Endovascular Management of Thrombosed Dialysis Vascular Circuits

Abstract

A functional hemodialysis vascular access is the lifeline for patients with end-stage kidney disease and is considered a major determinant of survival and quality of life in this patient population. Hemodialysis therapy can be performed via arteriovenous fistulas, arteriovenous grafts, and central venous catheters (CVCs). Following dialysis vascular access creation, the interplay between several pathologic mechanisms can lead to vascular luminal obstruction due to neointimal hyperplasia with subsequent stenosis, stasis, and eventually access thrombosis. Restoration of the blood flow in the vascular access circuit via thrombectomy is crucial to avoid the use of CVCs and to prolong the life span of the vascular access conduits. The fundamental principles of thrombectomy center around removing the thrombus from the thrombosed access and treating the underlying culprit vascular stenosis. Several endovascular devices have been utilized to perform mechanical thrombectomy and have shown comparable outcomes. Standard angioplasty balloons remain the cornerstone for the treatment of stenotic vascular lesions. The utility of drug-coated balloons in dialysis vascular access remains unsettled due to conflicting results from randomized clinical trials. Stent grafts are used to treat resistant and recurrent stenotic lesions and to control extravasation from a ruptured vessel that is not controlled by conservative measures. Overall, endovascular thrombectomy is the preferred modality of treatment for the thrombosed dialysis vascular conduits.

The prevalence of end-stage kidney disease (ESKD) continues to rise in the United States and, in 2018, the number of prevalent patients exceeded 785,000. Hemodialysis via a vascular access remains the dominant treatment modality for ESKD patients. Therefore, maintaining a functional dialysis vascular access is essential for patients on maintenance hemodialysis. ¹ There are three types of dialysis vascular accesses including arteriovenous fistula (AVF), arteriovenous graft (AVG), and central venous catheter (CVC). An AVF is created via a direct connection between an artery and a vein, and an AVG is created by connecting an artery to a vein via a bridging prosthetic graft. A functional dialysis vascular access requires good arterial inflow via a feeding artery and a patent outflow vein to maintain an adequate flow rate in the vascular circuit. Current guidelines recommend a patient-centered life plan approach for ESKD patients in which the choice of vascular access is dependent on several factors. ^{1 2}

Functional AVFs are associated with lower risk of thrombosis and venous stenosis but require longer maturation time and are plagued with high primary failure rate. ¹ On the other hand, AVGs can be functional within days following their creation, thereby minimizing the need for bridging CVCs but are associated with higher risk of venous stenosis and thrombosis. In fact, more than 50% of AVGs thrombose within 1 year of creation. ³

A dysfunctional dialysis vascular access is associated with high morbidity, mortality, and health care expenditures. ^{1 4} In the United States, less than 50% of all hemodialysis vascular accesses are patent after 3 years. Furthermore, almost 50% of all dialysis vascular accesses eventually fail: AVFs after a median of 3 to 7 years and AVGs after a median of 1 to 1.5 years. ^{3 5}

Both AVFs and AVGs are susceptible to mechanical obstruction due to venous stenosis resulting in subsequent access thrombosis. Dialysis vascular access thrombosis is the leading cause of AVF and AVG failure. ⁶ In this article, we will discuss the pathogenesis of vascular access thrombosis, diagnostic approach to access thrombosis, techniques and devices utilized for endovascular thrombectomy, and its associated complications.

Pathogenesis of Dialysis Vascular Access Thrombosis

Dialysis vascular access thrombosis is a serious complication, and it is usually caused by an underlying vascular stenosis. The location of the underlying stenotic lesion can vary depending on the type of AV access. While the juxta-anastomotic segment is the most common site for AVF stenosis, the venous anastomosis segment is the most common site for AVG stenosis. The pathogenesis of dialysis vascular access thrombosis is complex and involves several mechanisms that result in luminal obstruction and subsequent thrombosis. ^{6 7} Neointimal hyperplasia (NIH) is the primary etiology of most dialysis access stenoses. The pathophysiologic cascade of events involved in NIH can be categorized into several stages as shown in Fig. 1 .

Fig. 1.

Factors that contribute to pathogenesis of dialysis access thrombosis.

