The Use of Fibrinolytic Agents in the Salvage of Free Flaps: A Systematic Review
Abstract
:1. Introduction
2. Methods
Search Strategy and Article Selection
3. Results
3.1. Literature Search
3.2. Study Characteristics
3.3. Evidence Level
3.4. Flap Survival
3.5. Types of Flaps
3.6. Type of Thrombosis
3.7. Method of Application
3.8. Fibrinolytic Agents
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Copelli, C.; Tewfik, K.; Cassano, L.; Pederneschi, N.; Catanzaro, S.; Manfuso, A.; Cocchi, R. Management of free flap failure in head and neck surgery. Acta Otorhinolaryngol. Ital. 2017, 37, 387–392. [Google Scholar] [CrossRef]
- Bengur, F.B.; Saadoun, R.; Moroni, E.A.M.; Khan, N.I.; Bottegal, M.T.B.; Sridharan, S.; Kubik, M.W.; Solari, M.G. Venous Thromboembolism Rates After Free Flap Reconstruction of the Head and Neck Region. Ann. Plast. Surg. 2023, 90 (Suppl. S5), S447–S451. [Google Scholar] [CrossRef] [PubMed]
- Modarressi, A.; Schettini, A.V.; Rüegg, E.M.; Pittet-Cuénod, B. Venous thromboembolism events after breast reconstructions with DIEP free flaps in 192 consecutive case. Ann. Chir. Plast. Esthet. 2018, 63, 11–19. [Google Scholar] [CrossRef]
- Panchapakesan, V.; Addison, P.; Beausang, E.; Lipa, J.E.; Gilbert, R.W.; Neligan, P.C. Role of thrombolysis in free-flap salvage. J. Reconstr. Microsurg. 2003, 19, 523–529. [Google Scholar]
- Kim, J.H.; Yoon, S.; Kwon, H.; Oh, D.Y.; Jun, Y.J.; Moon, S.H. Safe and effective thrombolysis in free flap salvage: Intra-arterial urokinase infusion. PLoS ONE 2023, 18, e0282908. [Google Scholar] [CrossRef] [PubMed]
- Senchenkov, A.; Lemaine, V.; Tran, N.V. Management of perioperative microvascular thrombotic complications—The use of multiagent anticoagulation algorithm in 395 consecutive free flaps. J. Plast. Reconstr. Aesthetic Surg. 2015, 68, 1293–1303. [Google Scholar] [CrossRef] [PubMed]
- Escandón, J.M.; Ciudad, P.; Mayer, H.F.; Pencek, M.; Mantilla-Rivas, E.; Mohammad, A.; Langstein, H.N.; Manrique, O.J. Free flap transfer with supermicrosurgical technique for soft tissue reconstruction: A systematic review and meta-analysis. Microsurgery 2023, 43, 171–184. [Google Scholar] [CrossRef]
- Askari, M.; Fisher, C.; Weniger, F.G.; Bidic, S.; Lee, W.P.A. Anticoagulation therapy in microsurgery: A review. J. Hand Surg. 2006, 31, 836–846. [Google Scholar] [CrossRef]
- Smit, J.M.; Acosta, R.; Zeebregts, C.J.; Liss, A.G.; Anniko, M.; Hartman, E.H.M. Early reintervention of compromised free flaps improves success rate. Microsurgery 2007, 27, 612–616. [Google Scholar] [CrossRef]
- Shen, A.Y.; Lonie, S.; Lim, K.; Farthing, H.; Hunter-Smith, D.J.; Rozen, W.M. Free Flap Monitoring, Salvage, and Failure Timing: A Systematic Review. J. Reconstr. Microsurg. 2021, 37, 300–308. [Google Scholar] [CrossRef]
- Namgoong, S.; Yang, J.P.; Jeong, S.H.; Han, S.K.; Kim, W.K.; Dhong, E.S. Pharmacological thrombolysis: The last choice for salvaging free flaps. J. Plast. Surg. Hand Surg. 2018, 52, 367–374. [Google Scholar] [CrossRef] [PubMed]
- Brouwers, K.; Kruit, A.S.; Hummelink, S.; Ulrich, D.J.O. Management of free flap salvage using thrombolytic drugs: A systematic review. J. Plast. Reconstr. Aesthetic Surg. 2020, 73, 1806–1814. [Google Scholar] [CrossRef] [PubMed]
- Chang, E.I.; Mehrara, B.J.; Festekjian, J.H.; Da Lio, A.L.; Crisera, C.A. Vascular complications and microvascular free flap salvage: The role of thrombolytic agents. Microsurgery 2011, 31, 505–509. [Google Scholar] [CrossRef] [PubMed]
- Barhoum, F.; Tschaikowsky, K.; Koch, M.; Kapsreiter, M.; Sievert, M.; Müller, S.; Goncalves, M.; Traxdorf, M.; Scherl, C. Successful free flap salvage surgery with off-label use of Alteplase: A case report, review of the literature and our free flap salvage algorithm. Int. J. Surg. Case Rep. 2020, 75, 398–402. [Google Scholar] [CrossRef] [PubMed]
- Rinker, B.D.; Stewart, D.H.; Pu, L.L.Q.; Vasconez, H.C. Role of recombinant tissue plasminogen activator in free flap salvage. J. Reconstr. Microsurg. 2007, 23, 69–73. [Google Scholar] [CrossRef] [PubMed]
- Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. J. Clin. Epidemiol. 2009, 62, 1006–1012. [Google Scholar] [CrossRef] [PubMed]
- American Society of Plastic Surgeons ASPS Evidence Rating Scales. 2011. Available online: www.plasticsurgery.org/Documents/medical-professionals/health-policy/evidence-practice/ASPS-Rating-Scale-March-2011.pdf (accessed on 10 January 2011).
