Editor's Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia

Acute aortic occlusion Ankle brachial pressure index Anticoagulation Atrial fibrillation Acute limb ischaemia Activated partial thromboplastin time Acetylsalicylic acid Catheter directed thrombolysis Contrast enhanced magnetic resonance angiography Confidence interval Creatine kinase. (This is the same enzyme as creatine phosphokinase, often abbreviated CPK in older literature, and in some countries.) Cardiovascular Outcomes for People Using Anticoagulation Strategies C reactive protein Compartment syndrome Computed tomography angiography Direct oral anticoagulants Digital subtraction angiography Duplex ultrasound Electrocardiogram Extracorporeal membrane oxygenation Eurpean Society of Cardiology European Society for Vascular Surgery Endovascular aneurysm repair Hazard ratio Ischaemia reperfusion injury International unit Low molecular weight heparin Major adverse limb events National Hospital Discharge Survey Odds ratio Popliteal artery aneurysm Peripheral artery disease Pharmacomechanical thrombolysis Percutaneous transluminal angioplasty Randomised controlled trial Relative risk Recombinant tissue plasminogen activator Surgery vs. Thrombolysis for Ischaemia of the Lower Extremity Thrombolysis or Peripheral Arterial Surgery Unfractionated heparin Vascular Quality Initiative Writing committee The European Society for Vascular Surgery (ESVS) has developed guidelines for treating patients with acute limb ischaemia (ALI). The focus on the guidelines is on lower limb acute ischaemia; however recommendations are also made on acute upper limb ischaemia. The term acute leg ischaemia is not used, in order to avoid confusion, as the same abbreviation, “ALI”, may be used. These guidelines will provide guidance for emergency physicians; vascular, cardiovascular and general surgeons; angiologists; interventional radiologists; and radiologists. The target population comprises patients with acute lower and/or upper limb ischaemia. The guidelines, which are developed by specialists in the field, promote a high standard of care (based on evidence, whenever available). Guidelines should not be viewed as a legal standard of care. This document is a guiding support, and the care given to a patient will always be dependent on the individual (symptom variability, comorbidities, age, level of activity), and treatment setting (techniques available, local circumstances, and expertise). To further underline this supportive character of the Guidelines, non-European reviewers were invited to review the document, so that it could serve doctors treating patients globally. This is also the rationale behind the decision to publish all ESVS Guidelines as free to download, and why the ESVS Guidelines app also can be downloaded free of charge from the ESVS website (www.esvs.org). Members of the Writing Committee (WC) were selected by the ESVS to represent clinicians involved in the treatment of ALI and included vascular surgeons and interventional radiologists. Members of the WC have provided disclosure statements regarding all relationships that might be perceived as real or potential sources of conflicts of interest. These are filed and available from ESVS headquarters. Members of the WC received no financial support from any pharmaceutical, device, or surgical industry to develop these guidelines. The ESVS Guideline Committee was responsible for undertaking the review process. The final version was checked and approved by the WC and the Guideline Committee. The WC held an introductory meeting on 13/14 June 2018 in Uppsala, Sweden, where the list of topics and author tasks were determined. After the first draft was completed and internally reviewed, the WC met again on 14/15 January 2019 in Hamburg, Germany, to review and approve the wording of each recommendation. The Guidelines then underwent external reviews, and the final version of the document was approved on July 30th, 2019. Members of the WC agreed on a common systematic literature search strategy for each of the assigned chapters. The literature search of articles published from 1 January 1990, published