Can infection lead to Disseminated Intravascular Coagulation (DIC)?

Infection as a Cause of Disseminated Intravascular Coagulation (DIC)

Yes, infection is a major cause of Disseminated Intravascular Coagulation (DIC) and represents one of the most common underlying conditions triggering this life-threatening coagulation disorder. 1

Pathophysiology of Infection-Induced DIC

Infection, particularly sepsis, leads to DIC through several key mechanisms:

1. Inflammatory Cytokine Cascade:

   • Infections trigger a systemic inflammatory response with release of pro-inflammatory cytokines
   • These cytokines activate the tissue factor-dependent coagulation pathway 1, 2
   • Endotoxin from gram-negative bacteria can directly activate coagulation 1

2. Endothelial Dysfunction:

   • Infection causes significant endothelial cell injury (endotheliopathy) 1
   • Damaged endothelium loses its anticoagulant properties and becomes procoagulant
   • Terminal complement complex C5b-9 damages endothelial cell membranes 3

3. Dysregulation of Coagulation Systems:

   • Procoagulant activation: Upregulation of tissue factor expression, primarily by stimulated monocytes/macrophages 4
   • Anticoagulant impairment: Decreased function of natural anticoagulants (antithrombin, protein C pathway, tissue factor pathway inhibitor) 1, 4
   • Fibrinolysis suppression: Overproduction of plasminogen activator inhibitor-1 (PAI-1) 1, 4

Sepsis-Induced Coagulopathy (SIC) and DIC Progression

The International Society on Thrombosis and Haemostasis (ISTH) recognizes that infection-induced coagulopathy exists on a spectrum:

1. Sepsis-Induced Coagulopathy (SIC):

   • Early phase of coagulation dysfunction in sepsis 1
   • Characterized by thrombocytopenia, PT prolongation, and organ dysfunction
   • SIC diagnostic criteria include platelet count, PT-INR, and SOFA score 1
   • Represents a window for potential therapeutic intervention before progression to overt DIC

2. Overt DIC:

   • More advanced stage with widespread microvascular thrombosis
   • Characterized by consumption of platelets and coagulation factors
   • Can lead to both thrombotic and hemorrhagic complications
   • Diagnosed using the ISTH overt-DIC scoring system 1

Clinical Manifestations and Outcomes

Infection-induced DIC presents with:

• Microvascular thrombosis leading to organ dysfunction
• Potential for bleeding due to consumption of coagulation factors and platelets
• Symmetrical peripheral gangrene in severe cases 1
• High mortality rate (24.8% in septic patients with DIC according to a Japanese nationwide study) 1

Diagnostic Approach

The ISTH recommends a two-step diagnostic approach for sepsis patients with thrombocytopenia:

1. Step 1: Screen for SIC using:

   • Platelet count
   • PT-INR
   • SOFA score

2. Step 2: If SIC is present, evaluate for overt DIC using:

   • Platelet count
   • Prolonged prothrombin time
   • Fibrinogen levels
   • Fibrin-related markers (D-dimer) 1

Differential Diagnosis

It's important to differentiate sepsis-associated DIC from other thrombocytopenic conditions:

• Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic uremic syndrome (HUS)
• Heparin-induced thrombocytopenia
• Immune thrombocytopenia 5

Management Implications

Early recognition of infection-induced DIC is critical for improved outcomes:

• Aggressive treatment of the underlying infection is the cornerstone of management 2
• Anticoagulant therapy may be beneficial in patients with sepsis-associated DIC 1
• Therapeutic options may include unfractionated heparin, low-molecular-weight heparin, antithrombin, or recombinant soluble thrombomodulin 1

Important Clinical Considerations

• The resolution of DIC is strongly associated with improved survival 6
• Factors related to poor outcomes include high DIC score, high SOFA score, advanced age, and prolonged PT ratio 6
• Screening for DIC on ICU admission and repeating 2 days later is associated with lower mortality 1
• Endothelium-related biomarkers may improve early detection of DIC but are not yet routinely used in clinical practice 1

In conclusion, infection, particularly sepsis, is a well-established and common cause of DIC. The pathophysiology involves a complex interplay of inflammatory mediators, endothelial dysfunction, and dysregulated coagulation, ultimately leading to microvascular thrombosis and potential organ failure.