It is well known that ESKD causes a proinflammatory uremic milieu, which is characterized by oxidative stress and endothelial dysfunction. Additionally, certain genetic factors may also predispose to NIH and access thrombosis. ⁶ During dialysis vascular access creation, vascular injury can occur due to vessel manipulation, clamping, and hypoxia. ⁶ These events trigger a local inflammatory response with cytokine release and macrophage migration. Following vascular access creation, several hemodynamic stressors contribute to further endothelial injury including flow disturbances at the anastomosis sites, increased shear stress, and inward remodeling which subsequently results in vascular stenosis. ^{7 8} Following vascular access maturation, repeated needle cannulation of the vascular access during hemodialysis and in some cases angioplasty of the underlying vascular stenosis causes further endothelial injury and propagates further luminal narrowing. Moreover, ultrafiltration during hemodialysis often results in hypotension and hemoconcentration, which can potentially lead to vascular access thrombosis. ^{9 10} Taken together, the interplay of multiple factors between the uremic milieu of ESKD, hemodynamics disturbances, vascular injury induced by repeated needle cannulation, and angioplasty balloons leads to NIH, vascular luminal stenosis, blood stasis, and eventually vascular access thrombosis ( Fig. 2 ).

Fig. 2.

Stages of vascular access failure and thrombosis.

Diagnosis of Dialysis Vascular Access Thrombosis

The main predisposing factor to thrombosis is the low vascular access flow rate. ¹¹ While AVFs can stay patent at flow rates of 300 mL/min, the risk of thrombosis increases in AVGs when the flow rate drops below 600 mL/min threshold. This difference in thrombosis threshold between AVGs and AVFs is, in part, related to the lack of endothelial layer in AVGs. ^{11 12}

The diagnosis of dialysis access thrombosis is usually made on clinical grounds. The absence of thrill, bruit, or pulse within the vascular access is the key finding on physical examination. Although not usually required, the diagnosis can be confirmed by vascular access ultrasonography. Once the diagnosis of access thrombosis is established, thrombectomy should be performed as soon as possible to avoid CVC use and improve dialysis access survival. ¹³ Importantly, in thrombosed AVFs, inflammatory thrombophlebitis can occur, and it manifests as localized redness, pain, and tenderness over the AVF site. If these findings are encountered in a thrombosed AVG, then a superimposed AVG infection should be suspected. ¹⁴

Contraindications for Dialysis Vascular Access Thrombectomy

Timely performance of thrombectomy for a thrombosed access is of paramount importance to restore and maintain vascular access patency. ¹³ However, few contraindications do exist for endovascular thrombectomy. Quencer and Friedman classified these contraindications into absolute, relative, and temporary. ¹² Absolute contraindications include access infection, pulmonary hypertension, recent access creation, severe ipsilateral steal syndrome, and right-to-left shunt. On the other hand, hyperkalemia (K > 6 mEq/L), fluid overload, hemodynamic instability are considered temporary contraindications. However, mega fistula, contrast allergy, and recent intracranial hemorrhage or cardiac arrest are considered relative contraindications and should be evaluated on a case-by-case basis. ¹² In such situations, surgical thrombectomy can be performed. Of particular importance is the thrombosis of a recently created vascular access in which endovascular thrombectomy can cause rupture of the fresh surgical anastomotic site. Moreover, the presence of severe hyperkalemia and volume overload resulting from inadequate and missed dialysis treatments preceding the access thrombosis may require the insertion of a temporary CVC to perform urgent dialysis before proceeding with endovascular thrombectomy. ¹²

Fundamentals of Dialysis Vascular Access Thrombectomy

Maintaining a functional dialysis access is essential for the survival of patients on maintenance hemodialysis. Over the last two decades, endovascular thrombectomy has become the modality of choice for the treatment of vascular access thrombosis. ^{15 16} The operator must be aware of a few fundamental principles when performing endovascular thrombectomy. First, the location of the thrombus and the clot burden can vary depending on the type of the vascular access. In a clotted AVG, the thrombus usually occupies the entire length of the synthetic graft, whereas in a thrombosed AVF, the thrombus is often localized at the juxta-anastomotic segment. ¹⁷ Second, AVF thrombosis triggers an inflammatory response that leads to the adherence of the thrombus to the vessel wall with subsequent endothelial damage. This interaction between the inflammatory thrombus and vessel wall makes the clot more adherent to the vessel wall and, as a result, the thrombectomy of these AVFs can be more challenging compared with AVGs. As a result, the success rate for AVF thrombectomy declines significantly if thrombectomy is delayed by more than 2 to 3 days following AVF thrombosis. On the other hand, successful thrombectomy of AVG can be performed up to 2 weeks following AVG thrombosis. ¹⁰ The timeframe between vascular access thrombosis and reestablishment of access flow is an independent predictor of vascular access survival; therefore, it is imperative to perform thrombectomy in a timely manner. ^{13 18 19} Third, vascular access thrombosis within the first month of access creation usually requires surgical thrombectomy. Angioplasty of a fresh surgical anastomosis can disrupt the suture line, causing vessel rupture necessitating emergent surgical repair. Fourth, AVGs that require more than three thrombectomy procedures within 3 months often necessitate surgical revision. ¹⁷ Similarly, early AVF thrombosis following its creation often requires surgical revision. ^{16 17}

