Main Article Content
complications, thrombophilia, microsurgery, reconstructive surgical procedure, free tissue flaps
Background: Factor V Leiden is the most common form of inherited thrombophilic syndrome, affecting five per cent of caucasians. While increased rates of venous thromboembolic complications have been regularly reported in factor V Leiden patients, little is known about their risk of microvascular complications or flap failure rates in free-flap surgery. The aim of this review is to qualitatively review the published literature on outcomes of free-flap surgery in patients with factor V Leiden.
Methods: MEDLINE®, PubMed, EMBASE and Cochrane were searched from their dates of inception to March 2017. Nine studies of level IV evidence were included in this qualitative review. In total, these studies included 22 patients who underwent 24 free-flap operations.
Results: Nine flap failures were reported due to thrombotic complications. Even heterozygous factor V Leiden patients had a relatively high risk of free-flap failure (3/15 free flaps), and patients who were heterozygous for factor V Leiden and had other coexistent thrombophilias had an even higher failure rate (5/6 free flaps). However, the small sample size across the nine studies, as well as the inevitable publication bias, means that definitive conclusions cannot be drawn.
Conclusion: Despite factor V Leiden being a relatively common condition in Australia, current evidence for outcomes of free-flap reconstruction in this patient population is lacking.
2. Van Cott E, Khor B, Zehnder J. Factor V Leiden. Am J Hematol. 2016;91(1):46–49. https://doi.org/10.1002/ajh.24222 PMid:26492443
3. Shakeen K, Alraies M, Alraiyes A, Christie R. Factor V Leiden: how great is the risk of venous thromboembolism. Cleveland Clin J Med. 2012;79(4):265–72. https://doi.org/10.3949/ccjm.79a.11072 PMid:22473726
4. Gibson C, MacLennan A, Rudzki Z, Hague W, Haan E, Sharpe P, Priest K, Chan A, Dekker G, Khong T. The prevalence of inherited thrombophilias in a Caucasian Australian population. Pathology. 2005;37(2):160–63. https://doi.org/10.1080/00313020500058250 PMid:16028846
5. Kwok A, Agarwal J. An analysis of free flap failure using the ACS NSQIP database. Does flap site and flap type matter? Microsurgery. 2016;37(6). https://doi.org/10.1002/micr.30121 PMid:27714840
6. Spyropoulou A, Jeng S. Microsurgical coverage reconstruction in upper and lower extremities. Sem Plast Surg. 2010;24(1):34–42. https://doi.org/10.1055/s-0030-1253244 PMid:21286303 PMCid:PMC2887005
7. Froemel D, Fitzsimons S, Frank J, Sauerbier M, Meurer A, Barker J. A review of thrombosis and antithrombotic therapy in microvascular surgery. Eur Surg Research. 2013;50(1):32–43. https://doi.org/10.1159/000347182 PMid:23548333
8. Yu P, Chang D, Miller M, Reece G, Robb G. Analysis of 49 cases of flap compromise in 1310 free flaps for head and neck reconstruction. Head Neck. 2009;31(1):45–51. https://doi.org/10.1002/hed.20927 PMid:18972428
9. Masoomi H, Clark E, Paydar K, Evans G, Nguyen A, Kobayashi M, Wirth G. Predictive factors of free flap thrombosis in breast reconstruction surgery. Microsurgery. 2014;34(8):589–94. https://doi.org/10.1002/micr.22250 PMid:24665051
10. Makiguchi T, Hashikawa K, Sugiyama D, Yokoo S, Terashi H, Nibu K, Kumagai S, Tahara S. Risk factors of anastomotic thrombosis in 200 head and neck free flaps among Asian patients. Surg Sci. 2012;3:237–41. https://doi.org/10.4236/ss.2012.35046
11. Melbourne Haematology. Factor V (five) Leiden mutation. 2018. [web report] [cited 16 September 2018]. Available from: http://www.melbournehaematology.com.au/fact-sheets/factor-v-five-leiden-mutation.html.
