A 68-year-old man with newly diagnosed lung cancer presents with swelling of the right lower limb, calf pain, and a positive D-dimer. Compression ultrasound confirms a deep vein thrombosis. Which is the most common underlying mechanism of thrombosis in this patient?

## Cancer-Associated Thrombosis: Mechanism ### Clinical Context Malignancy is one of the most important risk factors for VTE, accounting for 10–20% of all thrombotic events. Lung cancer, in particular, is a high-risk malignancy for thromboembolism. ### Primary Mechanism: Hypercoagulability **Key Point:** Cancer-induced hypercoagulability is the **most common mechanism** of thrombosis in malignant disease. This occurs through: 1. **Tissue Factor (TF) expression** — cancer cells express TF on their surface, directly activating the extrinsic coagulation pathway 2. **Procoagulant release** — tumour cells release cancer procoagulant (CP), a cysteine protease that activates Factor X independently of Factor VII 3. **Platelet activation** — cancer cells activate platelets via P-selectin and other adhesion molecules, promoting platelet aggregation 4. **Thrombin generation** — increased circulating thrombin and thrombin-antithrombin (TAT) complexes 5. **Fibrinolysis suppression** — elevated plasminogen activator inhibitor-1 (PAI-1) reduces fibrinolytic activity ### Virchow's Triad in Cancer | Component | Mechanism | Contribution | |-----------|-----------|---------------| | **Hypercoagulability** | TF, CP, platelet activation, PAI-1 ↑ | **PRIMARY** (~80%) | | Stasis | Immobility, tumour mass effect | Secondary (~15%) | | Endothelial injury | Chemotherapy, central lines, invasion | Minor (~5%) | **High-Yield:** Adenocarcinomas (lung, gastric, pancreatic, colon) are the highest-risk histologies for VTE, more so than squamous cell or small-cell carcinomas. ### Why Not the Other Options? **Warning:** Do not confuse the mechanisms: - **Direct invasion** (option A) is rare and occurs only in advanced disease with direct vascular involvement - **External compression** (option C) causes stasis, which is a secondary mechanism in cancer - **Chemotherapy-induced platelet dysfunction** (option D) is not a primary driver of thrombosis; chemotherapy actually increases hypercoagulability **Clinical Pearl:** Cancer patients with VTE have a 2–3 fold higher risk of recurrent thrombosis and bleeding complications compared to non-cancer VTE. Anticoagulation is indicated, but the choice (LMWH vs. warfarin vs. DOAC) depends on renal function, drug interactions, and tumour type. ### Mnemonic for Cancer Procoagulants **"TF-CP-PAI"** → **T**issue **F**actor, **C**ancer **P**rocoagulant, **P**lasminogen **A**ctivator **I**nhibitor (the three pillars of cancer-induced hypercoagulability).