in English, was performed in the PubMed, Embase, Cardiosource Clinical Trials Database, and Cochrane Library databases up to 31 July 2018. The search was performed with the help of an information specialist (a clinical librarian). Reference checking and manual searching by the members of the WC added other relevant literature. In all, 6 549 unique abstracts were retrieved after duplicates were removed. The detailed literature search is described in Appendix S1 (see Supplementary Material). Selection of the literature was based on the information provided in the titles and abstracts of the retrieved studies. Only peer reviewed published literature and studies with predefined outcomes were considered. The selection process followed the pyramid of evidence, with aggregated evidence at the top of the pyramid (systematic reviews, meta-analyses), followed by randomised controlled trials (RCTs), and, finally, observational studies. Single case reports, abstracts, and in vitro studies were excluded, leaving expert opinion at the bottom of the pyramid. Articles published after the search date or in another language were only included if they were of paramount importance to these guidelines. After the second external review the members of the WC were asked to perform a second literature search within their area of responsibility to see if any important publications had been published between 31 July 2018 and 21 June 2019. The European Society of Cardiology (ESC) system was used for grading evidence and recommendations. A, B, or C reflects the level of current evidence (Fig. 1) and the strength of each recommendation was then determined to be either class I, IIa, IIb, or III (Fig. 2). The guidelines document underwent revision by members of the ESVS Guidelines Committee, and by external experts in the field. Each draft was revised according to the reviewers' suggestions and the final document was submitted to the European Journal of Vascular and Endovascular Surgery (EJVES) and the ESVS Guidelines Committee on 4 July 2019. ALI is characterised by a sudden decrease in arterial perfusion of the limb, with a potential threat to the survival of the limb, requiring urgent evaluation and management.1Acar R.D. Sahin M. Kirma C. One of the most urgent vascular circumstances: acute limb ischemia.SAGE Open Med. 2013; 1 (2050312113516110)Crossref PubMed Google Scholar ALI is considered when the symptom duration is less than two weeks.2Rutherford R.B. Baker J.D. Ernst C. Johnston K.W. Porter J.M. Ahn S. et al.Recommended standards for reports dealing with lower extremity ischemia: revised version.J Vasc Surg. 1997; 26: 517-538Abstract Full Text Full Text PDF PubMed Scopus (2282) Google Scholar, 3Norgren L. Hiatt W.R. Dormandy J.A. Nehler M.R. Harris K.A. Fowkes F.G. et al.Inter-society consensus for the management of peripheral arterial disease (TASC II).Eur J Vasc Endovasc Surg. 2007; 33: S1-S75Abstract Full Text Full Text PDF PubMed Scopus (2082) Google Scholar A symptom duration of greater than two weeks is usually considered to represent chronic limb ischaemia and is covered by other guidelines.4Aboyans V. Ricco J.B. Bartelink M.E.L. Bjorck M. Brodmann M. Cohnert et al.Editor's choice – 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2018; 55: 305-368Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar, 5Conte M.S. Bradbury A.W. Kolh P. White J.V. Dick F. Fitridge R. et al.Global vascular guidelines on the management of chronic limb-threatening ischemia.Eur J Vasc Endovasc Surg. 2019; 58 (S1–S109.e33)Abstract Full Text Full Text PDF Scopus (33) Google Scholar The most common causes of ALI are embolism, thrombosis of native arteries or reconstructions, peripheral arterial aneurysm, dissection, and traumatic arterial injury. The ischaemia is graded clinically according to the Rutherford ALI classification system (see Table 2).2Rutherford R.B. Baker J.D. Ernst C. Johnston K.W. Porter J.M. Ahn S. et al.Recommended standards for reports dealing with lower extremity ischemia: revised version.J Vasc Surg. 1997; 26: 517-538Abstract Full Text Full Text PDF PubMed Scopus (2282) Google Scholar Assessment determines