During the second wave of COVID-19 in India, a 38-year-old woman is admitted with severe pneumonia. Laboratory investigations reveal elevated D-dimer, prolonged PT/INR, and thrombocytopenia. Which of the following is the most common thrombotic complication in severe COVID-19?

## Thrombotic Complications in Severe COVID-19 ### Most Common: Pulmonary Embolism and Deep Vein Thrombosis **Key Point:** Venous thromboembolism (VTE), particularly pulmonary embolism (PE) and deep vein thrombosis (DVT), is the most frequent thrombotic complication in hospitalized COVID-19 patients, occurring in 4–27% of severe cases. ### Pathophysiology of COVID-19-Associated Thrombosis ```mermaid flowchart TD A[SARS-CoV-2 Infection]:::outcome --> B[Endothelial Injury via ACE2]:::action B --> C[Platelet Activation & Aggregation]:::action C --> D[Tissue Factor Upregulation]:::action D --> E[Thrombin Generation]:::action E --> F{Thrombotic Manifestation}:::decision F -->|Most Common| G[Pulmonary Embolism/DVT]:::urgent F -->|Less Common| H[Arterial Thrombosis]:::urgent F -->|Severe Cases| I[DIC with Microthrombi]:::urgent ``` ### Mechanisms of Hypercoagulability in COVID-19 1. **Endothelial dysfunction** — Direct viral invasion via ACE2 receptors on endothelial cells 2. **Platelet activation** — Elevated P-selectin, platelet-monocyte aggregates 3. **Tissue factor upregulation** — Increased TF expression on monocytes and endothelium 4. **Elevated von Willebrand factor** — Marker of endothelial injury 5. **Impaired fibrinolysis** — Elevated PAI-1, reduced tPA activity 6. **Inflammation-mediated coagulation** — IL-6, TNF-α, IL-1β drive TF expression ### Incidence of Thrombotic Complications | Complication | Incidence in Severe COVID-19 | Clinical Significance | | --- | --- | --- | | **Pulmonary embolism** | 4–27% | Most common; often asymptomatic | | **Deep vein thrombosis** | 2–15% | Often proximal; associated with PE | | **Acute MI** | 1–5% | Type 2 MI more common than STEMI | | **Stroke** | 1–3% | Ischemic > hemorrhagic | | **DIC** | <1% (fulminant cases) | Associated with mortality >50% | **High-Yield:** PE in COVID-19 is often **clinically silent** or atypical in presentation due to the underlying respiratory compromise. High clinical suspicion and D-dimer monitoring are essential. ### Risk Factors for VTE in COVID-19 - Severe pneumonia with hypoxemia - Prolonged immobilization - Elevated D-dimer and fibrinogen - Elevated IL-6 and CRP - Advanced age and comorbidities (diabetes, hypertension, obesity) **Clinical Pearl:** D-dimer is markedly elevated in severe COVID-19 (often >1000 ng/mL) and correlates with thrombotic risk. Serial D-dimer monitoring can help stratify risk and guide anticoagulation decisions. ### Prophylaxis and Management - **Pharmacological thromboprophylaxis** — LMWH or fondaparinux for all hospitalized COVID-19 patients - **Mechanical prophylaxis** — Sequential compression devices if anticoagulation contraindicated - **Therapeutic anticoagulation** — For confirmed VTE (LMWH or UFH preferred over DOACs in acute phase) [cite:Harrison 21e Ch 297]