What is Disseminated Intravascular Coagulation (DIC)?

Disseminated Intravascular Coagulation (DIC)

Disseminated Intravascular Coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation with loss of localization, which can originate from and cause damage to the microvasculature, potentially leading to organ dysfunction. 1

Definition and Pathophysiology

• DIC is not a primary disease but a mechanistic process that complicates various underlying conditions, characterized by simultaneous excessive coagulation activation and consumption of clotting factors 1, 2
• The International Society on Thrombosis and Haemostasis (ISTH) defines DIC as "an acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes" 1
• Endothelial injury is a critical component in DIC pathogenesis, often preceding coagulation disorders 1
• The syndrome involves widespread thrombin generation leading to both microvascular thrombosis and paradoxical bleeding due to consumption of platelets and coagulation factors 2

Primary Causes

• Sepsis is the most common cause of DIC, with significant endothelial dysfunction contributing to sepsis-induced coagulopathy 1, 2
• Other major causes include:
  • Trauma (especially with prolonged hypoxia or hypovolemia) 1
  • Malignancies (particularly adenocarcinomas and pancreatic cancer) 2
  • Severe liver failure (both acute and chronic forms) 1
  • Obstetric complications 3

Disease-Specific Mechanisms

• Sepsis-induced DIC involves significant endothelial dysfunction with high mortality (24.8% reported in a Japanese nationwide study) 1
• Cancer-associated DIC can present in three forms: procoagulant DIC, hyperfibrinolytic DIC, and subclinical DIC 2
• Liver disease-associated DIC involves multiple mechanisms:
  • Activation of coagulation factors in the low-flow portal system
  • Endotoxin absorption from intestines leading to inflammation
  • Hepatocyte necrosis with tissue factor release 1

Diagnostic Approach

• The ISTH released "overt-DIC diagnostic criteria" in 2001 for definitive diagnosis, identifying decompensated coagulation disorders through laboratory parameters 1
• Key laboratory findings include:
  • Decreased platelet count
  • Prolonged prothrombin time (PT)
  • Increased fibrin-related markers (D-dimer)
  • Decreased fibrinogen level 1
• Diagnosis requires the presence of an underlying disorder known to be associated with DIC 1
• For sepsis patients, the ISTH recommends screening for sepsis-induced coagulopathy (SIC), which represents the compensated phase of DIC 1
• Laboratory evidence of DIC should be sought before microvascular bleeding becomes evident 1

Clinical Manifestations

• The most common clinical manifestation is bleeding, occurring in the majority of acute cases 4
• Thrombosis occurs in less than 10% of acute cases but is more frequently encountered in chronic DIC associated with malignancy 4
• Organ dysfunction may develop if the microvascular damage is sufficiently severe 1
• DIC can present as either an acute decompensated or chronic compensated form, with different clinical features 2

Management Approach

• Treatment of the underlying disease and elimination of the trigger mechanism are the cornerstone therapeutic approaches 1, 5
• For severe or life-threatening hemorrhage:
  • Aggressive replacement with platelets, fresh plasma, and possibly cryoprecipitate is indicated 1, 4
  • Consider heparin anticoagulation in specific situations, particularly with predominant thrombotic manifestations 4
• For chronic DIC with thrombosis:
  • Heparin therapy is recommended as warfarin is ineffective 4
  • Long-term outpatient subcutaneous heparin may be required if the underlying condition persists 4
• Monitoring should include frequent estimation of platelet count, fibrinogen, PT, and activated partial thromboplastin time (APTT) 1
• Prolongation of PT and APTT to 1.5 times the normal value correlates with increased risk of clinical coagulopathy and requires correction 1

Recent Developments

• The ISTH has introduced the sepsis-induced coagulopathy (SIC) scoring system to detect the compensated phase of DIC in sepsis 1
• SIC is diagnosed in approximately 60% of sepsis patients, which is twice the incidence of overt DIC 1
• Emerging research focuses on endothelium-related biomarkers for earlier detection of DIC 1
• Potential anticoagulant therapies for SIC include heparin, antithrombin, and thrombomodulin, though robust evidence for their efficacy is still lacking 1