- Coriddi, M.; Myers, P.; Mehrara, B.; Nelson, J.; Cordeiro, P.G.; Disa, J.; Matros, E.; Dayan, J.; Allen, R.; McCarthy, C. Management of postoperative microvascular compromise and ischemia reperfusion injury in breast reconstruction using autologous tissue transfer: Retrospective review of 2103 flaps. Microsurgery 2022, 42, 109–116. [Google Scholar] [CrossRef] [PubMed]
- Chang, E.I.; Zhang, H.; Liu, J.; Yu, P.; Skoracki, R.J.; Hanasono, M.M. Analysis of risk factors for flap loss and salvage in free flap head and neck reconstruction. Head Neck 2016, 38, E771–E775. [Google Scholar] [CrossRef] [PubMed]
- Casey, W.J.; Craft, R.O.; Rebecca, A.M.; Smith, A.A.; Yoon, S. Intra-arterial tissue plasminogen activator: An effective adjunct following microsurgical venous thrombosis. Ann. Plast. Surg. 2007, 59, 520–525. [Google Scholar] [CrossRef]
- Khansa, I.; Chao, A.H.; Taghizadeh, M.; Nagel, T.; Wang, D.; Tiwari, P. A systematic approach to emergent breast free flap takeback: Clinical outcomes, algorithm, and review of the literature. Microsurgery 2013, 33, 505–513. [Google Scholar] [CrossRef]
- Mirzabeigi, M.N.; Wang, T.; Kovach, S.J.; Taylor, J.A.; Serletti, J.M.; Wu, L.C. Free flap take-back following postoperative microvascular compromise: Predicting salvage versus failure. Plast. Reconstr. Surg. 2012, 130, 579–589. [Google Scholar] [CrossRef]
- Bui, D.T.; Cordeiro, P.G.; Hu, Q.Y.; Disa, J.J.; Pusic, A.; Mehrara, B.J. Free flap reexploration: Indications, treatment, and outcomes in 1193 free flaps. Plast Reconstr Surg. 2007, 119, 2092–2100. [Google Scholar] [CrossRef] [PubMed]
- Yii, N.W.; Evans, G.R.D.; Miller, M.J.; Reece, G.P.; Langstein, H.; Chang, D.; Kroll, S.S.; Wang, B.; Robb, G.L. Thrombolytic Therapy: What Is Its Role in Free Flap Salvage? Ann. Plast. Surg. 2001, 46, 601–604. [Google Scholar] [CrossRef]
- Largo, R.D.; Selber, J.C.; Garvey, P.B.; Chang, E.I.; Hanasono, M.M.; Yu, P.; Butler, C.E.; Baumann, D.P. Outcome Analysis of Free Flap Salvage in Outpatients Presenting with Microvascular Compromise. Plast. Reconstr. Surg. 2018, 141, 20e–27e. [Google Scholar] [CrossRef]
- Serletti, J.M.; Moran, S.L.; Orlando, G.S.; O’Connor, T.; Herrera, H.R. Urokinase protocol for free-flap salvage following prolonged venous thrombosis. Plast. Reconstr. Surg. 1998, 102, 1947–1953. [Google Scholar] [CrossRef] [PubMed]
- Tall, J.; Björklund, T.C.; Skogh, A.C.D.; Arnander, C.; Halle, M. Vascular complications after radiotherapy in head and neck free flap reconstruction: Clinical outcome related to vascular biology. In Annals of Plastic Surgery; Lippincott Williams and Wilkins: Philadelphia, PA, USA, 2015; pp. 309–315. [Google Scholar]
- Nelson, J.A.; Fischer, J.P.; Grover, R.; Kovach, S.J.; Low, D.W.; Kanchwala, S.K.; Levin, L.S.; Serletti, J.M.; Wu, L.C. Vein grafting your way out of trouble: Examining the utility and efficacy of vein grafts in microsurgery. J. Plast. Reconstr. Aesthetic Surg. 2015, 68, 830–836. [Google Scholar] [CrossRef]
