Introduction

Acute limb ischemia (ALI) is defined as a sudden decrease in limb perfusion that threatens the viability of the limb. ALI is a vascular emergency and delay in diagnosis and management place patients at risk for limb loss and adverse events. Multiple endovascular techniques are now suitable to deal with this critical issue. Many endovascular suites carry an array of devices which can be used to treat acute limb patients. Catheter‐directed thrombolysis has emerged as the treatment of choice for many patients with threatened but salvageable limb with no contraindications to thrombolysis. We review the key steps to the management of this potentially life‐threatening clinical condition.

Procedure Planning, Equipment, and Considerations

Step 1. Diagnostic Angiography

Once the diagnosis of ALI is made, anticoagulation with intravenous heparin (goal PTT 60–80) should be initiated as soon as possible to prevent propagation of thrombus. Access site is obtained, which is often the contralateral common femoral artery of the affected limb. If available, initial diagnostic imaging to correctly identify the location of the occlusion and distal runoff is crucial in procedure planning. Commonly, aortoiliac angiography is obtained to identify any potential aortoiliac disease as a source of embolization as well as assessing the difficulty of catheter manipulation depending on the tortuosity, calcification, or narrow bifurcation angle. Subsequently, dedicated lower‐extremity angiography of the affected limb is obtained after “up and over” technique using support or guide catheter to identify the nature of occlusion. The length of the occlusion, collateral channels, distal reconstitution, as well as runoff vessels should be delineated. Appropriate guide sheath size should be chosen once the affected iliofemoral anatomy is known. Typically, a minimum of 5 Fr sheath is needed for lysis devices and larger sheaths are needed for thrombectomy devices.

Tip: Carefully, assess iliac anatomy for preexisting lesions or tortuosity as guiding sheaths may move and dissect if an extended overnight procedure is required.

Step 2. Crossing the Lesion

Depending on the nature and chronicity of the occlusion (Figure 11.1), thoughtful choice of the sheath length and support catheter can maximize the chance of crossing the lesion.

Initial approach can be using the hydrophilic guidewire, such as Glidewire (Terumo, Tokyo, Japan) or Aquatrack (Cordis, Fremont, CA, USA), to probe the lesion and “knuckling” of these guidewires allow for increased push while maintaining position within the vessel architecture. Successive wire escalation to guidewires with higher tipload may be necessary for occlusions with organized thrombus and underlying calcification. If unable to traverse the occlusion, thrombolytic agent administered through an endhole catheter can be considered to soften the proximal fibrin plug to increase the chance of crossing the occlusion after several hours.

• Tip: When wiring, a “soft” or “butter” feel to wire advancement strongly suggest acute, fresh thrombus.

Step 3. Thrombus Management

Thrombus management can be divided into two components: thrombolysis administration and mechanical adjunct therapy.

Thrombolytic administration can significantly modify the thrombus, especially in a long segment with significant thrombus burden. Types of thrombolytic agents are listed in Table 11.1. Alteplase^® is the most commonly used agent, which can be administered through a sidehole infusion catheter, such as Uni‐Fuse™ catheter (Angiodynamics, Queensbury, NY, USA) or EKOS™ catheter (BTG Interventional Medicine, London, UK) (Figure 11.2), that spans the length of the occlusion to evenly distribute the medication. An array of infusion catheters are currently available (Table 11.2). There is no standardized protocol for the dose and duration of thrombolysis administration and vary significantly across the institution. Commonly, an initial bolus dose is given upfront through the sidehole infusion catheter (i.e. 2–5 mg), followed by a low‐dose infusion (i.e. 0.5–1.0 mg/h fixed dose). There is no consensus on heparin use during thrombolytic infusion and risk of bleeding increases with therapeutic dose of heparin. Subtherapeutic dose of heparin may be acceptable to be infused through the sheath to prevent pericatheter thrombosis.

• Tip: tPA dosing is highly variable for acute limb cases. Interventionalists should be aware of tPA risks and contraindications (see Tables 11.3 and 11.4).

Patient should be carefully monitored for bleeding complications and blood test should be repeated to follow the level of fibrinogen and partial thromboplastin time.

• Tip: Consider reducing or stopping tPA infusion if fibrinogen drops <150 or by 50% of baseline values.

