Acute Limb Ischemia

Acute limb ischemia (ALI) is a major vascular emergency because of the rapid decrease in limb perfusion that causes a potential threat to limb viability. The majority of cases are caused by arterial thrombosis due to plaque progression or embolism, but ALI can also be caused by blockage of the venous drainage. The typical signs and symptoms of ALI are often referred to as the 6 Ps: pain, pallor, poikilothermia, paralysis, paresthesia, and pulselessness. The diagnosis is made on the basis of clinical findings and Doppler studies, but additional imaging may be required. Management is focused on revascularization. IV heparin is also administered. Nonviable limbs require amputation.

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Acute limb ischemia (ALI) is a vascular emergency caused by a rapid decrease in limb perfusion.


  • Incidence: 1.5 cases per 10,000 people per year
  • Frequency: men = women
  • More common in the elderly
  • The lower limb is affected in 80% of cases.


  • Arterial occlusion (most common):
    • Thrombosis:
      • Thrombosed atherosclerotic artery
      • Thrombosed bypass graft 
      • Thrombosed popliteal artery aneurysm
      • Popliteal adventitial cyst 
      • Hypercoagulable states (e.g., antiphospholipid antibody syndrome, heparin-induced thrombocytopenia) 
    • Embolism:
      • Thromboembolism (due to arrhythmias and/or sequelae of MI)
      • Atheroembolism (cholesterol emboli)
      • Paradoxical emboli
      • Septic emboli
    • Arterial dissection
    • Trauma:
      • Iatrogenic injury
      • Injuries of the lower extremities (e.g., posterior knee dislocations)
  • Venous occlusion: phlegmasia cerulea dolens (near-total occlusion of the deep venous system resulting in venous gangrene)
  • Other:
    • Ergotism
    • Vasopressor medications
    • HIV arteriopathy
    • Vasculitis
    • Compartment syndrome
    • Low-flow states:
      • Congestive heart failure
      • Hypovolemia
      • Hypotension


  • Common locations of vessel occlusion:
    • Thrombi:
      • Femoral artery
      • Popliteal artery
    • Emboli:
      • Aortic bifurcation
      • Iliac bifurcation
      • Femoral bifurcation
      • Popliteal bifurcation
  • Risk factors:
    • Smoking
    • Diabetes mellitus
    • Obesity
    • Arterial hypertension
    • High cholesterol
    • Sedentary lifestyle
    • Family history of vascular disease
  • Pathogenesis of ALI:
    • The initiating event of reduced perfusion leads to a switch to anaerobic metabolism.
    • Lactate production and acidosis 
    • Depletion of ATP stores
    • Dysfunction of Na+/K+-ATPase pump and sodium/calcium pump
    • Leakage of calcium into myocytes
    • Dysfunction of actin, myosin, proteases 
    • Development of muscle necrosis

Clinical Presentation

  • Occlusive arterial embolism presents with sudden onset of severe pain.
  • Arterial thrombosis is more indolent.
  • The 6 Ps of acute peripheral vessel occlusion :
    • Pain:
      • Sudden onset and constant
      • Worsens with passive movement
    • Pallor:
      • Seen in early stages
      • Later progresses to cyanosis
    • Poikilothermia (cold to the touch)
    • Paralysis
    • Paresthesia
    • Pulselessness


Acute limb ischemia is diagnosed on the basis of medical history, clinical presentation, physical examination, and vascular imaging.


  • Symptoms related to pain:
    • Onset
    • Location
    • Intensity
    • Presence of motor and sensory changes
  • Background information:
    • Recent interventions
    • Trauma
    • Presence or a family history of cardiovascular disease
    • Medications
  • Risk factors

Physical exam

Assess for the 6 Ps:

  • Pain
  • Pallor
  • Poikilothermia
  • Paralysis
  • Paresthesia
  • Pulselessness:
    • Palpation of the popliteal, femoral, dorsal artery of the foot, and posterior tibial arteries
    • Ankle brachial index bilaterally

