JACC: Cardiovascular Interventions
Inferior Vena Cava Thrombosis
Author + information
- Received September 8, 2015
- Revision received November 22, 2015
- Accepted December 17, 2015
- Published online April 11, 2016.
Author Information
- Mohamad Alkhouli, MDa,∗ (adnanalkhouli{at}gmail.com),
- Mohammad Morad, MDb,
- Craig R. Narins, MDa,c,
- Farhan Raza, MDd and
- Riyaz Bashir, MBBSd
- aDivision of Cardiovascular Disease, University of Rochester Medical Center, Rochester, New York
- bDepartment of Medicine, Temple University Hospital, Philadelphia, Pennsylvania
- cDepartment of Surgery, Section of Vascular Surgery, University of Rochester Medical Center, Rochester, New York
- dDivision of Cardiovascular Disease, Temple University Hospital, Philadelphia, Pennsylvania
- ↵∗Reprint requests and correspondence:
Dr. Mohamad Alkhouli, Division of Cardiovascular Disease, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.
Abstract
Thrombosis of the inferior vena cava (IVC) is an under-recognized entity that is associated with significant short- and long-term morbidity and mortality. In absence of a congenital anomaly, the most common cause of IVC thrombosis is the presence of an unretrieved IVC filter. Due to the substantial increase in the number of IVC filters placed in the United States and the very low filter retrieval rates, clinicians are faced with a very large population of patients at risk for developing IVC thrombosis. Nevertheless, there is a paucity of data and societal guidelines with regards to the diagnosis and management of IVC thrombosis. This paper aims to enhance the awareness of this uncommon, but morbid, condition by providing a concise, yet comprehensive, review of the etiology, diagnostic approaches, and treatment strategies in patients with IVC thrombosis.
- catheter-directed thrombolysis
- deep venous thrombosis
- inferior vena cava
- pharmacomechanical catheter-directed thrombolysis
- post-thrombotic syndrome
Inferior vena cava (IVC) thrombosis is an under-recognized entity that is associated with significant morbidity and mortality (1). It is estimated that 2.6% to 4.0% of patients with lower extremity deep vein thrombosis (DVT) have IVC thrombosis (2–5). However, the true incidence of IVC thrombosis may be underestimated due to the lack of standardized methods of its detection and reporting, as well as the exponential increase in the number of unretrieved IVC filters in the United States, a major predisposing factor to IVC thrombosis (5,6). The mortality rate of IVC thrombosis is twice as high as that of DVT confined to the lower extremities (2). If untreated, patients with IVC thrombosis will also suffer from significant morbidities: post-thrombotic syndrome (PTS) in up to 90%, disabling venous claudication in 45%, pulmonary embolism (PE) in 30%, and venous ulceration in 15% (1,3,4). Phlegmasia cerulea dolens and renal vein thrombosis are rare, but well-described, limb and life-threatening complications of IVC thrombosis (7).
In this review, we aim to enhance the awareness of this uncommon, but morbid, condition, and provide readers with a guide detailing the diagnosis and management of IVC thrombosis with special emphasis on contemporary endovascular treatment modalities.
Etiology
Congenitally abnormal IVC
IVC thrombosis is prevalent (60% to 80%) among patients with congenital IVC anomalies (8–10). These anomalies occur in 0.5% to 1% of the general population, and in 2% to 3% of patients with congenital cardiac defects (9,11). Congenital IVC anomalies can be classified into 3 anatomic categories (12) (Figure 1):
1. Infrarenal: duplicate IVC, persistent left-sided IVC, pre-aortic IVC, and absence of the infrarenal IVC
2. Renal: accessory left renal vein, retroaortic and circumaortic left renal vein
3. Suprarenal: absence of the hepatic IVC with azygos continuation, congenital caval stenosis or atresia, and IVC membranes
Graphic Illustration of the Most Common IVC Congenital Anomalies
IVC = inferior vena cava; L = left; R = right.
Adapted with permission from Truty et al. Congenital Anomalies of the Inferior Vena Cava and Left Renal Vein: Implications During Open Abdominal Aortic Aneurysm Reconstruction. Ann Vasc Surg 2007;21(2):186-97.