The fundamental principles of treating thrombosed vascular access are as follows: (1) remove the thrombus from the vascular conduit and (2) address the underlying culprit vascular luminal stenosis. The basic principles of performing vascular access thrombectomy are summarized in Fig. 3 . Overall, endovascular thrombectomy process is a multistep procedure that utilizes a combination of thrombolysis and mechanical thrombectomy using various devices to remove the obstructive clot, and angioplasty balloons and occasionally stents to address the underlying vascular stenosis. ^{15 16}

Fig. 3.

Multistep algorithmic approach of performing dialysis access thrombectomy.

Preparation for Dialysis Vascular Access Thrombectomy

Physical examination of the patient and the vascular access is crucial before proceeding to the interventional suite. Particular attention should be paid to any signs of volume overload and preprocedural hyperkalemia. Findings of volume overload and hyperkalemia may require delaying the thrombectomy procedure and placement of a temporary CVC for urgent dialysis. Informed consent should be obtained from the patient for the thrombectomy procedure as well as for possible CVC placement in case the thrombectomy is unsuccessful. Importantly, the informed consent should be obtained before any sedative is administered to the patient. An intravenous line should be established to administer agents such as midazolam and/or fentanyl for conscious sedation.

Dialysis Vascular Access Thrombectomy Procedure

1. Remove the Thrombus from the Vascular Conduit

The endovascular thrombectomy procedure is performed in the interventional suite where the patient's blood pressure, heart rate, oxygen saturation, and cardiac rhythm are continuously monitored. ¹⁵ Local anesthesia is achieved with 1 to 2% lidocaine and 2,000 to 5,000 IU of heparin is given systematically. ^{2 12 15 20} Two antegrade and retrograde access sheaths (usually 7 Fr) are inserted facing each other without overlapping. Then, a pullback venogram is performed to assess the outflow veins and vascular stenotic lesions. ²⁰ Several methods for endovascular thrombectomy have been described in the literature including thrombolysis and mechanical thrombectomy. ^{15 17 20}

Thrombolysis

Several thrombolytic agents such as urokinase, streptokinase, and tissue plasminogen activator (tPA) have been successfully used for thrombolysis of clotted dialysis vascular access. It is important to assess the patient for the presence of any contraindications to thrombolytic therapy such as recent surgery, bleeding disorder, recent episode of bleeding, and the presence of severe hypertension.

In the United States, tPA is the most commonly used thrombolytic agent. Tan et al described alteplase to be a safe and effective alternative to urokinase. ²¹ The technical success of the thrombolytic agents alone in reestablishing the flow in a thrombosed dialysis vascular access is modest and ranges from 33 to 80%. ¹⁵ Hence, pharmacologic thrombolysis is often combined with mechanical thrombectomy to improve postthrombectomy patency rate.

Mechanical Thrombectomy

Several combinations of pharmacologic thrombolysis and mechanical thrombectomy using different devices have been described in the literature with similar overall outcomes. ^{15 21} In general, the mechanical thrombectomy devices are divided into two broad categories: direct wall contact devices and hydrodynamic devices ( Fig. 3 ).

a. Direct wall contact devices: The luminal clot is removed via the pullback approach using a balloon or a rotational device that works by fragmenting the clot within the vessel by means of generating a hydrodynamic vortex created by the high speed (800–5,000 rpm) rotating impella. ²² Fogarty balloons (Edwards Laboratories, Santa Ana, CA), Arrow-Trerotola (Teleflex, Wayne, PA), and Cleaner XT Rotational Thrombectomy System (Argon Medical Devices, Plano, TX) are some examples of such devices. ^{15 23} These devices are inexpensive, disposable, and some of them can be used over the wire.