12. Wang T, Serletti J, Cuker A, McGrath J, Low D, Kovach S, Wu L. Free tissue transfer in the hypercoagulable patient: a review of 58 flaps. Plast Reconstr Surg. 2012;129(2):443–53. https://doi.org/10.1097/PRS.0b013e31823aec4d PMid:21987047
13. Wang T, Serletti J, Kolasinski S, Low D, Kovach S, Wu L. A review of 32 free flaps in patients with collagen vascular disorders. Plast Reconstr Surg. 2012;129(3):421e–27e. https://doi.org/10.1097/PRS.0b013e3182412a0b PMid:22373989
14. Davison S, Kessler C, Al-Attar A. Microvascular free flap failure caused by unrecognized hypercoagulability. Plast Reconstr Surg. 2009;124:490–95. https://doi.org/10.1097/PRS.0b013e3181adcf35 PMid:19644264
15. DeFazio M, Hung R, Han K, Bunting H, Evans K. Lower extremity flap salvage in thrombophilic patients: managing expectations in the setting of microvascular thrombosis. J Reconstr Microsurg. 2016;32(6):431–44. https://doi.org/10.1055/s-0035-1571249https://doi.org/10.1055/s-0034-1370339
16. Olsson E, Hoijer P. Activated protein C resistance due to factor V Leiden, elevated coagulation factor VIII and postoperative deep vein thrombosis in late breast reconstruction with a free TRAM flap: a report of two cases. Brit J Plast Surg. 2005;58:720–23. https://doi.org/10.1016/j.bjps.2004.12.024 PMid:15992531
17. Khansa I, Colakoglu S, Tomich D, Nguyen MD, Lee BT. Factor V Leiden associated with flap loss in microvascular breast reconstruction. Microsurgery. 2011;31:409–12. https://doi.org/10.1002/micr.20879 PMid:21503971
18. Arnljots B, Söderstsröm T, Svensson H. No correlation between activated protein C resistance and free flap failures in 100 consecutive patients. Plast Reconstr Surg. 1998; 101: 1850–853. https://doi.org/10.1097/00006534-199806000-00011 PMid:9623826
19. Handschin A, Guggenheim M, Calcagni M, Künzi W, Giovanoli P. Factor V Leiden mutation and thrombotic occlusion of microsurgical anastamosis after free TRAM flap. Clin Appl Thromb Hemost. 2010;16:199–203. https://doi.org/10.1177/1076029608325546 PMid:19022796
20. Vekris M, Ovrenovits M, Dova L, Beris AE, Soucacos PN, Kolaitis N, Vartholomatos G. Free functional muscle transfer failure and thrombophilic gene mutations as a potential risk factor: a case report. Microsurgery. 2007;27:88–90. https://doi.org/10.1002/micr.20312 PMid:17295258
21. Endara M, Nahabedian M. Free flap breast reconstruction in the hypercoagulable patient with a concomitant bleeding diathesis. Plast Reconstr Surg. 2013;132(1):180e–81e. https://doi.org/10.1097/PRS.0b013e3182910e79 PMid:23806944
22. Khouri R, Cooley B, Kunselman A, Landis R, Yeramian P, Ingram D, Natarajan N, Benes C, Wallemark C. A prospective study of microvascular free-flap surgery and outcome. Plast Reconstr Surg. 1998;102:711–21. https://doi.org/10.1097/00006534-199809010-00015 PMid:9727436
23. Patel N, Singhal D. Activated clotting time monitoring during osteocutaneous free fibula flap surgery. Plast Reconstr Surg. 2015;135(2):462e–63e. https://doi.org/10.1097/PRS.0000000000000906 PMid:25626845
24. Asai E, Okouchi M, Momiyama M, Kayikawa A, Ueda K. Free flap failure in an anticardiolipin antibody-positive patient with neoplasm: a case report. Microsurgery. 2010;30(3):238–41. https://doi.org/10.1002/micr.20734 PMid:20049910
25. Serletti J. Discussion. Microvascular free flap failure caused by unrecognized hypercoagulability. Plast Reconstr Surg. 2009;124(4):496–99. https://doi.org/10.1097/PRS.0b013e3181adcfab PMid:19644265
26. Davis M, Shell D, Marques M, Long J. Free flap failure secondary to dual thrombophilia. Microsurgery. 2009;29(1):62–65. https://doi.org/10.1002/micr.20553 PMid:18833574
27. Baker P, Chew B, Shoaib T. Thrombophilia and free flaps. J Plast Reconstr Aes. 2008;61(11):1388–89. https://doi.org/10.1016/j.bjps.2008.02.034 PMid:18640887
28. Spanio di Spilimbergo S, Rampazzo A, Squaquara R, Penzo M, Padula E. Hypercoagulability due to homocystinuria in a case of head and neck reconstruction resolved with combined systemic therapy. Plast Reconstr Surg. 2008;121(4):1508–9. https://doi.org/10.1097/01.prs.0000305361.01499.f6 PMid:18349682
29. Hoijer P, Olsson E. Elevated coagulation factor VIII, postoperative thrombosis and flap failure in late breast reconstruction with a free TRAM flap: a case report. J Plast Reconstr Aes. 2006;59(1):102–4. https://doi.org/10.1016/j.bjps.2005.06.003
30. Shaw R, Rogers S. Venous microvascular anastomotic failure due to prothrombin gene mutation. Plast Reconstr Surg. 2005;115(5):1451–52. https://doi.org/10.1097/01.PRS.0000157640.70913.AA PMid:15809636
31. Alaya C, Blackwell K. Protein C deficiency in microvascular head and neck reconstruction. Laryngoscope. 1999;109(2 Pt 1):259–65. https://doi.org/10.1097/00005537-199902000-00016 PMid:10890776
32. Barbour J, Iorio M, Gangopadhyay N, Myckatyn T. Lower extremity salvage complicated by recurrent microvascular thrombosis in a patient with congenital factor VII deficiency. Am Surg. 2014;80(4):417–19.
