A 52-year-old man with a 10-year history of smoking presents with sudden onset of severe pain and cyanosis of the right foot. Doppler ultrasound shows acute thrombosis of the femoral artery. Which is the most common underlying thrombotic disorder predisposing to acute arterial thrombosis in this clinical scenario?

## Most Common Cause of Acute Arterial Thrombosis ### Epidemiology & Pathophysiology Acute arterial thrombosis in adults is predominantly caused by **atherosclerotic plaque rupture with superimposed thrombosis**, particularly in the setting of established cardiovascular risk factors such as smoking, hypertension, diabetes, and dyslipidemia. The rupture of a vulnerable atherosclerotic plaque exposes tissue factor and collagen, triggering the extrinsic coagulation cascade and platelet aggregation. ### Why Atherosclerotic Plaque Rupture Is Most Common **Key Point:** Atherosclerotic disease accounts for >90% of acute arterial thrombosis cases in the general population. The presence of multiple risk factors (smoking, age >50) in this patient makes atherosclerotic plaque rupture the overwhelming most likely diagnosis. ### Comparison with Inherited Thrombophilias | Feature | Atherosclerotic Thrombosis | Inherited Thrombophilia | |---------|---------------------------|------------------------| | **Age of onset** | Typically >40 years | Often <40 years | | **Site** | Large/medium arteries | Veins > arteries | | **Risk factors** | Smoking, HTN, DM, dyslipidemia | Family history, recurrent events | | **Prevalence** | >90% of acute arterial events | <5% of arterial thrombosis | | **Presentation** | Acute limb ischemia, MI, stroke | DVT, PE, recurrent thrombosis | **High-Yield:** Inherited thrombophilias (Factor V Leiden, Protein C/S deficiency, Antithrombin III deficiency) predominantly cause **venous** thromboembolism, not acute arterial thrombosis. They are rare causes of arterial events and typically present in younger patients with a strong family history. ### Clinical Pearl The classic presentation of acute arterial thrombosis—sudden-onset severe pain, pallor, pulselessness, paresthesia, and paralysis (the "6 Ps")—in a middle-aged smoker with atherosclerotic risk factors should immediately direct thinking toward plaque rupture rather than a primary coagulation disorder. ### Mnemonic: Risk Factors for Atherosclerotic Thrombosis **ABCDE**: **A**ge, **B**lood pressure, **C**holesterol, **D**iabetes, **E**xcessive smoking [cite:Harrison 21e Ch 302]