrin degradation products (FDP), D-Dimer, diffuse bleeding , Red blood cell damage and hemolysis and consumption of platelets and coagulation factors

1. Bleeding. May manifest as Petechiae, echymosis, GI bleed, bleeding from catheters.
2. Renal dysfunction. Micro thrombosis of afferent arterioles may produce cortical ischemia or necrosis (renal thrombotic microangiopathy), and hypotension and/or sepsis can lead to acute tubular necrosis.   
3. Hepatic dysfunction. Jaundice is common in patients with DIC and may be due both to liver disease and increased bilirubin production secondary to hemolysis. In addition, hepatocellular injury may be produced by sepsis and hypotension.   
4. Respiratory dysfunction. Pulmonary hemorrhage with hemoptysis and dyspnea may result from damage to the pulmonary vascular endothelium. In addition, sepsis, trauma, and amniotic fluid embolism are causes of acute respiratory distress syndrome (ARDS) as well as DIC.  
5. Shock.   
6. Thromboembolism.   can cause bowel infarction, gangrene of fingers and toes. 
7. Central nervous system involvement. These include coma, delirium, and transient focal neurologic symptoms. Microthrombi, hemorrhage, and hypoperfusion all may contribute. 

• Thrombotic thrombocytopenic purpura 
• Heparin-induced thrombocytopenia 
• Severe liver disease 
• Hemolytic uremic syndrome 
• Vasculitis 

1. DIC vs. Liver disease: Factor VIII levels are normal or elevated in liver disease. Fibrinogen levels are elevated in liver disease but decreased in DIC.  
2. DIC vs. TTP: Normal PT/PTT in TTP  
3. DIC vs. Vit.K deficiency: correction of coagulopathy with Vit.K administration. 

• Laboratory investigation should include: aPTT, PT and thrombin time.
• Markers of FDP, LDH, Fibrinogen 
• Platelet and red cell count 
• Analysis of the blood smear 
• ​DIC can be diagnosed on the basis of the following findings: 
  • An initial platelet count < 100,000/µL or a rapid decline in the platelet count 
  • Prolongation of clotting times, such as the PT and the aPTT 
  • Presence of FDP in plasma 
  • High LDH, Low Fibrinogen ( <120) 
  • Low plasma levels of coagulation inhibitors, such as antithrombin III (a thrombin inhibitor) and alpha-2-antiplasmin (a plasmin inhibitor) 
  • Presence of microangiopathic changes and schistocytes on the peripheral blood smear. 

• Platelet transfusion if Plt<10, or for <20, if high risk for bleeding, or <50, if active bleeding or for procedures.  
• FFP transfusion for bleeding only. No data to suggest empiric correction of coagulopathy  
• Cryoprecipitate for fibrinogen less than 100 ( cryoprecipitate contains fibrinogen, FVIII, and vWF). 
• Low doses of continuous infusion heparin (5–10 U/kg per h)  may be effective in patients with low-grade DIC associated with solid tumor or APL or in a setting with recognized thrombosis. it is also indicated in Purpura fulminans and removal of a dead fetus 
• In acute DIC, the use of heparin is likely to aggravate bleeding. 
• Antifibrinolytic drugs (epsilon aminocaproic acid [EACA] or tranexamic acid)  :  Prevent fibrin degradation by plasmin and may reduce bleeding episodes in patients with DIC and confirmed hyperfibrinolysis. they also increase the risk of thrombosis, and concomitant use of heparin is indicated. 

1. Microangiopathic hemolytic anemia (Hallmark of disease). MAHA is defined as nonimmune hemolysis (i.e. negative direct antiglobulin test)  
2. Thrombocytopenia, often with purpura but not usually severe bleeding 
3. Renal dysfunction due to thrombotic microangiopathy. Urinalysis often is near normal with few casts and mild proteinuria. 
4. Neurologic abnormalities, such as confusion, headaches, seizures, transient aphasia, TIA and coma. 
5. Fever is rare; high fever with chills suggests sepsis and DIC rather than TTP-HUS 

• TTP-HUS is a clinical diagnosis, with noticeable ADAMS13 deficiency. However, ADAMTS13 activity levels cannot be used to determine initial therapy with plasma exchange, and definitive therapy with plasma exchange should not be delayed while determining ADAMTS13 activity levels because delays in initiating treatment may be fatal. 
• Peripheral smear showing schistocytes and reticulocytosis 
• Normal PT/PTT 
• Elevated LDH, reflecting both hemolysis and tissue damage due to systemic ischemia. Thus LDH levels can be followed to monitor response to treatment. 
• Low haptoglobin 
• Increase indirect bilirubin 
• Normal fibrinogen and D-dimer 

• Clinical diagnosis of TTP-HUS should prompt urgent initiation of plasma exchange therapy, which can be life-saving in this syndrome. 
• The mainstay of treatment for most patients with TTP-HUS is plasma exchange, which in the context of this syndrome refers to the removal of the patient’s plasma by pheresis and the replacement with donor plasma. Plasma exchange should be initiated even if there is some uncertainty about the diagnosis of TTP-HUS, as it is considered that the potential dangers of rapid deterioration from TTP-HUS exceed the significant risks of plasma exchange treatment. 
• Plasma exchange is more effective than plasma infusion in most adults with “classical” TTP-HUS because for the great majority of those who have decreased ADAMTS13 activity, the decreased activity is due to an inhibitory antibody.  
• Plasma exchange is initially performed daily until the platelet count has normalized and hemolysis largely ceased, as evidenced by a return of the serum lactate dehydrogenase (LDH) concentration to normal, or nearly normal, levels. 
• Corticosteroids and Rituximab may have a role in patients who don’t improve with plasmapheresis. 
• Folate supplementation is needed during active hemolysis. 
• Platelet transfusions are contraindicated except for life threatening bleeding. 

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