{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:20:43Z","timestamp":1784784043526,"version":"3.55.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T00:00:00Z","timestamp":1560297600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Frostbite is a cold injury that results in soft tissue loss and can lead to amputation. Vascular thrombosis following injury causes ischemic tissue damage. Despite understanding the pathology, its treatment has remained largely unchanged for over 30 years. Threatened extremities may be salvaged with thrombolytics to restore perfusion. The authors performed a systematic review to determine whether thrombolytic therapy is effective and to identify patients who may benefit from this treatment. The Pubmed, EBSCO, and Google Scholar databases were queried using the key words \u201cthrombolytics,\u201d \u201cfrostbite,\u201d \u201cfibrinolytics,\u201d and \u201ctPA.\u201d Studies written after 1990 in English met inclusion criteria. Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as administration of tPA, alteplase, urokinase, or streptokinase. Forty-two studies were identified and 17 included. Included were 1 randomized trial, 10 retrospective studies, 2 case series, and 4 case reports. One thousand eight hundred and forty-four limbs and digits in 325 patients were studied and 216 patients treated with thrombolytics and 346 amputations performed. The most common means of thrombolysis was intra-arterial tPA. The most common duration of therapy was 48 hours. Limb salvage rates ranged from 0% to 100% with a weighted average of 78.7%. Thrombolytics are a safe and effective treatment of severe frostbite. They represent the first significant advancement in frostbite treatment by preventing otherwise inevitable amputations warranting both greater utilization and further research to clarify the ideal thrombolytic protocol.<\/jats:p>","DOI":"10.1093\/jbcr\/irz097","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T08:39:49Z","timestamp":1560328789000},"page":"541-549","source":"Crossref","is-referenced-by-count":28,"title":["Thrombolytic Salvage of Threatened Frostbitten Extremities and Digits: A Systematic Review"],"prefix":"10.1093","volume":"40","author":[{"given":"James","family":"Drinane","sequence":"first","affiliation":[{"name":"Division of Plastic Surgery, Albany Medical Center, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasanth S","family":"Kotamarti","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Albany Medical Center, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery, Albany Medical Center, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Nair","sequence":"additional","affiliation":[{"name":"Albany Medical College, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Divanyan","sequence":"additional","affiliation":[{"name":"Albany Medical College, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm Z","family":"Roth","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Albany Medical Center, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashit","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Albany Medical Center, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A","family":"Ricci","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Albany Medical Center, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,11]]},"reference":[{"key":"2019081416352187400_CIT0001","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/ajpa.1330370204","article-title":"Frostbite in a pre-Columbian mummy","volume":"37","author":"Post","year":"1972","journal-title":"Am J Phys Anthropol"},{"key":"2019081416352187400_CIT0002","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1007\/s00270-017-1729-7","article-title":"Intra-arterial thrombolysis for extremity frostbite decreases digital amputation rates and hospital length of stay","volume":"40","author":"Patel","year":"2017","journal-title":"Cardiovasc Intervent Radiol"},{"key":"2019081416352187400_CIT0003","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.wem.2015.11.014","article-title":"A new proposal for management of severe frostbite in the austere environment","volume":"27","author":"Cauchy","year":"2016","journal-title":"Wilderness Environ Med"},{"key":"2019081416352187400_CIT0004","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.hcl.2009.06.004","article-title":"Cold injury","volume":"25","author":"Mohr","year":"2009","journal-title":"Hand Clin"},{"key":"2019081416352187400_CIT0005","doi-asserted-by":"crossref","first-page":"e323","DOI":"10.1097\/BCR.0000000000000245","article-title":"Use of intra-arterial thrombolytic therapy for acute treatment of frostbite in 62 patients with review of thrombolytic therapy in frostbite","volume":"37","author":"Gonzaga","year":"2016","journal-title":"J Burn Care Res"},{"key":"2019081416352187400_CIT0006","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/BCR.0000000000000135","article-title":"The emerging role of tissue plasminogen activator in the management of severe frostbite","volume":"36","author":"Ibrahim","year":"2014","journal-title":"J Burn Care Res"},{"key":"2019081416352187400_CIT0007","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/00005373-198302000-00013","article-title":"Frostbite injuries: a rational approach based on the pathophysiology","volume":"23","author":"McCauley","year":"1983","journal-title":"J Trauma"},{"key":"2019081416352187400_CIT0008","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.burns.2017.04.016","article-title":"The evolution of the Helsinki frostbite management protocol","volume":"43","author":"Lindford","year":"2017","journal-title":"Burns"},{"key":"2019081416352187400_CIT0009","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.1992.03480150014005","article-title":"Early