whether the limb is viable or irreversibly damaged. The distinction between grade IIa and IIb, and between grade IIb and III, can sometimes be challenging. Prompt diagnosis and revascularisation by means of catheter based thrombolysis and/or thrombaspiration or by open surgery reduces the risk of limb loss and death. Primary amputation is recommended in patients with irreversible (Class III) ischaemia. Despite urgent revascularisation, mortality and major amputation rates are high (for details see section 5, Registries and Quality Improvement).Table 2Clinical categories of acute limb ischaemia according to Rutherford2Rutherford R.B. Baker J.D. Ernst C. Johnston K.W. Porter J.M. Ahn S. et al.Recommended standards for reports dealing with lower extremity ischemia: revised version.J Vasc Surg. 1997; 26: 517-538Abstract Full Text Full Text PDF PubMed Scopus (2282) Google ScholarGradeCategorySensory lossMotor deficitPrognosisDoppler signalsArterialVenousIViableNoneNoneNo immediate threatAudibleAudibleIIAMarginally threatenedNone or minimal (toes)NoneSalvageable if promptly treatedInaudible∗In the original 1997 classification it was stated that arterial Doppler sounds are never present in Stage IIA, and that rigor (mortis) is always present in Stage III. However, it is the opinion of the Writing Committee that exceptions to these rules do exist, and a slight modification of the Rutherford classification from 1997 may be appropriate in the future.AudibleIIBImmediately threatenedMore than toesMild/moderateSalvageable if promptly revascularisedInaudibleAudibleIIIIrreversibleProfound, anaestheticProfound, paralysis (rigor∗)Major tissue loss amputation. Permanent nerve damage inevitableInaudibleInaudibleThis is an identical replica of the table in the 1997 publication by Rutherford et al.,2Rutherford R.B. Baker J.D. Ernst C. Johnston K.W. Porter J.M. Ahn S. et al.Recommended standards for reports dealing with lower extremity ischemia: revised version.J Vasc Surg. 1997; 26: 517-538Abstract Full Text Full Text PDF PubMed Scopus (2282) Google Scholar with the exception of the asterisks (∗).∗ In the original 1997 classification it was stated that arterial Doppler sounds are never present in Stage IIA, and that rigor (mortis) is always present in Stage III. However, it is the opinion of the Writing Committee that exceptions to these rules do exist, and a slight modification of the Rutherford classification from 1997 may be appropriate in the future. Open table in a new tab This is an identical replica of the table in the 1997 publication by Rutherford et al.,2Rutherford R.B. Baker J.D. Ernst C. Johnston K.W. Porter J.M. Ahn S. et al.Recommended standards for reports dealing with lower extremity ischemia: revised version.J Vasc Surg. 1997; 26: 517-538Abstract Full Text Full Text PDF PubMed Scopus (2282) Google Scholar with the exception of the asterisks (∗). The general rule for ESVS guidelines is to avoid covering groups of patients in multiple guidelines, as that may result in contradictions. For this reason, the following groups of patients are not covered by these guidelines. (i) Aortic dissection may result in ALI, most often as a result of compression of the true lumen or dynamic / static obstruction of flow in one or both of the iliac arteries. This condition is covered by the Management of Descending Thoracic Aorta Diseases: Clinical Practice Guidelines of the ESVS.6Riambau V. Bockler D. Brunkwall J. Cao P. Chiesa R. Coppi G. et al.Editor's choice – Management of descending thoracic aorta diseases: clinical practice guidelines of the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2017; 53: 4-52Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar (ii) ALI may occur as a complication of aortic surgery, but that issue is covered by the ESVS 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms.7Wanhainen A. Verzini F. Van Herzeele I. Allaire E. Bown M. Cohnert T. et al.Editor's choice – European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.Eur J Vasc Endovasc Surg. 2019; 57: 8-93Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar (iii) The ESVS has advanced plans to develop Clinical