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DOI: 10.1055/a-2687-0443
Revisiting Heparin-Induced Thrombocytopenia among Patients Undergoing Free Tissue Transfer: A Systematic Review

Abstract
Background
Heparin is frequently used to mitigate the risk of thrombosis in microsurgical free tissue transfer. Although rare, heparin-induced thrombocytopenia (HIT) is a severe, life-threatening complication that can arise in patients exposed to heparin products. This systematic review aims to examine patterns in demographics, flap characteristics, diagnostic approaches, and treatment protocols for HIT following free flap reconstruction.
Methods
A systematic search was conducted across PubMed, MEDLINE, and Web of Science, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Search terms included “heparin-induced thrombocytopenia,” “HIT syndrome,” “free flaps,” “microsurgery,” “plastic surgery,” and “reconstructive surgery.” Case reports or series written in English that presented patients developing HIT following free flap procedures were included. Eligibility criteria are accessible on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42025650125).
Results
A total of 15 articles were included, encompassing a total of 23 free flap reconstruction cases. The median patient age was 52 years, with male predominance (69.6). Lower extremity reconstruction was most common (47.8%), primarily using anterolateral thigh flaps (39.1%). Median 4T score was 6, median time to HIT diagnosis was 6 days, and median nadir platelet count was 72 × 103/μL. Thrombotic complications were common, with venous thrombosis (34.8%) predominating. Argatroban (26.1%) was the most frequently used alternative anticoagulant, while warfarin (30.4%) was the most common discharge medication. Overall flap survival was 43.5%. Meta-analysis revealed no significant difference in flap survival between anticoagulation strategies (95% CI: 0.38–2.63, p = 1.000).
Conclusion
HIT represents a rare but devastating complication in free flap reconstruction, with approximately half of the affected flaps failing despite intervention. Although no single anticoagulation strategy demonstrated superior outcomes, expeditious diagnosis and treatment may improve flap salvage rates. This review provides a foundation for developing standardized protocols for HIT management in microsurgical patients.
Publikationsverlauf
Eingereicht: 03. Mai 2025
Angenommen: 17. August 2025
Accepted Manuscript online:
21. August 2025
Artikel online veröffentlicht:
15. September 2025
© 2025. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
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References
- 1 Saber A, Hohman M, Dreyer M. Basic Flap Design. StatPearls. 2024 . Accessed June 11, 2024 at: https://www.ncbi.nlm.nih.gov/books/NBK563252/
- 2 Wilson JL, Morritt AN, Morrison WA. Avoiding complications. In: Flaps and Reconstructive Surgery. Elsevier; 2009. :pp. 117-124
- 3 Wong AK, Joanna Nguyen T, Peric M. et al. Analysis of risk factors associated with microvascular free flap failure using a multi-institutional database. Microsurgery 2015; 35 (01) 6-12
- 4 Stevens MN, Freeman MH, Shinn JR. et al. Preoperative predictors of free flap failure. Otolaryngol Head Neck Surg 2023; 168 (02) 180-187
- 5 Lee KT, Mun GH. The efficacy of postoperative antithrombotics in free flap surgery: a systematic review and meta-analysis. Plast Reconstr Surg 2015; 135 (04) 1124-1139
- 6 Arepally GM. Heparin-induced thrombocytopenia. Blood 2017; 129 (21) 2864-2872
- 7 Hogan M, Berger JS. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vasc Med 2020; 25 (02) 160-173
- 8 Stimac G, Walters ET, Elmarsafi T, Attinger C, Evans KK. Incidence of heparin-induced thrombocytopenia in lower-extremity free flap reconstruction correlates with the overall surgical population. J Plast Reconstr Aesthet Surg 2018; 71 (09) 1252-1259
- 9 Koster A, Nagler M, Erdoes G, Levy JH. Heparin-induced thrombocytopenia: perioperative diagnosis and management. Anesthesiology 2022; 136 (02) 336-344
- 10 Lee GM, Arepally GM. Heparin-induced thrombocytopenia. Hematology Am Soc Hematol Educ Program 2013; 2013 (01) 668-674
