A 58-year-old man with atrial fibrillation is started on warfarin for stroke prevention. After 5 days of therapy, he develops sudden severe left leg pain and swelling. On examination, there is cyanosis of the toes and a palpable cord in the calf. Which investigation is most appropriate to confirm the diagnosis of warfarin-induced thrombosis?

Explanation

## Clinical Presentation Analysis The patient presents with classic signs of **warfarin-induced venous thromboembolism (WIVTE)**, specifically protein C depletion syndrome occurring within the first 5 days of warfarin initiation. ### Pathophysiology of Warfarin-Induced Thrombosis **Key Point:** Warfarin depletes the vitamin K-dependent anticoagulant proteins (protein C and protein S) faster than it depletes the procoagulant factors (II, VII, IX, X). This transient hypercoagulable state in the first 3–5 days can precipitate thrombosis, particularly in patients with underlying protein C deficiency. ### Investigation of Choice **High-Yield:** **Compression ultrasonography (CUS)** is the gold standard and investigation of choice for suspected deep vein thrombosis (DVT) in the lower limbs because: 1. **Non-invasive, bedside-capable** — can be performed urgently at the patient's location 2. **High sensitivity and specificity** — >95% for proximal DVT, >90% for distal DVT 3. **Real-time visualization** — directly visualizes the thrombus and assesses compressibility of the vein 4. **No radiation or contrast exposure** — safe in acute settings 5. **Reproducible** — allows serial monitoring if needed ### Why CUS Over Other Modalities | Investigation | Advantage | Limitation | |---|---|---| | **Compression Ultrasonography** | Non-invasive, real-time, high sensitivity/specificity | Operator-dependent, limited in obese patients | | **CT Angiography** | Excellent for pulmonary embolism, visualizes distal veins | Radiation, contrast load, not first-line for DVT | | **Venography** | Gold standard anatomically | Invasive, phlebitis risk, rarely used now | | **MRI** | No radiation, excellent soft-tissue contrast | Expensive, time-consuming, not acute setting | **Clinical Pearl:** In warfarin-induced thrombosis, the thrombosis is typically **venous** (not arterial) and occurs in the **lower extremities** due to stasis and the hypercoagulable state. CUS will directly visualize the clot. ### Role of Other Investigations - **PT/INR:** Confirms anticoagulation status but does NOT diagnose thrombosis; it may paradoxically be subtherapeutic in WIVTE - **D-dimer:** Sensitive but non-specific; elevated in many conditions; not diagnostic - **CT angiography:** Overkill for DVT diagnosis; reserved for suspected PE or when CUS is inconclusive [cite:Harrison 21e Ch 297]