Most IVC anomalies are subclinical for many years due to well-developed collaterals. They are often discovered incidentally on abdominal imaging (10). However, thrombosis of the collateral channels or of their feeding vessel (often the common iliac vein) can lead to acute or subacute proximal DVT or findings of chronic venous insufficiency.
Congenitally normal IVC
Thrombosis of the IVC in the absence of congenital abnormalities is rare, and is usually a result of a predisposing hypercoagulable state along with an acquired pathology in the IVC or one of its adjacent structures (1,7,13,14).
1. Prothrombotic factors: thrombophilia, malignancy, oral contraceptives, smoking, obesity, pregnancy, hormonal replacement therapy, and nephrotic syndrome.
2. Abdominal pathology: renal cell tumor, abdominal masses producing extrinsic compression such as a very large uterine fibroid, Budd-Chiari syndrome, abdominal trauma/surgery, May-Thurner syndrome, and thrombotic occlusion of an IVC filter.
Thrombotic occlusion of IVC filters is of particular importance in the United States, where presumed overutilization of IVC filters and low retrieval rates have drawn recent attention. It is estimated that IVC filter placement rates in the United States in 2012 were 25 times that of an equivalent population in Europe (224,700 vs. 9,070) (6). Although the majority of implanted filters are retrievable in design and placed in patients without clinical indications for permanent caval interruption, the highest retrieval rate reported in the United States is only 34%, and some series have reported retrieval rates of <10% (6,15,16). Because late filter thrombosis has been reported in up to 33% of patients (4,6,17), we are faced with a large population of patients who are at risk for IVC thrombosis and its clinical sequelae. A systematic review by Fox and Kahn (18) suggested a significant increase in PTS and venous ulcers in patients with unretrieved IVC filters.
Clinical Presentation
The clinical presentation of IVC thrombosis is often ambiguous and varies significantly according to the acuity, the level, and the extent of thrombosis. Similar to those with lower extremity DVT, patients with IVC thrombosis commonly complain of leg heaviness, pain, swelling, and cramping. Nonspecific back and abdominal/pelvic pain along with scrotal swelling frequently precede leg symptoms (19). Because of its insidious onset, the diagnosis of IVC thrombosis is often made when signs and symptoms of clot migration and/or venous hypertension become apparent. Clot migration or embolization into the lungs and renal veins can manifest with dyspnea and oliguria, respectively (7,17,19). If left untreated, the majority of patients with IVC thrombosis will develop variable degrees of PTS, ranging from leg cramping and skin pigmentation to disabling claudication and or venous ulceration. On rare occasions, the development of large paraspinal collateral channels in chronic IVC occlusion can result in severe lumbar radicular pain, sciatica, and even cauda equina syndrome due to external compression of the spinal cord/peripheral nerves by these dilated veins.
Diagnostic Approach
The diagnosis of IVC thrombosis is challenging for several reasons. First, thrombosis of the IVC usually has an insidious onset and presents with nonspecific symptoms. Second, physicians are often not familiar with IVC thrombosis and may not entertain this diagnosis unless the patient has a proximal lower extremity DVT. Third, the majority of patients with lower extremities DVT do not have IVC thrombosis. Hence, screening all DVT patients for IVC thrombosis can be tedious, low-yield, and cost-ineffective. Fourth, no specific societal guidelines are currently available to aid with the diagnosis and management of IVC thrombosis.
Despite the paucity of data on the best diagnostic approach for IVC thrombosis, the literature suggest that screening for IVC thrombosis is reasonable among patients with a lower extremity DVT with high-risk features (Figure 2) (1,8,9,14,17,19,20).
A Suggested Algorithm for the Diagnosis of IVC Thrombosis
*A minority of patients with IVC thrombosis do not have a proximal iliofemoral DVT. **CT venography may require physician supervision due to the need of individual protocol modification for optimal delayed venous phase imaging. ¶MRI venography is contraindicated in patients with an indwelling IVC filter. AKI = acute kidney injury; CT = computed tomography; DVT = deep vein thrombosis; IJ = internal jugular vein; IVC = inferior vena cava; IVUS = intravascular ultrasound; MRI = magnetic resonance imaging.
