A 28-year-old man with sepsis secondary to Gram-negative bacteremia develops sudden-onset bleeding, thrombocytopenia, and low fibrinogen. Which of the following is the most common infectious cause of disseminated intravascular coagulation (DIC)?

Explanation

## Most Common Infectious Cause of DIC **Key Point:** Gram-negative bacterial sepsis, particularly meningococcemia (*Neisseria meningitidis*), is the most common infectious cause of DIC. ### Pathophysiology of Sepsis-Induced DIC Gram-negative bacteria trigger DIC through: 1. **Lipopolysaccharide (LPS) endotoxin** → TLR-4 activation 2. **Tissue factor (TF) upregulation** on monocytes and endothelial cells 3. **Thrombin generation** → platelet consumption and fibrinogen depletion 4. **Inflammatory cascade** (TNF-α, IL-6, IL-8) → endothelial damage and increased vascular permeability 5. **Fibrinolysis activation** → elevated D-dimer and FDP ### Why Gram-Negative Sepsis Is Worst **High-Yield:** Gram-negative endotoxin (LPS) is a potent activator of the extrinsic coagulation pathway: - LPS binds CD14 and TLR-4 on monocytes - Massive TF expression → thrombin burst - Platelet aggregation and consumption - Fibrinogen depletion - Activation of protein C pathway (but insufficient to control coagulation) **Clinical Pearl:** Meningococcemia is the classic presentation: - Fulminant sepsis with petechial/purpuric rash - DIC in >50% of cases - High mortality (20–40% even with antibiotics) - Waterhouse-Friderichsen syndrome (bilateral adrenal hemorrhage due to DIC) ### Comparison of Infectious Causes of DIC | Organism | Frequency of DIC | Mechanism | Severity | |----------|------------------|-----------|----------| | Gram-negative (esp. *N. meningitidis*) | Very high (>50%) | LPS → TF upregulation | Fulminant | | Gram-positive (*S. aureus*) | Moderate (10–20%) | Toxins + inflammatory mediators | Moderate to severe | | Candida spp. | Moderate (10–20%) | Fungal wall antigens + TF | Moderate | | Dengue virus | Low to moderate (5–15%) | Viral proteins + immune activation | Variable | ### Laboratory Findings in Sepsis-DIC | Parameter | Finding | |-----------|----------| | Platelet count | ↓↓ (often <50,000) | | Fibrinogen | ↓ (often <100 mg/dL) | | PT/INR | ↑ | | aPTT | ↑ | | D-dimer | ↑↑↑ (markedly elevated) | | FDP | ↑↑ | | Prothrombin time | Prolonged | | Thrombin time | Prolonged | ### DIC Scoring (ISTH Criteria) **Mnemonic: "PLATFIB-DD"** — Score based on: - **P**latelet count - **LAT**ency (fibrinogen) - **F**ibrin degradation products / D-dimer - **I**nternational normalized ratio (INR) - **B**lood findings Score ≥5 = overt DIC (>94% specificity) ### Management of Sepsis-Induced DIC 1. **Source control** — antibiotics, drainage, surgery 2. **Supportive care** — FFP, platelets, cryoprecipitate 3. **Anticoagulation** — low-dose heparin (controversial but often used) 4. **Activated protein C** — recombinant (drotrecogin alfa) — now largely abandoned due to lack of benefit 5. **Treat underlying sepsis** — the only definitive cure **Clinical Pearl:** DIC in sepsis is a marker of severe disease and poor prognosis. Resolution depends on controlling the infection; transfusion alone is temporizing. [cite:Harrison 21e Ch 295; Robbins 10e Ch 13]