Complications of Iliofemoral Thrombolysis and Stenting for Venous Disease





Introduction


Many patients with symptomatic iliofemoral deep vein thromboses (DVTs) are now undergoing intervention to minimize thrombus burden in order to decrease venous pressures and preserve valve function. For patients with extensive and/or severely symptomatic DVT, catheter-based intervention is standard of care. Current guidelines from the Society of Vascular Surgeons and American Venous Forum for treatment are acute proximal DVT with symptoms <14 days, good functional capacity, life expectancy greater than 1 year, phlegmasia cerulea dolens, and low bleeding risk.


Access for Catheter-Directed Thrombolysis


Successful catheter-directed thrombolysis (CDT) begins with access, for which preoperative assessment is helpful. Access should be obtained one level below the majority of the thrombus burden, often the ipsilateral popliteal vein with the patient in prone position. If the thrombus extends below the popliteal vein, access can be obtained in the small saphenous vein or one of the posterior tibial veins at the medial malleolus. If the thrombus is isolated to the iliac system, the ipsilateral femoral vein can be accessed with the patient in supine position. Alternatively, the contralateral femoral vein can be accessed for the up-and-over technique. Lastly, the internal jugular (IJ) can also be used; however, this is used less in acute situations, in which crossing is typically easy and thrombolysis usually necessary. One challenge with access from the contralateral femoral vein or jugular vein is that retrograde crossing of the valves can be more difficult.


Ultrasound-guided access should be obtained with a micropuncture system, with negative pressure on the attached syringe, partially filled with saline. Using ultrasound, the needle tip should be visualized entering the vein, as blood is not always seen in the syringe because of the thrombus. Multiple punctures, more likely without ultrasound guidance, can lead to hematoma and premature termination of the procedure.


An access venogram is performed via the micropuncture sheath to confirm location and visualize thrombus burden. It is important to use only gentle hand injections, not power injections, because of the risk of embolization. The microsheath is then upsized to a 6-French sheath to facilitate crossing of the thrombosed vein. Initial attempts are made with 0.035″ hydrophilic guidewire, such as a regular or stiff Angled Glidewire (Terumo, Somerset, New Jersey), along with a guiding catheter, such as a Glidecatheter (Terumo). An angled guiding catheter or wire is preferable to allow steering past the occlusions. Venograms are performed at various levels to visualize the extent of thrombus burden. Venogram is also performed once the catheter passes into the inferior vena cava (IVC) to confirm patency distal to the thrombus. If the entire thrombus burden is not treated, it is likely to fail because of continued outflow obstruction.


Once the lesion is crossed, there are several options. Thrombus removal can be achieved in one session, with pharmacomechanical thrombectomy, or in multiple sessions with thrombolysis with or without pharmacomechanical thrombectomy.


Thrombolysis


After confirming appropriate position by venogram, a multi-sideport infusion lysis catheter is placed. There are several options available including: Unifuse (AngioDynamics, Latham, NY), Cragg McNamara (Medtronic, Minneapolis, MN), EkoSonic (Boston Scientific, Marlborough, MA). The length of thrombus should be measured using a marking catheter or tape, intravascular ultrasound (IVUS) pullback, or measurements based on venogram. The catheter treatment zone is based on the length of the thrombus and ranges from 5 to 50 cm. Once the infusion catheter is in place, thrombolytic therapy is initiated, typically with 0.5–2 mg/h of recombinant tissue plasminogen activator (rtPA). The optimal dose has not been established. Lower doses may result in inadequate thrombus removal and higher doses may increase the risk of major bleeds. In addition to the rtPA, heparin is infused via the sheath to maintain sheath patency. There are no studies directly assessing the optimal dose of heparin during thrombolysis. Our practice is to use subtherapeutic levels (such as 500 U/h of unfractionated heparin); however, higher levels are sometimes used with higher thrombus burdens.


