What are the causes of Disseminated Intravascular Coagulation (DIC)?

Causes of Disseminated Intravascular Coagulation (DIC)

Disseminated Intravascular Coagulation (DIC) is always secondary to an underlying disorder, with the most common causes being sepsis, malignancy, obstetric complications, and trauma. 1

Major Categories of DIC Causes

Infectious Causes

• Sepsis/Severe infection - The most common trigger of DIC 1
  • Bacterial infections (gram-negative and gram-positive)
  • Viral infections (including COVID-19)
  • Fungal infections
  • Parasitic infections (malaria)

Malignancy-Related Causes

• Solid tumors - Particularly adenocarcinomas 1
  • Pancreatic cancer (highest risk)
  • Gastric cancer
  • Lung cancer
  • Prostate cancer (metastatic)
• Hematologic malignancies 2
  • Acute promyelocytic leukemia (APL) - Most strongly associated with hyperfibrinolytic DIC
  • Acute myeloid leukemia
  • Other leukemias and lymphomas

Obstetric Complications 3, 4

• Placental abruption
• Amniotic fluid embolism
• Preeclampsia/eclampsia/HELLP syndrome
• Retained stillbirth
• Septic abortion
• Acute fatty liver of pregnancy
• Massive obstetric hemorrhage

Trauma and Tissue Injury

• Severe trauma with tissue destruction
• Burns (extensive)
• Crush injuries
• Major surgery
• Head trauma

Vascular Disorders

• Aortic aneurysms
• Giant hemangiomas (Kasabach-Merritt syndrome)
• Severe vasculitis

Other Causes

• Acute liver failure
• Severe toxic or immunologic reactions
• Snake bites (certain species)
• Heat stroke
• Severe pancreatitis
• Transplant rejection

Pathophysiological Classification of DIC

DIC can be categorized into three subtypes based on pathophysiological mechanisms 1:

1. Procoagulant DIC

   • Predominant clinical feature: Thrombosis
   • Common causes: Pancreatic cancer, adenocarcinomas
   • Presentation: Arterial ischemia, venous thrombosis, pulmonary embolism

2. Hyperfibrinolytic DIC

   • Predominant clinical feature: Bleeding
   • Common causes: Acute promyelocytic leukemia, metastatic prostate cancer
   • Presentation: Widespread bruising, mucosal bleeding, CNS hemorrhage

3. Subclinical DIC

   • No obvious clinical symptoms
   • Laboratory abnormalities only (thrombocytopenia, hypofibrinogenemia, microangiopathic hemolytic anemia)
   • May remain chronic or progress to overt DIC

Pathophysiological Mechanisms

The pathogenesis of DIC involves 1:

1. Endothelial injury - An essential component of DIC pathophysiology

   • Varies by underlying cause (significant in sepsis, moderate in trauma)
   • Results in exposure of tissue factor

2. Systemic activation of coagulation

   • Tissue factor/thromboplastin release from damaged tissues
   • Excessive thrombin generation
   • Widespread fibrin deposition in microvasculature

3. Consumption of platelets and coagulation factors

   • Leads to bleeding tendency

4. Secondary fibrinolysis

   • Activated to remove excess fibrin
   • May become dysregulated, especially in certain malignancies

Clinical Pearls and Pitfalls

• Important pitfall: Focusing only on the DIC without identifying and treating the underlying cause will lead to treatment failure 5
• Key consideration: The pattern of DIC varies by underlying cause - cancer-associated DIC often presents with thrombosis, while sepsis and obstetric causes more commonly present with bleeding 1, 4
• Clinical pearl: Early recognition of subclinical DIC through laboratory screening in high-risk patients may improve outcomes 1
• Diagnostic challenge: Endothelial injury markers are not included in current diagnostic criteria despite their importance in pathophysiology 1

Remember that DIC is not a primary disease but an intermediary mechanism of disease that requires prompt identification and treatment of the underlying disorder for successful management 1, 5.