- Nelson, J.A.; Kim, E.M.; Eftakhari, K.; Low, D.W.; Kovach, S.J.; Wu, L.C.; Serletti, J.M. Late venous thrombosis in free flap breast reconstruction: Strategies for salvage after this real entity. Plast. Reconstr. Surg. 2012, 129, 8e–15e. [Google Scholar] [CrossRef]
- Bishop, J.L.; Vasudev, M.; Garcia, N.; Heslop, G.; Pham, T.T.; Hicks, M.D.; Chowdhury, F.; Grayson, J.W.; Goddard, J.A.; Tjoa, T.; et al. Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision. Otolaryngol.—Head Neck Surg. 2023, 168, 1353–1361. [Google Scholar] [CrossRef]
- Selber, J.C.; Soto-Miranda, M.A.; Liu, J.; Robb, G. The survival curve: Factors impacting the outcome of free flap take-backs. Plast. Reconstr. Surg. 2012, 130, 105–113. [Google Scholar] [CrossRef] [PubMed]
- Vijan, S.S.; Tran, N.V. Microvascular breast reconstruction pedicle thrombosis: How long can we wait? Microsurgery 2007, 27, 544–547. [Google Scholar] [CrossRef]
- Ihler, F.; Matthias, C.; Canis, M. Free flap salvage with subcutaneous injection of tissue plasminogen activator in head and neck patients. Microsurgery 2013, 33, 478–481. [Google Scholar] [CrossRef] [PubMed]
- Anavekar, N.S.; Lim, E.; Johnston, A.; Findlay, M.; Hunter-Smith, D.J. Minimally invasive late free flap salvage: Indications, efficacy and implications for reconstructive microsurgeons. J. Plast. Reconstr. Aesthetic Surg. 2011, 64, 1517–1520. [Google Scholar] [CrossRef]
- Trussler, A.P.; Watson, J.P.; Crisera, C.A. Late free-flap salvage with catheter-directed thrombolysis. Microsurgery 2008, 28, 217–222. [Google Scholar] [CrossRef] [PubMed]
- Egozi, D.; Fodor, L.; Ullmann, Y. Salvage of compromised free flaps in trauma cases with combined modalities. Microsurgery 2011, 31, 109–115. [Google Scholar] [CrossRef]
- Weinzweig, N.; Gonzalez, M. Free tissue failure is not an all-or-none phenomenon. Plast. Reconstr. Surg. 1995, 96, 648–660. [Google Scholar] [CrossRef]
- Lyons, A.J.; James, R.; Collyer, J. Free vascularised iliac crest graft: An audit of 26 consecutive cases. Br. J. Oral Maxillofac. Surg. 2005, 43, 210–214. [Google Scholar] [CrossRef]
- Tamplen, M.; Blackwell, K.; Jahan, R.; Nabili, V. Salvage of free-flaps in vessel-depleted mandibular osteoradionecrosis cases using catheter-directed thrombolysis and angioplasty. J. Reconstr. Microsurg. 2013, 29, 347–352. [Google Scholar] [PubMed]
- Goldberg, J.A.; Pederson, W.C.; Barwick, W.J. Salvage of free tissue transfers using thrombolytic agents. J. Reconstr. Microsurg. 1989, 5, 351–356. [Google Scholar] [CrossRef]
- D’Arpa, S.; Cordova, A.; Moschella, F. Pharmacological thrombolysis: One more weapon for free-flap salvage. Microsurgery 2005, 25, 477–480. [Google Scholar] [CrossRef]
- Bonde, C.T.; Heslet, L.; Jansen, E.; Elberg, J.J. Salvage of free flaps after venous thrombosis: Case report. Microsurgery 2004, 24, 298–301. [Google Scholar] [CrossRef]
- Tessler, O.; Vorstenbosch, J.; Jones, D.; Lalonde, S.; Zadeh, T. Heparin-induced thrombocytopenia and thrombosis as an under-diagnosed cause of flap failure in heparin-naive patients: A case report and systematic review of the literature. Microsurgery 2014, 34, 157–163. [Google Scholar] [CrossRef] [PubMed]