- 11 Arepally GM, Padmanabhan A. Heparin-induced thrombocytopenia: A focus on thrombosis. Arterioscler Thromb Vasc Biol 2021; 41 (01) 141-152
- 12 Medina ND, Mehan V, Schmidt ST. Heparin-induced thrombocytopenia leading to flap failure: Hirudo medicinalis and implications. Plast Reconstr Surg 2010; 125 (05) 217e-219e
- 13 Schleich AR, Oswald TM, Lineaweaver WC. Complete salvage of impending free flap failure in heparin induced thrombocytopenia by emergent institution of therapy with argatroban. J Plast Reconstr Aesthet Surg 2008; 61 (10) 1263-1264
- 14 Mehdizade T, Kelahmetoglu O, Gurkan V, Çetin G, Guneren E. Early suspicion of heparin-induced thrombocytopenia for successful free flap salvage: Reports of two cases. J Hand Microsurg 2021; 13 (03) 178-180
- 15 Nikolis A, Christopoulos A, Saint-Cyr M, Cordoba C, Guertin L, Harris PG. Recurrent venous thrombosis following free flap surgery: The role of heparin-induced thrombocytopenia. Can J Plast Surg 2003; 11 (01) 37-40
- 16 McMains CJ, Mather TL, Adamson KA. et al. Heparin-induced thrombocytopenia in lower extremity free tissue transfers. Microsurgery 2024; 44 (01) e31075
- 17 Segna E, Bolzoni AR, Baserga C, Baj A. Free flap loss caused by heparin-induced thrombocytopenia and thrombosis (HITT): a case report and literature review. Acta Otorhinolaryngol Ital 2016; 36 (06) 527-533
- 18 Zaman SR, Rawlins JM. Heparin induced thrombocytopaenia (HIT) as a cause of free flap failure in lower limb trauma. J Plast Reconstr Aesthet Surg 2014; 67 (06) 884-886
- 19 Yeap I, Karagiannis P, Ng SS, Langbart M. A proven perioperative protocol for free flap surgery in a patient with heparin-induced thrombocytopenia. J Plast Reconstr Aesthet Surg 2022; 75 (07) 2387-2440
- 20 Busch KH, Knobloch K, Vogt PM. Evidence for a locally limited form of heparin-induced thrombocytopenia in plastic reconstructive surgery?. Plast Reconstr Surg 2009; 124 (05) 277e-278e
- 21 Tremblay DM, Harris PG, Gagnon AR, Cordoba C, Brutus JP, Nikolis A. Heparin-induced thrombocytopenia syndrome as a cause of flap failure: a report of two cases. J Plast Reconstr Aesthet Surg 2008; 61 (01) 78-83
- 22 Habibi K, Lhuaire M, Privé S. et al. Intraoperative argatroban vessel irrigation during microsurgical anastomosis in heparin-induced thrombocytopenia patients: About two cases. J Plast Reconstr Aesthet Surg 2024; 88: 245-247
- 23 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 (02) 157-163
- 24 McCleave MJ. Free flap failure caused by heparin-induced thrombocytopenia. Microsurgery 2010; 30 (03) 251-252
- 25 Kaminsky AJ, Li SS, Copeland-Halperin LR, Miraliakbari R. The vastus lateralis free flap for lower extremity gustilo grade III reconstruction. Microsurgery 2017; 37 (03) 212-217
- 26 Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood 2012; 120 (20) 4160-4167
- 27 Aldekhayel S, Retrouvey H, Izadpanah A, Zadeh T. Free flap failure associated with heparin-induced thrombocytopenia: Is it preventable?. Plastic Surgery Case Studies. 2015; 1 (02) 45-48
- 28 Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J 2007; 83 (983) 575-582
- 29 Hirsh J, Heddle N, Kelton JG. Treatment of heparin-induced thrombocytopenia: a critical review. Arch Intern Med 2004; 164 (04) 361-369
- 30 Knobloch K, Gohritz A, Redeker J, Vogt PM. Heparin-induced thrombocytopenia in plastic surgery: do we take care enough?. Plast Reconstr Surg 2008; 122 (05) 1592-1593
- 31 Revelly E, Scala E, Rosner L. et al. How to solve the conundrum of heparin-induced thrombocytopenia during cardiopulmonary bypass. J Clin Med 2023; 12 (03) 786
- 32 Wanat-Hawthorne A, Tanaka K, Angona R, Feng C, Eaton M. Survey of practice pattern in patients with heparin-induced thrombocytopenia requiring cardiopulmonary bypass. Anesth Analg 2021; 133 (05) 1180-1186
- 33 Warkentin TE, Greinacher A. Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. Thromb Res 2021; 204: 40-51
- 34 Warkentin TE. Think of HIT. Hematology Am Soc Hematol Educ Program 2006; 408-414
- 35 jamovi. The jamovi project. jamovi. (Version 2.6). 2024 . Accessed August 25, 2025 at: https://www.jamovi.org
- 36 R Core Team. R: A language and environment for statistical computing. (Version 4.4). 2024 . Retrieved from https://cran.r-project.org . (R packages retrieved from CRAN snapshot 2024–08–07)