What oral antiplatelet and thrombolytic agents are recommended for severe frostbite?

Oral Antiplatelet Agents for Severe Frostbite

The primary oral antiplatelet agent recommended for severe frostbite is ibuprofen (400-600 mg every 6-8 hours), which should be initiated as soon as possible after rewarming to prevent prostaglandin-mediated vasoconstriction and further tissue damage. 1

Primary Oral Antiplatelet Therapy

Ibuprofen is the cornerstone oral agent for frostbite management:

• Mechanism: Decreases prostaglandin and thromboxane production that causes vasoconstriction, dermal ischemia, and progressive tissue damage 1
• Dosing: 400-600 mg every 6-8 hours for adults 1
• Timing: Should be started immediately after rewarming and continued long-term to prevent ongoing prostaglandin-mediated vasoconstriction 2
• Dual benefit: Provides both anti-inflammatory and anti-thrombotic effects while treating pain 1, 2

The American Heart Association and American Red Cross specifically recommend ibuprofen as part of evidence-based frostbite treatment protocols. 3

Alternative Oral Antiplatelet: Aspirin

Aspirin is mentioned as a potential alternative, though evidence is more limited:

• May be helpful in frostbite treatment, but supporting evidence is less robust than for ibuprofen 4
• Some protocols discharge patients on aspirin 325 mg daily for 30 days following thrombolytic therapy 5
• The evidence base for aspirin specifically in frostbite is weaker compared to ibuprofen 4

Important Distinction: Thrombolytics Are NOT Oral Agents

Critical caveat: The most effective thrombolytic therapy for severe frostbite—tissue plasminogen activator (tPA)—is administered intravenously or intra-arterially, NOT orally:

• tPA must be given within 24 hours of rewarming for maximum benefit 4, 6
• Intravenous tPA with heparin reduces predicted digit amputations from 174 at-risk digits to only 33 amputated (81% salvage rate) 6
• Intra-arterial thrombolytic therapy demonstrates 74.5% improvement in perfusion and 83.3% phalangeal salvage rates 7
• tPA is the most effective intervention for severe frostbite but requires hospital administration and monitoring 5, 6, 8

Agents NOT Recommended

Pentoxifylline has no supporting evidence in frostbite treatment despite its use in other vascular conditions—the American Heart Association and American Red Cross make no mention of it in their comprehensive frostbite guidelines. 3

Clinical Algorithm for Oral Agent Selection

For all frostbite patients after rewarming:

1. Start ibuprofen 400-600 mg every 6-8 hours immediately 1
2. Continue ibuprofen long-term to prevent ongoing vasoconstriction 2
3. If contraindications to ibuprofen exist (GI bleeding, renal impairment), aspirin may be considered as second-line, though evidence is limited 4

For severe frostbite with absent distal pulses or lack of perfusion on imaging:

• Oral agents alone are insufficient 6
• Transfer immediately to facility capable of administering IV/intra-arterial tPA within 24 hours of rewarming 5, 6
• Continue oral ibuprofen as adjunctive therapy 1

Critical Pitfalls to Avoid

• Do not delay tPA administration in severe cases thinking oral agents will suffice—patients with >24 hours cold exposure, >6 hours warm ischemia, or freeze-thaw cycles show poor response to delayed thrombolytic therapy 6
• Do not use aspirin and ibuprofen together without specific indication, as this increases bleeding risk without clear additional benefit in frostbite 5
• Do not assume oral agents replace the need for rapid rewarming (37-40°C water for 20-30 minutes)—this remains the primary initial intervention 1, 3