- Schubert, W.; Hunter, D.W.; Guzman-Stein, G.; Ahrenholz, D.H.; Solem, L.D.; Dressel, T.D.; Cunningham, B.L. Use of streptokinase for the salvage of a free flap: Case report and review of the use of thrombolytic therapy. Microsurgery 1987, 8, 117–121. [Google Scholar] [CrossRef]
- Atiyeh, B.S.; Fuleihan, N.S.; Musharafieh, R.S. Pharmacologic partial salvage of a failing free flap with recombinant tissue plasminogen activator (rt-PA). J. Reconstr. Microsurg. 1999, 15, 585–590. [Google Scholar] [CrossRef] [PubMed]
- Lee, D.S.; Jung SIl Kim, D.W.; Dhong, E.S. Anterograde intra-arterial urokinase injection for salvaging fibular free flap. Arch. Plast. Surg. 2013, 40, 251–255. [Google Scholar] [CrossRef]
- Zhang, S.L.; Ng, H.W. Primary thrombolysis for free flap surgery in head and neck reconstruction: A case report and review. Arch. Plast. Surg. 2021, 48, 511–517. [Google Scholar] [CrossRef]
- Hong, S.H.; Lee, K.T.; Pyon, J.K. Salvage of late flap compromise in deep inferior epigastric perforator flaps: To revise or not to revise. Arch. Plast. Surg. 2020, 47, 97–101. [Google Scholar] [CrossRef]
- Renaud, F.; Succo, E.; Alessi, M.C.; Legre, R.; Juhan-Vague, I. Iloprost and salvage of a free flap. Br. J. Plast. Surg. 1996, 49, 245–248. [Google Scholar] [CrossRef] [PubMed]
- Malhotra, G.; Patil, R.; Komma, V.N.R. Use of Tissue Plasminogen Activator to Salvage a Precious Free Tissue Transfer. J. Hand Microsurg. 2022, 14, 184–186. [Google Scholar] [CrossRef] [PubMed]
- Hsu, S.Y.; Cheng, H.T.; Manrique, O.; Hsu, Y.C. Anterograde injection of low-dose urokinase salvages free anterolateral thigh flap. Medicine 2017, 96, e7932. [Google Scholar] [CrossRef]
- Fudem, G.M.; Walton, R.L. Microvascular thrombolysis to salvage a free flap using human recombinant tissue plasminogen activator. J. Reconstr. Microsurg. 1989, 5, 231–234. [Google Scholar] [CrossRef]
- Wimbauer, J.M.; Heinrich, K.M.; Schwaiger, K.; Pumberger, P.; Koeninger, F.; Wechselberger, G.; Russe, E. Anterograde Injection of Alteplase Salvages Deep Inferior Epigastric Perforator Flap in Reconstructive Breast Surgery. Plast. Reconstr. Surg. Glob. Open 2022, 10, E4415. [Google Scholar] [CrossRef] [PubMed]
- Lipton, H.A.; Jupiter, J.B. Streptokinase salvage of a free-tissue transfer: Case report and review of the literature. Plast. Reconstr. Surg. 1987, 79, 977–981. [Google Scholar] [CrossRef] [PubMed]
- Agostini, T.; Lazzeri, D.; Agostini, V.; Spinelli, G.; Shokrollahi, K. Delayed free flap salvage after venous thrombosis. J. Craniofacial Surg. 2012, 23, e260–e261. [Google Scholar] [CrossRef] [PubMed]
- Chan, R.K.; Mathy, J.A.; Przylecki, W.; Guo, L.; Caterson, S.A. CASE REPORT Superior Gluteal Artery Perforator Flap Breast Reconstruction Salvage Following Late Venous Congestion after Discharge. Eplasty 2010, 10, e63. [Google Scholar] [PubMed]
- Coeugniet, E.; Al Yafi, M.N.; Lafrance, D.; Danino, M.A.; Soulez, G.; Nguyen, Q.; Harris, P. Microcirculatory Free Flap Failure with Patent Anastomosis Salvaged by in Situ Thrombolysis in Vulnerable Phase Burn. J. Burn. Care Res. 2019, 40, 718–722. [Google Scholar] [CrossRef] [PubMed]
