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Free-Flap Salvage by Thrombolytic Agents? An Evidence-Based Systemic Analysis

Cheng, Hsu-Tang M.D.; Lin, Fu-Yu M.D.; Chang, Sophia Chia-Ning M.D., Ph.D.

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Plastic and Reconstructive Surgery: April 2012 - Volume 129 - Issue 4 - p 766e-767e
doi: 10.1097/PRS.0b013e318245eab1
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Despite advances in microsurgery and the experience gained in clinical practice, failures caused by thrombosis at the site of microanastomosis remain a challenge to plastic surgeons. The failure rate of approximately 5 percent of all free-flap operations clinically has suggested that there may be a place for pharmacologic intervention at the time of threatened flap failure. However, there has been no consensus on the role of thrombolytic agents in free-flap salvage.

We performed a systematic literature review by searching the PubMed database from January of 1980 to December of 2010. We used the following keywords: “thrombolytic agents,” “streptokinase,” “urokinase,” “recombinant tissue plasminogen activator,” “free flap,” “free tissue transfer,” and “thrombosis.”

We excluded the non-English articles, studies in experimental animals, and digit or limb replantations. Two reviewers independently extracted data in two steps: titles and abstracts, and then full text articles. This search was supplemented by a review of reference lists of potentially eligible studies. Relevant studies were assigned a level of evidence according to the American Society of Plastic Surgeons Evidence Rating Scale for Therapy.

Through our electronic and reference search, we identified 22 citations. There were neither randomized controlled trials nor meta-analyses regarding our study topic. There were 15 case reports (level V evidence), three case series (level IV evidence), and four retrospective comparative studies (level III evidence). In the four retrospective comparative studies (Table 1),14 only one used a uniform thrombolytic agent (recombinant tissue plasminogen activator) with a standard dose of 2.5 mg and had a clearly defined indication of thrombolysis and its additive dose.1 In this study, though with a higher salvage rate by using the recombinant tissue plasminogen activator, there was no statistically significant difference between the treatment and control groups (p = 0.17). The indication for thrombolysis varied from “established extensive clot in either the arterial or the venous system,”2 to “no sufficient restoration of blood flow after blood clot evacuation,”1 to “failure to reestablish venous outflow after establishing good arterial inflow.”3 The salvage rate of the treatment groups ranged from 30 to 75 percent, and that of the control groups ranged from 29 to 67 percent.

Table 1
Table 1:
The Four Retrospective Comparative Studies

The literature on the clinical efficacy of thrombolytic agents in free-flap salvage has not been well documented; thus, this is a level II evidence-based systematic analysis. All of the findings come from the four retrospective comparative studies, and the equivocal results suggest that it is not possible to draw clear conclusions about the role of thrombolytic agents in free-flap salvage.

Further studies are needed regarding their indications, dosages, routes of administration, efficacy, safety, and patient randomization. Intensive flap monitoring at a specialized microsurgical intensive care unit by well-trained staff and urgent reexploration remain critical for free-flap salvage.

Hsu-Tang Cheng, M.D.

Department of Plastic Surgery, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan

Fu-Yu Lin, M.D.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Sophia Chia-Ning Chang, M.D., Ph.D.

Department of Plastic Surgery, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan


The authors have no financial interest to declare in relation to the content of this article.


1. Rinker BD, Stewart DH, Pu LL, Vasconez HC. Role of recombinant tissue plasminogen activator in free flap salvage. J Reconstr Microsurg. 2007;23:69–73.
2. Bui DT, Cordeiro PG, Hu QY, Disa JJ, Pusic A, Mehrara BJ. Free flap reexploration: Indications, treatment, and outcomes in 1193 free flaps. Plast Reconstr Surg. 2007;119:2092–2100.
3. Panchapakesan V, Addison P, Beausang E, Lipa JE, Gilbert RW, Neligan PC. Role of thrombolysis in free-flap salvage. J Reconstr Microsurg. 2003;19:523–530.
4. Yii NW, Evans GR, Miller MJ, et al.. Thrombolytic therapy: What is its role in free flap salvage? Ann Plast Surg. 2001;46:601–604.


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