Practice Guidelines on Vascular Trauma / Injuries. Thus, ALI secondary to trauma (iatrogenic or not) is not covered by these guidelines, except when discussing ALI in children (section 8, ALI in Children). (iv) Upper limb ALI is covered in section 7 (Diagnosis and Treatment of Upper Limb Acute Ischaemia), but treatment of patients who develop this condition during renal replacement therapy is covered by the Vascular Access 2018 Clinical Practice Guidelines of the ESVS.8Schmidli J. Widmer M.K. Basile C. de Donato G. Gallieni M. Gibbons C.P. et al.Editor's choice – Vascular access: 2018 clinical practice guidelines of the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2018; 55: 757-818Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar (v) Ischaemia may also develop secondary to deep venous thrombosis, and secondary low arterial blood flow, but this condition (phlegmasia cerulea dolens) is covered by the 2015 ESVS Venous Guidelines.9Wittens C. Davies A.H. Baekgaard N. Broholm R. Cavezzi A. Chastanet S. et al.Editor's choice – Management of chronic venous disease: clinical practice guidelines of the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2015; 49: 678-737Abstract Full Text Full Text PDF PubMed Scopus (266) Google Scholar (vi) Blue toe syndrome, when emboli lodge in the arteries of the toes (or fingers; often referred to as endarteries, as they lack collaterals) is often associated with great pain but is not covered by these guidelines, as the condition does not result in limb ischaemia. When this condition is suspected it is important to identify the source of embolism.4Aboyans V. Ricco J.B. Bartelink M.E.L. Bjorck M. Brodmann M. Cohnert et al.Editor's choice – 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2018; 55: 305-368Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar (vii) A number of uncommon causes of ALI are only mentioned for the sake of differential diagnosis (Table 1). The management of these rare diseases can be studied in textbooks. An invited editorial on the history of the treatment of ALI is published together with these Guidelines: “Where we have come from: a short history of surgery for ALI”.13Earnshaw J.J. Where we have come from: a short history of surgery for acute limb ischaemia.J Vasc Endovasc Surg. 2020; (in this issue)Abstract Full Text Full Text PDF Scopus (1) Google Scholar The true incidence of ALI is largely unknown owing to heterogeneous forms of presentation and treatment. Frequently, epidemiological studies include both ALI and chronic limb ischaemia, without clear differentiation. Also, there may be significant geographical variations due to ethnicity, accessibility, and quality of health care; most of the data on which these guidelines are based are from Western Europe and North America. Exceptionally, a publication reported on a Chinese population who underwent thrombolysis for ALI, with similar results to those reported from Europe and North America.14Ebben H.P. Jongkind V. Wisselink W. Hoksbergen A.W.J. Yeung K.K. Catheter directed thrombolysis protocols for peripheral arterial occlusions: a systematic review.Eur J Vasc Endovasc Surg. 2019; 57: 667-675Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar The EUCLID study (Examining Use of Ticagrelor in Peripheral Artery Disease) was a global RCT on ticagrelor treatment of patients with peripheral artery disease (PAD) and recruited 13 885 patients from 28 countries and 811 sites. They reported on two interesting subgroups: 642 (4.6%) patients who had critical limb ischaemia at baseline,3Norgren L. Hiatt W.R. Dormandy J.A. Nehler M.R. Harris K.A. Fowkes F.G. et al.Inter-society consensus for the management of peripheral arterial disease (TASC II).Eur J Vasc Endovasc Surg. 2007; 33: S1-S75Abstract Full Text Full Text PDF PubMed Scopus (2082) Google Scholar and 232 (1.7%) who developed ALI (0.8 per 100 patient years).15Hess C.N. Huang Z. Patel M.R. Baumgartner I. Berger J.S. Blomster J.I. et al.Acute limb ischemia in peripheral artery disease: insights from EUCLID.Circulation. 