- Ayhan, S.; Uygur, S.; Kucukoduk, I.; Sencan, A. Salvage of a congested DIEAP flap with subcutaneous recombinant tissue plasminogen activator treatment. J. Plast. Reconstr. Aesthetic Surg. 2009, 62, e453–e454. [Google Scholar] [CrossRef] [PubMed]
- Tran, N.V.; Bishop, A.T.; Convery, P.A.; Yu, A.Y. Venous congestive flap salvage with subcutaneous rtPA. Microsurgery 2006, 26, 370–372. [Google Scholar] [CrossRef] [PubMed]
- Tse, R.; Ross, D.; Gan, B.S. Late salvage of a free TRAM flap. Br. J. Plast. Surg. 2003, 56, 59–62. [Google Scholar] [CrossRef]
- Handschin, A.E.; Guggenheim, M.; Calcagni, M.; Künzi, W.; Giovanoli, P. Factor v leiden mutation and thrombotic occlusion of microsurgical anastomosis after free TRAM flap. Clin. Appl. Thromb./Hemost. 2010, 16, 199–203. [Google Scholar] [CrossRef]
- Wechselberger, G.; Schoeller, T.; Ohler, K.; Anderl, H.; Ninkovic, M. Flap salvage in a “flow-through” flap by manual thrombectomy plus thrombolytic therapy abstract. J. Reconstr. Microsurg. 1998, 14, 127–129. [Google Scholar] [CrossRef]
- Cangé, S.; Laberge, L.C.; Rivard, G.E.; Garel, L. Streptokinase in the management of limb arterial thrombosis following free-flap surgery. Plast. Reconstr. Surg. 1987, 79, 974–976. [Google Scholar] [CrossRef] [PubMed]
- Tonks, A.M.; Rees, M. Streptokinase salvage of a rectus abdominis free flap. Plast. Reconstr. Surg. 1995, 95, 933–934. [Google Scholar]
- Noordanus, R.P.; Joris Hage, J. Late salvage of a “free flap” phalloplasty: A case report. Microsurgery 1993, 14, 599–600. [Google Scholar] [CrossRef] [PubMed]
- Nikkhah, D.; Green, B.; Sapountzis, S.; Gilleard, O.; Sidhu, A.; Blackburn, A. Resurrection of an ALT flap with recombinant tissue plasminogen activator and heparin. Eur. J. Plast. Surg. 2016, 39, 221–224. [Google Scholar] [CrossRef]
- Collen, D. Molecular mechanism of action of newer thrombolytic agents. J. Am. Coll. Cardiol. 1987, 10 (Suppl. SB), 11B–15B. [Google Scholar]
- Ohman, E.M.; Harrington, R.A.; Cannon, C.P.; Agnelli, G.; Cairns, J.A.; Kennedy, J.W. Intravenous thrombolysis in acute myocardial infarction. Chest 2001, 119, 253S–277S. [Google Scholar] [CrossRef]
- Hepburn-Brown, M.; Darvall, J.; Hammerschlag, G. Acute pulmonary embolism: A concise review of diagnosis and management. Intern. Med. J. 2019, 49, 15–27. [Google Scholar] [CrossRef] [PubMed]
- Maizel, A.S.; Bookstein, J.J. Streptokinase, urokinase, and tissue plasminogen activator: Pharmacokinetics, relative advantages, and methods for maximizing rates and consistency of lysis. Cardiovasc. Intervent. Radiol. 1986, 9, 236–244. [Google Scholar] [CrossRef]
- Khan, I.A.; Gowda, R.M. Clinical perspectives and therapeutics of thrombolysis. Int. J. Cardiol. 2003, 91, 115–127. [Google Scholar] [CrossRef]
- Goodman Gilman, A.; Hardman, J.G.; Limbird, L.E.; Molinoff, P.B.; Ruddon, R.W. Goodman and Gilman’s the Pharmacological Basis of Therapeutics; Hardman, J.G., Limberd, L.E., Eds.-in-Chief; Molinoff, P.B., Ruddon, R.W., Eds.; Goodman Gilman, A., Consulting Ed.; McGraw-Hill: New York, NY, USA, 1996; pp. 1493–1495. Available online: https://unov.tind.io/record/68258 (accessed on 29 April 2024).