Once the diagnosis of IVC thrombosis is suspected, a careful review of the lower extremity duplex ultrasound is warranted. This study may offer clues about an upstream occlusion (loss of respirophasic variation, waveform blunting in the femoral vein, etc.) even when there is no evidence of infrainguinal DVT. A dedicated IVC duplex ultrasound is usually the modality of choice for initial screening. However, ultrasound is operator-dependent, and visualization of the IVC is frequently hampered due to bowel gas or obesity. Therefore, appropriately timed computed tomography (CT) and magnetic resonance (MR) imaging are essential for the diagnosis (13,21). There is no standard CT protocol for imaging of the IVC. The IVC is typically evaluated in the portal venous phase (60 to 70 s after contrast injection), but longer delays (90 to 180 s) should be considered if occlusive thrombus or low cardiac output are suspected (21). Magnetic resonance imaging is the most reliable technique for depicting the presence and extent of tumor thrombus, although limited availability and cost considerations prohibit its routine use. Familiarity with certain pitfalls in imaging of the IVC is critical to avoid missed or overdiagnoses. These pitfalls are primarily related to a flow-related phenomenon at the level of the renal veins, manifesting as a pseudo-filling defect because of the confluence of the enhanced blood in the renal veins and the unenhanced venous return from the lower body (21). It should be noted that MR venography in the presence of an existing IVC filter could be associated with ferromagnetic artifact, which may limit the reader’s ability to assess IVC patency. In these patients, CT venography may be the preferred diagnostic modality. Direct catheter venogram is the definitive diagnostic method. However, this more invasive method can be challenging if occlusive thrombus is present in the femoral and or popliteal access site. Figure 3 illustrates the utility of various diagnostic modalities in the diagnosis of IVC thrombosis.
Diagnostic Modalities for IVC Thrombosis
(A to C) Catheter venography (A) and CT venography (B) in a patient with massive compressive leiomyoma (inset). Note the decompression of the IVC after hysterectomy showing re-expansion of the IVC filter along with resolution of the thrombus (C). Dashed arrow indicates the IVC filter. Asterisk indicates a leiomyoma. (D) A renal (99m-technetium diethylene triamine pentaacetic acid [DPTA]) scan suggestive of renal vascular compromise due to severely reduced uptake of DPTA bilaterally. A′ shows a sudden drop in perfusion at the level of the kidneys (circled) compared with normal perfusion in the spleen (arrow). B′ illustrates a 60-s time activity curve with markedly delayed tracer uptake in the right and left renal arteries indicative of renal vascular compromise. C′ shows delayed (0 to 30 min) static images at 2-min intervals with persistent tracer uptake is seen in both kidneys at 30 min, suggestive of renal vascular obstruction. (E) Catheter venography in a patient with chronic IVC thrombosis and a prior IVC filter. Dashed arrow indicates the IVC filter. Double asterisks indicate significant collateral formation below the site of IVC occlusion. (F) CT venography in a patient with IVC thrombosis extending to the IVC/RA junction. White arrow indicates the IVC thrombus; dashed arrow indicates the IVC filter. LT = left; RT = right; other abbreviations as in Figure 2.
Dedicated imaging for complications of IVC thrombosis should be considered in the appropriate clinical context. These could include: 1) CT angiogram of the thorax to rule out PE may be considered in symptomatic patients. However, the overall management in not likely to change as anticoagulation is a key component in the treatment of IVC thrombosis; 2) nuclear renal scanning to rule out renal vascular compromise if renal vein thrombosis is suspected (Figure 3D); and 3) lumbar spine CT/MR to rule out spinal cord compression if symptoms of compressive neuropathy are present; and 4) finally, suprarenal IVC thrombus can be occasionally visible on echocardiography when detailed subcostal images are recorded (22)
Treatment of IVC Thrombosis
Anticoagulation is the mainstay of treatment for patients with IVC thrombosis. Adjunctive therapeutic modalities are useful in selected patients, depending on the acuity of their presentation (Central Illustration). Patients with acute (<14 days), and subacute (15 to 28 days) presentation who are not at high risk for bleeding might benefit from catheter-directed thrombolysis (CDT)/pharmacomechanical catheter-directed thrombolysis (PMCT) ± percutaneous transluminal angioplasty (PTA)/stenting, whereas those with chronic presentation (>28 days) might benefit from PTA/stenting alone with a limited role for CDT/PMCT (Figure 4).