• Fogarty balloon : The role of Fogarty balloon has been described in the literature using different methods. ^{20 23} For instance, Almehmi et al described the use of Fogarty in combination with no-wait lysis approach in declotting AVGs. The Fogarty balloon is usually inserted via the retrograde sheath and advanced toward the feeding artery to remove the arterial plug. After establishing the blood flow from the feeding artery, the clot burden is macerated, and angioplasty of the target lesion is performed using noncompliant angioplasty balloon ( Fig. 4 ). This approach has been shown to have a high technical success rate and shorter radiation and procedure time. ²⁰

• Arrow-Trerotola device : This device is made of a catheter-mounted wire nitinol basket and a handheld rotational drive unit that is powered via battery to rotate at 3,000 rpm.

Fig. 4.

Dialysis access thrombectomy using Fogarty balloon. ( a ) Two 7-Fr sheaths inserted in the arterial and venous sides of the graft (retrograde and antegrade, respectively). ( b ) Pullback contrast injection to determine the level of stenosis. ( c ) Removal of arterial plug using Fogarty balloon (arrow). ( d ) The arterial limb is patent (arrow—blood flowing from the sheath sidearm). ( e ) Angioplasty of the venous anastomosis (arrow—angioplasty balloon). ( f ) Final angiogram of the dialysis access showing patent flow.

After placing the catheter into the clotted graft, the wire basket is adjusted to the size of the access. Next, the catheter is connected to the rotational part to macerate the clot into 1- to 3-mm particles, which are then aspirated manually. ^{15 24}

However, it is worth noting that the disadvantage of using direct wall devices is the endothelial damage of the native vessels. ^{12 15}

b. Hydrodynamic (rheolytic, non-wall contact) devices : These are non-wall contact flow-based devices that use high-speed rotation to generate hydrodynamic vortex that ablates the thrombus and creates a negative pressure gradient, which, in turn, removes the clot microfragments into a collection bag without vessel wall contact. The hydrodynamic vortex is the result of high-speed fluid jets that produce the Venturi (rheolytic) effect. ^{12 15} Several devices are reported in the literature including AngioJet (Boston Scientific, Marlborough, MA), Oasis catheter (Boston Scientific, Natick, MA), Hydrolyzer (Cordis, Miami, FL), Amplatz thrombectomy device (Microvena, White Bear Lake, MN), and Straub Rotarex catheter (Straub Medical AG, Wangs, Switzerland).

• AngioJet catheter : This is a wire-guided catheter that is available in 4- to 6-Fr systems. The catheter is passed over a wire beyond the distal end of the thrombus and then the catheter is activated and drawn back into the clot. The catheter generates high-speed saline jets in a retrograde direction that produces a Venturi suction gradient. The generated fragments are then evacuated into the device.

It is worth noting that the success rate of restoring patency in a thrombosed dialysis vascular access using the above devices is more than 90%. ^{13 17 25 26}

2. Address the Underlying Culprit Vascular Luminal Stenosis

Dialysis access thrombosis is primarily caused by an underlying vascular stenosis that requires balloon angioplasty during the thrombectomy procedure to restore access patency and to avoid rethrombosis. ^{12 15 23} Different types of angioplasty balloons have been utilized to treat the stenotic lesions in the thrombosed vascular accesses. The standard angioplasty balloons used for dialysis vascular access stenosis are usually noncompliant and classified as high pressure, ultra-high pressure, cutting, or drug-coated balloons (DCBs). Generally, the high-pressure balloons are used to treat vascular access stenoses. ²⁷ Cutting balloons have been used to treat vascular stenotic lesions with good outcomes. ^{28 29 30} These balloons have three or four microsurgical sharp blades (atherotomes) that are longitudinally attached to the balloon surface. The atherotomes expand with balloon inflation in effect incising the stenotic lesion. ^{29 30} The utility of cutting balloons is limited by the lack of large, randomized trials, high cost, and the availability of other alternatives.

Role of Drug-Coated Balloons for the Management of Dialysis Vascular Access Stenosis

While the use of noncompliant balloons has been the modality of choice for the treatment of vascular access stenotic lesions in a dysfunctional access, their role is limited by poor patency and high restenosis rate. ³¹ This limitation is attributed to the barotraumatic injury of the treated vessel induced by angioplasty causing an inflammatory reaction, endothelial injury, local increase in smooth muscle proliferation, and subsequent NIH and restenosis. ^{9 28} Hence, DCBs have been developed to improve the patency of the dialysis vascular conduits following angioplasty. DCBs are designed to deliver an antiproliferative agent directly to the site of vascular stenosis to block the inward vascular remodeling and to prevent NIH. ^{32 33 34 35} In a meta-analysis of the use of DCBs in hemodialysis vascular access, Kennedy et al reported a significant improvement in the patency rate at 3, 6, 12, and 24 months. ³³ However, the mixed outcomes associated with DCB use in dialysis vascular access clinical trials and the high cost associated with their use limit the routine use of DCBs in clinical practice. ^{36 37 38}

