Why did an elderly patient with impaired mobility and normal‑pressure hydrocephalus develop an ischemic stroke after nine days of hospitalization despite prophylactic low‑dose enoxaparin (40 mg daily)?

Why Prophylactic Enoxaparin 40mg Failed to Prevent Stroke

This patient's stroke occurred because standard-dose enoxaparin 40mg once daily prevents venous thromboembolism (DVT/PE), not arterial ischemic stroke—the patient needed arterial antithrombotic therapy (aspirin or therapeutic anticoagulation if atrial fibrillation was present), not just VTE prophylaxis. 1

The Fundamental Mechanism Mismatch

Enoxaparin's Prophylactic Role is Limited to Venous Events

• Enoxaparin 40mg daily targets venous thromboembolism prevention (DVT and pulmonary embolism) in immobilized patients, not arterial stroke prevention 1, 2
• The PREVAIL trial demonstrated that enoxaparin 40mg once daily reduces DVT/PE risk by 43% compared to unfractionated heparin in immobilized stroke patients, but this addresses venous complications only 2
• Prophylactic-dose enoxaparin does not provide sufficient anticoagulation intensity to prevent arterial thrombosis, which requires either antiplatelet agents or therapeutic-dose anticoagulation 1

Arterial vs Venous Thrombosis Require Different Strategies

• Ischemic strokes arise from arterial thromboembolism—typically from cardiac sources (atrial fibrillation, valvular disease), large-vessel atherosclerosis, or small-vessel disease 1
• Prophylactic enoxaparin addresses the venous system, preventing clots in immobilized lower extremities that could embolize to the lungs 1, 2
• This patient needed arterial antithrombotic therapy (aspirin 160-325mg daily for atherothrombotic prevention, or therapeutic anticoagulation if atrial fibrillation was the culprit) in addition to VTE prophylaxis 1

Why This Patient Was at High Arterial Stroke Risk

Immobility Creates Dual Thrombotic Risk

• Nine days of immobility increases both venous AND arterial thrombotic risk through different mechanisms 1, 3
• Venous stasis promotes DVT/PE (which enoxaparin addresses) 2
• Prolonged immobility also increases arterial stroke risk through reduced cerebral perfusion, dehydration-induced hypercoagulability, and inflammatory activation—none of which prophylactic enoxaparin prevents 1, 3

Normal Pressure Hydrocephalus as a Stroke Risk Factor

• Patients with normal pressure hydrocephalus often have underlying cerebrovascular disease and impaired cerebral autoregulation 1
• Reduced mobility compounds cerebral hypoperfusion risk in watershed territories 1
• These patients require aggressive arterial stroke prevention, not just VTE prophylaxis 1

The Critical Gap in This Patient's Management

What Was Missing

• No arterial antithrombotic therapy was mentioned—aspirin should have been initiated unless contraindicated 1
• Cardiac monitoring to detect paroxysmal atrial fibrillation was likely not performed; 24-hour Holter or event-loop recording for several days detects occult arrhythmias that mandate therapeutic anticoagulation 1
• Cardiovascular risk factor assessment (diabetes, hypertension, hyperlipidemia) should have guided additional stroke prevention measures 1

Duration Limitations of Prophylaxis

• Enoxaparin prophylaxis should continue only until independent mobilization or maximum 8 days from hospital discharge, whichever comes first 3
• This patient received 9 days of prophylaxis, which is at the upper limit; extended prophylaxis beyond 8 days increases bleeding risk without mortality benefit per the EXCLAIM trial 3, 4
• The EXCLAIM study showed that extending enoxaparin prophylaxis to 28 additional days reduced VTE incidence (2.4% vs 8.0%) but increased major bleeding (1.5% vs 0%) with no improvement in clinically relevant outcomes or mortality 3, 4

What Should Have Been Done

Arterial Stroke Prevention Protocol

• Initiate aspirin 160-325mg daily for secondary stroke prevention unless contraindicated 1
• Perform 24-hour cardiac monitoring to detect atrial fibrillation; if present, switch to therapeutic anticoagulation (warfarin or direct oral anticoagulant) 1
• Assess and treat cardiovascular risk factors: hypertension, diabetes, hyperlipidemia 1

Appropriate VTE Prophylaxis

• Continue enoxaparin 40mg daily until independent ambulation or maximum 8 days from discharge 3
• Combine with early mobilization as soon as medically stable; mobilization reduces both venous and arterial thrombotic risk 1, 3, 5
• Add intermittent pneumatic compression devices for very high-risk immobile patients 1, 3

Monitoring for Complications

• Daily assessment for stroke progression (≥4-point increase in NIHSS score) 6
• Bleeding surveillance given dual antithrombotic therapy 3
• Hydration maintenance to reduce hypercoagulability 3, 5

Key Clinical Pitfall

The most common error is assuming VTE prophylaxis provides stroke protection—it does not. Prophylactic enoxaparin prevents DVT/PE in immobilized patients but offers no protection against arterial ischemic stroke. This patient needed both VTE prophylaxis (enoxaparin) AND arterial antithrombotic therapy (aspirin or therapeutic anticoagulation) to address the dual thrombotic risks of prolonged immobility. 1, 2