Treatment Algorithm for Patients With IVC Thrombosis
CDT = catheter-directed thrombolysis; PMCT = pharmacomechanical catheter-directed thrombectomy; PTA = percutaneous transluminal angioplasty; Tx = treatment; other abbreviations as in Figure 2.
Anticoagulation and compressive stockings
The American College of Chest Physicians (ACCP) guidelines on proximal DVT (23), recommend the use of parental anticoagulation in the acute phase, followed by 3 to 6 months of oral anticoagulation for provoked DVT and an extended period of anticoagulation (>12 months) for unprovoked DVT (23). Patients with IVC thrombosis have a large thrombus burden, are at significant risk of thrombosis-related morbidity and mortality, and often have uncorrectable risk factor for rethrombosis (congenital anomaly, remote unretrieved filter, and so on). There are no specific recommendations to guide anticoagulation management in patients with IVC thrombosis. In our practice, we initiate intravenous unfractionated heparin as soon as the diagnosis is suspected. If the patient is not a candidate for additional CDT/PMCT, we also start warfarin at the time of diagnosis and switch unfractionated heparin to enoxaparin upon discharge if the international normalized ratio is not therapeutic. Anticoagulation management of patients who undergo CDT/PMCT is summarized in Table 1.
Periprocedural Management of Anticoagulation and Antiplatelet Therapy in Patients With IVC Thrombosis
The routine use of compression stockings in patients with proximal DVT has been an area of debate. The ACCP guidelines recommend the use of graduated compression stockings (GCS) to reduce the incidence of PTS after acute proximal DVT (grade 2B), and a trial of GCS in patients with an established diagnosis of PTS (23). A recent randomized trial of GCS in patients with proximal DVT (SOX trial) found that compression stockings do not reduce the risk of PTS, and hence recommended against their use (24). However, several limitations of the study preclude its generalizability. In addition, patients with IVC thrombosis have massive thrombus burden and are at significant risk of developing disabling PTS (25). We therefore treat these patients with GCS, applying an ankle pressure of 30 to 40 mm Hg and a lower pressure higher up the leg. In the acute phase, bandages may be used to provide initial compressive therapy if GCS could not be fitted or if a rapid decrease in leg swelling and subsequent refitting of the GCS is expected.
Surgical thrombectomy and systemic thrombolysis
A large percentage of patients with proximal DVT treated with anticoagulation alone develop disabling PTS. Therefore, surgical thrombectomy and systemic thrombolysis have been investigated as complementary treatment to anticoagulation in those patients (26,27). Most published series of surgical thrombectomy studied patients with acute iliofemoral DVT, and reported high success rates and low operative mortality (28,29). However, iliofemoral thrombectomy is a minimally invasive surgery performed by advancing a Fogarty catheter through a femoral venotomy and removing the distal clots with massaging maneuvers. Inferior vena cava thrombectomy is a much more invasive surgery that requires direct caval venotomy ± temporary groin arteriovenous fistula creation and does not allow a concomitant treatment of residual stenosis after thrombectomy (30,31). Therefore, this modality has fallen out of favor and is now limited to patients with tumor-associated thrombus (1,32).
The use of systemic thrombolysis in proximal iliofemoral and iliocaval DVT has been assessed in several randomized trials (28,29,33,34). In these trials, streptokinase led to a complete clot lysis in 45% and partial lysis in 65% of patients, compared with <5% complete lysis and 20% partial lysis for anticoagulant therapy alone. Thrombolytic therapy also led to significant reduction in the rates of PTS. However, this benefit was outweighed by the high frequency of major bleeding complications (14% for streptokinase vs. 4% for heparin alone), which prevented systemic thrombolytic agents from gaining widespread adoption.