Role of Stents in Thrombosed Dialysis Vascular Access

Angioplasty alone for an underlying vascular access stenosis can be associated with poor vascular access patency rate. This usually occurs due to an underlying resistant and elastic stenotic lesion leading to recurrent vascular access thrombosis. ^{39 40} Furthermore, repeated angioplasty of the hemodialysis vascular access circuit may be complicated by extravasation and vessel rupture. It is within this context that different types of stents were developed to improve the dialysis access patency and prevent access rethrombosis. ⁴⁰ The primary indications for stent placement in a dialysis vascular access are recoil, vessel rupture ( Fig. 5 ), and recurrent stenosis ( Fig. 6 ). Three types of stents are available to treat dialysis vascular access dysfunction, including bare metal stents, smart stents, and stent grafts (covered stents). ^{40 41} The specific properties of the stent grafts used in dialysis vascular access are recently reviewed in details. ⁴⁰ As a disadvantage, the use of stents is often complicated by in-stent stenosis related to NIH, and, if untreated, will result eventually in thrombosis of the graft. Therefore, in-stent stenosis requires further angioplasty and sometimes stent deployment within the stent ( Fig. 7 ). Overall, there is evidence that suggests that stent-graft use in the dialysis vascular access may improve the patency rate compared with angioplasty alone. ⁴²

Fig. 5.

AVG rupture during thrombectomy (arrow) ( a ) treated with covered stent (arrow) ( b ).

Fig. 6.

Two patients ( a–c ) and ( d–f ) with frequent AVG thrombosis related to recurrent venous anastomosis stenotic lesion (arrows, a, d ) treated with covered stents (arrows, b, e ).

Fig. 7.

Intra-stent stenosis. ( a and b) Intra-stent stenosis at the thigh graft venous anastomosis (arrows). ( c and d ) Intra-stent stenosis with thrombosis noted in a left brachiocephalic vein treated with stenting ( e ).

Complications of Dialysis Vascular Access Thrombectomy

Several complications can occur during dialysis vascular access thrombectomy including vessel rupture, arterial embolism, pulmonary embolism, and peri-access hematoma. The incidence of clinically symptomatic pulmonary embolism following thrombectomy of a clotted dialysis access is very low. ⁴³ Peri-access localized hematomas are encountered in less than 3% and are usually treated conservatively. ²⁷ However, severe hematomas (Grade IV) can occur and usually require external pressure, stent graft placement, and in some cases surgical intervention ⁵ ( Fig. 5 ). Arterial embolism is the most feared complication of thrombectomy with a reported incidence of 0.4 to 7%. ^{12 15 44} Actions that can lower the risk of arterial embolism include minimizing manual compression of the vascular access, avoiding flushing of the sheaths after placement, avoiding reflux angiograms, and completely deflating the balloon when attempting to pass the balloon across the arterial anastomosis into the feeding artery. ¹² Treatment options of arterial embolism include back bleeding, balloon embolectomy, thrombolytic infusion, and surgical embolectomy ( Fig. 8 ). ¹²

Fig. 8.

Hemodialysis access thrombectomy complicated by arterial embolus in the brachial artery. The arteriogram shows the embolus at elbow level (arrow, a ) confirmed with selective cannulation of the affected segment (arrow, b ). The arterial embolus was treated successfully with local lytic infusion and Fogarty balloon (arrow, c— reperfused arterial segment).

Conclusions

Endovascular thrombectomy of the thrombosed dialysis vascular access circuits has a high technical success rate. Endovascular thrombectomy is performed using a combination of pharmacologic thrombolysis and mechanical removal of the clot. Treatment of the underlying vascular stenoses is critical to establish access patency and to prevent vascular access rethrombosis. The role of DCBs in the management of vascular access stenosis remains controversial due to the conflicting data from randomized clinical trials. Lastly, stent grafts can be used to treat resistant and recurrent stenotic lesions and to control extravasation from a ruptured vessel that is not controlled by conservative measures. Overall, endovascular thrombectomy is the preferred modality of treatment for the thrombosed dialysis vascular access, as it is safe, quick, and effective in restoring vascular access patency.