• Nuno Henriques Coelho Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
  • Rita Augusto Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
  • Evelise Pinto Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
  • Carolina Semião Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
  • João Ribeiro Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
  • João Peixoto Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar Vila Nova de Gaia/Espinho
  • Luís Fernandes Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
  • Victor Martins Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
  • Tiago Gregório Serviço de Medicina Interna, Centro Hospitalar de Vila Nova de Gaia/Espinho EPE; Departamento de Medicina da Comunidade, Informação e Decisão em Saúde (MEDCIDS), Faculdade de Medicina da Universidade do Porto
  • Alexandra Canedo Centro Hospitalar de Vila Nova de Gaia/Espinho, Serviço de Angiologia e Cirurgia Vascular
Keywords: acute limb ischemia, inflammatory biomarkers, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, treatment outcome, limb-loss, mortality


Introduction: In many areas of Medicine, biomarkers have been proving their value in disease management. The inclusion of inflammatory biomarkers in acute limb ischemia (ALI) decision-making remains debatable due to the scarce literature evidence. Nevertheless, much attention has been held towards the prognostic value of these simple, readily available and low-cost biomarkers might have. Therefore, this review aimed to identify studies that support the utility of preoperative inflammatory markers, such as the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR), for predicting ALI outcome.

Methods: A comprehensive systematic search was applied to Medline database to identify all the cohort studies that specifically investigated and compared the outcomes of ALI patients in relation to their preoperative inflammatory biomarkers.

Results: Four cohort studies were included in the review: two published citations, one research letter and one unpublished paper from the same authors of this review. In all studies, the primary outcomes were amputation and/or survival. All studies reported that higher NLR values were independently associated with adverse outcomes after treatment. One study stated that NLR ≥ 5.2 was found to have an 83% sensitivity and 63% specificity for predicting amputation within 30 days (Area Under Curve (AUC) 0.8) while other found that NLR ≥ 5.4 demonstrated to have a 90.5% sensitivity and 73.6% specificity for predicting 30-day amputation or death (AUC 0.86). Higher preoperative RDW, MPV, PLR and C-reactive protein were also reported as predictors of amputation in acute arterial thromboembolism patients in another study.

Conclusion: This review demonstrates that although limited literature exists, inflammatory biomarkers like NLR and PLR appear to have a role in ALI preoperative risk stratification. Definition of levels and trends of inflammatory biomarkers and their relationship with treatment outcome could be established through multicentric studies, influencing timing and intervention selection and leading to potential improvements in ALI morbimortality.


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1. Davis FM, Albright J, Ph D, Gallagher KA, Gurm S, Koenig GC, et al. Early outcomes following endovascular, open surgical, and hybrid revascularization for lower extremity acute limb ischemia. Ann Vasc Surg 2017;51:106–12. Doi: 10.1016/j.avsg.2017.12.025.
2. Björck M, Earnshaw JJ, Acosta S, Bastos F, Cochennec F, Debus ES, et al. European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia. Eur J Vasc Endovasc Surg 2020;59:173–218. Doi: 10.1016/j.ejvs.2019.09.006.
3. Aune S, Trippestad A. Operative mortality and long-term survival of patients operated on for acute Lower limb ischaemia. Eur J Vasc Endovasc Surg 1998;15:143–6. Doi: 10.1016/s1078-5884(98)80135-4.
4. Wang JC, Kim AH, Kashyap VS. Open surgical or endovascular revascularization for acute limb ischemia. J Vasc Surg 2016;63:270–8. Doi: 10.1016/j.jvs.2015.09.055.
5. Genovese EA, Chaer RA, Taha AG, Marone LK, Avgerinos E, Makaroun MS, et al. Risk factors for long-term mortality and amputation after open and endovascular treatment of acute limb ischemia. Ann Vasc Surg 2016;30:82–92. Doi: 10.1016/j.avsg.2015.10.004.
6. Ljungman C, Adami H O, Bergqvist D, Sparen P, Bergström R. Risk factors for early lower limb loss after embolectomy for acute arterial occlusion: A population based case control study. Br J Surg 1991;78:1482–5. Doi: 10.1002/bjs.1800781224.
7. Baril DT, Ghosh K, Rosen AB. Trends in the incidence, treatment, and outcomes of acute lower extremity ischemia in the United States Medicare population. J Vasc Surg 2014;60:669–77. Doi: 10.1016/j.jvs.2014.03.244.
8. Sanz, J A Brizuela; Fajardo, JA González; Taylor, JH; Solá, L Rio; Moreno, MF Munoz; Puerta CV. Design of a New Risk Score in Critical Limb Ischaemia : The ERICVA Model. Eur J Vasc Endovasc Surg 2016;51(1):90–9. Doi: 10.1016/j.ejvs.2015.09.025.
9. Brevetti G, Giugliano G, Brevetti L, Hiatt WR. Inflammation in Peripheral Artery Disease. Circulation 2010;122:1862–75.
10. Bhat TM, Afari ME, Garcia LA. Neutrophil lymphocyte ratio in peripheral vascular disease: a review. Expert Rev Cardiovasc Ther 2016;14(7):871–5. Doi: 10.1586/14779072.2016.1165091.
11. Lee JS, Kim NY, Na SH, Youn YH, Shin CS. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine (Baltimore) 2018;97:1–5. Doi: 10.1097/MD.0000000000011138.
12. Taşoǧlu I, Sert D, Colak N, Uzun A, Songur M, Ecevit A. Neutrophil-lymphocyte ratio and the platelet-lymphocyte ratio predict the limb survival in critical limb ischemia. Clin Appl Thromb 2014;20:645–50.
13. Watson JDB, Gifford SM, Clouse WD. Biochemical markers of acute limb ischemia, rhabdomyolysis, and impact on limb salvage. Semin Vasc Surg 2014;27:176–81. Doi: 10.1053/j.semvascsurg.2015.01.007.
14. Gary T, Pichler M, Belaj K, Hafner F, Gerger A, Froehlich H, et al. Platelet-to-Lymphocyte Ratio: A Novel Marker for Critical Limb Ischemia in Peripheral Arterial Occlusive Disease Patients. PLoS One 2013;8:1–5. Doi: 10.1371/journal.pone.0067688.
15. Choi DH, Kobayashi Y, Nishi T, Kim HK, Ki YJ, Kim SS, et al. Combination of mean platelet volume and neutrophil to lymphocyte ratio predicts long-term major adverse cardiovascular events after percutaneous coronary intervention. Angiology 2019;70:345–51. Doi: 10.1177/0003319718768658.
16. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration. PLoS Med 2009;6(7). Doi: 10.1371/journal.pmed.1000100.
17. Taşoǧlu I, Çiçek OF, Lafci G, Kadiro
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