Endovascular treatment of IVC thrombosis
Localized delivery of thrombolytic agents directly into the thrombus, also known as CDT, was considered as a potentially safer and more effective alternative to systemic thrombolysis (35). This modality has demonstrated safety and efficacy in multiple vascular beds, and has been increasingly utilized in the treatment of patients with acute IVC thrombosis (36–38). Disadvantages of CDT include the need for multiple treatment sessions in the angiography suite, lengthy infusion times (often up to 48 to 72 h) with attendant patient discomfort, need for meticulous monitoring for bleeding complications and longer intensive care stay. In addition, many patients with venous thrombosis present few days after the onset of their symptoms, making CDT alone less effective due to the rapid organization and fibrosis of the clot. Most of these issues have been addressed by adding mechanical thrombectomy techniques to CDT, which is referred to as PMCT. PMCT reduces the dose of thrombolytic used, critical care unit days as well as total hospital stay and charges (39–44). These devices work by adding low-energy high-frequency ultrasound waves to enhance thrombolysis (EKOS, Bothell, Washington), or by mechanically fragmentation the clot through PMCT via rotating sinusoidal dispersion wires (Trellis-8, Bacchus Vascular, Santa Clara, California) or pulsatile saline jets (AngioJet, Possis Medical, Minneapolis, Minnesota). Most recently, suction thrombectomy with the AngioVac veno-venous bypass system (Vortex Medical, Norwell, Massachusetts) was introduced to treat patients with massive clot burden (45).
Thrombus removal with PMCT in patients with proximal DVT has been shown in several observational studies to significantly reduce the incidence of PTS and improve quality of life (46–50). However, these studies were inconclusive with regards to the comparative safety outcomes of PMCT versus standard anticoagulation due to the small number of patients enrolled. This had led to conflicting guideline recommendations from the American Heart Association and ACCP on the use of PMCT in patients with proximal DVT (23,51). The more definitive NIH-sponsored trial ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) investigating the efficacy of PMCT versus standard anticoagulation therapy for treatment proximal DVT has recently completed enrollment, and may shed more light on the efficacy of contemporary PMCT techniques in these patients (52). Nevertheless, even though IVC thrombosis is classified under the category of proximal DVT, the aforementioned studies rarely include patients with IVC thrombosis. Therefore, the assumed benefit of PMCT in this subgroup of patients is largely extrapolative.
Despite the current lack of robust data or unified recommendations, the utilization rate of adjunctive mechanical modalities in the treatment of IVC thrombosis in the United States has increased from 16% in 2005 to 35% in 2011 (Figure 5) (38). This trend is likely due to the increasing recognition of the morbidity associated with IVC thrombosis and the limited effectiveness of traditional anticoagulation in its treatment. In the following text, we describe some commonly available options for percutaneous treatment of IVC thrombosis (Table 2).
Temporal Trends of CDT Utilization in The Treatment of IVC Thrombosis in the United States, 2005–2011
1 indicates catheter-directed thrombolysis (CDT). IVC = inferior vena cava thrombosis.
Comparison of Endovascular Treatment Modalities for Patients With IVC Thrombosis
Percutaneous treatment modalities
Peripheral infusion catheter-directed thrombolysis
Infusion catheters have side holes for uniform slow dispersion of therapeutic agents within the clotted segment. Typically, after the thrombus is crossed with a 0.035-inch wire (angled glide wire, Terumo, Tokyo, Japan), and an infusion catheter is advanced into the clotted segment. Our agent of choice alteplase (10 mg mixed in 1,000 ml of 0.9% NaCl), infused at a rate of 0.01 mg/kg/h to a maximum of 24 mg in 24 h (53). During infusion, hemoglobin, Partial thromboplastin time and fibrinogen levels are monitored every 4 to 6 h to minimize bleeding complications. A fibrinogen level of <150 mg/dl is associated with significantly higher risk of major bleeding during thrombolytic infusion (54). Therefore, it is our practice is to stop/decrease the infusion rate when the fibrinogen level drops below 100 mg/dl. Repeat venography is performed every 12 to 24 h to assess clot resolution. If the angiographic results are unsatisfactory (<50% of clot lysis), thrombolytic therapy can be repeated, but for a maximum duration of <96 h.
