Acute Limb Ischaemia

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Acute limb ischaemia (ALI) is defined as a sudden decrease in arterial blood flow to a limb that threatens its viability. It has an incidence of ~1.5 cases per 10,000 per year. 1

ALI is a vascular emergency and can lead to extensive tissue necrosis, which may ultimately result in limb amputation or even death.1

The vast majority of ALI cases involve the lower limbs.1

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ALI can be as a result of thrombosis, embolism or trauma.2

Thrombosis (80-85%) is most commonly due to plaque rupture in an atherosclerotic segment (thrombosis-in-situ) in patients with peripheral arterial disease (PAD).

A thrombus may also form in the context of:

  • Hypovolaemia
  • Thrombophilia
  • Hypotension
  • Malignancy

Embolism (10-15%) mainly arises from a thrombus in the left atrium (in association with atrial fibrillation) orΒ a mural thrombus (following a myocardial infarction).

Other sources include:

  • Prostheses (heart valves or bypass grafts)
  • Aneurysms (especially popliteal and abdominal aortic aneurysms)

Trauma (including iatrogenic, 5%) can be as a result of iatrogenic injury during interventional procedures, such as percutaneous coronary intervention. These have increased prevalence over the last two decades.

Risk factors

The risk factors for ALI are similar to the risk factors for peripheral arterial disease (PAD):1

  • Smoking
  • Diabetes mellitus
  • Obesity
  • Hypertension
  • Hypercholesterolaemia

However, not all patients with ALI will have the presence of risk factors.

Clinical features

The classical features of ALI are summarised as the six P’s (developing over a period of less than 2 weeks):1

The six P’s of acute limb ischaemia

  • Pain
  • Pallor
  • Pulselessness
  • Perishingly cold (poikilothermia)
  • Paraesthesia
  • Paralysis


Typical symptoms of ALI include:

  • Pain in the affected limb usually present at rest
  • Altered sensation (paresthesia)
  • Paralysis in the affected limb (this is a late sign)

OtherΒ important areas to coverΒ in the history include:

  • Past medical history: if an embolic cause is suspected, a detailed history should explore potential sources (e.g. atrial fibrillation, recent myocardial infarction).
  • Predisposing risk factors: ask about conditions predisposing to peripheral arterial disease (PAD), especially diabetes mellitus (a major risk factor), hypertension and hypercholesterolaemia.
  • Medication history: if the patient has established PAD, ask about medications (e.g. antiplatelets), and whether they are compliant with them.
  • Social history: it is important to establish the patient’s smoking habits, as smoking is the single biggest risk factor associated with PAD.1

Clinical examination

In the context of suspected ALI, a thorough peripheral vascular examination is necessary. See the Geeky Medics guide here for more information.

The clinical presentation of ALI can vary greatly but the most common findings are:1

  • Marble white appearance of the skin
  • Absent limb pulses on palpation
  • Cold limb

Less common findings, which usually appear in later stages, include:1

  • Paraesthesia (with reduced or complete loss of light touch sensation in the distal limb)
  • Paralysis (with the inability to wiggle toes or move fingers)
  • Muscle weakness
  • Gangrene

When assessing for limb ischaemia, a normal contralateral limb with palpable pulses is a sensitive sign for embolic occlusion in the abnormal limb.1

Embolic vs thrombotic acute limb ischaemia

It is important to try and distinguish embolic from thrombotic ALI.

As opposed to thrombotic ALI, the sudden nature of embolic ALI does not provide the body with sufficient time to build up compensatory collaterals. This makes urgent intervention in embolic ALI a necessity if the limb is to be salvaged.1,2,3

This table summarises the key differences between thrombotic and embolic ALI:

Clinical features Thrombosis Embolus
Onset Gradual, vague Sudden
Severity Less severe Severe
Peripheral arterial disease History of PAD symptoms Unlikely
Previous vascular surgery or endovascular interventions Likely Unlikely
Cardiac history Unlikely History of AF, recent MI
Clinical Examination
Appearance and feel Less cold, cyanotic Cold, mottled
Palpation of artery Hard, calcified Soft, tender
Contralateral leg pulses Absent Present

The Rutherford classification

In addition, the Rutherford classification for grading the severity of ALI is useful in determining limb viability. The Rutherford classification highlights the variability in the presentation of ALI.2

Stage Prognosis Findings Doppler Signal
Sensory loss Muscle weakness Pedal arteries Popliteal veins
I Limb viable, not immediately threatened None None Audible Audible
IIa Limb marginally threatened, salvageable if promptly treated Minimal (toes) None Often inaudible Audible
IIb Limb immediately threatened, salvageable with immediate revascularisation More than toes, pain at rest Mild or moderate Inaudible Audible
III Limb irreversibly damaged, major tissue loss or permanent nerve damage inevitable Profound, anaesthetic Paralysis Inaudible Inaudible

Differential diagnoses

The main differential diagnosis to consider isΒ critical limb ischaemia (CLI). It is important to differentiate between ALI and CLI due to differences in urgency and management.

