Can sepsis cause coagulopathy?

Can Sepsis Cause Coagulopathy?

Yes, sepsis definitively causes coagulopathy—this is a well-established, life-threatening complication that occurs through systemic activation of coagulation pathways, endothelial dysfunction, and inflammatory dysregulation. 1, 2

Pathophysiological Mechanisms

Sepsis triggers coagulopathy through multiple interconnected mechanisms:

Endothelial Dysfunction and Procoagulant Conversion:

• Inflammatory cytokines and microbial products convert the normally anticoagulant endothelium to a procoagulant state, exposing collagen fibers and activating von Willebrand factor 2
• Endothelial injury represents a critical early event that precedes the coagulation disorder itself 3
• This endothelial dysfunction is highly significant in sepsis-induced coagulopathy compared to other causes of DIC 3

Activation of Coagulation Pathways:

• Tissue factor pathway activation leads to widespread thrombin generation and fibrin deposition in the microvasculature 2, 4
• The contact factor pathway is simultaneously activated through factor XII 2
• This results in consumption of platelets and coagulation factors, eventually causing disseminated intravascular coagulation (DIC) 1, 5

Impairment of Natural Anticoagulants:

• All three major anticoagulant systems become dysfunctional: antithrombin, protein C pathway, and tissue factor pathway inhibitor 2
• Thrombomodulin expression decreases on endothelial cells, impairing protein C activation 2
• These natural anticoagulants are depleted through increased consumption, decreased production, and proteolytic cleavage 1

Suppression of Fibrinolysis:

• A hallmark feature distinguishing sepsis-associated DIC from other forms is excessive suppression of fibrinolysis 1
• Inflammatory cytokines dramatically increase plasminogen activator inhibitor-1 (PAI-1), blocking tissue plasminogen activator 1, 2
• This prothrombotic state is rarely seen in malignancy-associated DIC 1

Clinical Spectrum and Progression

Sepsis-Induced Coagulopathy (SIC) - The Early Phase:

• SIC represents the earlier, compensated phase before overt DIC develops 1
• The International Society on Thrombosis and Haemostasis (ISTH) developed SIC criteria specifically to identify patients at this earlier stage when intervention may be most beneficial 1
• SIC is diagnosed using three simple parameters: platelet count, PT-INR, and SOFA score (≥4 points indicates SIC) 1

Progression to Overt DIC:

• Overt DIC represents advanced coagulopathy with widespread microvascular thrombosis and consumption of clotting factors 1
• ISTH overt DIC criteria require ≥5 points based on platelet count, fibrin markers (FDP/D-dimer), prothrombin time, and fibrinogen 1
• The two conditions represent a continuum, with SIC typically preceding overt DIC 1

Clinical Manifestations

Laboratory Findings:

• Thrombocytopenia from platelet consumption is characteristic and correlates with mortality 1, 3, 5
• Prolonged prothrombin time reflecting factor consumption 3
• Elevated D-dimer and fibrin degradation products 3
• Decreased fibrinogen in advanced cases (though may initially be normal as an acute phase reactant) 3

Organ Dysfunction:

• Reduced tissue perfusion from microvascular thrombosis leads to multi-organ failure 1
• Unlike malignancy-associated DIC where bleeding predominates, sepsis-associated DIC primarily causes organ dysfunction 1
• Symmetrical peripheral gangrene (SPG) represents a devastating consequence with potential limb loss from microvascular thrombosis 1

Diagnostic Approach

Two-Step Sequential Screening (ISTH Recommendation):

1. Step 1: Screen all septic patients with thrombocytopenia (platelet count <150 × 10⁹/L) using SIC criteria 1
2. Step 2: If SIC criteria are met, assess for overt DIC using ISTH overt DIC criteria 1

This approach facilitates early recognition when therapeutic intervention is most likely beneficial 1

Clinical Significance

Mortality Impact:

• Coagulopathy is a leading factor associated with mortality in septic patients 5
• Sepsis is the most common cause of DIC, with mortality of 24.8% in Japanese nationwide data when DIC develops 3
• The severity of thrombocytopenia directly correlates with mortality risk 5, 6

Common Pitfall: Waiting for overt DIC criteria before recognizing coagulopathy—patients with advanced coagulopathy may have illness progression no longer amenable to benefit from anticoagulant therapy 1. Early screening using SIC criteria on ICU admission (and repeated 2 days later) is associated with lower mortality 1.