2019; 140: 556-565Crossref PubMed Scopus (0) Google Scholar Risk factors for the development of ALI in this cohort, with mainly benign chronic limb ischaemia, were previous peripheral revascularisation, atrial fibrillation (AF), and lower ankle brachial pressure index (ABI). Over the last century, there has been a general shift in aetiology from embolisation due to rheumatic or congenital valve disease in relatively young patients; to embolisation due to cardiac dysrhythmia; or in situ thrombosis in elderly patients.16Ljungman C. Adami H.O. Bergqvist D. Sparen P. Bergstrom 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: 1482-1485Crossref PubMed Scopus (0) Google Scholar, 17Acosta S. Kuoppala M. Update on intra-arterial thrombolysis in patients with lower limb ischemia.J Cardiovasc Surg. 2015; 56: 317-324PubMed Google Scholar It is important to note that ALI caused by native artery thrombosis or embolisation into an atherosclerotic vascular bed has increased in incidence, which has important implications for treatment.13Earnshaw J.J. Where we have come from: a short history of surgery for acute limb ischaemia.J Vasc Endovasc Surg. 2020; (in this issue)Abstract Full Text Full Text PDF Scopus (1) Google Scholar Validation of charts revealed three distinct categories of ALI: (i) lower limb arterial thrombo-embolism; (ii) acute exacerbation of chronic limb ischaemia; and (iii) iatrogenic ALI after revascularisation procedures. Approximately 70% of patients presented within two weeks of symptom onset, whereas 30% of patients presented with symptoms lasting more than two weeks. The cause of embolisation is usually attributed to AF or left ventricular mural thrombi after acute myocardial infarction, whereas acute thrombotic occlusions occur in individuals with a high atherosclerotic burden.18Korabathina R. Weintraub A.R. Price L.L. Kapur N.K. Kimmelstiel C.D. Iafrati M.D. et al.Twenty-year analysis of trends in the incidence and in-hospital mortality for lower-extremity arterial thromboembolism.Circulation. 2013; 128: 115-121Crossref PubMed Google Scholar Lower extremity embolisation due to aortic thrombi is a well known source of embolisation, and may be caused by manipulation of devices during endovascular repair of abdominal aortic aneurysm.19Toya N. Baba T. Kanaoka Y. Ohki T. Embolic complications after endovascular repair of abdominal aortic aneurysms.Surg Today. 2014; 44: 1893-1899Crossref PubMed Scopus (17) Google Scholar Historical data from Sweden and the UK have suggested an incidence of 3 – 14 per 100 000 person years, with a large majority of individuals being >80 years of age.20Dryjski M. Swedenborg J. Acute ischemia of the extremities in a metropolitan area during one year.J Cardiovasc Surg. 1984; 25: 518-522PubMed Google Scholar, 21Ljungman C. Holmberg L. Bergqvist D. Bergstrom R. Adami H.O. Amputation risk and survival after embolectomy for acute arterial ischaemia. Time trends in a defined Swedish population.Eur J Vasc Endovasc Surg. 1996; 11: 176-182Abstract Full Text PDF PubMed Scopus (24) Google Scholar, 22Davies B. Braithwaite B.D. Birch P.A. Poskitt K.R. Heather B.P. Earnshaw J.J. Acute leg ischaemia in Gloucestershire.Br J Surg. 1997; 84: 504-508Crossref PubMed Google Scholar, 23Grip O. Wanhainen A. Michaelsson K. Lindhagen L. Bjorck M. Open or endovascular revascularization in the treatment of acute lower limb ischaemia.Br J Surg. 2018; 105: 1598-1606Crossref PubMed Scopus (8) Google Scholar The largest contemporary epidemiological analysis of treatment of ALI used the National Hospital Discharge Survey (NHDS, USA).18Korabathina R. Weintraub A.R. Price L.L. Kapur N.K. Kimmelstiel C.D. Iafrati M.D. et al.Twenty-year analysis of trends in the incidence and in-hospital mortality for lower-extremity arterial thromboembolism.Circulation. 2013; 128: 115-121Crossref PubMed Google Scholar Some 1 092 811 hospital admissions from 1988 to 1997 were for acute arterial embolism or thrombosis of the lower limb; this was reduced to 670 704 from 1998 to 2007, implying a decrease in the incidence of arterial embolisation or thrombosis from 42.4 per 100 000 person years from 1988 to 1997 to 23.3 per 100 000 person years from 1998 to 2007. Hospital mortality also decreased from 8.3% to 6.3%. Unfortunately, this publication did not differentiate between embolism and thrombosis, and bypass thrombosis was excluded. In another epidemiological study of treatment of ALI in the Medicare population of the USA between the years 1998 and 2009, the incidence of ALI related hospital admissions decreased from 45.7 to 26.0 per 100 000 person years.24Baril D.T. Ghosh K. Rosen A.B. 