Patients undergoing thrombolysis are monitored in an intensive care unit (ICU) or step down unit and kept flat, with the limb straight to prevent kinking or displacement of the catheter. Routine laboratory work is recommended, including prothrombin time, partial thromboplastin time, hemoglobin/hematocrit and fibrinogen every 4–12 hours, in addition to neurovascular checks and monitoring the puncture site for bleeding. Fibrinogen monitoring is controversial. If the fibrinogen drops below 100 mg/dL, the rtPA infusion is reduced or discontinued to decrease risk of major bleeding. While the rtPA is held, therapeutic anticoagulation is administered via the catheter and saline via the sheath and the fibrinogen level is rechecked in 2–4 hours if the patient has not undergone repeat imaging. We find that a significant reduction in fibrinogen is usually an indicator that the thrombus burden has greatly decreased, and now the lytic agent is being infused more systemically indicating more urgent follow-up is needed. Repeat imaging routinely occurs after 12–24 hours, but is done earlier if fibrinogen greatly decreases or the patient demonstrates clinical signs of significant improvement. If thrombolysis is not complete at repeat imaging and repeat fibrinogen levels have adequately rebounded, rtPA can be restarted at half the dose, with close surveillance of fibrinogen levels and for signs of bleeding. Thrombolysis >72 hours greatly increases bleeding risk. Use of retrievable IVC filters to prevent pulmonary embolus during thrombolysis is controversial. However, recommendation for consideration of an IVC filter would be the following: (1) large thrombus burden involving the iliocaval segment; (2) free-floating thrombus in the iliocaval segment; (3) patient presenting with iliofemoral DVT and pulmonary embolus (PE); and (4) patients with poor cardiopulmonary reserve. If placed, once the threat of PE is no longer an issue, the retrievable ICV filter should be removed, usually at 4–6 weeks posttreatment. In addition, and in most circumstances, there is no need to stop anticoagulation during filter retrieval. Filters can easily be placed via the popliteal access. Two filters, Optease (Cordis, Santa Clara, CA) and Optional Elite (Argon Medical Devices, Frisco, TX), have a 70-cm treatment length. If access is more distal and a filter is desired, IJ placement may be necessary prior to accessing tibial veins because the delivery system for the filter will not reach from the tibial to the correct location in the IVC.


Complications from Venous Lysis


Pulmonary embolus (PE) can occur during thrombolysis. Fortunately, massive PE is extremely rare because treatment is ongoing with heparin and lytic agent infusing.


Bleeding: The most common complication from venous thrombolysis is access site hematoma, which typically does not require intervention. If a large hematoma develops, the patient may require transfusion. Hematoma evacuation and/or vein repair should be considered for patients who develop severe signs or symptoms such as skin necrosis, leg edema, or compression of adjacent structures.


Intracranial hemorrhage is a devastating, but rare, complication. It is important to obtain a head CT prior to initiation of fibrinolytic therapy in patients with concern for intracranial pathology. During thrombolysis, thrombolytic and anticoagulant medications should be immediately held if neurologic changes develop until intracranial bleed can be ruled out.


Hematuria, epistaxis, and gastrointestinal (GI) bleed can be minor or major and may require terminating thrombolysis if severe. Minor, non–life-threatening bleeding can be safely managed while continuing thrombolysis. GI bleeding typically requires cessation of lytic agent to reduce the risk for hemodynamically significant hemorrhage. If patients have a history of GI bleeding or known gastroesophageal varices, GI consultation should occur prior to initiating thrombolysis.


The CaVenT Study, a recent randomized control study looking at long-term outcomes of catheter directed thrombolysis versus standard anticoagulation for acute iliofemoral DVT, found minimal major complication in the treatment group. Of 90 patients on thrombolysis, there were 20 bleeding complications, 3 of which were major (1 abdominal wall hematoma requiring transfusion, 1 calf compartment syndrome requiring intervention, and 1 inguinal access site hematoma). There were no deaths, PE, or intracranial hemorrhage. Complications are reduced with meticulous patient selection and careful access with US guidance and micropuncture kits. Patients at high risk of complications during thrombolysis include elderly patients, recent cerebrovascular event, recent childbirth, patients who underwent recent (<1–2 weeks) major surgery (abdominal, neurologic, spinal, internal eye), trauma, known conditions prone to bleeding (such as GI ulcers and varices, intracranial pathology, bladder cancer), and patients with thrombocytopenia or other bleeding disorders. For these patients, thrombolysis may be contraindicated because of the unacceptably high risk of life-threatening bleeding. Also of concern are patients who would not be able to tolerate appropriate positioning for extended lengths of time, such as those with chronic lung disease, congestive heart failure, or dementia.


Pharmacomechanical Catheter-Directed Thrombolysis


Pharmacomechanical thrombectomy (PCMT) utilizes thrombolytic therapy combined with mechanical thrombectomy. PCMT is thought to macerate the thrombus, leading to improved penetration of the drug, immediate thrombus aspiration, and the potential for shorter treatment times. PCMT techniques have similar results to CDT alone in terms of thrombus removal. Advantages may include reduced dose of thrombolytic drug and shorter treatment times (with less or no ICU time), and shorter hospital stays.