Ultrasound-enhanced CDT
This system comprises a 5.2-F multilumen drug delivery catheter, an ultrasound core wire, and a controller (Figure 6A). The catheter is advanced over a guidewire to traverse the length of the thrombus, and the guidewire is exchanged for the ultrasound core wire. The thrombolytic agent is infused and ultrasound energy is turned on simultaneously. Ultrasound waves accelerate the thrombolysis process by disturbing the fibrin matrix within the thrombus, which exposes more binding sites for the thrombolytic agent, causing acoustic streaming, thus driving the thrombolytic deep into the thrombus. EKOS showed similar efficacy in thrombolysis, but possibly shorter treatment duration, compared with standard infusion catheters (35). Given the lack of evidence to suggest significant additional benefit over standard catheters and the added cost, the role of the EKOS catheter as a first-line device in patients with IVC thrombosis remains questionable. A prospective multicenter registry, ACCESS PTS (Accelerated Thrombolysis for Post Thrombotic Syndrome Using the EKOS System) study, is ongoing to further assess the safety and efficacy of the EKOS system combined with CDT among individuals with proximal chronic DVT and PTS.
Illustration of Endovascular Treatment Modalities for Patients With IVC Thrombosis
(A) The EKOS ultrasound-enhanced CDT system. (B) The AngioJet CDT + PMT rheolytic system. (C) The Trellis CDT + PMT system. (D) The AngioVac extracorporeal bypass aspiration system. (E) The AngioVac suction cannula. PMT = pharmacomechanical thrombolysis; other abbreviations as in Figures 2 and 4.
AngioJet rheolytic thrombectomy
This system is a combined PMCT system, which consists of 3 components: a single-use dual-lumen catheter, pump set, and a pump drive unit (Figure 6B). The catheter consists of one lumen supplying pressurized saline to the distal catheter tip, and a second lumen incorporating the first lumen, guidewire, and thrombus particulate debris. The drive unit/pump generates high-pressure (10,000 psi) pulsatile saline flow that exits the catheter tip through multiple retrograde-directed jets. These jets create a localized low-pressure zone (Bernoulli effect) for thrombus aspiration and maceration, and provide the driving force for evacuation of thrombus debris through the catheter (55). The system also has a PowerPulse Spray feature that allows direct infusion of thrombolytic drugs into the clot. In a typical case, the IVC clot is traversed with the AngioJet catheter over a 0.035-inch wire. The catheter outflow lumen is occluded and up to 10 mg of Alteplase diluted in 50 ml of saline is injected into the clot in a pulse spray fashion during catheter withdrawal. The thrombolytic agent is allowed 15 to 30 min to work before thrombectomy is performed with the outflow lumen reopened. The major advantage of the AngioJet system is its ability to reduce the duration and the dose of thrombolytic therapy. We have found the new Zellante AngioJet device to be particularly helpful in caval thrombosis patients.
The Trellis peripheral infusion system (isolated PMCT)
The Trellis has 2 occluding balloons, drug infusion holes, and mechanical fluid dispersion capabilities (Figure 6C). This catheter is placed in the clotted segment, and the 2 balloons are inflated to isolate the thrombus. Once the drug is dispersed through the catheter side holes, the catheter oscillates, mixing the thrombolytic drug into the blood clot. After 10 min, the remaining thrombolytic agent and the dissolved portion of the clot are aspirated. A potential advantage of this system is that it isolates the thrombus and provides targeted therapy. Utilizing the Trellis device for the treatment of iliofemoral and IVC thrombosis has been shown to decrease the duration and dose of thrombolytic therapy, and achieve a higher lytic success rate (41,56,57). Certain technical limitations of this device should be noted: First, the device is designed to treat short (10 to 30 cm) thrombotic segments. However, treating longer segments with sequential sessions or kissing balloon techniques has been reported (58). Second, the Trellis balloons may not expand enough to occlude a large IVC. Third, in case of IVC-filter thrombosis, the presence of the filter in the treatment zone may affect the rotational efficacy of the Trellis catheter. Finally, the Trellis device was recently subject to a Class I recall by the Food and Drug Administration due to mislabeling error of the balloon inflation ports, and is therefore temporarily off the market.
Suction thrombectomy: AngioVac veno-venous bypass
The AngioVac circuit is an extracorporeal veno-venous bypass system that is designed to remove large clots in an en-bloc fashion from large vasculature such as the IVC (Figures 6D and 6E), right heart, or proximal pulmonary artery. The system includes a 22-F coil-reinforced suction cannula with a balloon-expandable funnel-shaped distal tip and a 17-F reinfusion cannula. The suction cannula can be advanced to the clot via a femoral or internal jugular vein access. The venous blood along with the thrombus is drained via the tip of the suction cannula by a centrifugal pump and passed through a filter, which removes the thrombus and then reinfuses the venous blood into a central vein via a reinfusion cannula (Figure 7D). Several small series suggested a role for AngioVac in the treatment of IVC thrombosis (59–61). This modality is particularly useful in patients with acute IVC thrombosis and a contraindication to thrombolysis.