CLI is caused by chronic arterial occlusion due to peripheral arterial disease with symptoms lasting longer than 2 weeks. It is characterised by rest pain, non-healing ulcers and gangrene.1,2


Clinical features Acute limb ischaemia Critical limb ischaemia
Onset ≀ 2 weeks β‰₯ 2 weeks
Pulses Absent Reduced/absent
Pain Sudden, at rest, calf tenderness Gradual, at rest
Appearance Pale, β€œmarble white” Pink
Temperature Cold Warm
Other Paraesthesia, paralysis Ulcers, gangrene
Emergency? Yes No

Other diagnoses to consider include:1,2

  • Acute deep vein thrombosis
  • Peripheral neuropathy
  • Compartment syndrome
  • Thromboangiitis obliterans (Buerger disease)


Bedside investigations3

  • Duplex ultrasound/Doppler scan: to confirm the absence of pulses.
  • ECG: to look for atrial fibrillation.

Laboratory investigations3

  • Baseline blood tests (FBC, U&E, LFTs, coagulation).
  • Serum lactate: to assess the severity of ischaemia.
  • Thrombophilia screen (if no known risk factors for ALI).
  • Group and save:Β important to perform as the patient may require emergency surgical intervention.


  • CT/MR angiography: to guide revascularisation if the limb is viable, where delaying treatment is not threatening to limb viability.
  • Other (e.g. echocardiography if an embolus of cardiac origin is suspected).


Initial management3

  • Arrange emergency assessment by a vascular specialist
  • Systemic anticoagulation with heparin
  • Analgesia: paracetamol and an opioid

Medical management

Infrequently, anticoagulation alone may be sufficient if symptoms are mild or cease.3

Surgical management

Surgical (including endovascular) revascularisation is first-line.3

The exact form of intervention depends on the type of occlusion (i.e. thrombus vs embolus), duration of ischaemia, location, the viability of the limb and risks associated with treatment.3

Thrombotic aetiology

If the limb is viable and a thrombotic cause is suspected:

  • The first-line approach is percutaneous catheter-directedΒ thrombolysis.
  • Alternative options include:
    • Surgical thrombectomy
    • Percutaneous mechanical thrombus extraction
    • Bypass surgery

Embolic aetiology

If the limb is viable and an embolic cause is suspected:

  • The first-line approach is an embolectomy with a balloon catheter.
  • Alternative options include:
      • Percutaneous catheter-directed thrombolysis (with e.g. urokinase, alteplase, etc.)
      • Bypass surgery

If the limb is non-viable (i.e. showing signs of irreversible/permanent damage), it will require an amputation.

Long-term management

NICE recommends that all patients with peripheral arterial disease are aided in reducing their risk of cardiovascular disease through:4

  • Smoking cessation
  • Diet and exercise
  • Statin therapy and managing cholesterol
  • Preventing, diagnosing, and managing diabetes
  • Preventing, diagnosing, and managing hypertension
  • Antiplatelet therapy


ALI has a high mortality rate of 15-20% and a similarly high 30-day mortality rate of ~15% following surgical intervention.

Around a third of deaths result from metabolic complications, in the form of reperfusion injury.1

Surgical revascularisation causes sudden reperfusion of ischaemic tissue in the affected limb, which can, in turn, lead to reperfusion injury. This can consist of:

  • Massive oedema: resulting in compartment syndrome and hypovolaemic shock.
  • The sudden release of built-up substances which can lead to various systemic complications:
    • Hyperkalaemia due to the release of K+ ions: can cause cardiac arrhythmias.
    • Systemic acidosis from the release of H+ ions.
    • Acute kidney injury due to the release of myoglobin: patients may require emergency renal replacement therapy.

Other important complications to remember include:

  • Compartment syndrome due to oedema formation on reperfusion of the limb and confinement of the muscles in their tight fascia: can ultimately lead to muscle necrosis and is an emergency.
  • Peripheral nerve injury, which can lead to chronic severe neuropathic pain in the limb.
  • The psychosocial impact of limb amputation on the patient and associated physical morbidity (e.g. stump or phantom limb pain, immobility, etc).

Key points

  • Acute limb ischaemia is a sudden drop in perfusion to a limb which threatens its viability.
  • The most common causes are thrombosis in the context of atherosclerotic peripheral arterial disease or an embolus from the heart.
  • Clinical features are usually summarised as the six P’s: pain, pallor, pulselessness and a perishingly cold limb are the commonest, but it can also progress to include paraesthesia and paralysis.
  • Initial management involves an urgent vascular assessment from a specialist, anticoagulation, and analgesia.
  • Surgical management to revascularise the limb is first-line and depends on the type of occlusion, its location, the duration of ischaemia and limb viability.
  • If revascularisation is impossible, an amputation will be required.
  • Complications mainly arise from sudden reperfusion and include compartment syndrome, hyperkalaemia, acidosis, and acute kidney injury.


  1. NICE CKS. Peripheral arterial disease. Last revised in 2019. Available from: [LINK]
  2. Journal of Clinical Medicine. Acute Limb Ischaemia: An Update on Diagnosis and Management. Published in 2019. Available from: [LINK]
  3. BMJ Best Practice. Peripheral arterial disease. Last revised in 2018. Available from: [LINK]
  4. NICE. Peripheral arterial disease: diagnosis and management (CG147). Published in 2018. Available from: [LINK]


Mr Craig Nesbitt MBChB MD FRCS

Consultant Vascular and Endovascular Surgeon


Dr Chris Jefferies


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