Author | Level of Evidence | Cases | Fibrinolytic Agent | Method of Application | Timing of Revision p.o. | Flap Survival | Adverse Events |
---|---|---|---|---|---|---|---|
Kim et al., 2023 [5] | 3 | 16 | Urokinase mean 69,688 U (range: 30,000–100,000 U) | Infused into the arterial pedicle with venous drainage—no systemic circulation | 45.4 h (range: 24–88 h) | 13/16 (81.3%) | Two flaps with transient partial necrosis, 2 cases with hematoma at the donor site |
Coriddi et al., 2022 [18] | 3 | 26 | tPa mean 4.4 ± 2.5 mg | Arterial injection: When possible, a vein was opened—systemic circulation | 58.9 h ± 51.5 h | 16/26 (55.4%) | One flap was only partially salvaged, and adverse events n/a |
Chang et al., 2011 [13] | 3 | 33 | 7× urokinase mean 75,000 U; 26× tPa mean 2.5 mg | n/a | n/a | 28/33 (84.8%) | Two flaps with fat necrosis |
Rinker et al., 2007 [15] | 3 | 15 | tPa 2.5 mg, a second dose of 2.5 mg in 8 flaps | Arterial injection, vene is clamped—no systemic circulation | 14.1 h ± 13.9 h | 10/15 (66.7%) | Two patients went back to the OR due to bleeding complication |
Chang et al., 2016 [19] | 3 | 56 | n/a | n/a | n/a | 28/56 (50%) | One flap was only partially salvaged, and adverse events n/a |
Casey et al., 2007 [20] | 3 | 11 | tPa 2 mg | Arterial injection, venous anastomosis open to drain—no systemic circulation | n/a | 10/11 (90.9%) | One small fat necrosis |
Namgoong et al., 2018 [11] | 3 | 6 | Urokinase 100,000 U | Arterial injection, vene clamped/opened—no systemic circulation | mean of 50.8 h | 6/6 (100%) | 1× partial necrosis |
Khansa et al., 2013 [21] | 3 | 12 | tPa units n/a | n/a | 7× intraoperative, 5× n/a | 6/12 (50%) | n/a |
Mirzabeigi et al., 2012 [22] | 3 | 36 | 10× tPa, 10× urokinase, 3× streptokinase, 10× n/a—units n/a | Arterial injection—no systemic circulation | n/a | 21/36 (64%) | n/a |
Panchapakesan et al., 2003 [4] | 3 | 20 | n/a | Arterial injection, vene opened—no systemic circulation | mean of 32.8 h in salvaged flaps; mean of 63.8 h in lost flaps | 6/20 (30%) | 3× partial skin loss |
Bui et al., 2007 [23] | 3 | 20 | Streptokinase 50,000–250,000 U or tPa 5 to 20 mg | Arterial injection, artery, and vene clamped- no systemic circulation | n/a | 13/20 | n/a also, regarding partially salvaged |
Yii et al., 2001 [24] | 3 | 8 | 7× urokinase mean 100,000 U; 1× tPa 15 mg | Arterial injection—systemic circulation n/a | n/a | 6/8 (0.75%) | n/a |
Largo et al., 2018 [25] | 3 | 11 | n/a | n/a | n/a | 1/11 (9%) | One only partially salvaged, adverse events n/a |
Serletti et al., 1998 [26] | 3 | 5 | 5× urokinase 250,000 | Arterial injection—systemic circulation | mean of 3.6 days p.o (1 to 6 days) | 5/5 (100%) | 2× marginal loss of tissue, 1× fat necrosis, 1× fistula, no other adverse events |
Senchenkov et al., 2015 [6] | 3 | 14 | tPa—1 × 1 mg, 5 × 2 mg (redone 1x), 2 × 6 mg, 1× 10 mg, 1× unknown | Subcutaneously or arterial injection—systemic circulation n/a | n/a | 12/14 (86%) | 3× fat necrosis |
Tall et al., 2015 [27] | 3 | 6 | 1× streptokinase, 5× tPa (3–10 mg) | Arterial injection, vene was clamped—no systemic circulation | n/a | 5/6 (83%) | n/a |
Nelson et al., 2015 [28] | 3 | 16 | 5× tPa, 8× urokinase, 3× streptokinase | n/a | n/a | n/a | n/a |
Nelson et al., 2012 [29] | 3 | 7 | 5× urokinase 250,000 U, 2× tPa 2 mg | intra-arterial over 30 min—systemic circulation | n/a | 6/7 (86%) | 1× urokinase (partial salvage—Fat necrosis, transfuse 1 unit pRBCx), 1× pTa fat necrosis, 1× Urokinase Flap loss, transfuse 1 unit pRBC |
Bishop et al., 2023 [30] | 3 | 11 | tPa | n/a | n/a | n/a | n/a |
Selber et al., 2012 [31] | 3 | 63 | n/a | n/a | n/a | 25/63 (41%) | n/a |