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.e2)Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar The number of patients undergoing open revascularisation was reduced from 57.1% to 52.6%, while endovascular procedures were doubled, from 15.0% to 33.1%. Hospital mortality decreased from 12.0% to 9.0% and amputation rates from 8.1% to 6.4%, although the latter decrease was not statistically significant. One year mortality remained unchanged (41.0% vs. 42.5%). The one year amputation rate decreased over time from 14.8% to 11.0%. Similar amputation rates, mortality, and time trends were reported from Sweden.23Grip O. Wanhainen A. Michaelsson K. Lindhagen L. Bjorck M. Open or endovascular revascularization in the treatment of acute lower limb ischaemia.Br J Surg. 2018; 105: 1598-1606Crossref PubMed Scopus (8) Google Scholar, 25Grip O. Kuoppala M. Acosta S. Wanhainen A. Akeson J. Bjorck M. Outcome and complications after intra-arterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion.Br J Surg. 2014; 101: 1105-1112Crossref PubMed Google Scholar, 26Grip O. Wanhainen A. Acosta S. Bjorck M. Long-term outcome after thrombolysis for acute lower limb ischaemia.Eur J Vasc Endovasc Surg. 2017; 53: 853-861Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar One investigation from the National Inpatient Sample in the USA studied 162 240 patients with ALI from 2002 to 2013; 33 615 (20.7%) underwent thrombolysis. The authors concluded there could be an association between the increased use of thrombolysis and other endovascular procedures and improved outcome.27Bath J. Kim R.J. Dombrovskiy V.Y. Vogel T.R. Contemporary trends and outcomes of thrombolytic therapy for acute lower extremity ischemia.Vascular. 2019; 27: 71-77Crossref PubMed Scopus (0) Google Scholar There are few data on the level of major amputation after ALI, but in one large cohort study 34% of amputations done within 30 days were performed above the knee.25Grip O. Kuoppala M. Acosta S. Wanhainen A. Akeson J. Bjorck M. Outcome and complications after intra-arterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion.Br J Surg. 2014; 101: 1105-1112Crossref PubMed Google Scholar Better detection and medical treatment of AF and atherosclerotic disease has probably contributed to this decrease in the incidence of ALI.18Korabathina R. Weintraub A.R. Price L.L. Kapur N.K. Kimmelstiel C.D. Iafrati M.D. et al.Twenty-year analysis of trends in the incidence and in-hospital mortality for lower-extremity arterial thromboembolism.Circulation. 2013; 128: 115-121Crossref PubMed Google Scholar Primary prevention strategies, including smoking cessation advice, have also probably contributed.28Hussain M.A. Al-Omran M. Mamdani M. Eisenberg N. Premji A. Saldanha L. et al.Efficacy of a guideline-recommended risk-reduction program to improve cardiovascular and limb outcomes in patients with peripheral arterial disease.JAMA Surg. 2016; 151: 742-750Crossref PubMed Scopus (0) Google Scholar ALI is both a life and limb threatening disease. This makes decisions about best care complex. Often the limb is not salvageable owing to irreversible ischaemia, and amputation may be needed to save the patient's life; sometimes the patient is very frail and an attempt to save the limb will pose a significant risk to the patient's life. In 1994, in Gloucestershire, UK, 24% of individuals with ALI did not undergo a revascularisation attempt.22Davies B. Braithwaite B.D. Birch P.A. Poskitt K.R. Heather B.P. Earnshaw J.J. Acute leg ischaemia in Gloucestershire.Br J Surg. 1997; 84: 504-508Crossref PubMed Google Scholar However, these data may not reflect contemporary practice, and it may be questioned whether they are still valid. Decisions about care need to be made in a compassionate and sympathetic