1. Types of mechanical adjunct therapies to thrombolysis are listed in Table 11.5. These devices may also be considered when thrombolytic therapy is contraindicated to minimize the thrombus burden. Given the risk of distal embolization, especially in the setting of high thrombus burden and compromised distal runoff vasculature, embolic protection devices may be considered to avoid jeopardizing the distal vascular bed (Table 11.6).

   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   

   Generic name	Abbreviation	Brand name	Company	Half‐life	Clearance	Initial dose	Infusion duration	Total dose
   Alteplase	tPA	Activase® Cathflo activase®	Genentech	<5 min	Hepatic	2–5 mg	0.5–1.0 mg/h	40 mg maximum
   Reteplase	RPA	Retavase®	Centocor	13–16 min	Hepatic and renal	2–5 units	0.25–0.5 units/h	20 units maximum
   Tenecteplase	TNK	TNKase®	Genentech	20–24 min	Hepatic	1–5 mg	0.125–0.25 mg/h	NA

   

   
   
   
   
   • Tip: Filters can be easily deployed through 0.035″ support catheter to the desired location. To do this, place the end of the support catheter distal to the lesion and remove the wire. Insert the filter collapsed into the catheter, then advance the filter using the filter’s attached wire until it emerges from the support catheter. Carefully, walk out the support catheter.
   
   
   
   
   1. Aspiration thrombectomy can be performed with dual‐lumen, rapid‐exchange catheters such as Export^® (Medtronic, Minneapolis, MN, USA) or Pronto^® (Vascular Solutions, Minneapolis, MN, USA), and negative pressure created by pulling back on the syringe creates the vacuum for aspiration. Once the device is delivered proximal to the lesion, aspiration is started and continued as the catheter is advanced through the lesion. It is important to keep the suction on while pulling out to minimize the risk of dislodging any aspirated material. It is simple to use, but the efficacy of thrombus extraction is limited due to the drop‐off of vacuum created.

      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      

      Catheter	Company	Fr (Size)	Infusion/Treatment length (cm)	Shaft length (cm)	Max. wire size (inch.)	Key feature	Cons
      EKOS Endosonic Mach™	BTG	6 Fr	6, 12, 18, 24, 30, 40, 50	106, 135	0.035	Ultrasound Energy, less tPA required	Cost, Bedside EKOS machine required
      Uni‐fuse™	Angiodynamics	4–5 Fr	2, 5, 10, 15, 20, 30, 40, 50	45, 90, 135	0.035	Multiport or endhole “drip” function	No power infusion
      Cragg‐McNamara™ Valved Infusion Catheter	Medtronic	4–5 Fr	5, 10, 20, 30, 40, 50	40, 65, 100, 135	0.035	Occluding ball wire	No power infusion
      Fountain/Mistique®	Merit	4–5 Fr	5, 10	45, 90, 135	0.035	Forceful, pulsed injections	Multiple components

      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      

      tPA absolute contraindications
      1.	Prior intracranial hemorrhage
      2.	Known cerebral AVMs
      3.	Known cerebral neoplasm (primary or metastatic)
      4.	Ischemic stroke within 3 months
      5.	Suspected aortic dissection
      6.	Active bleeding or bleeding diathesis
      7.	Significant trauma within past 3 months

      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      

      tPA relative contraindications
      1.	Severe uncontrolled HTN (SBP >180 mmHg or DBP >110 mmHg)
      2.	Prolonged (>10 min) CPR
      3.	History of prior ischemic stroke (>3 months)
      4.	Major surgery <3 weeks
      5.	Recent internal hemorrhage (2–4 weeks)
      6.	Noncompressible vascular punctures
      7.	Pregnancy
      8.	Active peptic ulcer
      9.	Active use of anticoagulants

      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      

      	French size	Delivery platform	Wire size (inch)	Catheter length (cm)
      Aspiration
      Export	6–7 Fr	Rapid exchange	0.014	140–145
      Pronto	5.5–8 Fr	Rapid exchange	0.014	138
      Penumbra Indigo	3–8 Fr	Over the wire	0.035	132–150
      Rheolytic
      Angiojet	4–6 Fr	Over the wire	0.014 or 0.035	90–120
      Ultrasonic
      EKOS	5.4 Fr	Over the wire	0.035	106–135
      Laser TurboElite/Turbo‐Tandem	4–8 Fr	Over the wire	0.014–0.035	112–150
      	4–7 Fr	Rapid exchange	0.014	150