Vijan et al., 2007 [32] | 3 | 18 | rt-PA between 4 and 10 mg | Intra-arterial or intravenous—systemic circulation n/a | mean of 127 min in salvaged flaps; mean of 192 min in lost flaps | 10/18 (56%) | 6× superficial skin necrosis, 2× minor fat necrosis (>2 cm), 2× major fat necrosis (<2 cm) |
Ihler et al., 2013 [33] | 4 | 3 | tPa 2 mg | Multiple injections subcutaneously | mean of 96 h | 3/3 (100%) | 2× flap only partially salvaged |
Anavekar et al., 2011 [34] | 4 | 2 | 1× urokinase 100,000 U, 1× Urokinase 200,000 U, and another 100,000 the next day | Arterial injection—systemic circulation | 1× 21st p.o. day, 1× 30th p.o. day | 2/2 (100%) | none |
Trussler et al., 2008 [35] | 4 | 2 | 1× urokinase 1 mL/min for 24 h, Alteplase and Retevase for 24 h (no dosage) | Catheter-directed thrombolysis over 24 h—systemic circulation | 1× 12th p.o. day, 1× 6th p.o. day | 2/2 (100%) | 1× stroke 3 years after thrombolysis (urokinase), 1× fibrous nonunion of fibula flap—required fibro-osseous debridement 1 year after the initial operation (tPa) |
Egozi et al., 2011 [36] | 4 | 2 | 2× streptokinase 20,000–50,000 U | 1× infused into the arterial pedicle with venous drainage—no systemic circulation, 1× unknown | 1× intraoperative (saved), 1× n/a | 1/2 (50%) | 1× Partial distal necrosis |
Weinzweig et al., 1995 [37] | 4 | 1 | Streptokinase | Infused into the arterial pedicle with venous drainage—no systemic circulation | 8 h | 1/1 (100%) | Partial flap necrosis |
Lyons et al., 2005 [38] | 4 | 2 | 2× urokinase 250,000 U | intra-arterial, clamped—no systemic circulation | within 24 h | 2/2 (100%) | 2× extensive muscle necrosis |
Tamplen et al., 2013 [39] | 4 | 1 | 1× tPa | intra-arterial—systemic circulation | 8th p.o. day | 1/1 (100%) | none |
Goldberg et al., 1989 [40] | 4 | 6 | Streptokinase (2× 125,000 U in 1 flap, 3× 50,000), Urokinase 1× 100,000 U, 1× 50,000 U | 6× Arterial injection—5× no systemic circulation, 1× n/a | 2× intraoperative, 1 × 3 h, 1 × 7 h, 1 × 9 h (lost), 1 × 16 h p.o. | 5/6 (86%) | 1× Flap hematoma |
D’Arpa et al., 2005 [41] | 4 | 2 | 1× urokinase 100,000 U, 2× Urokinase 50,000 into other flap | 2× Infused into the arterial pedicle with vene opened—no systemic circulation | 1× 2nd p.o. day, 1× intraoperative | 2/2 (100%) | none |
Bonde et al., 2004 [42] | 4 | 2 | 50 mg rt-Pa (actilyse) and after 15 min another 50 mg | 1st dose into the arterial pedicle with vene opened—no systemic circulation/second dose after 15 min systemic | 1 × 14 h p.o., 1× 18 h. p.o. | 2/2 (100%) | none |
Tessler et al., 2014 [43] | 5 | 2 | 1× tPa 6 mg, 1× tPa 10 mg | closed-loop circuit—no systemic circulation | 1× 2nd p.o. day (lost), 1× 5th p.o. day | 1/2 (50%) | none |
Schubert et al., 1987 [44] | 5 | 1 | Streptokinase 7500 U | Arterial and venous branches clamped—no systemic circulation | intraoperative | 1/1 (100%) | 1× flap partially salvaged (20% lost) |
Atiyeh et al., 1999 [45] | 5 | 1 | tPa 4 mg | Arterial and venous infusion—systemic circulation | 18 h | 1/1 (100%) | 1× flap partially salvaged (50% lost) |
Lee et al., 2013 [46] | 5 | 1 | 1× urokinase 100,000 U | Arterial injection, flushed out of venae comittans—no systemic circulation | intraoperative | 1/1 (100%) | none |
Zhang et al., 2021 [47] | 5 | 1 | 2× tPa 10 mg in one flap = 20 mg | Arterial injection, both veins and artery clamped—no systemic circulation | intraoperative | 1/1 (100%) | Mild right periorbital hematoma |
Hong et al., 2020 [48] | 5 | 1 | Urokinase 55,000 U | Arterial injection, vene ligated—no systemic circulation | 144 h | 1/1 (100%) | n/a |
Barhoum et al., 2020 [14] | 5 | 1 | rt-PA 4 mg | Arterial injection, venous anastomosis opened—no systemic circulation | 11 h | 1/1 (100%) | slight superficial necrosis at the epidermis and a dehiscence at the cranial part |
Renaud et al., 1996 [49] | 5 | 1 | Urokinase 75,000 U | Arterial injection—systemic circulation n/a | intraoperative | 1/1 (100%) | none |