Initiation of PCMT is the same as CDT. Once access is obtained, the venogram is performed and the thrombus crossed. Decision regarding the type of PCMT will dictate sheath size. There are several types of pharmacomechanical devices currently available with different mechanisms of action:



  • 1.

    Hydrodynamic/rheolytic effect (Venturi effect): Angiojet (Boston Scientific, Marlborough, MA): This utilizes heparinized saline or rtPA jets to break up thrombus, which is then aspirated creating a local reduction in pressure to limit embolism. Angiojet Solente Zalente DVT is specifically designed for the iliofemoral vessels (≥6 mm), and Angiojet Solente Proxi can be used in the periphery for 3–6-mm vessels. Angiojet Zalente requires an 8-French sheath over a 0.035″ wire system. The Zalente catheter is placed at the proximal end of the thrombus, power pulse mode is initiated, and then the catheter is advanced to the most distal end, delivering rtPA into the thrombus. During this mode, no thrombus or blood is aspirated. After a dwell time of ideally 30 minutes, the unit is changed out of power pulse and mechanical thrombectomy is performed. In order to maximize thrombus removal, the catheter is rotated 90 degrees following each pass because the suction ports are not multidirectional and rotation of the device allows approximation of the tip closer to the wall, thereby permitting better treatment of the thrombus.


  • 2.

    Rotational devices: Arrow Trerotola Percutaneous thrombectomy device (Teleflex, Wayne, PA): These devices cause microfragmentation of the thrombus by rotating blades or baskets. They require a 7-French sheath with a 0.025″ wire. A handheld, battery-operated catheter rotates the 9 mm fragmentation basket at 3000 rpm macerating the thrombus into small <2-mm fragments, which are then aspirated or microembolized and cleared by the pulmonary circulation.


  • 3.

    Mixing devices: Trellis Peripheral Infusion System (Medtronic, Minneapolis, MN) and Cleaner (Argon Medical Devices, Frisco, TX). These devices use oscillating sinusoidal wires, which disrupts the thrombus and have side ports for injection of the thrombolytic. Trellis is currently off the market. It used a sinusoidal wire between two balloons to localize the treatment area and prevent embolization. Cleaner XT uses a 6-French sheath for the 9-mm rotating sinusoidal wire or a 7-French sheath for the Cleaner15, with a 15-mm rotating sinusoidal wire (more suited for iliofemoral DVT). This is a battery-operated handheld device, which macerates the thrombus and allows wall contact, which facilitates removal of more chronic/adherent thrombus. The device can potentially be used with IVC filter thrombosis. It is important to note that the device is inserted “bareback” through the sheath, not over a wire. It is steerable and effective for straightforward anatomy; however, wire access is lost, which can be challenging with tortuous anatomy or with tight lesions that were initially difficult to traverse.


  • 4.

    Ultrasound (US) Assisted Thrombectomy: EKOS Sonicare (Boston Scientific, Marlborough, MA). CDT assisted by high-frequency, low-energy US, which disrupts the fibrin in the thrombus to expose the underlying plasminogen, allows better penetration and efficiency of the thrombolytic drug. Treatment times are longer than with PCMT devices, but less than standard CDT. Single-setting thrombolysis is not an option with this device. It utilizes a 6-French sheath over a 0.035″ wire. To prevent catheter thrombosis, the catheter must be immediately prepped in the angiography suite with heparin or attached to the thrombolytic drip. Kinking of the catheter can also be problematic.


  • 5.

    Aspiration Catheters: Indigo System (Penumbra, Alameda, CA) and Angiovac (AngioDynamics, Latham, NY). These devices do not use mechanical thrombectomy or thrombolytic medications. A guidewire is placed through the sheath and then a thin-walled, wide lumen, nontapered catheter is placed to engage the thrombus. The thrombus is then removed with negative pressure from a 30-mL syringe or suction. Multiple passes are usually required. There is less risk of hemolysis than with PCMT, but more blood loss. Indigo uses continuous suction to remove the clot burden, and the separator within the catheter helps to break up the thrombus once retrieved to maintain patency of the catheter and prevent embolization. Angiovac is specifically designed as a venous drainage cannula for extracorporeal circulation and thrombus removal during this process. It is utilized more often to treat pulmonary emboli but can be helpful for IVC thrombus. The device is very large (22 French) and rigid, requiring a 26-French sheath, and requires general anesthesia and a perfusionist.



Data to inform the use of PCMT devices for DVT are limited. The Peripheral Use of Angiojet Rheolytic Thrombectomy with a Variety of Catheter Lengths (PEARL Registry), a multicenter study, found no difference in thrombus removal, rethrombosis, or quality of life at 1 year with Angiojet, Angiojet with thrombolysis, or thrombolysis prior to or following Angiojet thrombectomy.