      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      
      

      Device name	Company	Sizes (mm)	Sheath size	Pore size (μm)	Pros	Cons
      SpiderFx	Medtronic	3.0–6.0	6 Fr	50–200	Guidewire of choice, can use with manual or mechanical thrombectomy	Filter migration
      FilterwireEZ	Boston Scientific	2.5–5.5	6 Fr	80		Must use device wire
      EmboShield Nav6	Abbott	2.5–7 mm (vessel size)	5/6 Fr	140	Independently movable BareWire® can be workhouse, primary crossing wire	Must use BareWire, Difficult to deploy with tortuous vessel anatomy

      
      
   2. Penumbra Indigo^® (Penumbra, Inc., Alameda, CA, USA) (Figure 11.3), on the other hand, allows for continuous aspiration without the drop‐off of the vacuum for maximizing the aspiration power. Similarly, the device is delivered proximal to the lesion with the switch in the “off” position, then switch is turned to continuously allow aspiration as the catheter is advanced through the lesion. Separator catheter introduced inside the aspiration lumen can be used in tandem to break up the resistant thrombus during continuous aspiration. There are varieties of lineup of catheter by size; CAT8 (8 Fr) offers most efficient aspiration in the iliofemoral arteries while CAT3 (3.4 Fr) allows for treatment in the tibial arteries.

      

      
      
      
      
      • Tip: The Indigo CAT RX^® (6 Fr) is the only device in the Penumbra family that can be used on a rapid‐exchange (0.014″) wire and can be used with distal embolic protection.
      
      
   3. Angiojet^® (Boston Scientific, Marlborough, MA, USA) rheolytic thrombectomy device is a double lumen, over the wire catheter that delivers high‐pressure saline and creates a vacuum that breaks up the thrombus and suctions these fragments back out of the catheter. It can also allow delivery of tPA into the thrombus with Power Pulse™ Lytic Delivery mode to soften the organized thrombus. It is recommended to keep the device run time to less than 10 minutes to prevent excessive hemolysis, which may result in possible acute renal failure.
      
   4. EKOS can facilitate efficacy of thrombolysis by using high‐frequency ultrasound waves to accelerate thrombus dissolution. The ultrasound core wire delivers the ultrasonic waves as the thrombolytic agents are infused through the drug delivery lumen. The treatment zones can range from 6 to 50 cm, and the correct catheter should be selected from the baseline diagnostic angiography. The infusion catheter has three lumens: drug infusion port, coolant port, and main central coolant lumen. Thrombolytic agents are administered through the drug infusion port for the bolus and the continuous infusion dose of tPA. The black ultrasonic core catheter is introduced through the main central coolant lumen and screwed in at the end to be connected to the console machine.
      
   5. Excimer laser thrombectomy delivers bursts of ultraviolet light to photoablate the lesion including thrombus, plaque, or calcium. Laser catheter should be advanced over the guidewire at a slow rate of less than 1 mm per second through the entire length of the treatment zone.

• Tip: The Spectranetics Turbo‐Tandem™ catheter combines a 7 Fr laser guide catheter with 2 mm excimer laser ablation catheter to create more robust treatment arc which allows for less passes. Excimer laser catheters can also be used without a wire but have difficulty navigating tortuous anatomy.

Step 4. Treating Underlying Lesion

Angiography after thrombus management can often identify the underlying lesion that contributed to the acute thrombus formation.

If the lesion appears to be amenable to conventional endovascular treatment, balloon angioplasty and/or stenting should be performed as a preferred approach. Given the extensive controversy on drug‐coated balloons, the decision to use these devices should be carefully discussed with the patient and the team.

• Tip: Use of a covered stent may be helpful to trap focal thrombus (or aneurysmal areas), but adequate debulking should be done first to ensure no “toothpasting” of clot distally.

Surgical revascularization may need to be discussed depending on the anatomy, thrombus burden, and refractoriness to the endovascular treatment.