Malhotra et al., 2020 [50] | 5 | 1 | 1× rt-PA 2 mg | Arterial injection, vene opened—no systemic circulation | 20 h | 1/1 (100%) | none |
Hsu et al., 2017 [51] | 5 | 1 | 1× urokinase 60,000 U | Arterial injection, vene opened, and artery clamped- no systemic circulation | 32 h | 1/1 (100%) | none |
Fudem et al., 1989 [52] | 5 | 1 | tPa 4 mg | Intravenous—systemic circulation | 4th p.o. day | 1/1 (100%) | small hematoma on the donor site |
Wimbauer et al., 2022 [53] | 5 | 1 | tPa 2 mg | Arterial injection, Artery, and vene clamped—no systemic circulation | 12 h | 1/1 (100%) | none |
Lipton et al., 1987 [54] | 5 | 1 | 1× streptokinase 60,000 U | Infused into the arterial pedicle with venous drainage—no systemic circulation | 41.5 h | 1/1 (100%) | none |
Agostini et al., 2012 [55] | 5 | 1 | 1× urokinase 400,000 U | Arterial injection—systemic circulation n/a | 12 h | 1/1 (100%) | n/a |
Chan et al., 2010 [56] | 5 | 1 | tPa—dose n/a | Arterial injection—no systemic circulation | 5th p.o. day | 1/1 (100%) | none |
Coeugniet et al., 2019 [57] | 5 | 1 | tPa, 1 mg/h = 24 mg | Arterial with Katheter—1 mg/h for 24 h—systemic circulation | day of operation | 1/1 (100%) | Required 10 packed red blood cell transfusions. |
Ayhan et al., 2009 [58] | 5 | 1 | rt-PA 2 mg | Subcutaneously | after 36 h | 1/1 (100%) | Small lateral skin and fat necrosis |
Tran et al., 2006 [59] | 5 | 1 | 1× rt-PA 4 mg after 12 h, 1× rt-PA 2 mg rt-PA, 2 mg on p.o. day 6 | intra-arterial—systemic circulation | after 12 h | 1/1 (100%) | 5 × 5 cm fat necrosis |
Tse et al., 2003 [60] | 5 | 1 | 1× streptokinase 30,000 U | intra-arterial, clamped—no systemic circulation | 11th p.o. day | 1/1 (100%) | Partial flaps loss 20% |
Handschin et al., 2010 [61] | 5 | 1 | 1× urokinase 100,000 U and another n/a dosis of urokinase on p.o. day 15 | Intra-arterial—systemic circulation | 3rd p.o. day | 1/1 (100%) | 50% flap loss |
Wechselberger et al., 1998 [62] | 5 | 1 | 1× streptokinase 100,000 U | Infused into the arterial pedicle with vene opened—no systemic circulation | 46 h | 1/1 (100%) | none |
Cangé et al., 1987 [63] | 5 | 1 | Streptokinase 5000 U per hour | Catheter-directed thrombolysis for 41 h—systemic circulation | after 12 h | 0/1 (0%) | small hematoma on the donor site |
Tonks et al., 1995 [64] | 5 | 1 | 1× streptokinase 20,000 U | intra-arterial, artery clamped, vene remained open—systemic circulation | intraoperative | 1/1 (100%) | none |
Noordanus et al., 1993 [65] | 5 | 1 | 1× streptokinase 100,000 U | Infused into the arterial pedicle with vene opened—no systemic circulation | 19th p.o. days | 1/1 (100%) | small wound dehiscence—self-healing |
Nikkhah et al., 2015 [66] | 5 | 1 | rt-PA 4 mg | Infused into the arterial pedicle with vene opened—no systemic circulation | 4th p.o. day | 1/1 (100%) | n/a |
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Mandal, P.; Moshammer, M.; Hecker, A.; Smolle, C.; Carnieletto, M.; Mayrhofer, M.; Schintler, M.; Winter, R.; Kamolz, L.P. The Use of Fibrinolytic Agents in the Salvage of Free Flaps: A Systematic Review. J. Pers. Med. 2024, 14, 800. https://doi.org/10.3390/jpm14080800
Mandal P, Moshammer M, Hecker A, Smolle C, Carnieletto M, Mayrhofer M, Schintler M, Winter R, Kamolz LP. The Use of Fibrinolytic Agents in the Salvage of Free Flaps: A Systematic Review. Journal of Personalized Medicine. 2024; 14(8):800. https://doi.org/10.3390/jpm14080800
Chicago/Turabian StyleMandal, Patrick, Maximilian Moshammer, Andrzej Hecker, Christian Smolle, Martina Carnieletto, Marcel Mayrhofer, Michael Schintler, Raimund Winter, and Lars Peter Kamolz. 2024. "The Use of Fibrinolytic Agents in the Salvage of Free Flaps: A Systematic Review" Journal of Personalized Medicine 14, no. 8: 800. https://doi.org/10.3390/jpm14080800