News Release

Clot-dissolving agent may be beneficial in treatment of severe frostbite

Peer-Reviewed Publication

JAMA Network

A preliminary study suggests that a blood clot-dissolving medication that is administered to some patients following a stroke or heart attack may help to reduce the risk of amputation following severe frostbite, according to a report in the June issue of Archives of Surgery, one of the JAMA/Archives journals.

Frostbite treatment has remained essentially the same for the past 25 years, according to background information in the article. “Today, traditional therapy consists of tissue rewarming, prolonged watchful waiting and often delayed amputation,” the authors write. “While many other areas of burns, trauma and critical care have advanced significantly in their treatment modalities, the saying ‘Frostbite in January, amputate in July’ is still relevant today.”

Kevin J. Bruen, M.D., and colleagues at the University of Utah, Salt Lake City, studied the anti-clotting agent tissue plasminogen activator (tPA) for the treatment of frostbite beginning in 2001. Patients who were admitted with severe frostbite underwent imaging studies to assess blood flow to the affected limb. From 2001 to 2006, six patients with abnormal blood flow on angiography received tPA within 24 hours of severe frostbite injury. These individuals were compared with 25 frostbite patients treated from 1995 to 2006 who did not receive tPA, plus one who received tPA more than 24 hours after injury.

Among the six patients who received tPA within 24 hours of injury, six of 59 (10 percent) affected fingers or toes were amputated, compared with 97 of 234 (41 percent) among those who did not receive tPA. “Moreover, no proximal [closer to the body than the fingers or toes] amputations were required in the patients who received tPA within 24 hours in our series,” the authors write. “The control group underwent 14 proximal amputations, including five below the knee. The preservation of limbs, which maximizes patient functional outcome, is perhaps the greatest benefit conferred by use of tPA in frostbite injury.”

The researchers suspect tPA helps reduce the injury caused when frozen skin is warmed again. Inflammation during thawing typically stimulates clotting that blocks small blood vessels, leading to cell death. Because tPA reverses this clotting, blood flow is restored before permanent damage is done.

“Based on the dramatic improvements in perfusion [blood flow] and reduction in rates of amputations when tPA was administered within 24 hours of frostbite injury, we anticipate the continued use of tPA in patients who are admitted to our institution with acute frostbite,” the authors write. “Candidates for this therapy are patients who present with severe frostbite as suggested by full-thickness tissue involvement, hemorrhagic blisters and abnormal perfusion on either angiogram or pyrophosphate scanning. Initiation of therapy within 24 hours of rewarming also appears to be necessary. Exclusion criteria would include superficial frostbite, involvement of the tips of the distal phalanges and contraindications to tPA, including concurrent trauma, neurological impairment or recent surgery or hemorrhage.”

“Additional studies are warranted to confirm our findings and to determine the best methods of assessing tissue damage and administering thrombolytics [anti-clotting drugs] in terms of timing, duration and route,” they conclude.

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(Arch Surg. 2007;142:546-553. Available pre-embargo to the media at www.jamamedia.org.)

Editor’s Note: Support for this project was provided by departmental and division funds from the Department of Surgery and the Burn Center at the University of Utah. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.


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