The Acute Venous Thrombosis: Thrombus removal with Adjunctive Catheter Directed Thrombolysis (ATTRACT) Trial comparing PCMT with anticoagulation alone found no benefit in its primary endpoint of reduced Villalta score for grading postthrombotic syndrome in the CDT/PMT group compared with anticoagulation alone at 2 years; however, secondary subgroup analysis suggested there is potential benefit in cases of acute iliofemoral DVT and those with more severe symptoms (with inadequate statistical power to assess these subgroups fully).


Complications Following Percutaneous Pharmacomechanical Thrombectomy


Patients are at risk of specific, device-related complications in addition to standard bleeding complications from CDT. Vedantham et al. found a 2.8% rate of major bleeding, 0.5% rate of symptomatic PE, and a 3.9% overall rate of major complications. PCMT decreases infusion time and thrombolytic dose and can decrease or eliminate ICU stays. However, procedure times are significantly longer because of the dwell-time requirements of the thrombolytic agent. There is a potential increase in radiation exposure for the patient (which may be offset by fewer procedures) and increased cost in the angiography suite (staff and procedure room time).


The most studied devices are Angiojet (Boston Scientific, Marlborough, MA) and Trellis (Medtronic, Minneapolis, MN).




  • Rheolytic (Angiojet): Because of forceful pulse spray and aspiration, hemolysis is common. This is proportional to time and volume of treatment and usually resolves within 48 hours. When severe, hemolysis can lead to hyperkalemia and renal failure. Patients should be adequately hydrated and volume and time recommendations from the manufacturer observed. Volume overload can occur as a result of fluid administered with alteplase and saline jets for maceration, and care must therefore be taken in patients with congestive heart or renal failure. Bradycardia can occur, particularly in the more central locations, but resolves with pausing the device and resuming once bradycardia disappears, typically within minutes. Incomplete thrombus dissolution and distal embolization can also occur.



  • Rotational and mixing: These devices can potentially cause endothelial damage as a result of wall contact from the rotating baskets or oscillating wires, although we are not aware of any reports of this complication. Perforation in the venous system is far less catastrophic than in the arterial system and can be managed conservatively with cessation of thrombolytic, while larger perforations may require cessation of anticoagulation. More aggressive intervention is rarely necessary. If the patient is hemodynamically unstable, management options include balloon deployment at the site of rupture to tamponade the injury or covered-stent placement. Most covered stents are too small and all are off-label for the venous system. If stent-graft placement is required, IVUS should be used to prevent undersizing, which would lead to continued extravasation. These devices also have a risk of PE, especially when used without thrombolytic agents. Park et al. showed no increased incidence of PE between CDT, CDT + Trerotola, or Trerotola. Trerotola (Teleflex, Wayne, PA) is a rotating, expandable basket device, designed for dialysis access. However, in this study, they placed IVC filters in 95% of patients, therefore the risk without IVC filter placement cannot be assessed.



The role of IVC filter placement during percutaneous endovenous intervention is controversial. Sharifi et al. found that among 141 patients undergoing percutaneous venous interventions, CTA or V/Q identified a reduced risk of PE in the filter group (1 PE-filter; 8 PE-control; P=0.048). There were no differences in mortality or postprocedure symptoms. Identified risk factors for iatrogenic PE included PE at admission, severely symptomatic DVT (erythema, edema, pain, and induration), DVT involving two or more venous segments, venous diameter ≥7 mm, and normal venous anatomy.


Stenting


Patients who present with acute iliofemoral DVT often have an underlying stenotic lesion. Prior to completing the procedure, venous stenosis should be evaluated using IVUS in addition to venography. The most common form of May-Thurner syndrome involves compression of the left common iliac vein by the right common iliac artery and spine, just below the iliocaval junction. There are multiple other sites of potential iliac vein compression, from crossing internal iliac arteries, as well as pathologic findings, including aneurysms, tumors, etc. In patients with swelling but without thrombosis, iliac venous compression may be suspected on duplex US if there are no respiratory variations and a lack of response to Valsalva maneuver. Patients undergoing thrombolysis or PCMT with identified compression have >70% risk of DVT recurrence without treating the venous obstruction/compression with an appropriate stent.


IVUS is critical for the diagnosis of venous stenosis. Formal venography has been shown to be inadequate to identify stenosis and compressive lesions ( Fig. 36.1 ).


Apr 3, 2021 | Posted by in VASCULAR SURGERY | Comments Off on Complications of Iliofemoral Thrombolysis and Stenting for Venous Disease
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