33. Mann C. Observational research methods. Research design II: cohort, cross sectional, and case-control studies. Emerg Med J. 2003; 20: 54–60. https://doi.org/10.1136/emj.20.1.54 PMid:12533370 PMCid:PMC1726024
34. Bui D, Cordeiro P, Hu Q,Disa J, Pusic A, Mehrara B. Free flap reexploration: indications, treatment, and outcomes in 1193 free flaps. Plast Reconstr Surg. 2007;119:2092–100. https://doi.org/10.1097/01.prs.0000260598.24376.e1 PMid:17519706
35. Wong A, Nguyen J, Peric M, Shahabi A, Vidar E, Hwang B, Niknam Leilabadi S, Chan L, Urata M. Analysis of risk factors associated with microvascular free flap failure using a multi-institutional database. Microsurgery. 2015;35:6–12. https://doi.org/10.1002/micr.22223 PMid:24431159
36. Frederick J, Sweeny L, Carroll W, Peters G, Rosenthal E. Outcomes in head and neck reconstruction by surgical site and donor site. Laryngoscope. 2013;123:1612–17. https://doi.org/10.1002/lary.23775 PMid:23686870 PMCid:PMC3695001
37. Pohlenz P, Klatt J, Schon M, Blessmann L, Li R. Microvascular free flaps in head and neck surgery: complications and outcome of 1000 flaps. Int J Oral Maxillofac Surg. 2012;41:739–43. https://doi.org/10.1016/j.ijom.2012.02.012 PMid:22424757
38. Pannucci C, Kovach S, Cuker A. Microsurgery and the hypercoagulable state: a hematologist’s perspective. Plast Reconstr Surg. 2015;136(4):545E–52E. https://doi.org/10.1097/PRS.0000000000001591 PMid:26397274
39. Askari M, Fisher C, Weniger F, Bidic S, Lee W. Anticoagulation therapy in microsurgery: a review. J Hand Surg. 2006;31:836–46. https://doi.org/10.1016/j.jhsa.2006.02.023 PMid:16713852
40. Conrad M, Adams Jr W. Pharmacologic optimization of microsurgery in the new millenium. Plast Reconstr Surg. 2001;108(7):2088–96. https://doi.org/10.1097/00006534-200112000-00042 https://doi.org/10.1097/00006534-200112000-00041 PMid:11743407
41. Fischer J, Fox J, Nelson J, Kovach S, Serletti J. A longitudinal assessment of outcomes and healthcare resource utilization after immediate breast reconstruction: comparing implant- and autologous-based breast reconstruction. Ann Surg. 2015;262:692–99. https://doi.org/10.1097/SLA.0000000000001457 PMid:26366550
42. Fischer J, Sieber B, Nelson J, Cleveland E, Kovach S, Wu L, Kanchwala S, Serletti J. Comprehensive outcome and cost analysis of free tissue transfer for breast reconstruction: an experience with 1303 flaps. Plast Reconstr Surg. 2013;131:195–203. https://doi.org/10.1097/PRS.0b013e318277856f PMid:23357982
43. Friedman T, O’Brien Coon D, Michaels J, Botempo F, Young V, Clavijo J, Rubin J. Hereditary coagulopathies: practical diagnosis and management for the plastic surgeon. Plast Reconstr Surg. 2010;125(5):1544–52. https://doi.org/10.1097/PRS.0b013e3181d51344 PMid:20440173
44. Caprini J. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;122:269–79.
45. Pannucci C, Bailey S, Dreszer G, Wachtman C, Zumsteg J, Jaber R, Hamill J, Hume K, Rubin J, Neligan P, Kalliainen L, Hoxworth R, Pusic A, Wilkins E. Validation of the Caprini Risk Assessment Model in plastic and reconstructive surgery patients. J Am Coll Surg. 2011;212(1):105–12. https://doi.org/10.1016/j.jamcollsurg.2010.08.018 PMid:21093314 PMCid:PMC3052944
46. Jeong H, Miller T, Davis K, Matthew A, Lysikowski J, Lazcano E, Reed G, Kenkel J. Application of the Caprini Risk Assessment Model in evaluation of non-venous thromboembolism complications in plastic and reconstructive surgery patients. Aesthet Surg J. 2014;34(1):87–95. https://doi.org/10.1177/1090820X13514077 PMid:24327763
47. Sezgin B. A better understanding of hypercoagulability in the microsurgical setting. In: Shiffman M, ed. Breast Reconstruction: Art, Science, and New Clinical Techniques. Switzerland: Springer International 2016, pp. 1437–46. https://doi.org/10.1007/978-3-319-18726-6_142