Combined Suction Thrombectomy and CDT/PMCT in a Patient With Massive IVC Thrombosis
(A) Suction thrombectomy with the AngioVac aspiration catheter (arrow). (B) Catheter venography performed via left femoral vein access (asterisk), revealing significant residual thrombus in the IVC and the iliac veins. Inset (B′) shows the filtered clot during suction thrombectomy with the AngioVac system. (C) Catheter venography performed via left femoral vein access (asterisk), revealing near complete resolution of the iliocaval thrombosis after CDT/PMCT with the AngioJet system. PMCT = pharmacomechanical catheter-directed thrombolysis; other abbreviations as in Figures 2 and 4.
In contemporary practice, operators view these devices as complementary rather than alternative tools that can be often be used in conjunction with CDT in selected patients (Figure 7).
Adjunctive Imaging and Interventions
Angioplasty/stent
Fibrotic transformation of the thrombus occurs within 2 weeks of clot formation (4). Because patients with IVC thrombosis often present late, they usually have a combination of acute soft thrombus and a chronic fibrotic thrombus. Although the acute thrombus can effectively be treated with PMCT, the fibrotic component is less amenable to these therapies, resulting in high frequency of residual luminal stenosis after PMCT (Figure 8). Untreated residual stenosis following thrombectomy is associated with high rates of recurrent DVT. In a large series of iliocaval thrombosis patients treated with surgical thrombectomy, the rate of recurrent DVT was 73% in those with untreated residual outflow stenosis versus 13% in those who had venoplasty/stenting of residual stenosis (p < 0.01) (62). Adjunctive balloon angioplasty and stenting to restore venous patency in patients with iliocaval DVT is also effective in preventing the recurrence of thrombosis, reducing PTS, enabling healing of venous ulcers, and improving quality-of-life measures (63–66). In contemporary U.S. practice, 60% of patients who undergo PMCT for IVC thrombosis received balloon venoplasty ± stenting (38). Several technical considerations should be emphasized when IVC stenting is entertained:
1. Choice of IVC stent: one limitation of stenting in the IVC is the limited choice of stents suitable for use in the IVC. Only 2 stainless steel stents, the Wallstent (Boston Scientific Corporation, Natick, Massachusetts), the Z-stent (Cook, Bloomington, Indiana) are available in large enough sizes for IVC stenting (up to 24 mm and 35 mm, respectively). The Wallstent offers strength and flexibility but suffers from foreshortening, which make precise placement challenging. The Z-stent offers a few advantages over the Wallstent, due to its minimal foreshortening, more radial force, and its larger interstices; however, it has large fixing spines and therefore carries a higher risk of caval perforation (67).
2. Stenting across IVC filters: in cases of IVC filter-related thrombosis, the residual stenosis after PMCT is frequently located within the filter. Stenting across the filter might, therefore, be necessary to ensure patency of the caval outflow. Many operators have expressed reluctance to dilate the filter-bearing segment for fear of tearing the IVC, fracturing or displacing filters, or increasing the risk for subsequent PE. However, in a large series of patients undergoing IVC stenting for chronically occluded IVC, stenting across the filter was safe and did not result in an increased morbidity or mortality (64).
3. Stenting across the iliocaval bifurcation: In the majority of cases of IVC thrombosis, the thrombus extends into the iliocaval confluence. Stenting across the iliocaval confluence may also be necessary if significant lesions are present after PMCT. Although multiple techniques have been described for stenting of the iliocaval bifurcation, the kissing stents technique seems to yield the best long-term patency rates (63,65).
4. External compression: If clinically indicated, removal of external compressive masses may lead to spontaneous decompression of the IVC (Figures 3A to 3C). However, if surgical relief of the external compression is not possible, stenting of the IVC is appropriate and technically feasible.