data suggest clot-dissolving drug may help save frostbitten limbs from amputation","volume":"267","author":"Skolnick","year":"1992","journal-title":"JAMA"},{"key":"2019081416352187400_CIT0010"},{"key":"2019081416352187400_CIT0011","author":"National Health Service"},{"key":"2019081416352187400_CIT0012","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1046\/j.1445-2197.2003.02748.x","article-title":"Methodological index for non-randomized studies (MINORS): development and validation of a new instrument","volume":"73","author":"Slim","year":"2003","journal-title":"ANZ J Surg"},{"key":"2019081416352187400_CIT0013","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/BCR.0000000000000426","article-title":"Time matters in severe frostbite: assessment of limb\/digit salvage on the individual patient level","volume":"38","author":"Nygaard","year":"2017","journal-title":"J Burn Care Res"},{"key":"2019081416352187400_CIT0014","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1056\/NEJMcpc0910088","article-title":"Case records of the Massachusetts General Hospital. Case 41-2009. A 16-year-old boy with hypothermia and frostbite","volume":"361","author":"Sheridan","year":"2009","journal-title":"N Engl J Med"},{"key":"2019081416352187400_CIT0015","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4103\/0974-2700.99709","article-title":"Using thrombolytics in frostbite injury","volume":"5","author":"Gross","year":"2012","journal-title":"J Emerg Trauma Shock"},{"key":"2019081416352187400_CIT0016","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.amj.2010.08.006","article-title":"Thrombolytic therapy in the acute management of frostbite injuries","volume":"30","author":"Wagner","year":"2011","journal-title":"Air Med J"},{"key":"2019081416352187400_CIT0017","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/1938640011422596","article-title":"Efficacy of intravenous tissue plasminogen activator in frostbite patients and presentation of a treatment protocol for frostbite patients","volume":"4","author":"Johnson","year":"2011","journal-title":"Foot Ankle Spec"},{"key":"2019081416352187400_CIT0018","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.annemergmed.2012.12.003","article-title":"Two patients with frostbite","volume":"62","author":"Dolbec","year":"2013","journal-title":"Ann Emerg Med"},{"key":"2019081416352187400_CIT0019","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1007\/s00270-009-9584-9","article-title":"Treatment of bilateral hand frostbite using transcatheter arterial thrombolysis after papaverine infusion","volume":"32","author":"Saemi","year":"2009","journal-title":"Cardiovasc Intervent Radiol"},{"key":"2019081416352187400_CIT0020","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1007\/s00270-017-1729-7","article-title":"Intra-arterial Thrombolysis for Extremity Frostbite Decreases Digital Amputation Rates and Hospital Length of Stay","volume":"40","author":"Srinivasa","year":"2017","journal-title":"Cardiovasc Intervent Radiol"},{"key":"2019081416352187400_CIT0021","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.jvir.2016.04.027","article-title":"Catheter-directed intraarterial thrombolysis as part of a multidisciplinary management protocol of frostbite injury","volume":"27","author":"Tavri","year":"2016","journal-title":"J Vasc Interv Radiol"},{"key":"2019081416352187400_CIT0022","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1001\/archsurg.142.6.546","article-title":"Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy","volume":"142","author":"Bruen","year":"2007","journal-title":"Arch Surg"},{"key":"2019081416352187400_CIT0023","doi-asserted-by":"crossref","first-page":"e877","DOI":"10.1097\/BCR.0000000000000512","article-title":"The use of thrombolytic therapy in the treatment of frostbite injury","volume":"38","author":"Wexler","year":"2017","journal-title":"J Burn Care Res"},{"key":"2019081416352187400_CIT0024","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.burns.2017.01.013","article-title":"The use of intravenous tPA for the treatment of severe frostbite","volume":"43","author":"Jones","year":"2017","journal-title":"Burns"},{"key":"2019081416352187400_CIT0025","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1161\/CIRCULATIONAHA.113.005544","article-title":"Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism","volume":"129","author":"Kucher","year":"2014","journal-title":"Circulation"},{"key":"2019081416352187400_CIT0026","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1053\/jhsu.2000.16357","article-title":"The value of technetium 99 scintigraphy in the prognosis of amputation in severe frostbite injuries of the extremities: a retrospective study of 92 severe frostbite injuries","volume":"25","author":"Cauchy","year":"2000","journal-title":"J Hand Surg Am"}],"container-title":["Journal of Burn Care &amp; Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jbcr\/advance-article-pdf\/doi\/10.1093\/jbcr\/irz097\/28932284\/irz097.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jbcr\/article-pdf\/40\/5\/541\/29163579\/irz097.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T12:08:30Z","timestamp":1565957310000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbcr\/article\/40\/5\/541\/5514180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,11]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,6,11]]},"published-print":{"date-parts":[[2019,8,14]]}},"URL":"https:\/\/doi.org\/10.1093\/jbcr\/irz097","relation":{},"ISSN":["1559-047X","1559-0488"],"issn-type":[{"value":"1559-047X","type":"print"},{"value":"1559-0488","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,9]]},"published":{"date-parts":[[2019,6,11]]}}}