Diagnostic testing

  • Categories of ischemia are based on clinical signs and Doppler results:
    • Viable limb:
      • Absence of pain at rest, sensory loss, and/or muscle weakness
      • Arterial and venous flows are present.
    • Threatened limb:
      • Minimal sensory loss
      • Mild-to-moderate muscle weakness
      • Absent arterial Doppler tones
      • Requires urgent intervention
    • Irreversible ischemic damage:
      • Sensory loss, paralysis, and/or permanent nerve damage
      • Absent arterial and venous Doppler tones
      • Revascularization may result in rhabdomyolysis and AKI.
  • Vascular imaging:
    • Doppler ultrasonography shows the absence of blood flow distal to the site of occlusion.
    • Confirmatory imaging:
      • Digital-subtraction angiography, CTA, or MRA
      • Perform in viable and marginally threatened limb ischemia
      • Use CTA cautiously because of iodinated contrast material.
  • Supporting studies:
    • ECG
    • Echocardiography
    • CBC
    • Blood chemistry
    • Coagulation studies
    • Creatine kinase
Intraoperative angiogram

Intraoperative angiogram:
A: Superficial femoral and popliteal artery occlusion
B: Femoropopliteal predilatation
C: Postprocedural result after plaque excision with TurboHawk

Image: “Intraoperative angiogram” by Translational Medicine @ UniSa. License: CC BY 2.5


The treatment approach depends on the severity or category of ischemic injury:

  • Treatment starts with IV heparin infusion.
  • Irreversible ischemia: amputation
  • Threatened limb ischemia:
    • Catheter-based revascularization:
      • Catheter-directed thrombolysis
      • Percutaneous mechanical thrombectomy
      • Percutaneous aspiration thrombectomy
    • Surgery:
      • Open thromboembolectomy
      • Bypass surgery
    • Should be done within 6 hours
  • Viable limb:
    • CTA/MRA to localize site of occlusion
    • Revascularization: endovascular or surgical approach
    • Should be done within 6–24 hours


  • Reperfusion injury:
    • Production of highly reactive oxygen species resulting in tissue injury
    • Acidosis and hyperkalemia occur due to leakage from damaged cells.
    • Rhabdomyolysis
    • Cardiac arrhythmia
    • Acute tubular necrosis 
  • Compartment syndrome: 
    • Increased capillary permeability leads to edema and elevation of compartment pressure that results in circulatory collapse.
    • Requires fasciotomy
  • Chronic pain syndrome: prolonged ischemia leads to permanent nerve damage, resulting in chronic pain.

Differential Diagnosis

  • Critical chronic limb ischemia: condition defined as > 2 weeks of chronic ischemic pain in an extremity at rest plus ankle pressure < 50 mmHg or toe pressure < 30 mmHg. Patients may present with claudication, resting pain, hyperesthesia, dependent rubor, and pallor during limb elevation. Untreated chronic limb ischemia may progress to gangrene. Diagnosis is made on the basis of history, physical examination, and findings of vascular imaging. Management is with revascularization. 
  • Phlegmasia: rare complication of acute deep vein thrombosis (DVT) characterized by increased venous pressure resulting in decreased tissue perfusion. Patients present with extremity edema, cyanosis, and severe pain. The condition may progress to gangrene. Diagnosis is made on the basis of clinical examination and Doppler findings that show extensive thrombus in the deep venous system. Management is variable and includes conservative treatment, an endovascular approach, or surgery.
  • Compartment syndrome: emergency condition caused by increased intracompartmental pressure (ICP) > 30 mmHg within a closed fascial space causing reduced tissue perfusion. Patients present with paresthesia, pallor, pulselessness, and severe pain that worsens with passive stretching. Diagnosis is made on the basis of clinical findings. Measurement of ICP is not necessary. Radiographs should be obtained if a fracture is suspected. Management involves immediate surgical fasciotomy. 


  1. Obara, H., Matsubara, K., Kitagawa, Y. (2018). Acute limb ischemia. Annals of Vascular Diseases 11:443–448.
  2. Sarwar, S., Narra, S., Munir, A. (2009). Phlegmasia cerulea dolens. Texas Heart Institute Journal 36:76–77.
  3. Cevik, Y., Kavalci, C. (2010). Hair tourniquet syndrome. Annals of Saudi Medicine 30(5):416–417.
  4. Callum, K., Bradbury, A. (2000). ABC of arterial and venous disease: Acute limb ischaemia. BMJ 320:764–767.
  5. Norgren, L., et al. (2007). Inter-society consensus for the management of peripheral arterial disease (TASC II). Journal of Vascular Surgery 45(Suppl S):S5–S67.

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