Adjunctive Balloon Angioplasty and Stenting in Patients with IVC Thrombosis
(A) Cavogram in a patient with chronic IVC thrombosis and severe PTS following CDT with EKOS. Significant residual IVC stenosis is seen due to the chronicity of the thrombosis. Arrow indicates the IVC filter. B shows restoration of flow in the IVC after adjunction balloon angioplasty and stenting (dashed arrow) with 2 self-expanding stents. (C) Cavogram in a patient with acute IVC thrombosis. Complete occlusion of the IVC is seen at the level of the filter (arrow). D shows acceptable results (>50% clot lysis) following 1 treatment session with AngioJet and 12-h tissue-type plasminogen activator infusion via a fountain catheter. PTS = post-thrombotic syndrome; other abbreviations as in Figures 2 and 4.
Finally, it should be noted that the iliocaval system is a low pressure system and routine follow-up with duplex ultrasonography, CT, or catheter venography is necessary to maintain primary assisted patency.
Intravascular ultrasound
Intravascular ultrasound can help provide very useful complementary information on the underlying pathology behind clot formation and help guide therapy (e.g., in patients with suspected renal vein thrombosis or May-Thurner syndrome). It can also be used to evaluate thrombus burden, degree of stenosis, and adjacent structures (Figure 9). Occasionally, intravascular ultrasound can detect fibrous bands, webs, spurs, and trabeculations seen in recanalized DVT, which may be missed on traditional venography.
Illustration of IVUS Utility in the Treatment of IVC Thrombosis
(A) Invasive venography of a patient presenting with IVC thrombosis. Large residual thrombus is seen at and above the level of the IVC filter after PMCT with AngioJet. Severe IVC stenosis is seen near the IVC/right atrial junction and is confirmed with IVUS imaging (inset). (B and C) IVUS guided stenting of the IVC below (B) and above (C) the IVC filter. The IVC stenosis at the IVC/RA junction was hemodynamically significant (gradient >10 mm Hg), and was therefore stented to prevent recurrent IVC thrombosis. Abbreviations as in Figures 2, 4, and 7.
Diagnosis and Management of Inferior Vena Cava Thrombosis
Prophylactic IVC filters
A major concern related to PMCT in the IVC has been development of PE; however, the data on the use of IVC filters as an adjunct to PMCT remain controversial. In contemporary U.S. practice, ∼20% of patients received a prophylactic IVC filter before or at the time of PMCT (38). Although it is intuitive to assume that the use of mechanical thrombectomy devices will increase the risk of distal embolization, a study of 40 patients who had retrievable filters placed before CDT and removed after the procedure found no correlation between the use of these devices and the detection of embolized clot in the filters (68). Most operators opt to place a retrievable IVC filter in the infrarenal or suprarenal segments of IVC only in high-risk patients such as those with large floating thrombus and those with diminished lung reserve (68,69). Given the significant morbidity associated with IVC filter thrombosis, removal of these filters as soon as possible should be planned at the outset.
Conclusions
IVC thrombosis is an under-recognized entity that is associated with significant short- and long-term morbidity. The diagnosis of IVC thrombosis is challenging, and a high index of suspicion is required. Knowledge of the pitfalls of noninvasive IVC imaging is essential to select the appropriate and the highest yield modality. Once the diagnosis is confirmed, immediate treatment is warranted to avoid the acute and chronic complications of this disease. The limited effectiveness of anticoagulation alone, and the unfavorable risk/benefit ratio of systemic thrombolysis and surgical thrombectomy, led to the development and the widespread utilization of CDT ± PMCT in the treatment of IVC thrombosis. In the absence of randomized trials or societal guidelines, careful case selection and technical expertise in CDT ± PMCT are essential for successful endovascular management of IVC thrombosis.
Footnotes
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- ACCP
- American College of Chest Physicians
- CDT
- catheter-directed thrombolysis
- CT
- computed tomography
- DVT
- deep vein thrombosis
- GCS
- graduated compression stockings
- IVC
- inferior vena cava
- MR
- magnetic resonance
- PE
- pulmonary embolism
- PMCT
- pharmacomechanical catheter-directed thrombolysis
- PTA
- percutaneous transluminal angioplasty
- PTS
- post-thrombotic syndrome
- Received September 8, 2015.
- Revision received November 22, 2015.
- Accepted December 17, 2015.
- American College of Cardiology Foundation
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