way but based on available clinical evidence, and after discussion with patients and their relatives. Patients are often elderly and their ability to comprehend the complexities of their situation, while in pain and often on opiate analgesia, is difficult. There may be issues such as the ability to consent. Clinicians must ensure appropriate consent is obtained before treatment. The following list of factors should be taken into account before deciding on treatment. Patients suffering from underlying or associated diseases may need specific considerations concerning the therapeutic approach. ALI is usually a disease of the elderly, is associated with general frailty, and may be an end of life problem.29Campbell W.B. Ridler B.M. Szymanska T.H. Two-year follow-up after acute thromboembolic limb ischaemia: the importance of anticoagulation.Eur J Vasc Endovasc Surg. 2000; 19: 169-173Abstract Full Text PDF PubMed Scopus (17) Google Scholar Recognising when a patient is dying is important, and not always easy. This situation, when the thrombosis is part of ending life, is sometimes referred to as agonal thrombosis. For example, in a small series of patients who developed ALI while in hospital with other medical conditions, none survived active treatment.22Davies B. Braithwaite B.D. Birch P.A. Poskitt K.R. Heather B.P. Earnshaw J.J. Acute leg ischaemia in Gloucestershire.Br J Surg. 1997; 84: 504-508Crossref PubMed Google Scholar The elderly may tolerate an embolectomy but not do so well if a distal bypass is needed to save the limb. The benefit of revascularisation in nonagenarians with lower limb ischaemia is limited by high mortality at one year.30Saarinen E. Vuorisalo S. Kauhanen P. Alback A. Venermo M. The benefit of revascularization in nonagenarians with lower limb ischemia is limited by high mortality.Eur J Vasc Endovasc Surg. 2015; 49: 420-425Abstract Full Text Full Text PDF PubMed Google Scholar These patients often present with concomitant emboli to other arterial beds, and they may die from embolic stroke or embolic bowel ischaemia. Arterial thrombosis may also be associated with an underlying malignancy causing prothrombotic states, including patients being actively treated, for example with chemotherapy. The malignancy is usually advanced, and treatment often has dismal results. Limb salvage rates are poor and most patients are not alive six months later, usually as a result of their underlying cancer.31Morris-Stiff G. Lewis M.H. Surgical treatment of acute limb ischaemia in the presence of malignancy.Int J Surg. 2010; 8: 233-235Crossref PubMed Scopus (0) Google Scholar Decisions about the management of patients with malignancy should be individualised with the help of oncologists, as active treatment in selected patients can yield good results both from treatment of the leg and the cancer.32Mouhayar E. Tayar J. Fasulo M. Aoun R. Massey M. Abi-Aad S. et al.Outcome of acute limb ischemia in cancer patients.Vasc Med. 2014; 19: 112-117Crossref PubMed Scopus (4) Google Scholar, 33Tsang J.S. Naughton P.A. O'Donnell J. Wang T.T. Moneley D.S. Kelly C.J. et al.Acute limb ischemia in cancer patients: should we surgically intervene?.Ann Vasc Surg. 2011; 25: 954-960Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar In a prospective study from Denmark with 26 years of follow up, patients with ALI and a newly diagnosed cancer had a higher risk of amputation than similar patients without cancer (hazard ratio [HR] 0.09 vs. 0.06), and patients with cancer also had a higher mortality rate (HR 0.67 vs. 0.37).34Nicolajsen C.W. Dickenson M.H. Budtz-Lilly J. Eldrup N. Frequency of cancer in patients operated on for acute peripheral arterial thrombosis and the impact on prognosis.J Vasc Surg. 2015; 62: 1598-1606Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar This is more important than the patient's general fitness. Elderly patients may be living alone and independent but need to move to residential accommodation if they become an amputee. A threat to their independence could be an argument for taking extra risks to try and obtain limb salvage. Similarly, understanding limb function is important.